Professor Bob W Snow

Research Area: Global Health
Technology Exchange: Computational biology
Scientific Themes: Tropical Medicine & Global Health
Keywords: GIS, malaria, public health and mapping
Web Links:

Bob has worked in Africa since 1984. He is Professor of Tropical Public Health at the Centre for Tropical Medicine, Nuffield Department of Medicine, University of Oxford and Chairman of the Malaria Public Health Department of the KEMRI-Wellcome Trust - University of Oxford Collaborative Programme in Kenya.

Bob's work began with the first African clinical trials of Insecticide-treated bed nets (ITN) between 1985-1987 at the UK's Medical Research Council labs at Farafenni, The Gambia. His interest in the role ITN play in child survival and the need for equitable access has continued for over 25 years, ensuring that a body of science drives national and international policy to guarantee that these interventions reach the most biologically and economically vulnerable communities free of charge across Africa.  

Bob's research interests are founded in trying to understand the complex epidemiology of malaria parasite exposure, clinical disease outcomes and optimized, targeted approaches to reducing the malaria burden in Africa. In January 1989, Bob moved to Kilifi, on the Kenyan coast, to establish epidemiological studies in an area surrounding the rural district hospital. Over the last 25 years, this programme has grown into a multidisciplinary internationally recognized centre of research excellence. In 1996, Bob moved to Nairobi to expand the Oxford-Kenyan programme, investigating the epidemiology of severe malaria and malaria mortality across the region, including the establishment of the Pan-African collaboration known as the Mapping Malaria Risk in Africa (MARA/ARMA) collaboration with partners at the MRC in South Africa. MARA served as a prelude to the Malaria Atlas Project (MAP), a global initiative, founded by Bob in 2005. From 2010, this project is co-directed from Kenya with Dr Abdisalan Mohamed Noor, supporting a more effective way of working directly with national, malaria endemic country partners and governments across the African continent and the Arabian Peninsula.

As chairman of various national malaria control programme workshops he continues to promote the value of science in malaria policy development across the region. Working through various international agencies, Bob has been able to maintain a strategic, evidence-based argument for a continued focus on malaria control and disease reduction in Africa and sustain a focus of attention on financing control in poor, high burden countries across the continent. He provided keynote addresses at to the UK's All-Party Parliamentary Group on Malaria and Neglected Tropical Diseases in 2010, the 19th Roll Back Malaria Partnership Board meeting in Lusaka in 2010 and presentations on the need for effective use of evidence to prioritize control and elimination ambitions to ministers of health and various health departments in Kenya, Swaziland, Namibia, Djibouti, Mali, Uganda, Zanzibar, The Gambia, Ethiopia, Nigeria and the Kingdom of Saudi Arabia between 2007-2013. The research from the Malaria Public Health Department has provided the evidence to articulate a science-driven realistic malaria policy to those charged with setting agenda's internationally and nationally and has incrementally improved the use of this research to guide priorities in malaria control. 

Bob is committed to developing science capacity and the research-to-policy agenda in Africa. He has supervised 16 post-graduates through their doctoral programmes, seven masters students and has supported five post-doctoral fellows. Bob supports the Kenyan Programme's director, and long time colleague since they worked together in The Gambia, Professor Kevin Marsh, in the evolution and future strategic direction of the wider Kenyan-Oxford programme through to 2020. 

Bob has published over 380 articles on malaria with an h-index of over 80 from 22,400 life-time citations. In 2009 he was ranked joint 3rd highest malaria citation author as part of the Wellcome Trust 10 year review and the 5th most cited EU malaria scientist between 1997 and 2007

Bob is a technical advisor to the Kenyan Government. Among other international advisory panels he is a committed advisory board member of the UKs Malaria No More and the Against Malaria Foundation, that was recently voted best charity by the independent auditor, GiveWell. He is supported by the Wellcome Trust (UK) as a Principal Fellow and was made a Fellow of the Academy of Medical Sciences in 2008.

Name Department Institution Country
Dr Catherine Linard L'Université libre de Bruxelles Belgium
Dr Socé Fall RBM-AFRO Congo Brazzaville
Dr Hoda Atta WHO-EMRO, Malaria Control & Elimination Egypt
Dr Ghasem Zamani WHO-EMRO, Malaria Control & Elimination Egypt
Professor Umberto D’Alessandro Medical Research Council Gambia
Richard Kamwi Ministry of Health & Social Welfare Namibia
Professor Ibrahim El Hassan University of Jazan Saudi Arabia
Dr Jamal Amran WHO-EMRO, Malaria Control & Elimination Somalia
Professor Mukhtar Maowia Institute of Endemic Diseases University of Khartoum Sudan
Dr Khalid El Mardi National Vector Borne Disease Programme Sudan
Dr Catherine Goodman London School of Hygiene and Tropical Medicine United Kingdom
Professor Feiko ter Kuile Liverpool School of Tropical Medicine United Kingdom
Professor Mike English Tropical Medicine Oxford University, Nairobi Kenya
Dr Yazome Ye ICF Measure Programme United States
Dr Alex Rowe Centers for Disease Control United States
Professor Caroline Buckee Center for Communicable Disease Dynamics, Epidemiology Harvard School of Public Health United States
Dr Bruce Larsen Boston University, Center for International Health United States
Dr Abdinasir Amin ICF Measure Programme Kenya
Professor David Hamer Zambia Center for Applied Health Research & Development Zambia
Professor Alex Welte South African Centre for Epidemiology & Mathematical Analysis, Stellenbosh South Africa
Dr Fabrizio Molteni National Malaria Control Programme, Dar es Salaam Tanzania
Dr Julie Makani Tropical Medicine Oxford University, Dar es Salaam Tanzania
Dr Yeka Adoke Makerere University, Kampala Uganda
Dr Ali al Sharani Ministry of health, Aseer Saudi Arabia
Dr Adel Al Jasari National Malaria control Programme, Sana’a Yemen
Professor Maureen Coetzee Witts university, Johannesburg South Africa
Dr Ogoboro Doumba Malaria Reseach & Training Centre, Bamako Mali
Dr Sam Smith National Malaria Control Programme, Freetown Sierra Leone
Dr Rebecca Kiptui National Malaria Control Programme, Nairobi Kenya
Dr Sarah Staedke Uganda Malaria Surveillance Project, Makerere University, Kampala Uganda
Dr Milijaona Randrianarivelojosia Institute Pasteur, Antananarivo Madagascar
Dr Jean-Francois Trape Institute of Research and Development, Dakar Senegal
Professor David Schellenberg London School of Hygiene & Tropical Medicine, London United Kingdom
Professor Sir Brian Greenwood London School of Hygiene & Tropical Medicine, London United Kingdom
Professor Peter Diggle University of Lancaster, Lancaster United Kingdom
Professor Benn Sartorius University of Kwa Zulu Natal, Durban South Africa
Mogeni P, Williams TN, Fegan G, Nyundo C, Bauni E, Mwai K, Omedo I, Njuguna P et al. 2016. Age, Spatial, and Temporal Variations in Hospital Admissions with Malaria in Kilifi County, Kenya: A 25-Year Longitudinal Observational Study. PLoS Med, 13 (6), pp. e1002047. | Show Abstract | Read more

BACKGROUND: Encouraging progress has been seen with reductions in Plasmodium falciparum malaria transmission in some parts of Africa. Reduced transmission might lead to increasing susceptibility to malaria among older children due to lower acquired immunity, and this has implications for ongoing control strategies. METHODS AND FINDINGS: We conducted a longitudinal observational study of children admitted to Kilifi County Hospital in Kenya and linked it to data on residence and insecticide-treated net (ITN) use. This included data from 69,104 children aged from 3 mo to 13 y admitted to Kilifi County Hospital between 1 January 1990 and 31 December 2014. The variation in malaria slide positivity among admissions was examined in logistic regression models using the following predictors: location of the residence, calendar time, the child's age, ITN use, and the enhanced vegetation index (a proxy for soil moisture). The proportion of malaria slide-positive admissions declined from 0.56 (95% confidence interval [CI] 0.54-0.58) in 1998 to 0.07 (95% CI 0.06-0.08) in 2009 but then increased again through to 0.24 (95% CI 0.22-0.25) in 2014. Older children accounted for most of the increase after 2009 (0.035 [95% CI 0.030-0.040] among young children compared to 0.22 [95% CI 0.21-0.23] in older children). There was a nonlinear relationship between malaria risk and prevalence of ITN use within a 2 km radius of an admitted child's residence such that the predicted malaria positive fraction varied from ~0.4 to <0.1 as the prevalence of ITN use varied from 20% to 80%. In this observational analysis, we were unable to determine the cause of the decline in malaria between 1998 and 2009, which pre-dated the dramatic scale-up in ITN distribution and use. CONCLUSION: Following a period of reduced transmission, a cohort of older children emerged who have increased susceptibility to malaria. Further reductions in malaria transmission are needed to mitigate the increasing burden among older children, and universal ITN coverage is a promising strategy to achieve this goal.

Mackinnon MJ, Ndila C, Uyoga S, Macharia A, Snow RW, Band G, Rautanen A, Rockett KA, Kwiatkowski DP, Williams TN. 2016. Environmental Correlation Analysis for Genes Associated with Protection against Malaria. Mol Biol Evol, 33 (5), pp. 1188-1204. | Show Abstract | Read more

Genome-wide searches for loci involved in human resistance to malaria are currently being conducted on a large scale in Africa using case-control studies. Here, we explore the utility of an alternative approach-"environmental correlation analysis, ECA," which tests for clines in allele frequencies across a gradient of an environmental selection pressure-to identify genes that have historically protected against death from malaria. We collected genotype data from 12,425 newborns on 57 candidate malaria resistance loci and 9,756 single nucleotide polymorphisms (SNPs) selected at random from across the genome, and examined their allele frequencies for geographic correlations with long-term malaria prevalence data based on 84,042 individuals living under different historical selection pressures from malaria in coastal Kenya. None of the 57 candidate SNPs showed significant (P < 0.05) correlations in allele frequency with local malaria transmission intensity after adjusting for population structure and multiple testing. In contrast, two of the random SNPs that had highly significant correlations (P < 0.01) were in genes previously linked to malaria resistance, namely, CDH13, encoding cadherin 13, and HS3ST3B1, encoding heparan sulfate 3-O-sulfotransferase 3B1. Both proteins play a role in glycoprotein-mediated cell-cell adhesion which has been widely implicated in cerebral malaria, the most life-threatening form of this disease. Other top genes, including CTNND2 which encodes δ-catenin, a molecular partner to cadherin, were significantly enriched in cadherin-mediated pathways affecting inflammation of the brain vascular endothelium. These results demonstrate the utility of ECA in the discovery of novel genes and pathways affecting infectious disease.

Karuri SW, Snow RW. 2016. Forecasting paediatric malaria admissions on the Kenya Coast using rainfall. Glob Health Action, 9 pp. 29876. | Show Abstract | Read more

BACKGROUND: Malaria is a vector-borne disease which, despite recent scaled-up efforts to achieve control in Africa, continues to pose a major threat to child survival. The disease is caused by the protozoan parasite Plasmodium and requires mosquitoes and humans for transmission. Rainfall is a major factor in seasonal and secular patterns of malaria transmission along the East African coast. OBJECTIVE: The goal of the study was to develop a model to reliably forecast incidences of paediatric malaria admissions to Kilifi District Hospital (KDH). DESIGN: In this article, we apply several statistical models to look at the temporal association between monthly paediatric malaria hospital admissions, rainfall, and Indian Ocean sea surface temperatures. Trend and seasonally adjusted, marginal and multivariate, time-series models for hospital admissions were applied to a unique data set to examine the role of climate, seasonality, and long-term anomalies in predicting malaria hospital admission rates and whether these might become more or less predictable with increasing vector control. RESULTS: The proportion of paediatric admissions to KDH that have malaria as a cause of admission can be forecast by a model which depends on the proportion of malaria admissions in the previous 2 months. This model is improved by incorporating either the previous month's Indian Ocean Dipole information or the previous 2 months' rainfall. CONCLUSIONS: Surveillance data can help build time-series prediction models which can be used to anticipate seasonal variations in clinical burdens of malaria in stable transmission areas and aid the timing of malaria vector control.

El Hassan IM, Sahly A, Alzahrani MH, Alhakeem RF, Alhelal M, Alhogail A, Alsheikh AA, Assiri AM et al. 2015. Progress toward malaria elimination in Jazan Province, Kingdom of Saudi Arabia: 2000-2014. Malar J, 14 (1), pp. 444. | Show Abstract | Read more

BACKGROUND: The draft Global Technical Strategy for malaria aims to eliminate malaria from at least 10 countries by 2020. Yemen and Saudi Arabia remain the last two countries on the Arabian Peninsula yet to achieve elimination. Over the last 50 years, systematic efforts to control malaria in the Kingdom of Saudi Arabia has successfully reduced malaria cases to a point where malaria is now constrained largely to Jazan Province, the most south-western area along the Red Sea. The progress toward elimination in this province is reviewed between 2000 and 2014. METHODS: Data were obtained from the Ministry of Health case-reporting systems, activity reports, unpublished consultants reports, and relevant scientific published papers. Sub-provincial population data were obtained the national household censuses undertaken in 2004 and 2010. Rainfall data were obtained from the Meteorological Department in Jazan. RESULTS: Between 2000 and 2014 there were 5522 locally acquired cases of malaria and 9936 cases of imported malaria. A significant reduction in locally acquired malaria cases was observed from 2000 to 2014, resulting in an average annual incidence (2010-2014) of 0.3 cases per 10,000 population. Conversely imported cases, since 2000, remain consistent and higher than locally acquired cases, averaging between 250 and 830 cases per year. The incidence of locally acquired cases is heterogeneous across the Province, with only a few health districts contributing the majority of the cases. The overall decline in malaria case incidence can be attributed to coincidental expansion of control efforts and periods of exceptionally low rainfall. CONCLUSIONS: Jazan province is poised to achieve malaria elimination. There is a need to change from a policy of passive case detection to reactively and proactively detecting infectious reservoirs that require new approaches to surveillance. These should be combined with advanced epidemiological tools to improve the definitions of epidemiological receptive and hotspot malaria risk mapping. The single largest threat currently remains the risks posed by imported infections from Yemen.

Okoyo C, Mwandawiro C, Kihara J, Simiyu E, Gitonga CW, Noor AM, Njenga SM, Snow RW. 2015. Comparing insecticide-treated bed net use to Plasmodium falciparum infection among schoolchildren living near Lake Victoria, Kenya. Malar J, 14 (1), pp. 515. | Show Abstract | Read more

BACKGROUND: Under trial conditions insecticide-treated nets have been shown to provide significant clinical and mortality protection under a range of malaria transmission intensity conditions. There are, however, few operational impact data, notably in very intense transmission conditions. This study, reports on malaria infection among Kenyan schoolchildren living in areas of intense malaria transmission and their reported use of insecticide-treated bed nets. METHODS: 5188 children in 54 schools were randomly sampled from seven counties surrounding Lake Victoria between May and June 2014. A questionnaire was administered to schoolchildren in classes 2-6 on the use of a long-lasting, insecticide-treated net (LLIN) the night before the survey and provided a single blood sample for a rapid diagnostic test for malaria infection. Analysis of the impact of insecticide-treated net use on malaria prevalence was undertaken using a multivariable, mixed effects, logistic regression at 95% confidence interval (CI), taking into account hierarchical nature of the data and results adjusted for school clusters. RESULTS: The overall prevalence of malaria infection was 48.7%, two-thirds (67.9%) of the children reported using LLIN, 91.3% of the children reported that their households own at least one LLIN and the household LLIN coverage was 2.5 persons per one LLIN. The prevalence of infection showed variation across the counties, with prevalence being highest in Busia (66.9%) and Homabay (51.8%) counties, and lowest in Migori County (29.6%). Generally, malaria parasite prevalence differed between age groups and gender with the highest prevalence occurring in children below 7 years (50.6%) and males (52.2%). Adjusting for county and school, there was a significant reduction in odds of malaria infection among the schoolchildren who reported LLIN use the previous night by 14 % (aOR 0.86, 95% CI 0.74-0.98, P < 0.027). CONCLUSION: Malaria transmission continues to be high around Lake Victoria. Despite evidence of increasing pyrethroid resistance and the likely overall efficacy of LLIN distributed several years prior to the survey, LLIN continue to provide protection against infection among school-aged children.

Makani J, Mgaya J, Balandya E, Msami K, Soka D, Cox SE, Komba AN, Rwezaula S et al. 2015. Bacteraemia in sickle cell anaemia is associated with low haemoglobin: a report of 890 admissions to a tertiary hospital in Tanzania. Br J Haematol, 171 (2), pp. 273-276. | Show Abstract | Read more

Bacteraemia is a leading cause of morbidity in sickle cell anaemia (SCA), but information from studies in Africa is limited. We evaluated 890 admissions from 648 SCA patients at a tertiary hospital in Tanzania. Bacteraemia was present in 43 admissions (4·8%); isolates included Staphylococcus aureus (12/43; 28%), non-Typhi Salmonella (9/43; 21%), Streptococcus pneumoniae (3/43; 7%) and Salmonella Typhi (2/43; 5%). Compared to SCA patients without bacteraemia, SCA patients with bacteraemia had significantly lower haemoglobin [71 g/l vs. 62 g/l, odds ratio 0·72 (95% confidence interval 0·56-0·91), P < 0·01]. Further exploration is needed of the relationship between anaemia and bacterial infections in SCA in Africa.

van Eijk AM, Hill J, Noor AM, Snow RW, ter Kuile FO. 2015. Prevalence of malaria infection in pregnant women compared with children for tracking malaria transmission in sub-Saharan Africa: A systematic review and meta-analysis The Lancet Global Health, 3 (10), pp. e617-e628. | Show Abstract | Read more

© 2015 van Eijk et al.Background: In malarious areas, pregnant women are more likely to have detectable malaria than are their non-pregnant peers, and the excess risk of infection varies with gravidity. Pregnant women attending antenatal clinic for their first visit are a potential pragmatic sentinel group to track the intensity of malaria transmission; however, the relation between malaria prevalence in children, a standard measure to estimate malaria endemicity, and pregnant women has never been compared. Methods: We obtained data on malaria prevalence in pregnancy from the Malaria in Pregnancy Library (January, 2015) and data for children (0-59 months) were obtained from recently published work on parasite prevalence in Africa and the Malaria in Pregnancy Library. We used random effects meta-analysis to obtain a pooled prevalence ratio (PPR) of malaria in children versus pregnant women (during pregnancy, not at delivery) and by gravidity, and we used meta-regression to assess factors affecting the prevalence ratio. Findings: We used data from 18 sources that included 57 data points. There was a strong linear relation between the prevalence of malaria infection in pregnant women and children (r=0·87, p<0·0001). Prevalence was higher in children when compared with all gravidae (PPR=1·44, 95% CI 1·29-1·62; I<sup>2</sup>=80%, 57 studies), and against multigravidae (1·94, 1·68-2·24; I<sup>2</sup>=80%, 7 studies), and marginally higher against primigravidae (1·16, 1·05-1·29; I<sup>2</sup>=48%, 8 studies). PPR was higher in areas of higher transmission. Interpretation: Malaria prevalence in pregnant women is strongly correlated with prevalence data in children obtained from household surveys, and could provide a pragmatic adjunct to survey strategies to track trends in malaria transmission in Africa. Funding: The Malaria in Pregnancy Consortium, which is funded through a grant from the Bill & Melinda Gates Foundation to the Liverpool School of Tropical Medicine, UK; US Centers for Disease Control and Prevention; and Wellcome Trust, UK.

Noor AM, Kibuchi E, Mitto B, Coulibaly D, Doumbo OK, Snow RW. 2015. Sub-National Targeting of Seasonal Malaria Chemoprevention in the Sahelian Countries of the Nouakchott Initiative. PLoS One, 10 (8), pp. e0136919. | Show Abstract | Read more

BACKGROUND: Seasonal malaria chemoprevention (SMC) has been shown to be highly efficacious against clinical malaria in areas where transmission is acutely seasonal. SMC targeting depends on a complex interplay of climate, malaria transmission and population distribution. In this study a spatial decision support framework was developed to identify health districts suitable for the targeting of SMC across seven Sahelian countries and northern states of Nigeria that are members of the Nouakchott Initiative. METHODS: A spatially explicit decision support framework that links information on seasonality, age-structured population, urbanization, malaria endemicity and the length of transmission season was developed to inform SMC targeting in health districts. Thresholds of seasonality, population and receptive risks were defined to delineate SMC suitable health districts and define the age range of children for targeting. Numbers of children were then computed for the period 2015-2020 in SMC districts. For 2015, this was combined with maps of length of malaria transmission seasons and WHO recommended treatment regimen to quantify the number of tablets required across the SMC health districts. RESULTS: A total of 597 Sahelian health districts were mapped, out of which 478 (80.1%) were considered suitable for SMC based on seasonality and endemicity thresholds. These districts had an estimated 119.8 million (85%) of the total population in 2015. In the six years from 2015-2020, it is estimated that a total of 158 million children 3m to <5 years, 121 million of whom were in rural areas, will need SMC to achieve universal coverage in the Sahel. If the upper age limit of SMC targeted children was increased to <10 years in low transmission districts, a total 177 million overall, of whom 135 million were rural children, will require chemoprevention in 2015-2020. In 2015 alone, an estimated 49-72 million SP tablets and 148-217 million AQ tablets will be needed to cover all or rural children respectively under the different scenarios of upper age limits. CONCLUSIONS: Our proposed framework provides a standardised approach to support targeting and scale up of SMC by the countries of the Nouakchott Initiative. Our analysis suggests that the vast majority of the population in this region are likely to benefit from SMC and substantial resources will be required to reach universal coverage each year.

van Eijk AM, Hill J, Noor AM, Snow RW, ter Kuile FO. 2015. Prevalence of malaria infection in pregnant women compared with children for tracking malaria transmission in sub-Saharan Africa: a systematic review and meta-analysis. Lancet Glob Health, 3 (10), pp. e617-e628. | Show Abstract | Read more

BACKGROUND: In malarious areas, pregnant women are more likely to have detectable malaria than are their non-pregnant peers, and the excess risk of infection varies with gravidity. Pregnant women attending antenatal clinic for their first visit are a potential pragmatic sentinel group to track the intensity of malaria transmission; however, the relation between malaria prevalence in children, a standard measure to estimate malaria endemicity, and pregnant women has never been compared. METHODS: We obtained data on malaria prevalence in pregnancy from the Malaria in Pregnancy Library (January, 2015) and data for children (0-59 months) were obtained from recently published work on parasite prevalence in Africa and the Malaria in Pregnancy Library. We used random effects meta-analysis to obtain a pooled prevalence ratio (PPR) of malaria in children versus pregnant women (during pregnancy, not at delivery) and by gravidity, and we used meta-regression to assess factors affecting the prevalence ratio. FINDINGS: We used data from 18 sources that included 57 data points. There was a strong linear relation between the prevalence of malaria infection in pregnant women and children (r=0·87, p<0·0001). Prevalence was higher in children when compared with all gravidae (PPR=1·44, 95% CI 1·29-1·62; I(2)=80%, 57 studies), and against multigravidae (1·94, 1·68-2·24; I(2)=80%, 7 studies), and marginally higher against primigravidae (1·16, 1·05-1·29; I(2)=48%, 8 studies). PPR was higher in areas of higher transmission. INTERPRETATION: Malaria prevalence in pregnant women is strongly correlated with prevalence data in children obtained from household surveys, and could provide a pragmatic adjunct to survey strategies to track trends in malaria transmission in Africa. FUNDING: The Malaria in Pregnancy Consortium, which is funded through a grant from the Bill & Melinda Gates Foundation to the Liverpool School of Tropical Medicine, UK; US Centers for Disease Control and Prevention; and Wellcome Trust, UK.

Githinji S, Jones C, Malinga J, Snow RW, Talisuna A, Zurovac D. 2015. Development of a text-messaging intervention to improve treatment adherence and post-treatment review of children with uncomplicated malaria in western Kenya. Malar J, 14 (1), pp. 320. | Show Abstract | Read more

BACKGROUND: Patients' low adherence to artemisinin-based combination therapy has been reported in areas of Kenya bordering the Lake Victoria region, where the burden of malaria remains high. A randomized controlled trial is underway to determine the efficacy of short message service (SMS) text reminders on adherence to artemether-lumefantrine and post-treatment review of children under the age of five. This paper reports on the iterative process of intervention and delivery system development. METHODS: An intervention development workshop involving the research team and other stakeholders was held to determine the content of the text messages. Three focus group discussions were conducted to test caregivers' understanding of the messages developed during the workshop. The tested messages were refined and incorporated into an automated SMS distribution system and piloted with 20 caregivers drawn from facilities neighbouring the study sites. The automated SMS distribution system was repeatedly refined following the pilot and implemented at the start of the trial. RESULTS: The content of SMS messages underwent major revisions following the focus group discussions. Technical terms and abbreviations were replaced with simplified general terms. Message sign-off was modified to reflect the name of health facility, removing references to health workers. Day 3 post-treatment review visit reminder was modified to state the purpose of the visit while wording 'day 28' was added to the last post-treatment review visit reminder to help the caregiver recall the appointment date. The unscheduled visit prompt was modified to reflect flexibility and practicality of taking the child back to the facility if unwell. Reception of SMS reminders during the pilot was low with only 169/240 (70%) of scheduled messages delivered to the caregivers. The automated distribution system underwent major refinement and repeated testing following the pilot until effective delivery of all scheduled messages was achieved and sustained over a period of 3 months. CONCLUSIONS: Text message interventions should be carefully developed, tested and refined before implementation to ensure they are written in the most appropriate way for their target population. SMS distribution systems should be rigorously tested to ensure efficient delivery of the messages before they are deployed.

Wasunna B, Okiro EA, Webster J, Todd J, Snow RW, Jones C. 2015. The Impact of a Community Awareness Strategy on Caregiver Treatment Seeking Behaviour and Use of Artemether-Lumefantrine for Febrile Children in Rural Kenya. PLoS One, 10 (7), pp. e0130305. | Show Abstract | Read more

BACKGROUND: Access to prompt and effective treatment is the cornerstone for malaria control. Population Services International in collaboration with the Ministry of Health launched a malaria behaviour change communication intervention in Nyanza province, Kenya. The initiative aimed to improve: symptom recognition and prompt access to government health facilities for febrile children; effective treatment with the recommended first-line drug artemether-lumefantrine (AL) in public health facilities and adherence to the AL regimen. METHODS: Pre- and post-intervention cross-sectional household surveys were used to evaluate the impact of the intervention on prompt and correct use of AL for febrile children below five years of age. The primary outcome was the proportion of children below five years of age with fever in the last 14 days accessing AL within 48 hours of fever onset. RESULTS: There was an increase from 62.8% pre-intervention to 79.4% post-intervention (95% CI: 11.1, 22.1) in caregivers who reported seeking formal treatment promptly (on the same day, or next day) for their febrile children. However, there was a decrease in the use of government health facilities in the post-intervention period. There was a small increase in the proportion of children accessing AL within 48 hours of fever onset [18.4% vs 23.5% (0.1-10.0)]. CONCLUSION: The findings of this evaluation demonstrate that interventions that target only one sector may have a limited impact on improvements in prompt and effective treatment where multiple sources of treatments are sought for febrile illness. Additionally, the context in which an intervention is implemented is likely to influence the process and outcomes.

Snow RW, Kibuchi E, Karuri SW, Sang G, Gitonga CW, Mwandawiro C, Bejon P, Noor AM. 2015. Changing Malaria Prevalence on the Kenyan Coast since 1974: Climate, Drugs and Vector Control. PLoS One, 10 (6), pp. e0128792. | Show Abstract | Read more

BACKGROUND: Progress toward reducing the malaria burden in Africa has been measured, or modeled, using datasets with relatively short time-windows. These restricted temporal analyses may miss the wider context of longer-term cycles of malaria risk and hence may lead to incorrect inferences regarding the impact of intervention. METHODS: 1147 age-corrected Plasmodium falciparum parasite prevalence (PfPR2-10) surveys among rural communities along the Kenyan coast were assembled from 1974 to 2014. A Bayesian conditional autoregressive generalized linear mixed model was used to interpolate to 279 small areas for each of the 41 years since 1974. Best-fit polynomial splined curves of changing PfPR2-10 were compared to a sequence of plausible explanatory variables related to rainfall, drug resistance and insecticide-treated bed net (ITN) use. RESULTS: P. falciparum parasite prevalence initially rose from 1974 to 1987, dipped in 1991-92 but remained high until 1998. From 1998 onwards prevalence began to decline until 2011, then began to rise through to 2014. This major decline occurred before ITNs were widely distributed and variation in rainfall coincided with some, but not all, short-term transmission cycles. Emerging resistance to chloroquine and introduction of sulfadoxine/pyrimethamine provided plausible explanations for the rise and fall of malaria transmission along the Kenyan coast. CONCLUSIONS: Progress towards elimination might not be as predictable as we would like, where natural and extrinsic cycles of transmission confound evaluations of the effect of interventions. Deciding where a country lies on an elimination pathway requires careful empiric observation of the long-term epidemiology of malaria transmission.

Mmbando BP, Mgaya J, Cox SE, Mtatiro SN, Soka D, Rwezaula S, Meda E, Msaki E et al. 2015. Negative Epistasis between Sickle and Foetal Haemoglobin Suggests a Reduction in Protection against Malaria. PLoS One, 10 (5), pp. e0125929. | Show Abstract | Read more

BACKGROUND: Haemoglobin variants, Sickle (HbS) and foetal (HbF) have been associated with malaria protection. This study explores epistatic interactions between HbS and HbF on malaria infection. METHODS: The study was conducted between March 2004 and December 2013 within the sickle cell disease (SCD) programme at Muhimbili National Hospital, Tanzania. SCD status was categorized into HbAA, HbAS and HbSS using hemoglobin electrophoresis and High Performance Liquid Chromatography (HPLC). HbF levels were determined by HPLC. Malaria was diagnosed using rapid diagnostic test and/or blood film. Logistic regression and generalized estimating equations models were used to evaluate associations between SCD status, HbF and malaria. FINDINGS: 2,049 individuals with age range 0-70 years, HbAA 311(15.2%), HbAS 241(11.8%) and HbSS 1,497(73.1%) were analysed. At enrolment, malaria prevalence was significantly higher in HbAA 13.2% compared to HbAS 1.24% and HbSS 1.34% (p<0.001). Mean HbF was lower in those with malaria compared to those without malaria in HbAA (0.43% vs 0.82%) but was the reverse in HbSS (8.10% vs 5.59%). An increase in HbF was associated with a decrease in risk of malaria OR=0.50 (95%CI: 0.28, 0.90; p=0.021) in HbAA, whereas for HbSS the risk of malaria increased OR=2.94 (1.44, 5.98; p=0.003). A similar pattern was seen during multiple visits; HbAA OR=0.52 (0.34, 0.80; p=0.003) vs HbSS OR=2.01 (1.27, 3.23; p=0.003). CONCLUSION: Higher prevalence of malaria in HbAA compared to HbAS and HbSS confirmed the protective effect of HbS. Lower prevalence of malaria in HbAA with high HbF supports a protective effect of HbF. However, in HbSS, the higher prevalence of malaria with high levels of HbF suggests loss of malaria protection. This is the first epidemiological study to suggest a negative epistasis between HbF and HbS on malaria.

Talisuna AO, Noor AM, Okui AP, Snow RW. 2015. The past, present and future use of epidemiological intelligence to plan malaria vector control and parasite prevention in Uganda. Malar J, 14 (1), pp. 158. | Show Abstract | Read more

BACKGROUND: An important prelude to developing strategies to control infectious diseases is a detailed epidemiological evidence platform to target cost-effective interventions and define resource needs. METHODS: A review of published and un-published reports of malaria vector control and parasite prevention in Uganda was conducted for the period 1900-2013. The objective was to provide a perspective as to how epidemiological intelligence was used to design malaria control before and during the global malaria eradication programme (GMEP) and to contrast this with the evidence generated in support of the Roll Back Malaria (RBM) initiative from 1998 to date. RESULTS: During the GMEP era, comprehensive investigations were undertaken on the effectiveness of vector and parasite control such as indoor residual house-spraying (IRS) and mass drug administration (MDA) at different sites in Uganda. Nationwide malariometric surveys were undertaken between 1964 and 1967 to provide a profile of risk, epidemiology and seasonality leading to an evidence-based national cartography of risk to characterize the diversity of malaria transmission in Uganda. At the launch of the RBM initiative in the late 1990s, an equivalent level of evidence was lacking. There was no contemporary national evidence-base for the likely impact of insecticide-treated nets (ITN), no new malariometric data, no new national cartography of malaria risk or any evidence of tailored intervention delivery based on variations in the ecology of malaria risk in Uganda. DISCUSSION: Despite millions of dollars of overseas development assistance over the last ten years in ITN, and more recently the resurrection of the use of IRS, the epidemiological impact of vector control remains uncertain due to an absence of nationwide basic parasite and vector-based field studies. CONCLUSION: Readily available epidemiological data should become the future business model to maximize malaria funding from 2015. Over the next five to ten years, accountability, impact analysis, financial business cases supported by a culture of data use should become the new paradigm by which malaria programmes, governments and their development partners operate.

Snow RW. 2015. Global malaria eradication and the importance of Plasmodium falciparum epidemiology in Africa. BMC Med, 13 (1), pp. 23. | Show Abstract | Read more

The global agenda for malaria has, once again, embraced the possibility of eradication. As history has shown, there will be no single magic bullet that can be applied to every epidemiological setting. Africa has a diverse malaria ecology, lending itself to some of the highest disease burden areas of the world and a wide range of clinical epidemiological patterns making control with our current tools challenging. This commentary highlights why the epidemiology of Plasmodium falciparum malaria in Africa should not be forgotten when planning an eradication strategy, and why forgetting Africa will, once again, be the single largest threat to any hope for global eradication.

Githinji S, Kigen S, Memusi D, Nyandigisi A, Wamari A, Muturi A, Jagoe G, Ziegler R, Snow RW, Zurovac D. 2014. Using mobile phone text messaging for malaria surveillance in rural Kenya. Malar J, 13 (1), pp. 107. | Show Abstract | Read more

BACKGROUND: Effective surveillance systems are required to track malaria testing and treatment practices. A 26-week study "SMS for Life" was piloted in five rural districts of Kenya to examine whether SMS reported surveillance data could ensure real-time visibility of accurate data and their use by district managers to impact on malaria case-management. METHODS: Health workers from 87 public health facilities used their personal mobile phones to send a weekly structured SMS text message reporting the counts of four basic surveillance data elements to a web-based system accessed by district managers. Longitudinal monitoring of SMS reported data through the web-based system and two rounds of cross-sectional health facility surveys were done to validate accuracy of data. RESULTS: Mean response rates were 96% with 87% of facilities reporting on time. Fifty-eight per cent of surveillance data parameters were accurately reported. Overall mean testing rates were 37% with minor weekly variations ranging from 32 to 45%. Overall test positivity rate was 24% (weekly range: 17-37%). Ratio of anti-malarial treatments to test positive cases was 1.7:1 (weekly range: 1.3:1-2.2:1). District specific trends showed fluctuating patterns in testing rates without notable improvement over time but the ratio of anti-malarial treatments to test positive cases improved over short periods of time in three out of five districts. CONCLUSIONS: The study demonstrated the feasibility of using simple mobile phone text messages to transmit timely surveillance data from peripheral health facilities to higher levels. However, accuracy of data reported was suboptimal. Future work should focus on improving quality of SMS reported surveillance data.

Otieno G, Githinji S, Jones C, Snow RW, Talisuna A, Zurovac D. 2014. The feasibility, patterns of use and acceptability of using mobile phone text-messaging to improve treatment adherence and post-treatment review of children with uncomplicated malaria in western Kenya. Malar J, 13 (1), pp. 44. | Show Abstract | Read more

BACKGROUND: Trials evaluating the impact of mobile phone text-messaging to support management of acute diseases, such as malaria, are urgently needed in Africa. There has been however a concern about the feasibility of interventions that rely on access to mobile phones among caregivers in rural areas. To assess the feasibility and inform development of an intervention to improve adherence to malaria medications and post-treatment review, mobile phone network, access, ownership and use among caregivers in western Kenya was assessed. METHODS: A cross-sectional survey based on outpatient exit interviews was undertaken among caregivers of children with malaria at four trial facilities. The main outcomes were proportions of caregivers that have mobile signal at home; have access to mobile phones; are able to read; and use text-messaging. Willingness to receive text-message reminders was also explored. Descriptive analyses were performed. RESULTS: Of 400 interviewed caregivers, the majority were female (93.5%), mothers of the sick children (87.8%) and able to read (97.3%). Only 1.7% of caregivers were without any education. Nearly all (99.8%) reported access to a mobile signal at home. 93.0% (site range: 89-98%) had access to a mobile phone within their household while 73.8% (site range: 66-78%) possessed a personal phone. Among caregivers with mobile phone access, 93.6% (site range: 85-99%) used the phone to receive text-messages. Despite only 19% having electricity at home nearly all (99.7%) caregivers reported that they would be able to have permanent phone access to receive text-messages in the next 28 days. Willingness to receive text-message reminders was nearly universal (99.7%) with 41.7% of caregivers preferring texts in English, 32.3% in Kiswahili and 26.1% in Dholuo. CONCLUSIONS: Despite concerns that the feasibility of text-messaging interventions targeting caregivers may be compromised in rural high malaria risk areas in Kenya, very favourable conditions were found with respect to mobile network, access and ownership of phones, use of text-messaging and minimum literacy levels required for successful intervention delivery. Moreover, there was a high willingness of caregivers to receive text-message reminders. Impact evaluations of carefully tailored text-messaging interventions targeting caregivers of children with malaria are timely and justified.

Snow RW. 2014. Sixty years trying to define the malaria burden in Africa: have we made any progress? BMC Med, 12 (1), pp. 227. | Show Abstract | Read more

Controversy surrounds the precise numbers of malaria deaths and clinical episodes in Africa. This would not have surprised malariologists working in Africa 60 years ago as they began to unravel the enigma that is 'malaria'. Malaria is a complex disease manifesting as a multitude of symptoms, degrees of severity and indirect morbid consequences. Clinical immunity develops quickly and the presence of infection cannot always be used to distinguish between malaria and other illnesses. During the 1950s and 1960s parasite prevalence was used in preference to statistics on malaria mortality and morbidity. An argument is made for a resurrection of this measure of the quantity of malaria across Africa as a more reliable means to understand the impact of control.

Alegana VA, Wright JA, Nahzat SM, Butt W, Sediqi AW, Habib N, Snow RW, Atkinson PM, Noor AM. 2014. Modelling the incidence of Plasmodium vivax and Plasmodium falciparum malaria in Afghanistan 2006-2009. PLoS One, 9 (7), pp. e102304. | Show Abstract | Read more

BACKGROUND: Identifying areas that support high malaria risks and where populations lack access to health care is central to reducing the burden in Afghanistan. This study investigated the incidence of Plasmodium vivax and Plasmodium falciparum using routine data to help focus malaria interventions. METHODS: To estimate incidence, the study modelled utilisation of the public health sector using fever treatment data from the 2012 national Malaria Indicator Survey. A probabilistic measure of attendance was applied to population density metrics to define the proportion of the population within catchment of a public health facility. Malaria data were used in a Bayesian spatio-temporal conditional-autoregressive model with ecological or environmental covariates, to examine the spatial and temporal variation of incidence. FINDINGS: From the analysis of healthcare utilisation, over 80% of the population was within 2 hours' travel of the nearest public health facility, while 64.4% were within 30 minutes' travel. The mean incidence of P. vivax in 2009 was 5.4 (95% Crl 3.2-9.2) cases per 1000 population compared to 1.2 (95% Crl 0.4-2.9) cases per 1000 population for P. falciparum. P. vivax peaked in August while P. falciparum peaked in November. 32% of the estimated 30.5 million people lived in regions where annual incidence was at least 1 case per 1,000 population of P. vivax; 23.7% of the population lived in areas where annual P. falciparum case incidence was at least 1 per 1000. CONCLUSION: This study showed how routine data can be combined with household survey data to model malaria incidence. The incidence of both P. vivax and P. falciparum in Afghanistan remain low but the co-distribution of both parasites and the lag in their peak season provides challenges to malaria control in Afghanistan. Future improved case definition to determine levels of imported risks may be useful for the elimination ambitions in Afghanistan.

Cited:

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Scopus

Noor AM, Kinyoki DK, Mundia CW, Kabaria CW, Mutua JW, Alegana VA, Fall IS, Snow RW. 2014. The changing risk of Plasmodium falciparum malaria infection in Africa: 2000-10: A spatial and temporal analysis of transmission intensity The Lancet, 383 (9930), pp. 1739-1747. | Show Abstract | Read more

Background Over a decade ago, the Roll Back Malaria Partnership was launched, and since then there has been unprecedented investment in malaria control. We examined the change in malaria transmission intensity during the period 2000-10 in Africa. Methods We assembled a geocoded and community Plasmodium falciparum parasite rate standardised to the age group 2-10 years (PfPR2-10) database from across 49 endemic countries and territories in Africa from surveys undertaken since 1980. The data were used within a Bayesian space-time geostatistical framework to predict PfPR2-10 in 2000 and 2010 at a 1 × 1 km spatial resolution. Population distribution maps at the same spatial resolution were used to compute populations at risk by endemicity class and estimate population-adjusted PfPR2-10 (PAPfPR2-10) for each of the 44 countries for which predictions were possible for each year. Findings Between 2000 and 2010, the population in hyperendemic (>50% to 75% PfPR2-10) or holoendemic (>75% PfPR2-10) areas decreased from 218·6 million (34·4%) of 635·7 million to 183·5 million (22·5%) of 815·7 million across 44 malaria-endemic countries. 280·1 million (34·3%) people lived in areas of mesoendemic transmission (>10% to 50% PfPR 2-10) in 2010 compared with 178·6 million (28·1%) in 2000. Population in areas of unstable or very low transmission (<5% PfPR 2-10) increased from 131·7 million people (20·7%) in 2000 to 219·0 million (26·8%) in 2010. An estimated 217·6 million people, or 26·7% of the 2010 population, lived in areas where transmission had reduced by at least one PfPR2-10 endemicity class. 40 countries showed a reduction in national mean PAPfPR2-10. Only ten countries contributed 87·1% of the population living in areas of hyperendemic or holoendemic transmission in 2010. Interpretation Substantial reductions in malaria transmission have been achieved in endemic countries in Africa over the period 2000-10. However, 57% of the population in 2010 continued to live in areas where transmission remains moderate to intense and global support to sustain and accelerate the reduction of transmission must remain a priority. Funding Wellcome Trust. Copyright © Noor et al.

Zurovac D, Githinji S, Memusi D, Kigen S, Machini B, Muturi A, Otieno G, Snow RW, Nyandigisi A. 2014. Major improvements in the quality of malaria case-management under the "test and treat" policy in Kenya. PLoS One, 9 (3), pp. e92782. | Show Abstract | Read more

BACKGROUND: Monitoring implementation of the "test and treat" case-management policy for malaria is an important component of all malaria control programmes in Africa. Unfortunately, routine information systems are commonly deficient to provide necessary information. Using health facility surveys we monitored health systems readiness and malaria case-management practices prior to and following implementation of the 2010 "test and treat" policy in Kenya. METHODS/FINDINGS: Between 2010 and 2013 six national, cross-sectional, health facility surveys were undertaken. The number of facilities assessed ranged between 172 and 176, health workers interviewed between 216 and 237 and outpatient consultations for febrile patients evaluated between 1,208 and 2,408 across six surveys. Comparing baseline and the last survey results, all readiness indicators showed significant (p<0.005) improvements: availability of parasitological diagnosis (55.2% to 90.7%); RDT availability (7.5% to 69.8%); total artemether-lumefantrine (AL) stock-out (27.2% to 7.0%); stock-out of one or more AL packs (59.5% to 21.6%); training coverage (0 to 50.2%); guidelines access (0 to 58.1%) and supervision (17.9% to 30.8%). Testing increased by 34.0% (23.9% to 57.9%; p<0.001) while testing and treatment according to test result increased by 34.2% (15.7% to 49.9%; p<0.001). Treatment adherence for test positive patients improved from 83.3% to 90.3% (p = 0.138) and for test negative patients from 47.9% to 83.4% (p<0.001). Significant testing and treatment improvements were observed in children and adults. There was no difference in practices with respect to the type and result of malaria test (RDT vs microscopy). Of eight dosing, dispensing and counseling tasks, improvements were observed for four tasks. Overall AL use for febrile patients decreased from 63.5% to 35.6% (p<0.001). CONCLUSIONS: Major improvements in the implementation of "test and treat" policy were observed in Kenya. Some gaps towards universal targets still remained. Other countries facing similar needs and challenges may consider health facility surveys to monitor malaria case-management.

Maes P, Harries AD, Van den Bergh R, Noor A, Snow RW, Tayler-Smith K, Hinderaker SG, Zachariah R, Allan R. 2014. Can timely vector control interventions triggered by atypical environmental conditions prevent malaria epidemics? A case-study from Wajir County, Kenya. PLoS One, 9 (4), pp. e92386. | Show Abstract | Read more

BACKGROUND: Atypical environmental conditions with drought followed by heavy rainfall and flooding in arid areas in sub-Saharan Africa can lead to explosive epidemics of malaria, which might be prevented through timely vector-control interventions. OBJECTIVES: Wajir County in Northeast Kenya is classified as having seasonal malaria transmission. The aim of this study was to describe in Wajir town the environmental conditions, the scope and timing of vector-control interventions and the associated resulting burden of malaria at two time periods (1996-1998 and 2005-2007). METHODS: This is a cross-sectional descriptive and ecological study using data collected for routine program monitoring and evaluation. RESULTS: In both time periods, there were atypical environmental conditions with drought and malnutrition followed by massive monthly rainfall resulting in flooding and animal/human Rift Valley Fever. In 1998, this was associated with a large and explosive malaria epidemic (weekly incidence rates peaking at 54/1,000 population/week) with vector-control interventions starting over six months after the massive rainfall and when the malaria epidemic was abating. In 2007, vector-control interventions started sooner within about three months after the massive rainfall and no malaria epidemic was recorded with weekly malaria incidence rates never exceeding 0.5 per 1,000 population per week. DISCUSSION AND CONCLUSION: Did timely vector-control interventions in Wajir town prevent a malaria epidemic? In 2007, the neighboring county of Garissa experienced similar climatic events as Wajir, but vector-control interventions started six months after the heavy un-seasonal rainfall and large scale flooding resulted in a malaria epidemic with monthly incidence rates peaking at 40/1,000 population. In conclusion, this study suggests that atypical environmental conditions can herald a malaria outbreak in certain settings. In turn, this should alert responsible stakeholders about the need to act rapidly and preemptively with appropriate and wide-scale vector-control interventions to mitigate the risk.

Alegana VA, Atkinson PM, Wright JA, Kamwi R, Uusiku P, Katokele S, Snow RW, Noor AM. 2013. Estimation of malaria incidence in northern Namibia in 2009 using Bayesian conditional-autoregressive spatial-temporal models. Spat Spatiotemporal Epidemiol, 7 pp. 25-36. | Show Abstract | Read more

As malaria transmission declines, it becomes increasingly important to monitor changes in malaria incidence rather than prevalence. Here, a spatio-temporal model was used to identify constituencies with high malaria incidence to guide malaria control. Malaria cases were assembled across all age groups along with several environmental covariates. A Bayesian conditional-autoregressive model was used to model the spatial and temporal variation of incidence after adjusting for test positivity rates and health facility utilisation. Of the 144,744 malaria cases recorded in Namibia in 2009, 134,851 were suspected and 9893 were parasitologically confirmed. The mean annual incidence based on the Bayesian model predictions was 13 cases per 1000 population with the highest incidence predicted for constituencies bordering Angola and Zambia. The smoothed maps of incidence highlight trends in disease incidence. For Namibia, the 2009 maps provide a baseline for monitoring the targets of pre-elimination.

Bennett A, Kazembe L, Mathanga DP, Kinyoki D, Ali D, Snow RW, Noor AM. 2013. Mapping malaria transmission intensity in Malawi, 2000-2010. Am J Trop Med Hyg, 89 (5), pp. 840-849. | Show Abstract | Read more

Substantial development assistance has been directed towards reducing the high malaria burden in Malawi over the past decade. We assessed changes in transmission over this period of malaria control scale-up by compiling community Plasmodium falciparum rate (PfPR) data during 2000-2011 and used model-based geostatistical methods to predict mean PfPR2-10 in 2000, 2005, and 2010. In addition, we calculated population-adjusted prevalences and populations at risk by district to inform malaria control program priority setting. The national population-adjusted PfPR2-10 was 37% in 2010, and we found no evidence of change over this period of scale-up. The entire population of Malawi is under meso-endemic transmission risk, with those in districts along the shore of Lake Malawi and Shire River Valley under highest risk. The lack of change in prevalence confirms modeling predictions that when compared with lower transmission, prevalence reductions in high transmission settings require greater investment and longer time scales.

Tatem AJ, Garcia AJ, Snow RW, Noor AM, Gaughan AE, Gilbert M, Linard C. 2013. Millennium development health metrics: where do Africa's children and women of childbearing age live? Popul Health Metr, 11 (1), pp. 11. | Show Abstract | Read more

The Millennium Development Goals (MDGs) have prompted an expansion in approaches to deriving health metrics to measure progress toward their achievement. Accurate measurements should take into account the high degrees of spatial heterogeneity in health risks across countries, and this has prompted the development of sophisticated cartographic techniques for mapping and modeling risks. Conversion of these risks to relevant population-based metrics requires equally detailed information on the spatial distribution and attributes of the denominator populations. However, spatial information on age and sex composition over large areas is lacking, prompting many influential studies that have rigorously accounted for health risk heterogeneities to overlook the substantial demographic variations that exist subnationally and merely apply national-level adjustments.Here we outline the development of high resolution age- and sex-structured spatial population datasets for Africa in 2000-2015 built from over a million measurements from more than 20,000 subnational units, increasing input data detail from previous studies by over 400-fold. We analyze the large spatial variations seen within countries and across the continent for key MDG indicator groups, focusing on children under 5 and women of childbearing age, and find that substantial differences in health and development indicators can result through using only national level statistics, compared to accounting for subnational variation.Progress toward meeting the MDGs will be measured through national-level indicators that mask substantial inequalities and heterogeneities across nations. Cartographic approaches are providing opportunities for quantitative assessments of these inequalities and the targeting of interventions, but demographic spatial datasets to support such efforts remain reliant on coarse and outdated input data for accurately locating risk groups. We have shown here that sufficient data exist to map the distribution of key vulnerable groups, and that doing so has substantial impacts on derived metrics through accounting for spatial demographic heterogeneities that exist within nations across Africa.

Zurovac D, Otieno G, Kigen S, Mbithi AM, Muturi A, Snow RW, Nyandigisi A. 2013. Ownership and use of mobile phones among health workers, caregivers of sick children and adult patients in Kenya: cross-sectional national survey. Global Health, 9 (1), pp. 20. | Show Abstract | Read more

BACKGROUND: The rapid growth in mobile phone penetration and use of Short Message Service (SMS) has been seen as a potential solution to improve medical and public health practice in Africa. Several studies have shown effectiveness of SMS interventions to improve health workers' practices, patients' adherence to medications and availability of health facility commodities. To inform policy makers about the feasibility of facility-based SMS interventions, the coverage data on mobile phone ownership and SMS use among health workers and patients are needed. METHODS: In 2012, a national, cross-sectional, cluster sample survey was undertaken at 172 public health facilities in Kenya. Outpatient health workers and caregivers of sick children and adult patients were interviewed. The main outcomes were personal ownership of mobile phones and use of SMS among phone owners. The predictors analysis examined factors influencing phone ownership and SMS use. RESULTS: The analysis included 219 health workers and 1,177 patients' respondents (767 caregivers and 410 adult patients). All health workers possessed personal mobile phones and 98.6% used SMS. Among patients' respondents, 61.2% owned phones and 71.4% of phone owners used SMS. The phone ownership and SMS use was similar between caregivers of sick children and adult patients. The respondents who were male, more educated, literate and living in urban area were significantly more likely to own the phone and use SMS. The youngest respondents were less likely to own phones, however when the phones were owned, younger age groups were more likely to use SMS. Respondents living in wealthier areas were more likely to own phones; however when phones are owned no significant association between the poverty and SMS use was observed. CONCLUSIONS: Mobile phone ownership and SMS use is ubiquitous among Kenyan health workers in the public sector. Among patients they serve the coverage in phone ownership and SMS use is lower and disparities exist with respect to gender, age, education, literacy, urbanization and poverty. Some of the disparities on SMS use can be addressed through the modalities of mHealth interventions and enhanced implementation processes while further growth in mobile phone penetration is needed to reduce the ownership gap.

Noor AM, Uusiku P, Kamwi RN, Katokele S, Ntomwa B, Alegana VA, Snow RW. 2013. The receptive versus current risks of Plasmodium falciparum transmission in northern Namibia: implications for elimination. BMC Infect Dis, 13 (1), pp. 184. | Show Abstract | Read more

BACKGROUND: Countries aiming for malaria elimination need to define their malariogenic potential, of which measures of both receptive and current transmission are major components. As Namibia pursues malaria elimination, the importation risks due to cross-border human population movements with higher risk neighboring countries has been identified as a major challenge. Here we used historical and contemporary Plasmodium falciparum prevalence data for Namibia to estimate receptive and current levels of malaria risk in nine northern regions. We explore the potential of these risk maps to support decision-making for malaria elimination in Namibia. METHODS: Age-corrected geocoded community P. falciparum rate PfPR2-10 data from the period 1967-1992 (n = 3,260) and 2009 (n = 120) were modeled separately within a Bayesian model-based geostatistical (MBG) framework. A full Bayesian space-time MBG model was implemented using the 1967-1992 data to make predictions for every five years from 1969 to 1989. These maps were used to compute the maximum mean PfPR2-10 at 5 x 5 km locations in the northern regions of Namibia to estimate receptivity. A separate spatial Bayesian MBG was fitted to the 2009 data to predict current risk of malaria at similar spatial resolution. Using a high-resolution population map for Namibia, population at risk by receptive and current endemicity by region and population adjusted PfPR2-10 by health district were computed. Validations of predictions were undertaken separately for the historical and current risk models. RESULTS: Highest receptive risks were observed in the northern regions of Caprivi, Kavango and Ohangwena along the border with Angola and Zambia. Relative to the receptive risks, over 90% of the 1.4 million people across the nine regions of northern Namibia appear to have transitioned to a lower endemic class by 2009. The biggest transition appeared to have occurred in areas of highest receptive risks. Of the 23 health districts, 12 had receptive PAPfPR2-10 risks of 5% to 18% and accounted for 57% of the population in the north. Current PAPfPR2-10 risks was largely <5% across the study area. CONCLUSIONS: The comparison of receptive and current malaria risks in the northern regions of Namibia show health districts that are most at risk of importation due to their proximity to the relatively higher transmission northern neighbouring countries, higher population and modeled receptivity. These health districts should be prioritized as the cross-border control initiatives are rolled out.

Wesolowski A, Eagle N, Noor AM, Snow RW, Buckee CO. 2013. The impact of biases in mobile phone ownership on estimates of human mobility. J R Soc Interface, 10 (81), pp. 20120986. | Show Abstract | Read more

Mobile phone data are increasingly being used to quantify the movements of human populations for a wide range of social, scientific and public health research. However, making population-level inferences using these data is complicated by differential ownership of phones among different demographic groups that may exhibit variable mobility. Here, we quantify the effects of ownership bias on mobility estimates by coupling two data sources from the same country during the same time frame. We analyse mobility patterns from one of the largest mobile phone datasets studied, representing the daily movements of nearly 15 million individuals in Kenya over the course of a year. We couple this analysis with the results from a survey of socioeconomic status, mobile phone ownership and usage patterns across the country, providing regional estimates of population distributions of income, reported airtime expenditure and actual airtime expenditure across the country. We match the two data sources and show that mobility estimates are surprisingly robust to the substantial biases in phone ownership across different geographical and socioeconomic groups.

Kangwana BP, Kedenge SV, Noor AM, Alegana VA, Nyandigisi AJ, Pandit J, Fegan GW, Todd JE, Snow RW, Goodman CA. 2013. The effect of an anti-malarial subsidy programme on the quality of service provision of artemisinin-based combination therapy in Kenya: a cluster-randomized, controlled trial. Malar J, 12 (1), pp. 81. | Show Abstract | Read more

BACKGROUND: Many patients with suspected malaria in sub-Saharan Africa seek treatment from private providers, but this sector suffers from sub-standard medicine dispensing practices. To improve the quality of care received for presumptive malaria from the highly accessed private retail sector in western Kenya, subsidized pre-packaged artemether-lumefantrine (AL) was provided to private retailers, together with a one day training for retail staff on malaria diagnosis and treatment, job aids and community engagement activities. METHODS: The intervention was assessed using a cluster-randomized, controlled design. Provider and mystery-shopper cross-sectional surveys were conducted at baseline and eight months post-intervention to assess provider practices. Data were analysed based on cluster-level summaries, comparing control and intervention arms. RESULTS: On average, 564 retail outlets were interviewed per year. At follow-up, 43% of respondents reported that at least one staff member had attended the training in the intervention arm. The intervention significantly increased the percentage of providers knowing the first line treatment for uncomplicated malaria by 24.2% points (confidence interval (CI): 14.8%, 33.6%; adjusted p=0.0001); the percentage of outlets stocking AL by 31.7% points (CI: 22.0%, 41.3%; adjusted p=0.0001); and the percentage of providers prescribing AL for presumptive malaria by 23.6% points (CI: 18.7%, 28.6%; adjusted p=0.0001). Generally outlets that received training and job aids performed better than those receiving one or none of these intervention components. CONCLUSION: Overall, subsidizing ACT and retailer training can significantly increase the percentage of outlets stocking and selling AL for the presumptive treatment of malaria, but further research is needed on strategies to improve the provision of counselling advice to retail customers.

Pindolia DK, Garcia AJ, Huang Z, Smith DL, Alegana VA, Noor AM, Snow RW, Tatem AJ. 2013. The demographics of human and malaria movement and migration patterns in East Africa. Malar J, 12 (1), pp. 397. | Show Abstract | Read more

INTRODUCTION: The quantification of parasite movements can provide valuable information for control strategy planning across all transmission intensities. Mobile parasite carrying individuals can instigate transmission in receptive areas, spread drug resistant strains and reduce the effectiveness of control strategies. The identification of mobile demographic groups, their routes of travel and how these movements connect differing transmission zones, potentially enables limited resources for interventions to be efficiently targeted over space, time and populations. METHODS: National population censuses and household surveys provide individual-level migration, travel, and other data relevant for understanding malaria movement patterns. Together with existing spatially referenced malaria data and mathematical models, network analysis techniques were used to quantify the demographics of human and malaria movement patterns in Kenya, Uganda and Tanzania. Movement networks were developed based on connectivity and magnitudes of flow within each country and compared to assess relative differences between regions and demographic groups. Additional malaria-relevant characteristics, such as short-term travel and bed net use, were also examined. RESULTS: Patterns of human and malaria movements varied between demographic groups, within country regions and between countries. Migration rates were highest in 20-30 year olds in all three countries, but when accounting for malaria prevalence, movements in the 10-20 year age group became more important. Different age and sex groups also exhibited substantial variations in terms of the most likely sources, sinks and routes of migration and malaria movement, as well as risk factors for infection, such as short-term travel and bed net use. CONCLUSION: Census and survey data, together with spatially referenced malaria data, GIS and network analysis tools, can be valuable for identifying, mapping and quantifying regional connectivities and the mobility of different demographic groups. Demographically-stratified HPM and malaria movement estimates can provide quantitative evidence to inform the design of more efficient intervention and surveillance strategies that are targeted to specific regions and population groups.

Okiro EA, Kazembe LN, Kabaria CW, Ligomeka J, Noor AM, Ali D, Snow RW. 2013. Childhood malaria admission rates to four hospitals in Malawi between 2000 and 2010. PLoS One, 8 (4), pp. e62214. | Show Abstract | Read more

INTRODUCTION: The last few years have witnessed rapid scaling-up of key malaria interventions in several African countries following increases in development assistance. However, there is only limited country-specific information on the health impact of expanded coverage of these interventions. METHODS: Paediatric admission data were assembled from 4 hospitals in Malawi reflecting different malaria ecologies. Trends in monthly clinical malaria admissions between January 2000 and December 2010 were analysed using time-series models controlling for covariates related to climate and service use to establish whether changes in admissions can be related to expanded coverage of interventions aimed at reducing malaria infection. RESULTS: In 3 of 4 sites there was an increase in clinical malaria admission rates. Results from time series models indicate a significant month-to-month increase in the mean clinical malaria admission rates at two hospitals (trend P<0.05). At these hospitals clinical malaria admissions had increased from 2000 by 41% to 100%. Comparison of changes in malaria risk and ITN coverage appear to correspond to a lack of disease declines over the period. Changes in intervention coverage within hospital catchments showed minimal increases in ITN coverage from <6% across all sites in 2000 to maximum of 33% at one hospital site by 2010. Additionally, malaria transmission intensity remained unchanged between 2000-2010 across all sites. DISCUSSION: Despite modest increases in coverage of measures to reduce infection there has been minimal changes in paediatric clinical malaria cases in four hospitals in Malawi. Studies across Africa are increasingly showing a mixed set of impact results and it is important to assemble more data from more sites to understand the wider implications of malaria funding investment. We also caution that impact surveillance should continue in areas where intervention coverage is increasing with time, for example Malawi, as decline may become evident within a period when coverage reaches optimal levels.

Noor AM, Alegana VA, Kamwi RN, Hansford CF, Ntomwa B, Katokele S, Snow RW. 2013. Malaria control and the intensity of Plasmodium falciparum transmission in Namibia 1969-1992. PLoS One, 8 (5), pp. e63350. | Show Abstract | Read more

BACKGROUND: Historical evidence of the levels of intervention scale up and its relationships to changing malaria risks provides important contextual information for current ambitions to eliminate malaria in various regions of Africa today. METHODS: Community-based Plasmodium falciparum prevalence data from 3,260 geo-coded time-space locations between 1969 and 1992 were assembled from archives covering an examination of 230,174 individuals located in northern Namibia. These data were standardized the age-range 2 to less than 10 years and used within a Bayesian model-based geo-statistical framework to examine the changes of malaria risk in the years 1969, 1974, 1979, 1984 and 1989 at 5×5 km spatial resolution. This changing risk was described against rainfall seasons and the wide-scale use of indoor-residual house-spraying and mass drug administration. RESULTS: Most areas of Northern Namibia experienced low intensity transmission during a ten-year period of wide-scale control activities between 1969 and 1979. As control efforts waned, flooding occurred, drug resistance emerged and the war for independence intensified the spatial extent of moderate-to-high malaria transmission expanded reaching a peak in the late 1980s. CONCLUSIONS: Targeting vectors and parasite in northern Namibia was likely to have successfully sustained a situation of low intensity transmission, but unraveled quickly to a peak of transmission intensity following a sequence of events by the early 1990s.

Buckee CO, Wesolowski A, Eagle NN, Hansen E, Snow RW. 2013. Mobile phones and malaria: Modeling human and parasite travel Travel Medicine and Infectious Disease, 11 (1), pp. 15-22. | Show Abstract | Read more

Human mobility plays an important role in the dissemination of malaria parasites between regions of variable transmission intensity. Asymptomatic individuals can unknowingly carry parasites to regions where mosquito vectors are available, for example, undermining control programs and contributing to transmission when they travel. Understanding how parasites are imported between regions in this way is therefore an important goal for elimination planning and the control of transmission, and would enable control programs to target the principal sources of malaria. Measuring human mobility has traditionally been difficult to do on a population scale, but the widespread adoption of mobile phones in low-income settings presents a unique opportunity to directly measure human movements that are relevant to the spread of malaria. Here, we discuss the opportunities for measuring human mobility using data from mobile phones, as well as some of the issues associated with combining mobility estimates with malaria infection risk maps to meaningfully estimate routes of parasite importation.

Snow RW, Amratia P, Zamani G, Mundia CW, Noor AM, Memish ZA, Al Zahrani MH, Al Jasari A, Fikri M, Atta H. 2013. The malaria transition on the Arabian Peninsula: progress toward a malaria-free region between 1960-2010. Adv Parasitol, 82 pp. 205-251. | Show Abstract | Read more

The transmission of malaria across the Arabian Peninsula is governed by the diversity of dominant vectors and extreme aridity. It is likely that where malaria transmission was historically possible it was intense and led to a high disease burden. Here, we review the speed of elimination, approaches taken, define the shrinking map of risk since 1960 and discuss the threats posed to a malaria-free Arabian Peninsula using the archive material, case data and published works. From as early as the 1940s, attempts were made to eliminate malaria on the peninsula but were met with varying degrees of success through to the 1970s; however, these did result in a shrinking of the margins of malaria transmission across the peninsula. Epidemics in the 1990s galvanised national malaria control programmes to reinvigorate control efforts. Before the launch of the recent global ambition for malaria eradication, countries on the Arabian Peninsula launched a collaborative malaria-free initiative in 2005. This initiative led a further shrinking of the malaria risk map and today locally acquired clinical cases of malaria are reported only in Saudi Arabia and Yemen, with the latter contributing to over 98% of the clinical burden.

Pullan RL, Gitonga C, Mwandawiro C, Snow RW, Brooker SJ. 2013. Estimating the relative contribution of parasitic infections and nutrition for anaemia among school-aged children in Kenya: a subnational geostatistical analysis BMJ Open, 3 (2), pp. e001936-e001936. | Show Abstract | Read more

Objectives: To quantify geographical variation in the relative contribution of parasitic infections, socioeconomic factors and malnutrition in the aetiology of anaemia among schoolchildren across Kenya, thereby providing a rational basis for the targeting of an integrated school health package. Design: Nationally representative cross-sectional survey data were collected using standard protocols. For all included children, data were recorded on haemoglobin (Hb) concentration and common parasitic infections (Plasmodium falciparum, hookworm and schistosomes) and socioeconomic indicators. Ecological proxies of malnutrition and food security were generated using Demographic and Health Survey and UN Food and Agriculture Organization food security data, respectively. Spatially explicit, multilevel models were used to quantify impact upon child Hb concentration. Setting: Randomly selected schools in ecologically diverse settings across Kenya. Main outcome measures: Mean Hb concentration adjusted for infection, nutritional and socioeconomic risk factors; associated risk ratios and adjusted Population Attributable Fractions (PAFs) for anaemia, by region. Results: Data were available for 16 941 children in 167 schools; mean Hb was 122.1 g/l and 35.3% of children were anaemic. In multivariate analysis, mean Hb was significantly lower in boys and younger children. Severe malnutrition and interactions between P falciparum and hookworm infections were significantly associated with lower Hb, with greater impacts seen for coinfected children. The contribution of risk factors to anaemia risk varied by province: in 14-year-old girls, PAFs ranged between 0% and 27.6% for P falciparum, 0% and 29% for hookworm and 0% and 18.4% for severe malnutrition. Conclusions: The observed geographical heterogeneity in the burden of anaemia attributable to different aetiological factors has important implications for the rational targeting of antianaemia interventions that can be included in an integrated school health programme.

Buckee CO, Wesolowski A, Eagle NN, Hansen E, Snow RW. 2013. Mobile phones and malaria: modeling human and parasite travel. Travel Med Infect Dis, 11 (1), pp. 15-22. | Show Abstract | Read more

Human mobility plays an important role in the dissemination of malaria parasites between regions of variable transmission intensity. Asymptomatic individuals can unknowingly carry parasites to regions where mosquito vectors are available, for example, undermining control programs and contributing to transmission when they travel. Understanding how parasites are imported between regions in this way is therefore an important goal for elimination planning and the control of transmission, and would enable control programs to target the principal sources of malaria. Measuring human mobility has traditionally been difficult to do on a population scale, but the widespread adoption of mobile phones in low-income settings presents a unique opportunity to directly measure human movements that are relevant to the spread of malaria. Here, we discuss the opportunities for measuring human mobility using data from mobile phones, as well as some of the issues associated with combining mobility estimates with malaria infection risk maps to meaningfully estimate routes of parasite importation.

Kedenge SV, Kangwana BP, Waweru EW, Nyandigisi AJ, Pandit J, Brooker SJ, Snow RW, Goodman CA. 2013. Understanding the impact of subsidizing artemisinin-based combination therapies (ACTs) in the retail sector--results from focus group discussions in rural Kenya. PLoS One, 8 (1), pp. e54371. | Show Abstract | Read more

BACKGROUND: There is considerable interest in the potential of private sector subsidies to increase availability and affordability of artemisinin-based combination therapies (ACTs) for malaria treatment. A cluster randomized trial of such subsidies was conducted in 3 districts in Kenya, comprising provision of subsidized packs of paediatric ACT to retail outlets, training of retail staff, and community awareness activities. The results demonstrated a substantial increase in ACT availability and coverage, though patient counselling and adherence were suboptimal. We conducted a qualitative study in order to understand why these successes and limitations occurred. METHODOLOGY/PRINCIPAL FINDINGS: Eighteen focus group discussions were conducted, 9 with retailers and 9 with caregivers, to document experiences with the intervention. Respondents were positive about intervention components, praising the focused retailer training, affordable pricing, strong promotional activities, dispensing job aids, and consumer friendly packaging, which are likely to have contributed to the positive access and coverage outcomes observed. However, many retailers still did not stock ACT, due to insufficient supplies, lack of capital and staff turnover. Advice to caregivers was poor due to insufficient time, and poor recall of instructions. Adherence by caregivers to dosing guidelines was sub-optimal, because of a wish to save tablets for other episodes, doses being required at night, stopping treatment when the child felt better, and the number and bitter taste of the tablets. Caregivers used a number of strategies to obtain paediatric ACT for older age groups. CONCLUSIONS/SIGNIFICANCE: This study has highlighted that important components of a successful ACT subsidy intervention are regular retailer training, affordable pricing, a reliable supply chain and community mobilization emphasizing patient adherence and when to seek further care.

Githinji S, Kigen S, Memusi D, Nyandigisi A, Mbithi AM, Wamari A, Muturi AN, Jagoe G, Barrington J, Snow RW, Zurovac D. 2013. Reducing stock-outs of life saving malaria commodities using mobile phone text-messaging: SMS for life study in Kenya. PLoS One, 8 (1), pp. e54066. | Show Abstract | Read more

BACKGROUND: Health facility stock-outs of life saving malaria medicines are common across Africa. Innovative ways of addressing this problem are urgently required. We evaluated whether SMS based reporting of stocks of artemether-lumefantrine (AL) and rapid diagnostic tests (RDT) can result in reduction of stock-outs at peripheral facilities in Kenya. METHODS/FINDINGS: All 87 public health facilities in five Kenyan districts were included in a 26 week project. Weekly facility stock counts of four AL packs and RDTs were sent via structured incentivized SMS communication process from health workers' personal mobile phones to a web-based system accessed by district managers. The mean health facility response rate was 97% with a mean formatting error rate of 3%. Accuracy of stock count reports was 79% while accuracy of stock-out reports was 93%. District managers accessed the system 1,037 times at an average of eight times per week. The system was accessed in 82% of the study weeks. Comparing weeks 1 and 26, stock-out of one or more AL packs declined by 38 percentage-points. Total AL stock-out declined by 5 percentage-points and was eliminated by the end of the project. Stock-out declines of individual AL packs ranged from 14 to 32 percentage-points while decline in RDT stock-outs was 24 percentage-points. District managers responded to 44% of AL and 73% of RDT stock-out signals by redistributing commodities between facilities. In comparison with national trends, stock-out declines in study areas were greater, sharper and more sustained. CONCLUSIONS: Use of simple SMS technology ensured high reporting rates of reasonably accurate, real-time facility stock data that were used by district managers to undertake corrective actions to reduce stock-outs. Future work on stock monitoring via SMS should focus on assessing response rates without use of incentives and demonstrating effectiveness of such interventions on a larger scale.

Omumbo JA, Noor AM, Fall IS, Snow RW. 2013. How well are malaria maps used to design and finance malaria control in Africa? PLoS One, 8 (1), pp. e53198. | Show Abstract | Read more

INTRODUCTION: Rational decision making on malaria control depends on an understanding of the epidemiological risks and control measures. National Malaria Control Programmes across Africa have access to a range of state-of-the-art malaria risk mapping products that might serve their decision-making needs. The use of cartography in planning malaria control has never been methodically reviewed. MATERIALS AND METHODS: An audit of the risk maps used by NMCPs in 47 malaria endemic countries in Africa was undertaken by examining the most recent national malaria strategies, monitoring and evaluation plans, malaria programme reviews and applications submitted to the Global Fund. The types of maps presented and how they have been used to define priorities for investment and control was investigated. RESULTS: 91% of endemic countries in Africa have defined malaria risk at sub-national levels using at least one risk map. The range of risk maps varies from maps based on suitability of climate for transmission; predicted malaria seasons and temperature/altitude limitations, to representations of clinical data and modelled parasite prevalence. The choice of maps is influenced by the source of the information. Maps developed using national data through in-country research partnerships have greater utility than more readily accessible web-based options developed without inputs from national control programmes. Although almost all countries have stratification maps, only a few use them to guide decisions on the selection of interventions allocation of resources for malaria control. CONCLUSION: The way information on the epidemiology of malaria is presented and used needs to be addressed to ensure evidence-based added value in planning control. The science on modelled impact of interventions must be integrated into new mapping products to allow a translation of risk into rational decision making for malaria control. As overseas and domestic funding diminishes, strategic planning will be necessary to guide appropriate financing for malaria control.

Talisuna AO, Karema C, Ogutu B, Juma E, Logedi J, Nyandigisi A, Mulenga M, Mbacham WF et al. 2012. Mitigating the threat of artemisinin resistance in Africa: improvement of drug-resistance surveillance and response systems. Lancet Infect Dis, 12 (11), pp. 888-896. | Show Abstract | Read more

Artemisinin-resistant Plasmodium falciparum malaria has emerged in western Cambodia and has been detected in western Thailand. The situation is ominously reminiscent of the emergence of resistance to chloroquine and to sulfadoxine-pyrimethamine several decades ago. Artemisinin resistance is a major threat to global public health, with the most severe potential effects in sub-Saharan Africa, where the disease burden is highest and systems for monitoring and containment of resistance are inadequate. The mechanisms that underlie artemisinin resistance are not fully understood. The main phenotypic trait associated with resistance is a substantial delay in parasite clearance, so far reported in southeast Asia but not in Africa. One of the pillars of the WHO global plan for artemisinin resistance containment is to increase monitoring and surveillance. In this Personal View, we propose strategies that should be adopted by malaria-endemic countries in Africa: resource mobilisation to reactivate regional surveillance networks, establishment of baseline parasite clearance profiles to serve as benchmarks to track emerging artemisinin resistance, improved data sharing to allow pooled analyses to identify rare events, modelling of risk factors for drug resistance, and development and validation of new approaches to monitor resistance.

Gitonga CW, Kihara JH, Njenga SM, Awuondo K, Noor AM, Snow RW, Brooker SJ. 2012. Use of rapid diagnostic tests in malaria school surveys in Kenya: does their under-performance matter for planning malaria control? Am J Trop Med Hyg, 87 (6), pp. 1004-1011. | Show Abstract | Read more

Malaria rapid diagnostic tests (RDTs) are known to yield false-positive results, and their use in epidemiologic surveys will overestimate infection prevalence and potentially hinder efficient targeting of interventions. To examine the consequences of using RDTs in school surveys, we compared three RDT brands used during a nationwide school survey in Kenya with expert microscopy and investigated the cost implications of using alternative diagnostic approaches in identifying localities with differing levels of infection. Overall, RDT sensitivity was 96.1% and specificity was 70.8%. In terms of classifying districts and schools according to prevalence categories, RDTs were most reliable for the < 1% and > 40% categories and least reliable in the 1-4.9% category. In low-prevalence settings, microscopy was the most expensive approach, and RDT results corrected by either microscopy or polymerase chain reaction were the cheapest. Use of polymerase chain reaction-corrected RDT results is recommended in school malaria surveys, especially in settings with low-to-moderate malaria transmission.

Noor AM, ElMardi KA, Abdelgader TM, Patil AP, Amine AA, Bakhiet S, Mukhtar MM, Snow RW. 2012. Malaria risk mapping for control in the republic of Sudan. Am J Trop Med Hyg, 87 (6), pp. 1012-1021. | Show Abstract | Read more

Evidence shows that malaria risk maps are rarely tailored to address national control program ambitions. Here, we generate a malaria risk map adapted for malaria control in Sudan. Community Plasmodium falciparum parasite rate (PfPR) data from 2000 to 2010 were assembled and were standardized to 2-10 years of age (PfPR(2-10)). Space-time Bayesian geostatistical methods were used to generate a map of malaria risk for 2010. Surfaces of aridity, urbanization, irrigation schemes, and refugee camps were combined with the PfPR(2-10) map to tailor the epidemiological stratification for appropriate intervention design. In 2010, a majority of the geographical area of the Sudan had risk of < 1% PfPR(2-10). Areas of meso- and hyperendemic risk were located in the south. About 80% of Sudan's population in 2011 was in the areas in the desert, urban centers, or where risk was < 1% PfPR(2-10). Aggregated data suggest reducing risks in some high transmission areas since the 1960s.

Gitonga CW, Edwards T, Karanja PN, Noor AM, Snow RW, Brooker SJ. 2012. Plasmodium infection, anaemia and mosquito net use among school children across different settings in Kenya. Trop Med Int Health, 17 (7), pp. 858-870. | Show Abstract | Read more

OBJECTIVE: To investigate risk factors, including reported net use, for Plasmodium infection and anaemia among school children and to explore variations in effects across different malaria ecologies occurring in Kenya. METHODS: This study analysed data for 49 975 school children in 480 schools surveyed during a national school malaria survey, 2008-2010. Mixed effects logistic regression was used to investigate factors associated with Plasmodium infection and anaemia within different malaria transmission zones. RESULTS: Insecticide-treated net (ITN) use was associated with reduction in the odds of Plasmodium infection in coastal and western highlands epidemic zones and among boys in the lakeside high transmission zone. Other risk factors for Plasmodium infection and for anaemia also varied by zone. Plasmodium infection was negatively associated with increasing socio-economic status in all transmission settings, except in the semi-arid north-east zone. Plasmodium infection was a risk factor for anaemia in lakeside high transmission, western highlands epidemic and central low-risk zones, whereas ITN use was only associated with lower levels of anaemia in coastal and central zones and among boys in the lakeside high transmission zone. CONCLUSIONS: The risk factors for Plasmodium infection and anaemia, including the protective associations with ITN use, vary according to malaria transmission settings in Kenya, and future efforts to control malaria and anaemia should take into account such heterogeneities among school children.

Wesolowski A, Eagle N, Noor AM, Snow RW, Buckee CO. 2012. Heterogeneous mobile phone ownership and usage patterns in Kenya. PLoS One, 7 (4), pp. e35319. | Show Abstract | Read more

The rapid adoption of mobile phone technologies in Africa is offering exciting opportunities for engaging with high-risk populations through mHealth programs, and the vast volumes of behavioral data being generated as people use their phones provide valuable data about human behavioral dynamics in these regions. Taking advantage of these opportunities requires an understanding of the penetration of mobile phones and phone usage patterns across the continent, but very little is known about the social and geographical heterogeneities in mobile phone ownership among African populations. Here, we analyze a survey of mobile phone ownership and usage across Kenya in 2009 and show that distinct regional, gender-related, and socioeconomic variations exist, with particularly low ownership among rural communities and poor people. We also examine patterns of phone sharing and highlight the contrasting relationships between ownership and sharing in different parts of the country. This heterogeneous penetration of mobile phones has important implications for the use of mobile technologies as a source of population data and as a public health tool in sub-Saharan Africa.

Sudoi RK, Githinji S, Nyandigisi A, Muturi A, Snow RW, Zurovac D. 2012. The magnitude and trend of artemether-lumefantrine stock-outs at public health facilities in Kenya. Malar J, 11 (1), pp. 37. | Show Abstract | Read more

BACKGROUND: Health facility stock-outs of artemether-lumefantrine (AL), the common first-line therapy for uncomplicated malaria across Africa, adversely affect effective malaria case-management. They have been previously reported on various scales in time and space, however the magnitude of the problem and trends over time are less clear. Here, 2010-2011 data are reported from public facilities in Kenya where alarming stock-outs were revealed in 2008. METHODS: Data were collected between January 2010 and June 2011 as part of 18 monthly cross-sectional surveys undertaken at nationally representative samples of public health facilities. The primary monitoring indicator was total stock-out of all four weight-specific AL packs. The secondary indicators were stock-outs of at least one AL pack and individual stock-outs for each AL pack. Monthly proportions and summary means of the proportions over the monitoring period were measured for each indicator. Stock-out trends were assessed using linear regression. RESULTS: The number of surveyed facilities across 18 time points ranged between 162 and 176 facilities. The stock-out means of the proportion of health facilities were 11.6% for total AL stock-out, 40.6% for stock-out of at least one AL pack, and between 20.5% and 27.4% for stock-outs of individual AL packs. Monthly decrease of the total AL stock-out was 0.005% (95% CI: -0.5 to +0.5; p = 0.983). Monthly decrease in the stock-out of at least one AL pack was 0.7% (95% CI: -1.5 to +0.3; p = 0.058) while stock-outs of individual AL packs decreased monthly between 0.2% for AL 24-pack and 0.7% for AL six-pack without statistical significance for any of the weight-specific packs. CONCLUSIONS: Despite lower levels of AL stock-outs compared to the reports in 2008, the stock-outs at Kenyan facilities during 2010-2011 are still substantial and of particular worry for the most detrimental:- simultaneous absence of any AL pack. Only minor decrease was observed in the stock-outs of individual AL packs. Recently launched interventions to eliminate AL stock-outs in Kenya are fully justified.

Zurovac D, Talisuna AO, Snow RW. 2012. Mobile phone text messaging: tool for malaria control in Africa. PLoS Med, 9 (2), pp. e1001176. | Read more

Brooker SJ, Pullan RL, Gitonga CW, Ashton RA, Kolaczinski JH, Kabatereine NB, Snow RW. 2012. Plasmodium-helminth coinfection and its sources of heterogeneity across East Africa. J Infect Dis, 205 (5), pp. 841-852. | Show Abstract | Read more

BACKGROUND: Plasmodium-helminth coinfection can have a number of consequences for infected hosts, yet our knowledge of the epidemiology of coinfection across multiple settings is limited. This study investigates the distribution and heterogeneity of coinfection with Plasmodium falciparum and 3 major helminth species across East Africa. METHODS: Cross-sectional parasite surveys were conducted among 28 050 children in 299 schools across a range of environmental settings in Kenya, Uganda, and Ethiopia. Data on individual, household, and environmental risk factors were collected and a spatially explicit Bayesian modeling framework was used to investigate heterogeneities of species infection and coinfection and their risk factors as well as school- and individual-level associations between species. RESULTS: Broad-scale geographical patterns of Plasmodium-helminth coinfection are strongly influenced by the least common infection and by species-specific environmental factors. At the individual level, there is an enduring positive association between P. falciparum and hookworm but no association between P. falciparum and Schistosoma species. However, the relative importance of such within-individual associations is less than the role of spatial factors in influencing coinfection risks. CONCLUSIONS: Patterns of coinfection seem to be influenced more by the distribution of the least common species and its environmental risk factors, rather than any enduring within-individual associations.

Abdelgader TM, Ibrahim AM, Elmardi KA, Githinji S, Zurovac D, Snow RW, Noor AM. 2012. Progress towards implementation of ACT malaria case-management in public health facilities in the Republic of Sudan: a cluster-sample survey. BMC Public Health, 12 (1), pp. 11. | Show Abstract | Read more

BACKGROUND: Effective malaria case-management based on artemisinin-based combination therapy (ACT) and parasitological diagnosis is a major pillar within the 2007-2012 National Malaria Strategic Plan in the Sudan. Three years after the launch of the strategy a health facility survey was undertaken to evaluate case-management practices and readiness of the health facilities and health workers to implement a new malaria case-management strategy. METHODS: A cross-sectional, cluster sample survey was undertaken at public health facilities in 15 states of Sudan. Data were collected using quality-of-care assessment methods. The main outcomes were the proportions of facilities with ACTs and malaria diagnostics; proportions of health workers exposed to malaria related health systems support activities; and composite and individual indicators of case-management practices for febrile outpatients stratified by age, availability of ACTs and diagnostics, use of malaria diagnostics, and test result. RESULTS: We evaluated 244 facilities, 294 health workers and 1,643 consultations for febrile outpatients (425 < 5 years and 1,218 ≥ 5 years). Health facility and health worker readiness was variable: chloroquine was available at only 5% of facilities, 73% stocked recommended artesunate and sulfadoxine/pyrimethamine (AS+SP), 51% had the capacity to perform parasitological diagnosis, 53% of health workers had received in-service training on ACTs, 24% were trained in the use of malaria Rapid Diagnostic Tests, and 19% had received a supervisory visit including malaria case-management. At all health facilities 46% of febrile patients were parasitologically tested and 35% of patients were both, tested and treated according to test result. At facilities where AS+SP and malaria diagnostics were available 66% of febrile patients were tested and 51% were both, tested and treated according to test result. Among test positive patients 64% were treated with AS+SP but 24% were treated with artemether monotherapy. Among test negative patients only 17% of patients were treated for malaria. The majority of ACT dispensing and counseling practices were suboptimal. CONCLUSIONS: Five years following change of the policy from chloroquine to ACTs and 3 years before the end of the new malaria strategic plan chloroquine was successfully phased out from public facilities in Sudan, however, an important gap remained in the availability of ACTs, diagnostic capacities and coverage with malaria case-management activities. The national scale-up of diagnostics, using the findings of this survey as well as future qualitative research, should present an opportunity not only to expand existing testing capacities but also to implement effective support interventions to bridge the health systems gaps and support corrective case-management measures, including the discontinuation of artemether monotherapy treatment.

Jones CO, Wasunna B, Sudoi R, Githinji S, Snow RW, Zurovac D. 2012. "Even if you know everything you can forget": health worker perceptions of mobile phone text-messaging to improve malaria case-management in Kenya. PLoS One, 7 (6), pp. e38636. | Show Abstract | Read more

This paper presents the results of a qualitative study to investigate the perceptions and experiences of health workers involved in a a cluster-randomized controlled trial of a novel intervention to improve health worker malaria case-management in 107 government health facilities in Kenya. The intervention involved sending text-messages about paediatric outpatient malaria case-management accompanied by "motivating" quotes to health workers' mobile phones. Ten malaria messages were developed reflecting recommendations from the Kenyan national guidelines. Two messages were delivered per day for 5 working days and the process was repeated for 26 weeks (May to October 2009). The accompanying quotes were unique to each message. The intervention was delivered to 119 health workers and there were significant improvements in correct artemether-lumefantrine (AL) management both immediately after the intervention (November 2009) and 6 months later (May 2010). In-depth interviews with 24 health workers were undertaken to investigate the possible drivers of this change. The results suggest high acceptance of all components of the intervention, with the active delivery of information in an on the job setting, the ready availability of new and stored text messages and the perception of being kept 'up to date' as important factors influencing practice. Applying the construct of stages of change we infer that in this intervention the SMS messages were operating primarily at the action and maintenance stages of behaviour change achieving their effect by creating an enabling environment and providing a prompt to action for the implementation of case management practices that had already been accepted as the clinical norm by the health workers. Future trials testing the effectiveness of SMS reminders in creating an enabling environment for the establishment of new norms in clinical practice as well as in providing a prompt to action for the implementation of the new case-management guidelines are justified.

Zurovac D, Larson BA, Sudoi RK, Snow RW. 2012. Costs and cost-effectiveness of a mobile phone text-message reminder programmes to improve health workers' adherence to malaria guidelines in Kenya. PLoS One, 7 (12), pp. e52045. | Show Abstract | Read more

BACKGROUND: Simple interventions for improving health workers' adherence to malaria case-management guidelines are urgently required across Africa. A recent trial in Kenya showed that text-message reminders sent to health workers' mobile phones improved management of pediatric outpatients by 25 percentage points. In this paper we examine costs and cost-effectiveness of this intervention. METHODS/FINDINGS: We evaluate costs and cost-effectiveness in 2010 USD under three implementation scenarios: (1) as implemented under study conditions in study areas; (2) if the intervention was routinely implemented by the Ministry of Health (MoH) in the same areas; and (3) if the intervention was scaled up nationally. Under study conditions, intervention costs were 19,342 USD, of which 45% were for developing and pretesting text-messages, 12% for developing text-message distribution system, 29% for collecting health workers' phone numbers, and 13% were costs of sending text-messages and monitoring of the system. If the intervention was implemented in the same areas by the MoH, the costs would be 28% lower (13,920 USD) due to lower costs of collecting health workers' numbers. The cost of national scale-up would be 97,350 USD, and the majority of these costs (66%) would be for sending text-messages. The cost per additional child correctly managed was 0.50 USD under study conditions, 0.36 USD if implemented by the MoH in the same area, and estimated at only 0.03 USD if implemented nationally. Even if the effect size was only 5% or the cost on the national scale was 400% higher than estimated, the cost per additional child correctly managed would be only 0.16 USD. CONCLUSIONS: A simple text-messaging intervention improving health worker adherence to malaria guidelines is effective and inexpensive. Further research is justified to optimize delivery of the intervention and expand targets beyond children and malaria disease.

Pindolia DK, Garcia AJ, Wesolowski A, Smith DL, Buckee CO, Noor AM, Snow RW, Tatem AJ. 2012. Human movement data for malaria control and elimination strategic planning. Malar J, 11 (1), pp. 205. | Show Abstract | Read more

Recent increases in funding for malaria control have led to the reduction in transmission in many malaria endemic countries, prompting the national control programmes of 36 malaria endemic countries to set elimination targets. Accounting for human population movement (HPM) in planning for control, elimination and post-elimination surveillance is important, as evidenced by previous elimination attempts that were undermined by the reintroduction of malaria through HPM. Strategic control and elimination planning, therefore, requires quantitative information on HPM patterns and the translation of these into parasite dispersion. HPM patterns and the risk of malaria vary substantially across spatial and temporal scales, demographic and socioeconomic sub-groups, and motivation for travel, so multiple data sets are likely required for quantification of movement. While existing studies based on mobile phone call record data combined with malaria transmission maps have begun to address within-country HPM patterns, other aspects remain poorly quantified despite their importance in accurately gauging malaria movement patterns and building control and detection strategies, such as cross-border HPM, demographic and socioeconomic stratification of HPM patterns, forms of transport, personal malaria protection and other factors that modify malaria risk. A wealth of data exist to aid filling these gaps, which, when combined with spatial data on transport infrastructure, traffic and malaria transmission, can answer relevant questions to guide strategic planning. This review aims to (i) discuss relevant types of HPM across spatial and temporal scales, (ii) document where datasets exist to quantify HPM, (iii) highlight where data gaps remain and (iv) briefly put forward methods for integrating these datasets in a Geographic Information System (GIS) framework for analysing and modelling human population and Plasmodium falciparum malaria infection movements.

Noor AM, Alegana VA, Patil AP, Moloney G, Borle M, Yusuf F, Amran J, Snow RW. 2012. Mapping the receptivity of malaria risk to plan the future of control in Somalia. BMJ Open, 2 (4), pp. e001160-e001160. | Show Abstract | Read more

OBJECTIVES: To measure the receptive risks of malaria in Somalia and compare decisions on intervention scale-up based on this map and the more widely used contemporary risk maps. DESIGN: Cross-sectional community Plasmodium falciparum parasite rate (PfPR) data for the period 2007-2010 corrected to a standard age range of 2 to <10 years (PfPR(2-10)) and used within a Bayesian space-time geostatistical framework to predict the contemporary (2010) mean PfPR(2-10) and the maximum annual mean PfPR(2-10) (receptive) from the highest predicted PfPR(2-10) value over the study period as an estimate of receptivity. SETTING: Randomly sampled communities in Somalia. PARTICIPANTS: Randomly sampled individuals of all ages. MAIN OUTCOME MEASURE: Cartographic descriptions of malaria receptivity and contemporary risks in Somalia at the district level. RESULTS: The contemporary annual PfPR(2-10) map estimated that all districts (n=74) and population (n=8.4 million) in Somalia were under hypoendemic transmission (≤10% PfPR(2-10)). Of these, 23% of the districts, home to 13% of the population, were under transmission of <1% PfPR(2-10). About 58% of the districts and 55% of the population were in the risk class of 1% to <5% PfPR(2-10). In contrast, the receptivity map estimated 65% of the districts and 69% of the population were under mesoendemic transmission (>10%-50% PfPR(2-10)) and the rest as hypoendemic. CONCLUSION: Compared with maps of receptive risks, contemporary maps of transmission mask disparities of malaria risk necessary to prioritise and sustain future control. As malaria risk declines across Africa, efforts must be invested in measuring receptivity for efficient control planning.

Gitonga CW, Edwards T, Karanja PN, Noor AM, Snow RW, Brooker SJ. 2012. Plasmodium infection, anaemia and mosquito net use among school children across different settings in Kenya Tropical Medicine and International Health, 17 (7), pp. 858-870. | Show Abstract | Read more

Objective To investigate risk factors, including reported net use, for Plasmodium infection and anaemia among school children and to explore variations in effects across different malaria ecologies occurring in Kenya. Methods This study analysed data for 49975 school children in 480 schools surveyed during a national school malaria survey, 2008-2010. Mixed effects logistic regression was used to investigate factors associated with Plasmodium infection and anaemia within different malaria transmission zones. Results Insecticide-treated net (ITN) use was associated with reduction in the odds of Plasmodium infection in coastal and western highlands epidemic zones and among boys in the lakeside high transmission zone. Other risk factors for Plasmodium infection and for anaemia also varied by zone. Plasmodium infection was negatively associated with increasing socio-economic status in all transmission settings, except in the semi-arid north-east zone. Plasmodium infection was a risk factor for anaemia in lakeside high transmission, western highlands epidemic and central low-risk zones, whereas ITN use was only associated with lower levels of anaemia in coastal and central zones and among boys in the lakeside high transmission zone. Conclusions The risk factors for Plasmodium infection and anaemia, including the protective associations with ITN use, vary according to malaria transmission settings in Kenya, and future efforts to control malaria and anaemia should take into account such heterogeneities among school children. © 2012 Blackwell Publishing Ltd.

Linard C, Gilbert M, Snow RW, Noor AM, Tatem AJ. 2012. Population distribution, settlement patterns and accessibility across Africa in 2010. PLoS One, 7 (2), pp. e31743. | Show Abstract | Read more

The spatial distribution of populations and settlements across a country and their interconnectivity and accessibility from urban areas are important for delivering healthcare, distributing resources and economic development. However, existing spatially explicit population data across Africa are generally based on outdated, low resolution input demographic data, and provide insufficient detail to quantify rural settlement patterns and, thus, accurately measure population concentration and accessibility. Here we outline approaches to developing a new high resolution population distribution dataset for Africa and analyse rural accessibility to population centers. Contemporary population count data were combined with detailed satellite-derived settlement extents to map population distributions across Africa at a finer spatial resolution than ever before. Substantial heterogeneity in settlement patterns, population concentration and spatial accessibility to major population centres is exhibited across the continent. In Africa, 90% of the population is concentrated in less than 21% of the land surface and the average per-person travel time to settlements of more than 50,000 inhabitants is around 3.5 hours, with Central and East Africa displaying the longest average travel times. The analyses highlight large inequities in access, the isolation of many rural populations and the challenges that exist between countries and regions in providing access to services. The datasets presented are freely available as part of the AfriPop project, providing an evidence base for guiding strategic decisions.

Wesolowski A, Eagle N, Tatem AJ, Smith DL, Noor AM, Snow RW, Buckee CO. 2012. Quantifying the impact of human mobility on malaria. Science, 338 (6104), pp. 267-270. | Show Abstract | Read more

Human movements contribute to the transmission of malaria on spatial scales that exceed the limits of mosquito dispersal. Identifying the sources and sinks of imported infections due to human travel and locating high-risk sites of parasite importation could greatly improve malaria control programs. Here, we use spatially explicit mobile phone data and malaria prevalence information from Kenya to identify the dynamics of human carriers that drive parasite importation between regions. Our analysis identifies importation routes that contribute to malaria epidemiology on regional spatial scales.

Alegana VA, Wright JA, Pentrina U, Noor AM, Snow RW, Atkinson PM. 2012. Spatial modelling of healthcare utilisation for treatment of fever in Namibia. Int J Health Geogr, 11 (1), pp. 6. | Show Abstract | Read more

BACKGROUND: Health care utilization is affected by several factors including geographic accessibility. Empirical data on utilization of health facilities is important to understanding geographic accessibility and defining health facility catchments at a national level. Accurately defining catchment population improves the analysis of gaps in access, commodity needs and interpretation of disease incidence. Here, empirical household survey data on treatment seeking for fever were used to model the utilisation of public health facilities and define their catchment areas and populations in northern Namibia. METHOD: This study uses data from the Malaria Indicator Survey (MIS) of 2009 on treatment seeking for fever among children under the age of five years to characterize facility utilisation. Probability of attendance of public health facilities for fever treatment was modelled against a theoretical surface of travel times using a three parameter logistic model. The fitted model was then applied to a population surface to predict the number of children likely to use a public health facility during an episode of fever in northern Namibia. RESULTS: Overall, from the MIS survey, the prevalence of fever among children was 17.6% CI [16.0-19.1] (401 of 2,283 children) while public health facility attendance for fever was 51.1%, [95%CI: 46.2-56.0]. The coefficients of the logistic model of travel time against fever treatment at public health facilities were all significant (p < 0.001). From this model, probability of facility attendance remained relatively high up to 180 minutes (3 hours) and thereafter decreased steadily. Total public health facility catchment population of children under the age five was estimated to be 162,286 in northern Namibia with an estimated fever burden of 24,830 children. Of the estimated fevers, 8,021 (32.3%) were within 30 minutes of travel time to the nearest health facility while 14,902 (60.0%) were within 1 hour. CONCLUSION: This study demonstrates the potential of routine household surveys to empirically model health care utilisation for the treatment of childhood fever and define catchment populations enhancing the possibilities of accurate commodity needs assessment and calculation of disease incidence. These methods could be extended to other African countries where detailed mapping of health facilities exists.

Snow RW, Amratia P, Kabaria CW, Noor AM, Marsh K. 2012. The changing limits and incidence of malaria in Africa: 1939-2009. Adv Parasitol, 78 pp. 169-262. | Show Abstract | Read more

Understanding the historical, temporal changes of malaria risk following control efforts in Africa provides a unique insight into what has been and might be archived towards a long-term ambition of elimination on the continent. Here, we use archived published and unpublished material combined with biological constraints on transmission accompanied by a narrative on malaria control to document the changing incidence of malaria in Africa since earliest reports pre-second World War. One result is a more informed mapped definition of the changing margins of transmission in 1939, 1959, 1979, 1999 and 2009.

Lawford H, Zurovac D, O'Reilly L, Hoibak S, Cowley A, Munga S, Vulule J, Juma E, Snow RW, Allan R. 2011. Adherence to prescribed artemisinin-based combination therapy in Garissa and Bunyala districts, Kenya. Malar J, 10 (1), pp. 281. | Show Abstract | Read more

BACKGROUND: Following the development of resistance to anti-malarial mono-therapies, malaria endemic countries in Africa now use artemisinin-based combination therapy (ACT) as recommended first-line treatment for uncomplicated malaria. Patients' adherence to ACT is an important factor to ensure treatment efficacy, as well as to reduce the likelihood of parasite resistance to these drugs. This study reports adherence to a specific ACT, artemether-lumefantrine (AL), under conditions of routine clinical practice in Kenya. METHOD: The study was undertaken in Garissa and Bunyala districts among outpatients of five government health facilities. Patients treated with AL were visited at home four days after having been prescribed the drug. Respondents (patients ≥ 15 years and caregivers of patients < 15 years) were interviewed using a standardized questionnaire, AL blister packs were physically inspected and the adherence status of patients was then recorded. Multivariate logistic regression modelling was used to determine predictors of adherence. RESULTS: Of the 918 patients included in the study, 588 (64.1%) were 'probably adherent', 291 (31.7%) were 'definitely non-adherent' and 39 (4.2%) were 'probably non-adherent'. Six factors were found to be significant predictors of adherence: patient knowledge of the ACT dosing regimen (odds ratio (OR) = 1.76; 95% CI = 1.32-2.35), patient age (OR = 1.65; 95% CI = 1.02-1.85), respondent age (OR = 1.37; 95% CI = 1.10-2.48), whether a respondent had seen AL before (OR = 1.46; 95% CI = 1.08-1.98), whether a patient had reported dislikes to AL (OR = 0.62 95% CI = 0.47-0.82) and whether a respondent had waited more than 24 hours to seek treatment (OR = 0.73; 95% CI = 0.54-0.99). CONCLUSION: Overall, adherence to AL was found to be low in both Garissa and Bunyala districts, with patient knowledge of the AL dosing regimen found to be the strongest predictor of adherence. Interventions aimed at increasing community awareness of the AL dosing regimen, use of child friendly formulations and improving health workers' prescribing practices are likely to ensure higher adherence to AL and eventual treatment success.

Zurovac D, Sudoi RK, Akhwale WS, Ndiritu M, Hamer DH, Rowe AK, Snow RW. 2011. The effect of mobile phone text-message reminders on Kenyan health workers' adherence to malaria treatment guidelines: a cluster randomised trial. Lancet, 378 (9793), pp. 795-803. | Show Abstract | Read more

BACKGROUND: Health workers' malaria case-management practices often differ from national guidelines. We assessed whether text-message reminders sent to health workers' mobile phones could improve and maintain their adherence to treatment guidelines for outpatient paediatric malaria in Kenya. METHODS: From March 6, 2009, to May 31, 2010, we did a cluster-randomised controlled trial at 107 rural health facilities in 11 districts in coastal and western Kenya. With a computer-generated sequence, health facilities were randomly allocated to either the intervention group, in which all health workers received text messages on their personal mobile phones on malaria case-management for 6 months, or the control group, in which health workers did not receive any text messages. Health workers were not masked to the intervention, although patients were unaware of whether they were in an intervention or control facility. The primary outcome was correct management with artemether-lumefantrine, defined as a dichotomous composite indicator of treatment, dispensing, and counselling tasks concordant with Kenyan national guidelines. The primary analysis was by intention to treat. The trial is registered with Current Controlled Trials, ISRCTN72328636. FINDINGS: 119 health workers received the intervention. Case-management practices were assessed for 2269 children who needed treatment (1157 in the intervention group and 1112 in the control group). Intention-to-treat analysis showed that correct artemether-lumefantrine management improved by 23·7 percentage-points (95% CI 7·6-40·0; p=0·004) immediately after intervention and by 24·5 percentage-points (8·1-41·0; p=0·003) 6 months later. INTERPRETATION: In resource-limited settings, malaria control programmes should consider use of text messaging to improve health workers' case-management practices. FUNDING: The Wellcome Trust.

Mudhune SA, Okiro EA, Noor AM, Zurovac D, Juma E, Ochola SA, Snow RW. 2011. The clinical burden of malaria in Nairobi: a historical review and contemporary audit. Malar J, 10 (1), pp. 138. | Show Abstract | Read more

BACKGROUND: Widespread urbanization over the next 20 years has the potential to drastically change the risk of malaria within Africa. The burden of the disease, its management, risk factors and appropriateness of targeted intervention across varied urban environments in Africa remain largely undefined. This paper presents a combined historical and contemporary review of the clinical burden of malaria within one of Africa's largest urban settlements, Nairobi, Kenya. METHODS: A review of historical reported malaria case burdens since 1911 within Nairobi was undertaken using archived government and city council reports. Contemporary information on out-patient case burdens due to malaria were assembled from the National Health Management and Information System (HMIS). Finally, an audit of 22 randomly selected health facilities within Nairobi was undertaken covering 12 months 2009-2010. The audit included interviews with health workers, and a checklist of commodities and guidelines necessary to diagnose, treat and record malaria. RESULTS: From the 1930's through to the mid-1960's malaria incidence declined coincidental with rapid population growth. During this period malaria notification and prevention were a priority for the city council. From 2001-2008 reporting systems for malaria were inadequate to define the extent or distribution of malaria risk within Nairobi. A more detailed facility review suggests, however that malaria remains a common diagnosis (11% of all paediatric diagnoses made) and where laboratories (n = 15) exist slide positivity rates are on average 15%. Information on the quality of diagnosis, slide reading and whether those reported as positive were imported infections was not established. The facilities and health workers included in this study were not universally prepared to treat malaria according to national guidelines or identify foci of risks due to shortages of national first-line drugs, inadequate record keeping and a view among some health workers (17%) that slide negative patients could still have malaria. CONCLUSION: Combined with historical evidence there is a strong suggestion that very low risks of locally acquired malaria exist today within Nairobi's city limits and this requires further investigation. To be prepared for effective prevention and case-management of malaria among a diverse, mobile population in Nairobi requires a major paradigm shift and investment in improved quality of malaria diagnosis and case management, health system strengthening and case reporting.

Kangwana BP, Kedenge SV, Noor AM, Alegana VA, Nyandigisi AJ, Pandit J, Fegan GW, Todd JE, Brooker S, Snow RW, Goodman CA. 2011. The impact of retail-sector delivery of artemether-lumefantrine on malaria treatment of children under five in Kenya: a cluster randomized controlled trial. PLoS Med, 8 (5), pp. e1000437. | Show Abstract | Read more

BACKGROUND: It has been proposed that artemisinin-based combination therapy (ACT) be subsidised in the private sector in order to improve affordability and access. This study in western Kenya aimed to evaluate the impact of providing subsidized artemether-lumefantrine (AL) through retail providers on the coverage of prompt, effective antimalarial treatment for febrile children aged 3-59 months. METHODS AND FINDINGS: We used a cluster-randomized, controlled design with nine control and nine intervention sublocations, equally distributed across three districts in western Kenya. Cross-sectional household surveys were conducted before and after the delivery of the intervention. The intervention comprised provision of subsidized packs of paediatric ACT to retail outlets, training of retail outlet staff, and community awareness activities. The primary outcome was defined as the proportion of children aged 3-59 months reporting fever in the past 2 weeks who started treatment with AL on the same day or following day of fever onset. Data were collected using structured questionnaires and analyzed based on cluster-level summaries, comparing control to intervention arms, while adjusting for other covariates. Data were collected on 2,749 children in the target age group at baseline and 2,662 at follow-up. 29% of children experienced fever within 2 weeks before the interview. At follow-up, the percentage of children receiving AL on the day of fever or the following day had risen by 14.6% points in the control arm (from 5.3% [standard deviation (SD): 3.2%] to 19.9% [SD: 10.0%]) and 40.2% points in the intervention arm (from 4.7% [SD: 3.4%] to 44.9% [SD: 11.7%]). The percentage of children receiving AL was significantly greater in the intervention arm at follow-up, with a difference between the arms of 25.0% points (95% confidence interval [CI]: 14.1%, 35.9%; unadjusted p = 0.0002, adjusted p = 0.0001). No significant differences were observed between arms in the proportion of caregivers who sought treatment for their child's fever by source, or in the child's adherence to AL. CONCLUSIONS: Subsidizing ACT in the retail sector can significantly increase ACT coverage for reported fevers in rural areas. Further research is needed on the impact and cost-effectiveness of such subsidy programmes at a national scale. TRIAL REGISTRATION: Current Controlled Trials ISRCTN59275137 and Kenya Pharmacy and Poisons Board Ethical Committee for Clinical Trials PPB/ECCT/08/07.

Lubell Y, Staedke SG, Greenwood BM, Kamya MR, Molyneux M, Newton PN, Reyburn H, Snow RW et al. 2011. Likely health outcomes for untreated acute febrile illness in the tropics in decision and economic models; a Delphi survey. PLoS One, 6 (2), pp. e17439. | Show Abstract | Read more

BACKGROUND: Modelling is widely used to inform decisions about management of malaria and acute febrile illnesses. Most models depend on estimates of the probability that untreated patients with malaria or bacterial illnesses will progress to severe disease or death. However, data on these key parameters are lacking and assumptions are frequently made based on expert opinion. Widely diverse opinions can lead to conflicting outcomes in models they inform. METHODS AND FINDINGS: A Delphi survey was conducted with malaria experts aiming to reach consensus on key parameters for public health and economic models, relating to the outcome of untreated febrile illnesses. Survey questions were stratified by malaria transmission intensity, patient age, and HIV prevalence. The impact of the variability in opinion on decision models is illustrated with a model previously used to assess the cost-effectiveness of malaria rapid diagnostic tests. Some consensus was reached around the probability that patients from higher transmission settings with untreated malaria would progress to severe disease (median 3%, inter-quartile range (IQR) 1-5%), and the probability that a non-malaria illness required antibiotics in areas of low HIV prevalence (median 20%). Children living in low transmission areas were considered to be at higher risk of progressing to severe malaria (median 30%, IQR 10-58%) than those from higher transmission areas (median 13%, IQR 7-30%). Estimates of the probability of dying from severe malaria were high in all settings (medians 60-73%). However, opinions varied widely for most parameters, and did not converge on resurveying. CONCLUSIONS: This study highlights the uncertainty around potential consequences of untreated malaria and bacterial illnesses. The lack of consensus on most parameters, the wide range of estimates, and the impact of variability in estimates on model outputs, demonstrate the importance of sensitivity analysis for decision models employing expert opinion. Results of such models should be interpreted cautiously. The diversity of expert opinion should be recognised when policy options are debated.

Nourein AB, Abass MA, Nugud AH, El Hassan I, Snow RW, Noor AM. 2011. Identifying residual foci of Plasmodium falciparum infections for malaria elimination: the urban context of Khartoum, Sudan. PLoS One, 6 (2), pp. e16948. | Show Abstract | Read more

BACKGROUND: Identifying the location and size of residual foci of infections is critical where malaria elimination is the primary goal. Here the spatial heterogeneity of Plasmodium falciparum infections within the urban extent of Khartoum state in Sudan is investigated using data from cross-sectional surveys undertaken from 1999 to 2008 to inform the Khartoum Malaria Free Initiative (KMFI). METHODS: From 1999-2008 the KMFI undertook cross-sectional surveys of 256 clusters across 203 random samples of residential blocks in the urban Khartoum state in September of each year. Within sampled blocks, at least five persons, including at least one child under the age of five years, were selected from each household. Blood smears were collected from the sampled individuals to examine the presence of P. falciparum parasites. Residential blocks were mapped. Data were analysed for spatial clustering using the Bernoulli model and the significance of clusters were tested using the Kulldorff scan statistic. RESULTS: A total of 128,510 malaria slide examinations were undertaken during the study period. In 1999, overall prevalence was 2.5%, rising to 3.2% in 2000 and consistently staying below 1% in subsequent years. From 2006, over 90% of all surveyed clusters reported no infections. Spatial clustering of infections was present in each year but not statistically significant in the years 2001, 2002, 2004 and 2008. Spatial clusters of high infection were often located at the junction of the Blue and White Niles. CONCLUSION: Persisting foci of malaria infection in Khartoum are likely to distort wide area assessments and disproportionately affect future transmission within the city limits. Improved investments in surveillance that combines both passive and active case detection linked to a geographic information system and a more detailed analysis of the location and stability of foci should be undertaken to facilitate and track malaria elimination in the state of Khartoum.

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Van Eijk AM, Hill J, Alegana VA, Kirui V, Gething PW, ter Kuile FO, Snow RW. 2011. Coverage of malaria protection in pregnant women in sub-Saharan Africa: A synthesis and analysis of national survey data The Lancet Infectious Diseases, 11 (3), pp. 190-207. | Show Abstract | Read more

Background: Insecticide-treated nets and intermittent preventive treatment with sulfadoxine-pyrimethamine are recommended for the control of malaria during pregnancy in endemic areas in Africa, but there has been no analysis of coverage data at a subnational level. We aimed to synthesise data from national surveys about these interventions, accounting for disparities in malaria risk within national borders. Methods: We extracted data for specific strategies for malaria control in pregnant women from national malaria policies from endemic countries in Africa. We identified the most recent national household cluster-sample surveys recording intermittent preventive treatment with sulfadoxine-pyrimethamine and use of insecticide-treated nets. We reconciled data to subnational administrative units to construct a model to estimate the number of pregnant women covered by a recommended intervention in 2007. Findings: 45 (96%) of 47 countries surveyed had a policy for distribution of insecticide-treated nets for pregnant women; estimated coverage in 2007 was 4·7 million (17%) of 27·7 million pregnancies at risk of malaria in 32 countries with data. 39 (83%) of 47 countries surveyed had an intermittent preventive treatment policy; in 2007, an estimated 6·4 million (25%) of 25·6 million pregnant women received at least one dose of treatment and 19·8 million (77%) visited an antenatal clinic (31 countries). Estimated coverage was lowest in areas of high-intensity transmission of malaria. Interpretation: Despite success in a few countries, coverage of insecticide-treated nets and intermittent preventive treatment in pregnant African women is inadequate; increased efforts towards scale-up are needed. Funding: The Malaria in Pregnancy Consortium and Wellcome Trust. © 2011 Elsevier Ltd.

Noor AM, Mohamed MB, Mugyenyi CK, Osman MA, Guessod HH, Kabaria CW, Ahmed IA, Nyonda M et al. 2011. Establishing the extent of malaria transmission and challenges facing pre-elimination in the Republic of Djibouti. BMC Infect Dis, 11 (1), pp. 121. | Show Abstract | Read more

BACKGROUND: Countries aiming for malaria elimination require a detailed understanding of the current intensity of malaria transmission within their national borders. National household sample surveys are now being used to define infection prevalence but these are less efficient in areas of exceptionally low endemicity. Here we present the results of a national malaria indicator survey in the Republic of Djibouti, the first in sub-Saharan Africa to combine parasitological and serological markers of malaria, to evaluate the extent of transmission in the country and explore the potential for elimination. METHODS: A national cross-sectional household survey was undertaken from December 2008 to January 2009. A finger prick blood sample was taken from randomly selected participants of all ages to examine for parasitaemia using rapid diagnostic tests (RDTs) and confirmed using Polymerase Chain Reaction (PCR). Blood spots were also collected on filter paper and subsequently used to evaluate the presence of serological markers (combined AMA-1 and MSP-119) of Plasmodium falciparum exposure. Multivariate regression analysis was used to determine the risk factors for P. falciparum infection and/or exposure. The Getis-Ord G-statistic was used to assess spatial heterogeneity of combined infections and serological markers. RESULTS: A total of 7151 individuals were tested using RDTs of which only 42 (0.5%) were positive for P. falciparum infections and confirmed by PCR. Filter paper blood spots were collected for 5605 individuals. Of these 4769 showed concordant optical density results and were retained in subsequent analysis. Overall P. falciparum sero-prevalence was 9.9% (517/4769) for all ages; 6.9% (46/649) in children under the age of five years; and 14.2% (76/510) in the oldest age group (≥50 years). The combined infection and/or antibody prevalence was 10.5% (550/4769) and varied from 8.1% to 14.1% but overall regional differences were not statistically significant (χ2=33.98, p=0.3144). Increasing age (p<0.001) and decreasing household wealth status (p<0.001) were significantly associated with increasing combined P. falciparum infection and/or antibody prevalence. Significant P. falciparum hot spots were observed in Dikhil region. CONCLUSION: Malaria transmission in the Republic of Djibouti is very low across all regions with evidence of micro-epidemiological heterogeneity and limited recent transmission. It would seem that the Republic of Djibouti has a biologically feasible set of pre-conditions for elimination, however, the operational feasibility and the potential risks to elimination posed by P. vivax and human population movement across the sub-region remain to be properly established.

Okiro EA, Bitira D, Mbabazi G, Mpimbaza A, Alegana VA, Talisuna AO, Snow RW. 2011. Increasing malaria hospital admissions in Uganda between 1999 and 2009. BMC Med, 9 (1), pp. 37. | Show Abstract | Read more

BACKGROUND: Some areas of Africa are witnessing a malaria transition, in part due to escalated international donor support and intervention coverage. Areas where declining malaria rates have been observed are largely characterized by relatively low baseline transmission intensity and rapid scaling of interventions. Less well described are changing patterns of malaria burden in areas of high parasite transmission and slower increases in control and treatment access. METHODS: Uganda is a country predominantly characterized by intense, perennial malaria transmission. Monthly pediatric admission data from five Ugandan hospitals and their catchments have been assembled retrospectively across 11 years from January 1999 to December 2009. Malaria admission rates adjusted for changes in population density within defined catchment areas were computed across three time periods that correspond to periods where intervention coverage data exist and different treatment and prevention policies were operational. Time series models were developed adjusting for variations in rainfall and hospital use to examine changes in malaria hospitalization over 132 months. The temporal changes in factors that might explain changes in disease incidence were qualitatively examined sequentially for each hospital setting and compared between hospital settings RESULTS: In four out of five sites there was a significant increase in malaria admission rates. Results from time series models indicate a significant month-to-month increase in the mean malaria admission rates at four hospitals (trend P < 0.001). At all hospitals malaria admissions had increased from 1999 by 47% to 350%. Observed changes in intervention coverage within the catchments of each hospital showed a change in insecticide-treated net coverage from <1% in 2000 to 33% by 2009 but accompanied by increases in access to nationally recommended drugs at only two of the five hospital areas studied. CONCLUSIONS: The declining malaria disease burden in some parts of Africa is not a universal phenomena across the continent. Despite moderate increases in the coverage of measures to reduce infection and disease without significant coincidental increasing access to effective medicines to treat disease may not lead to severe disease burden reductions in high transmission areas of Africa. More data is needed from a wider range of malaria settings to provide an honest tracking progress of the impact of scaled intervention coverage in Africa.

Gething PW, Van Boeckel TP, Smith DL, Guerra CA, Patil AP, Snow RW, Hay SI. 2011. Modelling the global constraints of temperature on transmission of Plasmodium falciparum and P. vivax. Parasit Vectors, 4 (1), pp. 92. | Show Abstract | Read more

BACKGROUND: Temperature is a key determinant of environmental suitability for transmission of human malaria, modulating endemicity in some regions and preventing transmission in others. The spatial modelling of malaria endemicity has become increasingly sophisticated and is now central to the global scale planning, implementation, and monitoring of disease control and regional efforts towards elimination, but existing efforts to model the constraints of temperature on the malaria landscape at these scales have been simplistic. Here, we define an analytical framework to model these constraints appropriately at fine spatial and temporal resolutions, providing a detailed dynamic description that can enhance large scale malaria cartography as a decision-support tool in public health. RESULTS: We defined a dynamic biological model that incorporated the principal mechanisms of temperature dependency in the malaria transmission cycle and used it with fine spatial and temporal resolution temperature data to evaluate time-series of temperature suitability for transmission of Plasmodium falciparum and P. vivax throughout an average year, quantified using an index proportional to the basic reproductive number. Time-series were calculated for all 1 km resolution land pixels globally and were summarised to create high-resolution maps for each species delineating those regions where temperature precludes transmission throughout the year. Within suitable zones we mapped for each pixel the number of days in which transmission is possible and an integrated measure of the intensity of suitability across the year. The detailed evaluation of temporal suitability dynamics provided by the model is visualised in a series of accompanying animations. CONCLUSIONS: These modelled products, made available freely in the public domain, can support the refined delineation of populations at risk; enhance endemicity mapping by offering a detailed, dynamic, and biologically driven alternative to the ubiquitous empirical incorporation of raw temperature data in geospatial models; and provide a rich spatial and temporal platform for future biological modelling studies.

Elmardi KA, Noor AM, Githinji S, Abdelgadir TM, Malik EM, Snow RW. 2011. Self-reported fever, treatment actions and malaria infection prevalence in the northern states of Sudan. Malar J, 10 (1), pp. 128. | Show Abstract | Read more

BACKGROUND: The epidemiology of fevers and their management in areas of low malaria transmission in Africa is not well understood. The characteristics of fever, its treatment and association with infection prevalence from a national household sample survey in the northern states of Sudan, an area that represents historically low parasite prevalence, are examined in this study. METHODS: In October-November 2009, a cluster sample cross-sectional household malaria indicator survey was undertaken in the 15 northern states of the Sudan. Data on household assets and individual level information on age, sex, whether the individual had a fever in the last 14 days and on the day of survey, actions taken to treat the fever including diagnostic services and drugs used and their sources were collected. Consenting household members were asked to provide a finger-prick blood sample and examined for malaria parasitaemia using a rapid diagnostic test (RDT). All proportions and odds ratios were weighted and adjusted for clustering. RESULTS: Of 26,471 respondents 19% (n = 5,299) reported a history of fever within the last two weeks prior to the survey and 8% had fever on the day of the survey. Only 39% (n = 2,035) of individuals with fever in last two weeks took any action, of which 43% (n = 875) were treated with anti-malarials. About 44% (n = 382) of malaria treatments were done using the nationally recommended first-line therapy artesunate+sulphadoxine-pryrimethamine (AS+SP) and 13% (n = 122) with non-recommended chloroquine or SP. Importantly 33.9% (n = 296) of all malaria treatments included artemether monotherapy, which is internationally banned for the treatment of uncomplicated malaria. About 53% of fevers had some form of parasitological diagnosis before treatment. On the day of survey, 21,988 individuals provided a finger-prick blood sample and only 1.8% were found positive for Plasmodium falciparum. Infection prevalence was higher among individuals who had fever in the last two weeks (OR = 3.4; 95%CI = 2.6 - 4.4, p < 0.001) or reported fever on the day of survey (OR = 6.2; 95%CI = 4.4 - 8.7, p < 0.001) compared to those without a history of fever. CONCLUSION: Across the northern states of the Sudan, the period prevalence of fever is low. The proportion of fevers that are likely to be malaria is very low. Consequently, parasitological diagnosis of all fevers before treatment is an appropriate strategy for malaria case-management. Improved regulation and supervision of health workers is required to increase the use of diagnostics and remove the practice of prescribing artemisinin monotherapy.

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Manh BH, Clements ACA, Thieu NQ, Hung NM, Hung LX, Hay SI, Hien TT, Wertheim HFL, Snow RW, Horby P. 2011. Social and environmental determinants of malaria in space and time in Viet Nam International Journal for Parasitology, 41 (1), pp. 109-116. | Show Abstract | Read more

The malaria burden in Viet Nam has been in decline in recent decades, but localised areas of high transmission remain. We used spatiotemporal analytical tools to determine the social and environmental drivers of malaria risk and to identify residual high-risk areas where control and surveillance resources can be targeted. Counts of reported Plasmodium falciparum and Plasmodium vivax malaria cases by month (January 2007-December 2008) and by district were assembled. Zero-inflated Poisson regression models were developed in a Bayesian framework. Models had the percentage of the district's population living below the poverty line, percent of the district covered by forest, median elevation, median long-term average precipitation, and minimum temperature included as fixed effects, and terms for temporal trend and residual district-level spatial autocorrelation. Strong temporal and spatial heterogeneity in counts of malaria cases was apparent. Poverty and forest cover were significantly associated with an increased count of malaria cases but the magnitude and direction of associations between climate and malaria varied by socio-ecological zone. There was a declining trend in counts of malaria cases during the study period. After accounting for the social and environmental fixed effects, substantial spatial heterogeneity was still evident. Unmeasured factors which may contribute to this residual variation include malaria control activities, population migration and accessibility to health care. Forest-related activities and factors encompassed by poverty indicators are major drivers of malaria incidence in Viet Nam. © 2010 Australian Society for Parasitology Inc.

Stern DI, Gething PW, Kabaria CW, Temperley WH, Noor AM, Okiro EA, Shanks GD, Snow RW, Hay SI. 2011. Temperature and malaria trends in highland East Africa. PLoS One, 6 (9), pp. e24524. | Show Abstract | Read more

There has been considerable debate on the existence of trends in climate in the highlands of East Africa and hypotheses about their potential effect on the trends in malaria in the region. We apply a new robust trend test to mean temperature time series data from three editions of the University of East Anglia's Climatic Research Unit database (CRU TS) for several relevant locations. We find significant trends in the data extracted from newer editions of the database but not in the older version for periods ending in 1996. The trends in the newer data are even more significant when post-1996 data are added to the samples. We also test for trends in the data from the Kericho meteorological station prepared by Omumbo et al. We find no significant trend in the 1979-1995 period but a highly significant trend in the full 1979-2009 sample. However, although the malaria cases observed at Kericho, Kenya rose during a period of resurgent epidemics (1994-2002) they have since returned to a low level. A large assembly of parasite rate surveys from the region, stratified by altitude, show that this decrease in malaria prevalence is not limited to Kericho.

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Scopus

Tatem AJ, Campiz N, Gething PW, Snow RW, Linard C. 2011. The effects of spatial population dataset choice on estimates of population at risk of disease Population Health Metrics, 9 | Show Abstract | Read more

Background: The spatial modeling of infectious disease distributions and dynamics is increasingly being undertaken for health services planning and disease control monitoring, implementation, and evaluation. Where risks are heterogeneous in space or dependent on person-to-person transmission, spatial data on human population distributions are required to estimate infectious disease risks, burdens, and dynamics. Several different modeled human population distribution datasets are available and widely used, but the disparities among them and the implications for enumerating disease burdens and populations at risk have not been considered systematically. Here, we quantify some of these effects using global estimates of populations at risk (PAR) of P. falciparum malaria as an example.Methods: The recent construction of a global map of P. falciparum malaria endemicity enabled the testing of different gridded population datasets for providing estimates of PAR by endemicity class. The estimated population numbers within each class were calculated for each country using four different global gridded human population datasets: GRUMP (~1 km spatial resolution), LandScan (~1 km), UNEP Global Population Databases (~5 km), and GPW3 (~5 km). More detailed assessments of PAR variation and accuracy were conducted for three African countries where census data were available at a higher administrative-unit level than used by any of the four gridded population datasets.Results: The estimates of PAR based on the datasets varied by more than 10 million people for some countries, even accounting for the fact that estimates of population totals made by different agencies are used to correct national totals in these datasets and can vary by more than 5% for many low-income countries. In many cases, these variations in PAR estimates comprised more than 10% of the total national population. The detailed country-level assessments suggested that none of the datasets was consistently more accurate than the others in estimating PAR. The sizes of such differences among modeled human populations were related to variations in the methods, input resolution, and date of the census data underlying each dataset. Data quality varied from country to country within the spatial population datasets.Conclusions: Detailed, highly spatially resolved human population data are an essential resource for planning health service delivery for disease control, for the spatial modeling of epidemics, and for decision-making processes related to public health. However, our results highlight that for the low-income regions of the world where disease burden is greatest, existing datasets display substantial variations in estimated population distributions, resulting in uncertainty in disease assessments that utilize them. Increased efforts are required to gather contemporary and spatially detailed demographic data to reduce this uncertainty, particularly in Africa, and to develop population distribution modeling methods that match the rigor, sophistication, and ability to handle uncertainty of contemporary disease mapping and spread modeling. In the meantime, studies that utilize a particular spatial population dataset need to acknowledge the uncertainties inherent within them and consider how the methods and data that comprise each will affect conclusions. © 2011 Tatem et al; licensee BioMed Central Ltd.

Tatem AJ, Campiz N, Gething PW, Snow RW, Linard C. 2011. The effects of spatial population dataset choice on estimates of population at risk of disease. Popul Health Metr, 9 (1), pp. 4. | Show Abstract | Read more

BACKGROUND: The spatial modeling of infectious disease distributions and dynamics is increasingly being undertaken for health services planning and disease control monitoring, implementation, and evaluation. Where risks are heterogeneous in space or dependent on person-to-person transmission, spatial data on human population distributions are required to estimate infectious disease risks, burdens, and dynamics. Several different modeled human population distribution datasets are available and widely used, but the disparities among them and the implications for enumerating disease burdens and populations at risk have not been considered systematically. Here, we quantify some of these effects using global estimates of populations at risk (PAR) of P. falciparum malaria as an example. METHODS: The recent construction of a global map of P. falciparum malaria endemicity enabled the testing of different gridded population datasets for providing estimates of PAR by endemicity class. The estimated population numbers within each class were calculated for each country using four different global gridded human population datasets: GRUMP (~1 km spatial resolution), LandScan (~1 km), UNEP Global Population Databases (~5 km), and GPW3 (~5 km). More detailed assessments of PAR variation and accuracy were conducted for three African countries where census data were available at a higher administrative-unit level than used by any of the four gridded population datasets. RESULTS: The estimates of PAR based on the datasets varied by more than 10 million people for some countries, even accounting for the fact that estimates of population totals made by different agencies are used to correct national totals in these datasets and can vary by more than 5% for many low-income countries. In many cases, these variations in PAR estimates comprised more than 10% of the total national population. The detailed country-level assessments suggested that none of the datasets was consistently more accurate than the others in estimating PAR. The sizes of such differences among modeled human populations were related to variations in the methods, input resolution, and date of the census data underlying each dataset. Data quality varied from country to country within the spatial population datasets. CONCLUSIONS: Detailed, highly spatially resolved human population data are an essential resource for planning health service delivery for disease control, for the spatial modeling of epidemics, and for decision-making processes related to public health. However, our results highlight that for the low-income regions of the world where disease burden is greatest, existing datasets display substantial variations in estimated population distributions, resulting in uncertainty in disease assessments that utilize them. Increased efforts are required to gather contemporary and spatially detailed demographic data to reduce this uncertainty, particularly in Africa, and to develop population distribution modeling methods that match the rigor, sophistication, and ability to handle uncertainty of contemporary disease mapping and spread modeling. In the meantime, studies that utilize a particular spatial population dataset need to acknowledge the uncertainties inherent within them and consider how the methods and data that comprise each will affect conclusions.

Moonen B, Cohen JM, Snow RW, Slutsker L, Drakeley C, Smith DL, Abeyasinghe RR, Rodriguez MH, Maharaj R, Tanner M, Targett G. 2010. Operational strategies to achieve and maintain malaria elimination. Lancet, 376 (9752), pp. 1592-1603. | Show Abstract | Read more

Present elimination strategies are based on recommendations derived during the Global Malaria Eradication Program of the 1960s. However, many countries considering elimination nowadays have high intrinsic transmission potential and, without the support of a regional campaign, have to deal with the constant threat of imported cases of the disease, emphasising the need to revisit the strategies on which contemporary elimination programmes are based. To eliminate malaria, programmes need to concentrate on identification and elimination of foci of infections through both passive and active methods of case detection. This approach needs appropriate treatment of both clinical cases and asymptomatic infections, combined with targeted vector control. Draining of infectious pools entirely will not be sufficient since they could be replenished by imported malaria. Elimination will thus additionally need identification and treatment of incoming infections before they lead to transmission, or, more realistically, embarking on regional initiatives to dry up importation at its source.

Tatem AJ, Smith DL, Gething PW, Kabaria CW, Snow RW, Hay SI. 2010. Ranking of elimination feasibility between malaria-endemic countries. Lancet, 376 (9752), pp. 1579-1591. | Show Abstract | Read more

Experience gained from the Global Malaria Eradication Program (1955-72) identified a set of shared technical and operational factors that enabled some countries to successfully eliminate malaria. Spatial data for these factors were assembled for all malaria-endemic countries and combined to provide an objective, relative ranking of countries by technical, operational, and combined elimination feasibility. The analysis was done separately for Plasmodium falciparum and Plasmodium vivax, and the limitations of the approach were discussed. The relative rankings suggested that malaria elimination would be most feasible in countries in the Americas and Asia, and least feasible in countries in central and west Africa. The results differed when feasibility was measured by technical or operational factors, highlighting the different types of challenge faced by each country. The results are not intended to be prescriptive, predictive, or to provide absolute assessments of feasibility, but they do show that spatial information is available to facilitate evidence-based assessments of the relative feasibility of malaria elimination by country that can be rapidly updated.

Pullan RL, Bukirwa H, Snow RW, Brooker S. 2010. Heritability of Plasmodium parasite density in a rural Ugandan community. Am J Trop Med Hyg, 83 (5), pp. 990-995. | Show Abstract | Read more

Many factors influence variation in Plasmodium infection levels, including parasite/host genetics, immunity, and exposure. Here, we examine the roles of host genetics and exposure in determining parasite density, and test whether effects differ with age. Data for 1,711 residents of an eastern Ugandan community were used in pedigree-based variance component analysis. Heritability of parasite density was 13% (P < 0.001) but was not significant after controlling for shared household. Allowing variance components to vary between children (< 16 years) and adults (≥ 16 years) revealed striking age differences; 26% of variation could be explained by additively acting genes in children (P < 0.001), but there was no genetic involvement in adults. Domestic environment did not explain variation in children and explained 5% in adults (P = 0.09). Genetic effects are an important determinant of parasite density in children in this population, consistent with previous quantitative genetic studies of Plasmodium parasitaemia, although differences in environmental exposure play a lesser role.

Hay SI, Gething PW, Snow RW. 2010. India's invisible malaria burden. Lancet, 376 (9754), pp. 1716-1717. | Read more

Snow RW, Okiro EA, Gething PW, Atun R, Hay SI. 2010. Equity and adequacy of international donor assistance for global malaria control: an analysis of populations at risk and external funding commitments. Lancet, 376 (9750), pp. 1409-1416. | Show Abstract | Read more

BACKGROUND: Financing for malaria control has increased as part of international commitments to achieve the Millennium Development Goals (MDGs). We aimed to identify the unmet financial needs that would be biologically and economically equitable and would increase the chances of reaching worldwide malaria-control ambitions. METHODS: Populations at risk of stable Plasmodium falciparum or Plasmodium vivax transmission were calculated for 2007 and 2009 for 93 malaria-endemic countries to measure biological need. National per-person gross domestic product (GDP) was used to define economic need. An analysis of external donor assistance for malaria control was done for the period 2002-09 to compute overall and annualised per-person at-risk-funding commitments. Annualised malaria donor assistance was compared with independent predictions of funding needed to reach international targets of 80% coverage of best practices in case-management and effective disease prevention. Countries were ranked in relation to biological, economic, and unmet needs to examine equity and adequacy of support by 2010. FINDINGS: International financing for malaria control has increased by 166% (from $0·73 billion to $1·94 billion) since 2007 and is broadly consistent with biological needs. African countries have become major recipients of external assistance; however, countries where P vivax continues to pose threats to control ambitions are not as well funded. 21 countries have reached adequate assistance to provide a comprehensive suite of interventions by 2009, including 12 countries in Africa. However, this assistance was inadequate for 50 countries representing 61% of the worldwide population at risk of malaria-including ten countries in Africa and five in Asia that coincidentally are some of the poorest countries. Approval of donor funding for malaria control does not correlate with GDP. INTERPRETATION: Funding for malaria control worldwide is 60% lower than the US$4·9 billion needed for comprehensive control in 2010; this includes funding shortfalls for a wide range of countries with different numbers of people at risk and different levels of domestic income. More efficient targeting of financial resources against biological need and national income should create a more equitable investment portfolio that with increased commitments will guarantee sustained financing of control in countries most at risk and least able to support themselves. FUNDING: Wellcome Trust.

Noor AM, Alegana VA, Patil AP, Snow RW. 2010. Predicting the unmet need for biologically targeted coverage of insecticide-treated nets in Kenya. Am J Trop Med Hyg, 83 (4), pp. 854-860. | Show Abstract | Read more

In some countries the biological targeting of universal malaria prevention may offer optimal impact on disease and significant cost-savings compared with approaches that presume universal risk. Spatially defined data on coverage of treated nets from recent national household surveys in Kenya were used within a Bayesian geostatistical framework to predict treated net coverage nationally. When combined with the distributions of malaria risk and population an estimated 8.1 million people were not protected with treated nets in 2010 in biologically defined priority areas. After adjusting for the proportion of nets in use that were not long lasting, an estimated 5.5 to 6.3 million long-lasting treated nets would be required to achieve universal coverage in 2010 in Kenya in at-risk areas compared with 16.4 to 18.1 million nets if not restricted to areas of greatest malaria risk. In Kenya, this evidence-based approach could save the national program at least 55 million US dollars.

Wasunna B, Zurovac D, Bruce J, Jones C, Webster J, Snow RW. 2010. Health worker performance in the management of paediatric fevers following in-service training and exposure to job aids in Kenya. Malar J, 9 (1), pp. 261. | Show Abstract | Read more

BACKGROUND: Improving the way artemether-lumefantrine (AL) is provided to patients attending clinics is critical to maximize the benefit of this new medicine. In 2007, a new initiative was launched in one part of Kenya to improve malaria case-management through enhanced in-service training and provision of job aids. METHODS: An evaluation of the intervention using pre- and post-intervention cross sectional health facility surveys was conducted in Bondo district. The surveys included: audit of government health facilities, health worker structured interviews and exit interviews with caretakers of sick children below five years of age. The outcome indicators were the proportions of febrile children who had AL prescribed, AL dispensed, and four different dispensing and counseling tasks performed. RESULTS: At baseline 33 government health facilities, 48 health workers and 386 febrile child consultations were evaluated. At follow-up the same health facilities were surveyed and 36 health workers and 390 febrile child consultations evaluated. The findings show: 1) no health facility or health worker was exposed to all components of the intervention; 2) the proportion of health workers who received the enhanced in-service training was 67%; 3) the proportion of febrile children with uncomplicated malaria treated with the first-line anti-malarial drug, artemether-lumefantrine (AL), at health facilities where AL was in stock increased from 76.9% (95%CI: 69.4, 83.1) to 87.6% (95% CI: 82.5, 91.5); 4) there were modest but non-significant improvements in dispensing and counseling practices; and 5) when the analyses were restricted to health workers who received the enhanced in-service training and/or had received new guidelines and job aids, no significant improvements in reported case-management tasks were observed compared to baseline. CONCLUSION: In-service training and provision of job aids alone may not be adequate to improve the prescribing, dispensing and counseling tasks necessary to change malaria case-management practices and the inclusion of supervision and post-training follow-up should be considered in future clinical practice change initiatives.

Bui HM, Clements AC, Nguyen QT, Nguyen MH, Le XH, Hay SI, Tran TH, Wertheim HF, Snow RW, Horby P. 2011. Social and environmental determinants of malaria in space and time in Viet Nam. Int J Parasitol, 41 (1), pp. 109-116. | Show Abstract | Read more

The malaria burden in Viet Nam has been in decline in recent decades, but localised areas of high transmission remain. We used spatiotemporal analytical tools to determine the social and environmental drivers of malaria risk and to identify residual high-risk areas where control and surveillance resources can be targeted. Counts of reported Plasmodium falciparum and Plasmodium vivax malaria cases by month (January 2007-December 2008) and by district were assembled. Zero-inflated Poisson regression models were developed in a bayesian framework. Models had the percentage of the district's population living below the poverty line, percent of the district covered by forest, median elevation, median long-term average precipitation, and minimum temperature included as fixed effects, and terms for temporal trend and residual district-level spatial autocorrelation. Strong temporal and spatial heterogeneity in counts of malaria cases was apparent. Poverty and forest cover were significantly associated with an increased count of malaria cases but the magnitude and direction of associations between climate and malaria varied by socio-ecological zone. There was a declining trend in counts of malaria cases during the study period. After accounting for the social and environmental fixed effects, substantial spatial heterogeneity was still evident. Unmeasured factors which may contribute to this residual variation include malaria control activities, population migration and accessibility to health care. Forest-related activities and factors encompassed by poverty indicators are major drivers of malaria incidence in Viet Nam.

Cohen JM, Moonen B, Snow RW, Smith DL. 2010. How absolute is zero? An evaluation of historical and current definitions of malaria elimination. Malar J, 9 (1), pp. 213. | Show Abstract | Read more

Decisions to eliminate malaria from all or part of a country involve a complex set of factors, and this complexity is compounded by ambiguity surrounding some of the key terminology, most notably "control" and "elimination." It is impossible to forecast resource and operational requirements accurately if endpoints have not been defined clearly, yet even during the Global Malaria Eradication Program, debate raged over the precise definition of "eradication." Analogous deliberations regarding the meaning of "elimination" and "control" are basically nonexistent today despite these terms' core importance to programme planning. To advance the contemporary debate about these issues, this paper presents a historical review of commonly used terms, including control, elimination, and eradication, to help contextualize current understanding of these concepts. The review has been supported by analysis of the underlying mathematical concepts on which these definitions are based through simple branching process models that describe the proliferation of malaria cases following importation. Through this analysis, the importance of pragmatic definitions that are useful for providing malaria control and elimination programmes with a practical set of strategic milestones is emphasized, and it is argued that current conceptions of elimination in particular fail to achieve these requirements. To provide all countries with precise targets, new conceptual definitions are suggested to more precisely describe the old goals of "control" - here more exactly named "controlled low-endemic malaria" - and "elimination." Additionally, it is argued that a third state, called "controlled non-endemic malaria," is required to describe the epidemiological condition in which endemic transmission has been interrupted, but malaria resulting from onwards transmission from imported infections continues to occur at a sufficiently high level that elimination has not been achieved. Finally, guidelines are discussed for deriving the separate operational definitions and metrics that will be required to make these concepts relevant, measurable, and achievable for a particular environment.

Youssef RM, Alegana VA, Amran J, Noor AM, Snow RW. 2010. Fever prevalence and management among three rural communities in the North West Zone, Somalia. East Mediterr Health J, 16 (6), pp. 595-601. | Show Abstract

Between March and August 2008 we undertook 2 cross-sectional surveys among 1375 residents of 3 randomly selected villages in the district of Gebiley in the North-West Zone, Somalia. We investigated for the presence of malaria infection and the period prevalence of self-reported fever 14 days prior to both surveys. All blood samples examined were negative for both species of Plasmodium. The period prevalence of 14-day fevers was 4.8% in March and 0.6% in August; the majority of fevers (84.4%) were associated with other symptoms including cough, running nose and sore throat; 48/64 cases had resolved by the day of interview (mean duration 5.4 days). Only 18 (37.5%) fever cases were managed at a formal health care facility: 7 within 24 hours and 10 within 24-72 hours of onset. None of the fevers were investigated for malaria; they were treated with antibiotics, antipyretics and vitamins.

Gething PW, Smith DL, Patil AP, Tatem AJ, Snow RW, Hay SI. 2010. Climate change and the global malaria recession. Nature, 465 (7296), pp. 342-345. | Show Abstract | Read more

The current and potential future impact of climate change on malaria is of major public health interest. The proposed effects of rising global temperatures on the future spread and intensification of the disease, and on existing malaria morbidity and mortality rates, substantively influence global health policy. The contemporary spatial limits of Plasmodium falciparum malaria and its endemicity within this range, when compared with comparable historical maps, offer unique insights into the changing global epidemiology of malaria over the last century. It has long been known that the range of malaria has contracted through a century of economic development and disease control. Here, for the first time, we quantify this contraction and the global decreases in malaria endemicity since approximately 1900. We compare the magnitude of these changes to the size of effects on malaria endemicity proposed under future climate scenarios and associated with widely used public health interventions. Our findings have two key and often ignored implications with respect to climate change and malaria. First, widespread claims that rising mean temperatures have already led to increases in worldwide malaria morbidity and mortality are largely at odds with observed decreasing global trends in both its endemicity and geographic extent. Second, the proposed future effects of rising temperatures on endemicity are at least one order of magnitude smaller than changes observed since about 1900 and up to two orders of magnitude smaller than those that can be achieved by the effective scale-up of key control measures. Predictions of an intensification of malaria in a warmer world, based on extrapolated empirical relationships or biological mechanisms, must be set against a context of a century of warming that has seen marked global declines in the disease and a substantial weakening of the global correlation between malaria endemicity and climate.

Snow RW, Marsh K. 2010. Malaria in Africa: progress and prospects in the decade since the Abuja Declaration. Lancet, 376 (9735), pp. 137-139. | Read more

Okiro EA, Snow RW. 2010. The relationship between reported fever and Plasmodium falciparum infection in African children. Malar J, 9 (1), pp. 99. | Show Abstract | Read more

BACKGROUND: Fever has traditionally served as the entry point for presumptive treatment of malaria in African children. However, recent changes in the epidemiology of malaria across many places in Africa would suggest that the predictive accuracy of a fever history as a marker of disease has changed prompting calls for the change to diagnosis-based treatment strategies. METHODS: Using data from six national malaria indicator surveys undertaken between 2007 and 2009, the relationship between childhood (6-59 months) reported fever on the day of survey and the likelihood of coincidental Plasmodium falciparum infection recorded using a rapid diagnostic test was evaluated across a range of endemicities characteristic of Africa today. RESULTS: Of 16,903 children surveyed, 3% were febrile and infected, 9% were febrile without infection, 12% were infected but were not febrile and 76% were uninfected and not febrile. Children with fever on the day of the survey had a 1.98 times greater chance of being infected with P. falciparum compared to children without a history of fever on the day of the survey after adjusting for age and location (OR 1.98; 95% CI 1.74-2.34). There was a strong linear relationship between the percentage of febrile children with infection and infection prevalence (R2 = 0.9147). The prevalence of infection in reported fevers was consistently greater than would be expected solely by chance and this increased with increasing transmission intensity. The data suggest that in areas where community-based infection prevalence in childhood is above 34-37%, 50% or more of fevers are likely to be associated with infection. CONCLUSION: The potential benefits of diagnosis will depend on the prevalence of infection among children who report fever. The study has demonstrated a predictable relationship between parasite prevalence in the community and risks of infection among febrile children suggesting that current maps of parasite prevalence could be used to guide diagnostic strategies in Africa.

Bousema T, Youssef RM, Cook J, Cox J, Alegana VA, Amran J, Noor AM, Snow RW, Drakeley C. 2010. Serologic markers for detecting malaria in areas of low endemicity, Somalia, 2008. Emerg Infect Dis, 16 (3), pp. 392-399. | Show Abstract | Read more

Areas in which malaria is not highly endemic are suitable for malaria elimination, but assessing transmission is difficult because of lack of sensitivity of commonly used methods. We evaluated serologic markers for detecting variation in malaria exposure in Somalia. Plasmodium falciparum or P. vivax was not detected by microscopy in cross-sectional surveys of samples from persons during the dry (0/1,178) and wet (0/1,128) seasons. Antibody responses against P. falciparum or P. vivax were detected in 17.9% (179/1,001) and 19.3% (202/1,044) of persons tested. Reactivity against P. falciparum was significantly different between 3 villages (p<0.001); clusters of seroreactivity were present. Distance to the nearest seasonal river was negatively associated with P. falciparum (p = 0.028) and P. vivax seroreactivity (p = 0.016). Serologic markers are a promising tool for detecting spatial variation in malaria exposure and evaluating malaria control efforts in areas where transmission has decreased to levels below the detection limit of microscopy.

Abuya TO, Fegan G, Amin AA, Akhwale WS, Noor AM, Snow RW, Marsh V. 2010. Evaluating different dimensions of programme effectiveness for private medicine retailer malaria control interventions in Kenya. PLoS One, 5 (1), pp. e8937. | Show Abstract | Read more

BACKGROUND: Private medicine retailers (PMRs) are key partners in the home management of fevers in many settings. Current evidence on effectiveness for PMR interventions at scale is limited. This study presents evaluation findings of two different programs implemented at moderate scale targeting PMRs for malaria control in the Kisii and Kwale districts of Kenya. Key components of this evaluation were measurement of program performance, including coverage, PMR knowledge, practices, and utilization based on spatial analysis. METHODOLOGY/PRINCIPAL FINDINGS: The study utilized mixed quantitative methods including retail audits and surrogate client surveys based on post-intervention cross-sectional surveys in intervention and control areas and mapping of intervention outlets. There was a large and significant impact on PMR knowledge and practices of the program in Kisii, with 60.5% of trained PMRs selling amodiaquine medicines in adequate doses compared to 2.8% of untrained ones (OR; 53.5: 95% CI 6.7, 428.3), a program coverage of 69.7% targeted outlets, and a potential utilization of about 30,000 children under five. The evaluation in Kwale also indicates a significant impact with 18.8% and 2.3% intervention and control PMRs selling amodiaquine with correct advice, respectively (OR; 9.4: 95% CI 1.1, 83.7), a program coverage of 25.3% targeted outlets, and a potential utilization of about 48,000 children under five. A provisional benchmark of 7.5 km was a reasonable threshold distance for households to access PMR services. CONCLUSIONS/SIGNIFICANCE: This evaluation show that PMR interventions operationalized in the district level settings are likely to impact PMR knowledge and practices and lead to increased coverage of appropriate treatment to target populations. There is value of evaluating different dimensions of public health programs, including quality, spatial access, and implementation practice. This approach strengthens the potential contribution of pragmatic study designs to evaluating public health programs in the real world.

Pullan RL, Bukirwa H, Staedke SG, Snow RW, Brooker S. 2010. Plasmodium infection and its risk factors in eastern Uganda. Malar J, 9 (1), pp. 2. | Show Abstract | Read more

BACKGROUND: Malaria is a leading cause of disease burden in Uganda, although surprisingly few contemporary, age-stratified data exist on malaria epidemiology in the country. This report presents results from a total population survey of malaria infection and intervention coverage in a rural area of eastern Uganda, with a specific focus on how risk factors differ between demographic groups in this population. METHODS: In 2008, a cross-sectional survey was conducted in four contiguous villages in Mulanda, sub-county in Tororo district, eastern Uganda, to investigate the epidemiology and risk factors of Plasmodium species infection. All permanent residents were invited to participate, with blood smears collected from 1,844 individuals aged between six months and 88 years (representing 78% of the population). Demographic, household and socio-economic characteristics were combined with environmental data using a Geographical Information System. Hierarchical models were used to explore patterns of malaria infection and identify individual, household and environmental risk factors. RESULTS: Overall, 709 individuals were infected with Plasmodium, with prevalence highest among 5-9 year olds (63.5%). Thin films from a random sample of 20% of parasite positive participants showed that 94.0% of infections were Plasmodium falciparum and 6.0% were P. malariae; no other species or mixed infections were seen. In total, 68% of households owned at least one mosquito although only 27% of school-aged children reported sleeping under a net the previous night. In multivariate analysis, infection risk was highest amongst children aged 5-9 years and remained high in older children. Risk of infection was lower for those that reported sleeping under a bed net the previous night and living more than 750 m from a rice-growing area. After accounting for clustering within compounds, there was no evidence for an association between infection prevalence and socio-economic status, and no evidence for spatial clustering. CONCLUSION: These findings demonstrate that mosquito net usage remains inadequate and is strongly associated with risk of malaria among school-aged children. Infection risk amongst adults is influenced by proximity to potential mosquito breeding grounds. Taken together, these findings emphasize the importance of increasing net coverage, especially among school-aged children.

Linard C, Alegana VA, Noor AM, Snow RW, Tatem AJ. 2010. A high resolution spatial population database of Somalia for disease risk mapping. Int J Health Geogr, 9 (1), pp. 45. | Show Abstract | Read more

BACKGROUND: Millions of Somali have been deprived of basic health services due to the unstable political situation of their country. Attempts are being made to reconstruct the health sector, in particular to estimate the extent of infectious disease burden. However, any approach that requires the use of modelled disease rates requires reasonable information on population distribution. In a low-income country such as Somalia, population data are lacking, are of poor quality, or become outdated rapidly. Modelling methods are therefore needed for the production of contemporary and spatially detailed population data. RESULTS: Here land cover information derived from satellite imagery and existing settlement point datasets were used for the spatial reallocation of populations within census units. We used simple and semi-automated methods that can be implemented with free image processing software to produce an easily updatable gridded population dataset at 100 × 100 meters spatial resolution. The 2010 population dataset was matched to administrative population totals projected by the UN. Comparison tests between the new dataset and existing population datasets revealed important differences in population size distributions, and in population at risk of malaria estimates. These differences are particularly important in more densely populated areas and strongly depend on the settlement data used in the modelling approach. CONCLUSIONS: The results show that it is possible to produce detailed, contemporary and easily updatable settlement and population distribution datasets of Somalia using existing data. The 2010 population dataset produced is freely available as a product of the AfriPop Project and can be downloaded from: http://www.afripop.org.

Feachem RG, Phillips AA, Targett GA, Snow RW. 2010. Call to action: priorities for malaria elimination. Lancet, 376 (9752), pp. 1517-1521. | Read more

Okiro EA, Alegana VA, Noor AM, Snow RW. 2010. Changing malaria intervention coverage, transmission and hospitalization in Kenya. Malar J, 9 (1), pp. 285. | Show Abstract | Read more

BACKGROUND: Reports of declining incidence of malaria disease burden across several countries in Africa suggest that the epidemiology of malaria across the continent is in transition. Whether this transition is directly related to the scaling of intervention coverage remains a moot point. METHODS: Paediatric admission data from eight Kenyan hospitals and their catchments have been assembled across two three-year time periods: September 2003 to August 2006 (pre-scaled intervention) and September 2006 to August 2009 (post-scaled intervention). Interrupted time series (ITS) models were developed adjusting for variations in rainfall and hospital use by surrounding communities to show changes in malaria hospitalization over the two periods. The temporal changes in factors that might explain changes in disease incidence were examined sequentially for each hospital setting, compared between hospital settings and ranked according to plausible explanatory factors. RESULTS: In six out of eight sites there was a decline in Malaria admission rates with declines between 18% and 69%. At two sites malaria admissions rates increased by 55% and 35%. Results from the ITS models indicate that before scaled intervention in September 2006, there was a significant month-to-month decline in the mean malaria admission rates at four hospitals (trend P < 0.05). At the point of scaled intervention, the estimated mean admission rates for malaria was significantly less at four sites compared to the pre-scaled period baseline. Following scaled intervention there was a significant change in the month-to-month trend in the mean malaria admission rates in some but not all of the sites. Plausibility assessment of possible drivers of change pre- versus post-scaled intervention showed inconsistent patterns however, allowing for the increase in rainfall in the second period, there is a suggestion that starting transmission intensity and the scale of change in ITN coverage might explain some but not all of the variation in effect size. At most sites where declines between observation periods were documented admission rates were changing before free mass ITN distribution and prior to the implementation of ACT across Kenya. CONCLUSION: This study provides evidence of significant within and between location heterogeneity in temporal trends of malaria disease burden. Plausible drivers for changing disease incidence suggest a complex combination of mechanisms, not easily measured retrospectively.

Okara RM, Sinka ME, Minakawa N, Mbogo CM, Hay SI, Snow RW. 2010. Distribution of the main malaria vectors in Kenya. Malar J, 9 (1), pp. 69. | Show Abstract | Read more

BACKGROUND: A detailed knowledge of the distribution of the main Anopheles malaria vectors in Kenya should guide national vector control strategies. However, contemporary spatial distributions of the locally dominant Anopheles vectors including Anopheles gambiae, Anopheles arabiensis, Anopheles merus, Anopheles funestus, Anopheles pharoensis and Anopheles nili are lacking. The methods and approaches used to assemble contemporary available data on the present distribution of the dominant malaria vectors in Kenya are presented here. METHOD: Primary empirical data from published and unpublished sources were identified for the period 1990 to 2009. Details recorded for each source included the first author, year of publication, report type, survey location name, month and year of survey, the main Anopheles species reported as present and the sampling and identification methods used. Survey locations were geo-positioned using national digital place name archives and on-line geo-referencing resources. The geo-located species-presence data were displayed and described administratively, using first-level administrative units (province), and biologically, based on the predicted spatial margins of Plasmodium falciparum transmission intensity in Kenya for the year 2009. Each geo-located survey site was assigned an urban or rural classification and attributed an altitude value. RESULTS: A total of 498 spatially unique descriptions of Anopheles vector species across Kenya sampled between 1990 and 2009 were identified, 53% were obtained from published sources and further communications with authors. More than half (54%) of the sites surveyed were investigated since 2005. A total of 174 sites reported the presence of An. gambiae complex without identification of sibling species. Anopheles arabiensis and An. funestus were the most widely reported at 244 and 265 spatially unique sites respectively with the former showing the most ubiquitous distribution nationally. Anopheles gambiae, An. arabiensis, An. funestus and An. pharoensis were reported at sites located in all the transmission intensity classes with more reports of An. gambiae in the highest transmission intensity areas than the very low transmission areas. CONCLUSION: A contemporary, spatially defined database of the main malaria vectors in Kenya provides a baseline for future compilations of data and helps identify areas where information is currently lacking. The data collated here are published alongside this paper where it may help guide future sampling location decisions, help with the planning of vector control suites nationally and encourage broader research inquiry into vector species niche modeling.

Hay SI, Okiro EA, Gething PW, Patil AP, Tatem AJ, Guerra CA, Snow RW. 2010. Estimating the global clinical burden of Plasmodium falciparum malaria in 2007. PLoS Med, 7 (6), pp. e1000290. | Show Abstract | Read more

BACKGROUND: The epidemiology of malaria makes surveillance-based methods of estimating its disease burden problematic. Cartographic approaches have provided alternative malaria burden estimates, but there remains widespread misunderstanding about their derivation and fidelity. The aims of this study are to present a new cartographic technique and its application for deriving global clinical burden estimates of Plasmodium falciparum malaria for 2007, and to compare these estimates and their likely precision with those derived under existing surveillance-based approaches. METHODS AND FINDINGS: In seven of the 87 countries endemic for P. falciparum malaria, the health reporting infrastructure was deemed sufficiently rigorous for case reports to be used verbatim. In the remaining countries, the mapped extent of unstable and stable P. falciparum malaria transmission was first determined. Estimates of the plausible incidence range of clinical cases were then calculated within the spatial limits of unstable transmission. A modelled relationship between clinical incidence and prevalence was used, together with new maps of P. falciparum malaria endemicity, to estimate incidence in areas of stable transmission, and geostatistical joint simulation was used to quantify uncertainty in these estimates at national, regional, and global scales. Combining these estimates for all areas of transmission risk resulted in 451 million (95% credible interval 349-552 million) clinical cases of P. falciparum malaria in 2007. Almost all of this burden of morbidity occurred in areas of stable transmission. More than half of all estimated P. falciparum clinical cases and associated uncertainty occurred in India, Nigeria, the Democratic Republic of the Congo (DRC), and Myanmar (Burma), where 1.405 billion people are at risk. Recent surveillance-based methods of burden estimation were then reviewed and discrepancies in national estimates explored. When these cartographically derived national estimates were ranked according to their relative uncertainty and replaced by surveillance-based estimates in the least certain half, 98% of the global clinical burden continued to be estimated by cartographic techniques. CONCLUSIONS AND SIGNIFICANCE: Cartographic approaches to burden estimation provide a globally consistent measure of malaria morbidity of known fidelity, and they represent the only plausible method in those malaria-endemic countries with nonfunctional national surveillance. Unacceptable uncertainty in the clinical burden of malaria in only four countries confounds our ability to evaluate needs and monitor progress toward international targets for malaria control at the global scale. National prevalence surveys in each nation would reduce this uncertainty profoundly. Opportunities for further reducing uncertainty in clinical burden estimates by hybridizing alternative burden estimation procedures are also evaluated.

Gething PW, Kirui VC, Alegana VA, Okiro EA, Noor AM, Snow RW. 2010. Estimating the number of paediatric fevers associated with malaria infection presenting to Africa's public health sector in 2007. PLoS Med, 7 (7), pp. e1000301. | Show Abstract | Read more

BACKGROUND: As international efforts to increase the coverage of artemisinin-based combination therapy in public health sectors gather pace, concerns have been raised regarding their continued indiscriminate presumptive use for treating all childhood fevers. The availability of rapid-diagnostic tests to support practical and reliable parasitological diagnosis provides an opportunity to improve the rational treatment of febrile children across Africa. However, the cost effectiveness of diagnosis-based treatment polices will depend on the presumed numbers of fevers harbouring infection. Here we compute the number of fevers likely to present to public health facilities in Africa and the estimated number of these fevers likely to be infected with Plasmodium falciparum malaria parasites. METHODS AND FINDINGS: We assembled first administrative-unit level data on paediatric fever prevalence, treatment-seeking rates, and child populations. These data were combined in a geographical information system model that also incorporated an adjustment procedure for urban versus rural areas to produce spatially distributed estimates of fever burden amongst African children and the subset likely to present to public sector clinics. A second data assembly was used to estimate plausible ranges for the proportion of paediatric fevers seen at clinics positive for P. falciparum in different endemicity settings. We estimated that, of the 656 million fevers in African 0-4 y olds in 2007, 182 million (28%) were likely to have sought treatment in a public sector clinic of which 78 million (43%) were likely to have been infected with P. falciparum (range 60-103 million). CONCLUSIONS: Spatial estimates of childhood fevers and care-seeking rates can be combined with a relational risk model of infection prevalence in the community to estimate the degree of parasitemia in those fevers reaching public health facilities. This quantification provides an important baseline comparison of malarial and nonmalarial fevers in different endemicity settings that can contribute to ongoing scientific and policy debates about optimum clinical and financial strategies for the introduction of new diagnostics. These models are made publicly available with the publication of this paper.

Youssef RM, Alegana VA, Amran J, Noor AM, Snow RW. 2010. Fever prevalence and management among three rural communities in the North West Zone, Somalia Eastern Mediterranean Health Journal, 16 (6), pp. 460-466. | Show Abstract

Between March and August 2008 we undertook 2 cross-sectional surveys among 1375 residents of 3 randomly selected villages in the district of Gebiley in the North-West Zone, Somalia. We investigated for the presence of malaria infection and the period prevalence of self-reported fever 14 days prior to both surveys. All blood samples examined were negative for both species of Plasmodium. The period prevalence of 14-day fevers was 4.8% in March and 0.6% in August; the majority of fevers (84.4%) were associated with other symptoms including cough, running nose and sore throat; 48/64 cases had resolved by the day of interview (mean duration 5.4 days). Only 18 (37.5%) fever cases were managed at a formal health care facility: 7 within 24 hours and 10 within 24-72 hours of onset. None of the fevers were investigated for malaria; they were treated with antibiotics, antipyretics and vitamins.

Gitonga CW, Karanja PN, Kihara J, Mwanje M, Juma E, Snow RW, Noor AM, Brooker S. 2010. Implementing school malaria surveys in Kenya: towards a national surveillance system. Malar J, 9 (1), pp. 306. | Show Abstract | Read more

OBJECTIVE: To design and implement surveys of malaria infection and coverage of malaria control interventions among school children in Kenya in order to contribute towards a nationwide assessment of malaria. METHODS: The country was stratified into distinct malaria transmission zones based on a malaria risk map and 480 schools were visited between October 2008 and March 2010. Surveys were conducted in two phases: an initial opportunistic phase whereby schools were selected for other research purposes; and a second phase whereby schools were purposively selected to provide adequate spatial representation across the country. Consent for participation was based on passive, opt-out consent rather than written, opt-in consent because of the routine, low-risk nature of the survey. All children were diagnosed for Plasmodium infection using rapid diagnostic tests, assessed for anaemia and were interviewed about mosquito net usage, recent history of illness, and socio-economic and household indicators. Children's responses were entered electronically in the school and data transmitted nightly to Nairobi using a mobile phone modem connection. RDT positive results were corrected by microscopy and all results were adjusted for clustering using random effect regression modelling. RESULTS: 49,975 children in 480 schools were sampled, at an estimated cost of US$ 1,116 per school. The overall prevalence of malaria and anaemia was 4.3% and 14.1%, respectively, and 19.0% of children reported using an insecticide-treated net (ITN). The prevalence of infection showed marked variation across the country, with prevalence being highest in Western and Nyanza provinces, and lowest in Central, North Eastern and Eastern provinces. Nationally, 2.3% of schools had reported ITN use >60%, and low reported ITN use was a particular problem in Western and Nyanza provinces. Few schools reported having malaria health education materials or ongoing malaria control activities. CONCLUSION: School malaria surveys provide a rapid, cheap and sustainable approach to malaria surveillance which can complement household surveys, and in Kenya, show that large areas of the country do not merit any direct school-based control, but school-based interventions, coupled with strengthened community-based strategies, are warranted in western and coastal Kenya. The results also provide detailed baseline data to inform evaluation of school-based malaria control in Kenya.

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Hay SI, Gething PW, Snow RW. 2010. India's invisible malaria burden The Lancet, 376 (9754), pp. 1716-1717. | Read more

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Moonen B, Cohen JM, Snow RW, Slutsker L, Drakeley C, Smith DL, Abeyasinghe RR, Rodriguez MH, Maharaj R, Tanner M, Targett G. 2010. Operational strategies to achieve and maintain malaria elimination The Lancet, 376 (9752), pp. 1592-1603. | Show Abstract | Read more

Present elimination strategies are based on recommendations derived during the Global Malaria Eradication Program of the 1960s. However, many countries considering elimination nowadays have high intrinsic transmission potential and, without the support of a regional campaign, have to deal with the constant threat of imported cases of the disease, emphasising the need to revisit the strategies on which contemporary elimination programmes are based. To eliminate malaria, programmes need to concentrate on identification and elimination of foci of infections through both passive and active methods of case detection. This approach needs appropriate treatment of both clinical cases and asymptomatic infections, combined with targeted vector control. Draining of infectious pools entirely will not be sufficient since they could be replenished by imported malaria. Elimination will thus additionally need identification and treatment of incoming infections before they lead to transmission, or, more realistically, embarking on regional initiatives to dry up importation at its source. © 2010 Elsevier Ltd.

Dellicour S, Tatem AJ, Guerra CA, Snow RW, ter Kuile FO. 2010. Quantifying the number of pregnancies at risk of malaria in 2007: a demographic study. PLoS Med, 7 (1), pp. e1000221. | Show Abstract | Read more

BACKGROUND: Comprehensive and contemporary estimates of the number of pregnancies at risk of malaria are not currently available, particularly for endemic areas outside of Africa. We derived global estimates of the number of women who became pregnant in 2007 in areas with Plasmodium falciparum and P. vivax transmission. METHODS AND FINDINGS: A recently published map of the global limits of P. falciparum transmission and an updated map of the limits of P. vivax transmission were combined with gridded population data and growth rates to estimate total populations at risk of malaria in 2007. Country-specific demographic data from the United Nations on age, sex, and total fertility rates were used to estimate the number of women of child-bearing age and the annual rate of live births. Subregional estimates of the number of induced abortions and country-specific stillbirths rates were obtained from recently published reviews. The number of miscarriages was estimated from the number of live births and corrected for induced abortion rates. The number of clinically recognised pregnancies at risk was then calculated as the sum of the number of live births, induced abortions, spontaneous miscarriages, and stillbirths among the population at risk in 2007. In 2007, 125.2 million pregnancies occurred in areas with P. falciparum and/or P. vivax transmission resulting in 82.6 million live births. This included 77.4, 30.3, 13.1, and 4.3 million pregnancies in the countries falling under the World Health Organization (WHO) regional offices for South-East-Asia (SEARO) and the Western-Pacific (WPRO) combined, Africa (AFRO), Europe and the Eastern Mediterranean (EURO/EMRO), and the Americas (AMRO), respectively. Of 85.3 million pregnancies in areas with P. falciparum transmission, 54.7 million occurred in areas with stable transmission and 30.6 million in areas with unstable transmission (clinical incidence <1 per 10,000 population/year); 92.9 million occurred in areas with P. vivax transmission, 53.0 million of which occurred in areas in which P. falciparum and P. vivax co-exist and 39.9 million in temperate regions with P. vivax transmission only. CONCLUSIONS: In 2007, 54.7 million pregnancies occurred in areas with stable P. falciparum malaria and a further 70.5 million in areas with exceptionally low malaria transmission or with P. vivax only. These represent the first contemporary estimates of the global distribution of the number of pregnancies at risk of P. falciparum and P. vivax malaria and provide a first step towards a more informed estimate of the geographical distribution of infection rates and the corresponding disease burden of malaria in pregnancy.

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198

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Feachem RGA, Phillips AA, Hwang J, Cotter C, Wielgosz B, Greenwood BM, Sabot O, Rodriguez MH, Abeyasinghe RR, Ghebreyesus TA, Snow RW. 2010. Shrinking the malaria map: progress and prospects The Lancet, 376 (9752), pp. 1566-1578. | Show Abstract | Read more

In the past 150 years, roughly half of the countries in the world eliminated malaria. Nowadays, there are 99 endemic countries - 67 are controlling malaria and 32 are pursuing an elimination strategy. This four-part Series presents evidence about the technical, operational, and financial dimensions of malaria elimination. The first paper in this Series reviews definitions of elimination and the state that precedes it: controlled low-endemic malaria. Feasibility assessments are described as a crucial step for a country transitioning from controlled low-endemic malaria to elimination. Characteristics of the 32 malaria-eliminating countries are presented, and contrasted with countries that pursued elimination in the past. Challenges and risks of elimination are presented, including Plasmodium vivax, resistance in the parasite and mosquito populations, and potential resurgence if investment and vigilance decrease. The benefits of elimination are outlined, specifically elimination as a regional and global public good. Priorities for the next decade are described. © 2010 Elsevier Ltd.

Guerra CA, Howes RE, Patil AP, Gething PW, Van Boeckel TP, Temperley WH, Kabaria CW, Tatem AJ et al. 2010. The international limits and population at risk of Plasmodium vivax transmission in 2009. PLoS Negl Trop Dis, 4 (8), pp. e774. | Show Abstract | Read more

BACKGROUND: A research priority for Plasmodium vivax malaria is to improve our understanding of the spatial distribution of risk and its relationship with the burden of P. vivax disease in human populations. The aim of the research outlined in this article is to provide a contemporary evidence-based map of the global spatial extent of P. vivax malaria, together with estimates of the human population at risk (PAR) of any level of transmission in 2009. METHODOLOGY: The most recent P. vivax case-reporting data that could be obtained for all malaria endemic countries were used to classify risk into three classes: malaria free, unstable (<0.1 case per 1,000 people per annum (p.a.)) and stable (> or =0.1 case per 1,000 p.a.) P. vivax malaria transmission. Risk areas were further constrained using temperature and aridity data based upon their relationship with parasite and vector bionomics. Medical intelligence was used to refine the spatial extent of risk in specific areas where transmission was reported to be absent (e.g., large urban areas and malaria-free islands). The PAR under each level of transmission was then derived by combining the categorical risk map with a high resolution population surface adjusted to 2009. The exclusion of large Duffy negative populations in Africa from the PAR totals was achieved using independent modelling of the gene frequency of this genetic trait. It was estimated that 2.85 billion people were exposed to some risk of P. vivax transmission in 2009, with 57.1% of them living in areas of unstable transmission. The vast majority (2.59 billion, 91.0%) were located in Central and South East (CSE) Asia, whilst the remainder were located in America (0.16 billion, 5.5%) and in the Africa+ region (0.10 billion, 3.5%). Despite evidence of ubiquitous risk of P. vivax infection in Africa, the very high prevalence of Duffy negativity throughout Central and West Africa reduced the PAR estimates substantially. CONCLUSIONS: After more than a century of development and control, P. vivax remains more widely distributed than P. falciparum and is a potential cause of morbidity and mortality amongst the 2.85 billion people living at risk of infection, the majority of whom are in the tropical belt of CSE Asia. The probability of infection is reduced massively across Africa by the frequency of the Duffy negative trait, but transmission does occur on the continent and is a concern for Duffy positive locals and travellers. The final map provides the spatial limits on which the endemicity of P. vivax transmission can be mapped to support future cartographic-based burden estimations.

Mirghani SE, Nour BYM, Bushra SM, Hassan I, Snow RW, Noor AM. 2010. The spatial-temporal clustering of Plasmodium falciparum infection over eleven years in Gezira State, The Sudan Malaria Journal, 9 (Suppl 2), pp. P65-P65. | Read more

Mirghani SE, Nour BY, Bushra SM, Elhassan IM, Snow RW, Noor AM. 2010. The spatial-temporal clustering of Plasmodium falciparum infection over eleven years in Gezira State, The Sudan. Malar J, 9 (1), pp. 172. | Show Abstract | Read more

BACKGROUND: Malaria infection and disease exhibit microgeographic heterogeneity which if predictable could have implications for designing small-area intervention. Here, the space-time clustering of Plasmodium falciparum infections using data from repeat cross-sectional surveys in Gezira State, a low transmission area in northern Sudan, is investigated. METHODS: Data from cross-sectional surveys undertaken in January each year from 1999-2009 in 88 villages in the Gezira state were assembled. During each survey, about a 100 children between the ages two to ten years were sampled to examine the presence of P. falciparum parasites. In 2009, all the villages were mapped using global positioning systems. Cluster level data were analysed for spatial-only and space-time clustering using the Bernoulli model and the significance of clusters were tested using the Kulldorff scan statistic. RESULTS: Over the study period, 96,022 malaria slide examinations were undertaken and the P. falciparum prevalence was 8.6% in 1999 and by 2009 this had reduced to 1.6%. The cluster analysis showed the presence of one significant spatial-only cluster in each survey year and one significant space-time cluster over the whole study period. The primary spatial-only clusters in 10/11 years were either contained within or overlapped with the primary space-time cluster. CONCLUSION: The results of the study confirm the generally low malaria transmission in the state of Gezira and the presence of spatial and space-time clusters concentrated around a specific area in the south of the state. Improved surveillance data that allows for the analysis of seasonality, age and other risk factors need to be collected to design effective small area interventions as Gezira state targets malaria elimination.

Smith DL, Hay SI, Noor AM, Snow RW. 2009. Predicting changing malaria risk after expanded insecticide-treated net coverage in Africa. Trends Parasitol, 25 (11), pp. 511-516. | Show Abstract | Read more

The Roll Back Malaria (RBM) partnership has established goals for protecting vulnerable populations with locally appropriate vector control. In many places, these goals will be achieved by the mass distribution of insecticide treated bednets (ITNs). Mathematical models can forecast an ITN-driven realignment of malaria endemicity, defined by the Plasmodium falciparum parasite rate (PfPR) in children, to predict PfPR endpoints and appropriate program timelines for this change in Africa. The relative ease of measuring PfPR and its widespread use make it particularly suitable for monitoring and evaluation. This theory provides a method for context-dependent evaluation of ITN programs and a basis for setting rational ITN coverage targets over the next decade.

Brooker S, Kolaczinski JH, Gitonga CW, Noor AM, Snow RW. 2009. The use of schools for malaria surveillance and programme evaluation in Africa. Malar J, 8 (1), pp. 231. | Show Abstract | Read more

Effective malaria control requires information on both the geographical distribution of malaria risk and the effectiveness of malaria interventions. The current standard for estimating malaria infection and impact indicators are household cluster surveys, but their complexity and expense preclude frequent and decentralized monitoring. This paper reviews the historical experience and current rationale for the use of schools and school children as a complementary, inexpensive framework for planning, monitoring and evaluating malaria control in Africa. Consideration is given to (i) the selection of schools; (ii) diagnosis of infection in schools; (iii) the representativeness of schools as a proxy of the communities they serve; and (iv) the increasing need to evaluate interventions delivered through schools. Finally, areas requiring further investigation are highlighted.

Clements AC, Barnett AG, Cheng ZW, Snow RW, Zhou HN. 2009. Space-time variation of malaria incidence in Yunnan province, China. Malar J, 8 (1), pp. 180. | Show Abstract | Read more

BACKGROUND: Understanding spatio-temporal variation in malaria incidence provides a basis for effective disease control planning and monitoring. METHODS: Monthly surveillance data between 1991 and 2006 for Plasmodium vivax and Plasmodium falciparum malaria across 128 counties were assembled for Yunnan, a province of China with one of the highest burdens of malaria. County-level Bayesian Poisson regression models of incidence were constructed, with effects for rainfall, maximum temperature and temporal trend. The model also allowed for spatial variation in county-level incidence and temporal trend, and dependence between incidence in June-September and the preceding January-February. RESULTS: Models revealed strong associations between malaria incidence and both rainfall and maximum temperature. There was a significant association between incidence in June-September and the preceding January-February. Raw standardised morbidity ratios showed a high incidence in some counties bordering Myanmar, Laos and Vietnam, and counties in the Red River valley. Clusters of counties in south-western and northern Yunnan were identified that had high incidence not explained by climate. The overall trend in incidence decreased, but there was significant variation between counties. CONCLUSION: Dependence between incidence in summer and the preceding January-February suggests a role of intrinsic host-pathogen dynamics. Incidence during the summer peak might be predictable based on incidence in January-February, facilitating malaria control planning, scaled months in advance to the magnitude of the summer malaria burden. Heterogeneities in county-level temporal trends suggest that reductions in the burden of malaria have been unevenly distributed throughout the province.

Ye Y, Madise N, Ndugwa R, Ochola S, Snow RW. 2009. Fever treatment in the absence of malaria transmission in an urban informal settlement in Nairobi, Kenya. Malar J, 8 (1), pp. 160. | Show Abstract | Read more

BACKGROUND: In sub-Saharan Africa, knowledge of malaria transmission across rapidly proliferating urban centres and recommendations for its prevention or management remain poorly defined. This paper presents the results of an investigation into infection prevalence and treatment of recent febrile events among a slum population in Nairobi, Kenya. METHODS: In July 2008, a community-based malaria parasite prevalence survey was conducted in Korogocho slum, which forms part of the Nairobi Urban Health and Demographic Surveillance system. Interviewers visited 1,069 participants at home and collected data on reported fevers experienced over the preceding 14 days and details on the treatment of these episodes. Each participant was tested for malaria parasite presence with Rapid Diagnostic Test (RDT) and microscopy. Descriptive analyses were performed to assess the period prevalence of reported fever episodes and treatment behaviour. RESULTS: Of the 1,069 participants visited, 983 (92%) consented to be tested. Three were positive for Plasmodium falciparum using RDT; however, all were confirmed negative on microscopy. Microscopic examination of all 953 readable slides showed zero prevalence. Overall, from the 1,004 participants who have data on fever, 170 fever episodes were reported giving a relatively high period prevalence (16.9%, 95% CI:13.9%-20.5%) and higher among children below five years (20.1%, 95%CI:13.8%-27.8%). Of the fever episodes with treatment information 54.3% (95%CI:46.3%-62.2%) were treated as malaria using mainly sulphadoxine-pyrimethamine or amodiaquine, including those managed at a formal health facility. Only four episodes were managed using the nationally recommended first-line treatment, artemether-lumefantrine. CONCLUSION: The study could not demonstrate any evidence of malaria in Korogocho, a slum in the centre of Nairobi. Fever was a common complaint and often treated as malaria with anti-malarial drugs. Strategies, including testing for malaria parasites to reduce the inappropriate exposure of poor communities to expensive anti-malarial drugs provided by clinical services and drug vendors, should be a priority for district planners.

Brooker S, Kabatereine NB, Smith JL, Mupfasoni D, Mwanje MT, Ndayishimiye O, Lwambo NJ, Mbotha D et al. 2009. An updated atlas of human helminth infections: the example of East Africa. Int J Health Geogr, 8 (1), pp. 42. | Show Abstract | Read more

BACKGROUND: Reliable and updated maps of helminth (worm) infection distributions are essential to target control strategies to those populations in greatest need. Although many surveys have been conducted in endemic countries, the data are rarely available in a form that is accessible to policy makers and the managers of public health programmes. This is especially true in sub-Saharan Africa, where empirical data are seldom in the public domain. In an attempt to address the paucity of geographical information on helminth risk, this article describes the development of an updated global atlas of human helminth infection, showing the example of East Africa. METHODS: Empirical, cross-sectional estimates of infection prevalence conducted since 1980 were identified using electronic and manual search strategies of published and unpublished sources. A number of inclusion criteria were imposed for identified information, which was extracted into a standardized database. Details of survey population, diagnostic methods, sample size and numbers infected with schistosomes and soil-transmitted helminths were recorded. A unique identifier linked each record to an electronic copy of the source document, in portable document format. An attempt was made to identify the geographical location of each record using standardized geolocation procedures and the assembled data were incorporated into a geographical information system. RESULTS: At the time of writing, over 2,748 prevalence surveys were identified through multiple search strategies. Of these, 2,612 were able to be geolocated and mapped. More than half (58%) of included surveys were from grey literature or unpublished sources, underlining the importance of reviewing in-country sources. 66% of all surveys were conducted since 2000. Comprehensive, countrywide data are available for Burundi, Rwanda and Uganda. In contrast, information for Kenya and Tanzania is typically clustered in specific regions of the country, with few records from areas with very low population density and/or environmental conditions which are unfavourable for helminth transmission. Information is presented on the prevalence and geographical distribution for the major helminth species. CONCLUSION: For all five countries, the information assembled in the current atlas provides the most reliable, up-to-date and comprehensive source of data on the distribution of common helminth infections to guide the rational implementation of control efforts.

Skarbinski J, Ouma PO, Causer LM, Kariuki SK, Barnwell JW, Alaii JA, de Oliveira AM, Zurovac D et al. 2009. Effect of malaria rapid diagnostic tests on the management of uncomplicated malaria with artemether-lumefantrine in Kenya: a cluster randomized trial. Am J Trop Med Hyg, 80 (6), pp. 919-926. | Show Abstract

Shortly after Kenya introduced artemether-lumefantrine (AL) for first-line treatment of uncomplicated malaria, we conducted a pre-post cluster randomized controlled trial to assess the effect of providing malaria rapid diagnostic tests (RDTs) on recommended treatment (patients with malaria prescribed AL) and overtreatment (patients without malaria prescribed AL) in outpatients >/= 5 years old. Sixty health facilities were randomized to receive either RDTs plus training, guidelines, and supervision (TGS) or TGS alone. Of 1,540 patients included in the analysis, 7% had uncomplicated malaria. The provision of RDTs coupled with TGS emphasizing AL use only after laboratory confirmation of malaria reduced recommended treatment by 63%-points (P = 0.04), because diagnostic test use did not change (-2%-points), but health workers significantly reduced presumptive treatment with AL for patients with a clinical diagnosis of malaria who did not undergo testing (-36%-points; P = 0.03). Health workers generally adhered to RDT results when prescribing AL: 88% of RDT-positive and 9% of RDT-negative patients were treated with AL, respectively. Overtreatment was low in both arms and was not significantly reduced by the provision of RDTs (-12%-points, P = 0.30). RDTs could potentially improve malaria case management, but we urgently need to develop more effective strategies for implementing guidelines before large scale implementation.

Noor AM, Rage IA, Moonen B, Snow RW. 2009. Health service providers in Somalia: their readiness to provide malaria case-management. Malar J, 8 (1), pp. 100. | Show Abstract | Read more

BACKGROUND: Studies have highlighted the inadequacies of the public health sector in sub-Saharan African countries in providing appropriate malaria case management. The readiness of the public health sector to provide malaria case-management in Somalia, a country where there has been no functioning central government for almost two decades, was investigated. METHODS: Three districts were purposively sampled in each of the two self-declared states of Puntland and Somaliland and the south-central region of Somalia, in April-November 2007. A survey and mapping of all public and private health service providers was undertaken. Information was recorded on services provided, types of anti-malarial drugs used and stock, numbers and qualifications of staff, sources of financial support and presence of malaria diagnostic services, new treatment guidelines and job aides for malaria case-management. All settlements were mapped and a semi-quantitative approach was used to estimate their population size. Distances from settlements to public health services were computed. RESULTS: There were 45 public health facilities, 227 public health professionals, and 194 private pharmacies for approximately 0.6 million people in the three districts. The median distance to public health facilities was 6 km. 62.3% of public health facilities prescribed the nationally recommended anti-malarial drug and 37.7% prescribed chloroquine as first-line therapy. 66.7% of public facilities did not have in stock the recommended first-line malaria therapy. Diagnosis of malaria using rapid diagnostic tests (RDT) or microscopy was performed routinely in over 90% of the recommended public facilities but only 50% of these had RDT in stock at the time of survey. National treatment guidelines were available in 31.3% of public health facilities recommended by the national strategy. Only 8.8% of the private pharmacies prescribed artesunate plus sulphadoxine/pyrimethamine, while 53.1% prescribed chloroquine as first-line therapy. 31.4% of private pharmacies also provided malaria diagnosis using RDT or microscopy. CONCLUSION: Geographic access to public health sector is relatively low and there were major shortages of appropriate guidelines, anti-malarials and diagnostic tests required for appropriate malaria case management. Efforts to strengthen the readiness of the health sector in Somalia to provide malaria case management should improve availability of drugs and diagnostic kits; provide appropriate information and training; and engage and regulate the private sector to scale up malaria control.

Kangwana BB, Njogu J, Wasunna B, Kedenge SV, Memusi DN, Goodman CA, Zurovac D, Snow RW. 2009. Malaria drug shortages in Kenya: a major failure to provide access to effective treatment. Am J Trop Med Hyg, 80 (5), pp. 737-738. | Show Abstract

A key bench mark of successful therapeutic policy implementation, and thus effectiveness, is that the recommended drugs are available at the point of care. Two years after artemether-lumefathrine (AL) was introduced for the management of uncomplicated malaria in Kenya, we carried out a cross-sectional survey to investigate AL availability in government facilities in seven malaria-endemic districts. One of four of the surveyed facilities had none of the four AL weight-specific treatment packs in stock; three of four facilities were out of stock of at least one weight-specific AL pack, leading health workers to prescribe a range of inappropriate alternatives. The shortage was in large part caused by a delayed procurement process. National ministries of health and the international community must address the current shortcomings facing antimalarial drug supply to the public sector.

Nankabirwa J, Zurovac D, Njogu JN, Rwakimari JB, Counihan H, Snow RW, Tibenderana JK. 2009. Malaria misdiagnosis in Uganda--implications for policy change. Malar J, 8 (1), pp. 66. | Show Abstract | Read more

BACKGROUND: In Uganda, like in many other countries traditionally viewed as harbouring very high malaria transmission, the norm has been to recommend that febrile episodes are diagnosed as malaria. In this study, the policy implications of such recommendations are revisited. METHODS: A cross-sectional survey was undertaken at outpatient departments of all health facilities in four Ugandan districts. The routine diagnostic practices were assessed for all patients during exit interviews and a research slide was obtained for later reading. Primary outcome measures were the accuracy of national recommendations and routine malaria diagnosis in comparison with the study definition of malaria (any parasitaemia on expert slide examination in patient with fever) stratified by age and intensity of malaria transmission. Secondary outcome measures were the use, interpretation and accuracy of routine malaria microscopy. RESULTS: 1,763 consultations undertaken by 233 health workers at 188 facilities were evaluated. The prevalence of malaria was 24.2% and ranged between 13.9% in patients >or=5 years in medium-to-high transmission areas to 50.5% for children <5 years in very high transmission areas. Overall, the sensitivity and negative predictive value (NPV) of routine malaria diagnosis were high (89.7% and 91.6% respectively) while the specificity and positive predictive value (PPV) were low (35.6% and 30.8% respectively). However, malaria was under-diagnosed in 39.9% of children less than five years of age in the very high transmission area. At 48 facilities with functional microscopy, the use of malaria slide examination was low (34.5%) without significant differences between age groups, or between patients for whom microscopy is recommended or not. 96.2% of patients with a routine positive slide result were treated for malaria but also 47.6% with a negative result. CONCLUSION: Current recommendations and associated clinical practices result in massive malaria over-diagnosis across all age groups and transmission areas in Uganda. Yet, under-diagnosis is also common in children <5 years. The potential benefits of malaria microscopy are not realized. To address malaria misdiagnosis, Uganda's policy shift from presumptive to parasitological diagnosis should encompass introduction of malaria rapid diagnostic tests and substantial strengthening of malaria microscopy.

Hay SI, Guerra CA, Gething PW, Patil AP, Tatem AJ, Noor AM, Kabaria CW, Manh BH et al. 2009. A world malaria map: Plasmodium falciparum endemicity in 2007. PLoS Med, 6 (3), pp. e1000048. | Show Abstract | Read more

BACKGROUND: Efficient allocation of resources to intervene against malaria requires a detailed understanding of the contemporary spatial distribution of malaria risk. It is exactly 40 y since the last global map of malaria endemicity was published. This paper describes the generation of a new world map of Plasmodium falciparum malaria endemicity for the year 2007. METHODS AND FINDINGS: A total of 8,938 P. falciparum parasite rate (PfPR) surveys were identified using a variety of exhaustive search strategies. Of these, 7,953 passed strict data fidelity tests for inclusion into a global database of PfPR data, age-standardized to 2-10 y for endemicity mapping. A model-based geostatistical procedure was used to create a continuous surface of malaria endemicity within previously defined stable spatial limits of P. falciparum transmission. These procedures were implemented within a Bayesian statistical framework so that the uncertainty of these predictions could be evaluated robustly. The uncertainty was expressed as the probability of predicting correctly one of three endemicity classes; previously stratified to be an informative guide for malaria control. Population at risk estimates, adjusted for the transmission modifying effects of urbanization in Africa, were then derived with reference to human population surfaces in 2007. Of the 1.38 billion people at risk of stable P. falciparum malaria, 0.69 billion were found in Central and South East Asia (CSE Asia), 0.66 billion in Africa, Yemen, and Saudi Arabia (Africa+), and 0.04 billion in the Americas. All those exposed to stable risk in the Americas were in the lowest endemicity class (PfPR2-10 < or = 5%). The vast majority (88%) of those living under stable risk in CSE Asia were also in this low endemicity class; a small remainder (11%) were in the intermediate endemicity class (PfPR2-10 > 5 to < 40%); and the remaining fraction (1%) in high endemicity (PfPR2-10 > or = 40%) areas. High endemicity was widespread in the Africa+ region, where 0.35 billion people are at this level of risk. Most of the rest live at intermediate risk (0.20 billion), with a smaller number (0.11 billion) at low stable risk. CONCLUSIONS: High levels of P. falciparum malaria endemicity are common in Africa. Uniformly low endemic levels are found in the Americas. Low endemicity is also widespread in CSE Asia, but pockets of intermediate and very rarely high transmission remain. There are therefore significant opportunities for malaria control in Africa and for malaria elimination elsewhere. This 2007 global P. falciparum malaria endemicity map is the first of a series with which it will be possible to monitor and evaluate the progress of this intervention process.

Okiro EA, Al-Taiar A, Reyburn H, Idro R, Berkley JA, Snow RW. 2009. Age patterns of severe paediatric malaria and their relationship to Plasmodium falciparum transmission intensity. Malar J, 8 (1), pp. 4. | Show Abstract | Read more

BACKGROUND: The understanding of the epidemiology of severe malaria in African children remains incomplete across the spectrum of Plasmodium falciparum transmission intensities through which communities might expect to transition, as intervention coverage expands. METHODS: Paediatric admission data were assembled from 13 hospitals serving 17 communities between 1990 and 2007. Estimates of Plasmodium falciparum transmission intensity in these communities were assembled to be spatially and temporally congruent to the clinical admission data. The analysis focused on the relationships between community derived parasite prevalence and the age and clinical presentation of paediatric malaria in children aged 0-9 years admitted to hospital. RESULTS: As transmission intensity declined a greater proportion of malaria admissions were in older children. There was a strong linear relationship between increasing transmission intensity and the proportion of paediatric malaria admissions that were infants (R2 = 0.73, p < 0.001). Cerebral malaria was reported among 4% and severe malaria anaemia among 17% of all malaria admissions. At higher transmission intensity cerebral malaria was a less common presentation compared to lower transmission sites. There was no obvious relationship between the proportions of children with severe malaria anaemia and transmission intensity. CONCLUSION: As the intensity of malaria transmission declines in Africa through the scaling up of insecticide-treated nets and other vector control measures a focus of disease prevention among very young children becomes less appropriate. The understanding of the relationship between parasite exposure and patterns of disease risk should be used to adapt malaria control strategies in different epidemiological settings.

Noor AM, Mutheu JJ, Tatem AJ, Hay SI, Snow RW. 2009. Insecticide-treated net coverage in Africa: mapping progress in 2000-07. Lancet, 373 (9657), pp. 58-67. | Show Abstract | Read more

BACKGROUND: Insecticide-treated bednets (ITNs) provide a means to improve child survival across Africa. Sales figures of these nets and survey coverage data presented nationally mask inequities in populations at biological and economic risk, and do not allow for precision in the estimation of unmet commodity needs. We gathered subnational ITN coverage sample survey data from 40 malaria-endemic countries in Africa between 2000 and 2007. METHODS: We computed the projected ITN coverage among children aged less than 5 years for age-adjusted population data that were stratified according to malaria transmission risks, proximate determinants of poverty, and methods of ITN delivery. FINDINGS: In 2000, only 1.7 million (1.8%) African children living in stable malaria-endemic conditions were protected by an ITN and the number increased to 20.3 million (18.5%) by 2007 leaving 89.6 million children unprotected. Of these, 30 million were living in some of the poorest areas of Africa: 54% were living in only seven countries and 25% in Nigeria alone. Overall, 33 (83%) countries were estimated to have ITN coverage of less than 40% in 2007. On average, we noted a greater increase in ITN coverage in areas where free distribution had operated between survey periods. INTERPRETATION: By mapping the distribution of populations in relation to malaria risk and intervention coverage, we provide a means to track the future requirements for scaling up essential disease-prevention strategies. The present coverage of ITN in Africa remains inadequate and a focused effort to improve distribution in selected areas would have a substantial effect on the continent's malaria burden.

Noor AM, Alegana VA, Gething PW, Snow RW. 2009. A spatial national health facility database for public health sector planning in Kenya in 2008. Int J Health Geogr, 8 (1), pp. 13. | Show Abstract | Read more

BACKGROUND: Efforts to tackle the enormous burden of ill-health in low-income countries are hampered by weak health information infrastructures that do not support appropriate planning and resource allocation. For health information systems to function well, a reliable inventory of health service providers is critical. The spatial referencing of service providers to allow their representation in a geographic information system is vital if the full planning potential of such data is to be realized. METHODS: A disparate series of contemporary lists of health service providers were used to update a public health facility database of Kenya last compiled in 2003. These new lists were derived primarily through the national distribution of antimalarial and antiretroviral commodities since 2006. A combination of methods, including global positioning systems, was used to map service providers. These spatially-referenced data were combined with high-resolution population maps to analyze disparity in geographic access to public health care. FINDINGS: The updated 2008 database contained 5,334 public health facilities (67% ministry of health; 28% mission and nongovernmental organizations; 2% local authorities; and 3% employers and other ministries). This represented an overall increase of 1,862 facilities compared to 2003. Most of the additional facilities belonged to the ministry of health (79%) and the majority were dispensaries (91%). 93% of the health facilities were spatially referenced, 38% using global positioning systems compared to 21% in 2003. 89% of the population was within 5 km Euclidean distance to a public health facility in 2008 compared to 71% in 2003. Over 80% of the population outside 5 km of public health service providers was in the sparsely settled pastoralist areas of the country. CONCLUSION: We have shown that, with concerted effort, a relatively complete inventory of mapped health services is possible with enormous potential for improving planning. Expansion in public health care in Kenya has resulted in significant increases in geographic access although several areas of the country need further improvements. This information is key to future planning and with this paper we have released the digital spatial database in the public domain to assist the Kenyan Government and its partners in the health sector.

Cited:

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Scopus

English M, Reyburn H, Goodman C, Snow RW. 2009. Abandoning presumptive antimalarial treatment for febrile children aged less than five years - A case of running before we can walk? PLoS Medicine, 6 (1), pp. 0007-0009. | Show Abstract | Read more

Background to the debate: Current guidelines recommend that all fever episodes in African children be treated presumptively with antimalarial drugs. But declining malarial transmission in parts of sub-Saharan Africa, declining proportions of fevers due to malaria, and the availability of rapid diagnostic tests mean it may be time for this policy to change. This debate examines whether enough evidence exists to support abandoning presumptive treatment and whether African health systems have the capacity to support a shift toward laboratory-confirmed rather than presumptive diagnosis and treatment of malaria in children under five. © 2009 English et al.

English M, Reyburn H, Goodman C, Snow RW. 2009. Abandoning presumptive antimalarial treatment for febrile children aged less than five years--a case of running before we can walk? PLoS Med, 6 (1), pp. e1000015. | Show Abstract | Read more

BACKGROUND TO THE DEBATE: Current guidelines recommend that all fever episodes in African children be treated presumptively with antimalarial drugs. But declining malarial transmission in parts of sub-Saharan Africa, declining proportions of fevers due to malaria, and the availability of rapid diagnostic tests mean it may be time for this policy to change. This debate examines whether enough evidence exists to support abandoning presumptive treatment and whether African health systems have the capacity to support a shift toward laboratory-confirmed rather than presumptive diagnosis and treatment of malaria in children under five.

Patil AP, Okiro EA, Gething PW, Guerra CA, Sharma SK, Snow RW, Hay SI. 2009. Defining the relationship between Plasmodium falciparum parasite rate and clinical disease: statistical models for disease burden estimation. Malar J, 8 (1), pp. 186. | Show Abstract | Read more

BACKGROUND: Clinical malaria has proven an elusive burden to enumerate. Many cases go undetected by routine disease recording systems. Epidemiologists have, therefore, frequently defaulted to actively measuring malaria in population cohorts through time. Measuring the clinical incidence of malaria longitudinally is labour-intensive and impossible to undertake universally. There is a need, therefore, to define a relationship between clinical incidence and the easier and more commonly measured index of infection prevalence: the "parasite rate". This relationship can help provide an informed basis to define malaria burdens in areas where health statistics are inadequate. METHODS: Formal literature searches were conducted for Plasmodium falciparum malaria incidence surveys undertaken prospectively through active case detection at least every 14 days. The data were abstracted, standardized and geo-referenced. Incidence surveys were time-space matched with modelled estimates of infection prevalence derived from a larger database of parasite prevalence surveys and modelling procedures developed for a global malaria endemicity map. Several potential relationships between clinical incidence and infection prevalence were then specified in a non-parametric Gaussian process model with minimal, biologically informed, prior constraints. Bayesian inference was then used to choose between the candidate models. RESULTS: The suggested relationships with credible intervals are shown for the Africa and a combined America and Central and South East Asia regions. In both regions clinical incidence increased slowly and smoothly as a function of infection prevalence. In Africa, when infection prevalence exceeded 40%, clinical incidence reached a plateau of 500 cases per thousand of the population per annum. In the combined America and Central and South East Asia regions, this plateau was reached at 250 cases per thousand of the population per annum. A temporal volatility model was also incorporated to facilitate a closer description of the variance in the observed data. CONCLUSION: It was possible to model a relationship between clinical incidence and P. falciparum infection prevalence but the best-fit models were very noisy reflecting the large variance within the observed opportunistic data sample. This continuous quantification allows for estimates of the clinical burden of P. falciparum of known confidence from wherever an estimate of P. falciparum prevalence is available.

Okiro EA, Alegana VA, Noor AM, Mutheu JJ, Juma E, Snow RW. 2009. Malaria paediatric hospitalization between 1999 and 2008 across Kenya. BMC Med, 7 (1), pp. 75. | Show Abstract | Read more

BACKGROUND: Intervention coverage and funding for the control of malaria in Africa has increased in recent years, however, there are few descriptions of changing disease burden and the few reports available are from isolated, single site observations or are of reports at country-level. Here we present a nationwide assessment of changes over 10 years in paediatric malaria hospitalization across Kenya. METHODS: Paediatric admission data on malaria and non-malaria diagnoses were assembled for the period 1999 to 2008 from in-patient registers at 17 district hospitals in Kenya and represented the diverse malaria ecology of the country. These data were then analysed using autoregressive moving average time series models with malaria and all-cause admissions as the main outcomes adjusted for rainfall, changes in service use and populations-at-risk within each hospital's catchment to establish whether there has been a statistically significant decline in paediatric malaria hospitalization during the observation period. RESULTS: Among the 17 hospital sites, adjusted paediatric malaria admissions had significantly declined at 10 hospitals over 10 years since 1999; had significantly increased at four hospitals, and remained unchanged in three hospitals. The overall estimated average reduction in malaria admission rates was 0.0063 cases per 1,000 children aged 0 to 14 years per month representing an average percentage reduction of 49% across the 10 hospitals registering a significant decline by the end of 2008. Paediatric admissions for all-causes had declined significantly with a reduction in admission rates of greater than 0.0050 cases per 1,000 children aged 0 to 14 years per month at 6 of 17 hospitals. Where malaria admissions had increased three of the four sites were located in Western Kenya close to Lake Victoria. Conversely there was an indication that areas with the largest declines in malaria admission rates were areas located along the Kenyan coast and some sites in the highlands of Kenya. CONCLUSION: A country-wide assessment of trends in malaria hospitalizations indicates that all is not equal, important variations exist in the temporal pattern of malaria admissions between sites and these differences require more detailed investigation to understand what is required to promote a clinical transition across Africa.

Noor AM, Gething PW, Alegana VA, Patil AP, Hay SI, Muchiri E, Juma E, Snow RW. 2009. The risks of malaria infection in Kenya in 2009. BMC Infect Dis, 9 (1), pp. 180. | Show Abstract | Read more

BACKGROUND: To design an effective strategy for the control of malaria requires a map of infection and disease risks to select appropriate suites of interventions. Advances in model based geo-statistics and malaria parasite prevalence data assemblies provide unique opportunities to redefine national Plasmodium falciparum risk distributions. Here we present a new map of malaria risk for Kenya in 2009. METHODS: Plasmodium falciparum parasite rate data were assembled from cross-sectional community based surveys undertaken from 1975 to 2009. Details recorded for each survey included the month and year of the survey, sample size, positivity and the age ranges of sampled population. Data were corrected to a standard age-range of two to less than 10 years (PfPR2-10) and each survey location was geo-positioned using national and on-line digital settlement maps. Ecological and climate covariates were matched to each PfPR2-10 survey location and examined separately and in combination for relationships to PfPR2-10. Significant covariates were then included in a Bayesian geostatistical spatial-temporal framework to predict continuous and categorical maps of mean PfPR2-10 at a 1 x 1 km resolution across Kenya for the year 2009. Model hold-out data were used to test the predictive accuracy of the mapped surfaces and distributions of the posterior uncertainty were mapped. RESULTS: A total of 2,682 estimates of PfPR2-10 from surveys undertaken at 2,095 sites between 1975 and 2009 were selected for inclusion in the geo-statistical modeling. The covariates selected for prediction were urbanization; maximum temperature; precipitation; enhanced vegetation index; and distance to main water bodies. The final Bayesian geo-statistical model had a high predictive accuracy with mean error of -0.15% PfPR2-10; mean absolute error of 0.38% PfPR2-10; and linear correlation between observed and predicted PfPR2-10 of 0.81. The majority of Kenya's 2009 population (35.2 million, 86.3%) reside in areas where predicted PfPR2-10 is less than 5%; conversely in 2009 only 4.3 million people (10.6%) lived in areas where PfPR2-10 was predicted to be > or =40% and were largely located around the shores of Lake Victoria. CONCLUSION: Model based geo-statistical methods can be used to interpolate malaria risks in Kenya with precision and our model shows that the majority of Kenyans live in areas of very low P. falciparum risk. As malaria interventions go to scale effectively tracking epidemiological changes of risk demands a rigorous effort to document infection prevalence in time and space to remodel risks and redefine intervention priorities over the next 10-15 years.

Noor AM, Kirui VC, Brooker SJ, Snow RW. 2009. The use of insecticide treated nets by age: implications for universal coverage in Africa. BMC Public Health, 9 (1), pp. 369. | Show Abstract | Read more

BACKGROUND: The scaling of malaria control to achieve universal coverage requires a better understanding of the population sub-groups that are least protected and provide barriers to interrupted transmission. Here we examine the age pattern of use of insecticide treated nets (ITNs) in Africa in relation to biological vulnerabilities and the implications for future prospects for universal coverage. METHODS: Recent national household survey data for 18 malaria endemic countries in Africa were assembled to identify information on use of ITNs by age and sex. Age-structured medium variant projected population estimates for the mid-point year of the earliest and most recent national surveys were derived to compute the population by age protected by ITNs. RESULTS: All surveys were undertaken between 2005 and 2009, either as demographic health surveys (n = 12) or malaria indicator surveys (n = 6). Countries were categorized into three ITN use groups: <10%; 10 to <20%; and > or =20% and projected population estimates for the mid-point year of 2007 were computed. In general, the pattern of overall ITNs use with age was similar by country and across the three country groups with ITNs use initially high among children <5 years of age, sharply declining among the population aged 5-19 years, before rising again across the ages 20-44 years and finally decreasing gradually in older ages. For all groups of countries, the highest proportion of the population not protected by ITNs (38% - 42%) was among those aged 5-19 years. CONCLUSION: In malaria-endemic Africa, school-aged children are the least protected with ITNs but represent the greatest reservoir of infections. With increasing school enrollment rates, school-delivery of ITNs should be considered as an approach to reach universal ITNs coverage and improve the likelihood of impacting upon parasite transmission.

O'Meara WP, Bejon P, Mwangi TW, Okiro EA, Peshu N, Snow RW, Newton CR, Marsh K. 2008. Effect of a fall in malaria transmission on morbidity and mortality in Kilifi, Kenya. Lancet, 372 (9649), pp. 1555-1562. | Show Abstract | Read more

BACKGROUND: As efforts to control malaria are expanded across the world, understanding the role of transmission intensity in determining the burden of clinical malaria is crucial to the prediction and measurement of the effectiveness of interventions to reduce transmission. Furthermore, studies comparing several endemic sites led to speculation that as transmission decreases morbidity and mortality caused by severe malaria might increase. We aimed to assess the epidemiological characteristics of malaria in Kilifi, Kenya, during a period of decreasing transmission intensity. METHODS: We analyse 18 years (1990-2007) of surveillance data from a paediatric ward in a malaria-endemic region of Kenya. The hospital has a catchment area of 250 000 people. Clinical data and blood-film results for more than 61 000 admissions are reported. FINDINGS: Hospital admissions for malaria decreased from 18.43 per 1000 children in 2003 to 3.42 in 2007. Over 18 years of surveillance, the incidence of cerebral malaria initially increased; however, malaria mortality decreased overall because of a decrease in incidence of severe malarial anaemia since 1997 (4.75 to 0.37 per 1000 children) and improved survival among children admitted with non-severe malaria. Parasite prevalence, the mean age of children admitted with malaria, and the proportion of children with cerebral malaria began to change 10 years before hospitalisation for malaria started to fall. INTERPRETATION: Sustained reduction in exposure to infection leads to changes in mean age and presentation of disease similar to those described in multisite studies. Changes in transmission might not lead to immediate reductions in incidence of clinical disease. However, longitudinal data do not indicate that reductions in transmission intensity lead to transient increases in morbidity and mortality.

Borrmann S, Peto T, Snow RW, Gutteridge W, White NJ. 2008. Revisiting the design of phase III clinical trials of antimalarial drugs for uncomplicated Plasmodium falciparum malaria. PLoS Med, 5 (11), pp. e227. | Read more

Zurovac D, Tibenderana JK, Nankabirwa J, Ssekitooleko J, Njogu JN, Rwakimari JB, Meek S, Talisuna A, Snow RW. 2008. Malaria case-management under artemether-lumefantrine treatment policy in Uganda. Malar J, 7 (1), pp. 181. | Show Abstract | Read more

BACKGROUND: Case-management with artemether-lumefantrine (AL) is one of the key strategies to control malaria in many African countries. Yet, the reports on translation of AL implementation activities into clinical practice are scarce. Here the quality of AL case-management is reported from Uganda; approximately one year after AL replaced combination of chloroquine and sulphadoxine-pyrimethamine (CQ+SP) as recommended first line treatment for uncomplicated malaria. METHODS: A cross-sectional survey, using a range of quality of care assessment tools, was undertaken at all government and private-not-for-profit facilities in four Ugandan districts. Main outcome measures were AL prescribing, dispensing and counseling practices in comparison with national guidelines, and factors influencing health workers decision to 1) treat for malaria, and 2) prescribe AL. RESULTS: 195 facilities, 232 health workers and 1,763 outpatient consultations were evaluated. Of 1,200 patients who needed treatment with AL according to guidelines, AL was prescribed for 60%, CQ+SP for 14%, quinine for 4%, CQ for 3%, other antimalarials for 3%, and 16% of patients had no antimalarial drug prescribed. AL was prescribed in the correct dose for 95% of patients. Only three out of seven AL counseling and dispensing tasks were performed for more than 50% of patients. Patients were more likely to be treated for malaria if they presented with main complaint of fever (OR = 5.22; 95% CI: 3.61-7.54) and if they were seen by supervised health workers (OR = 1.63; 95% CI: 1.06-2.50); however less likely if they were treated by more qualified health workers (OR = 0.61; 95% CI: 0.40-0.93) and presented with skin problem (OR = 0.29; 95% CI: 0.15-0.55). AL was more likely prescribed if the appropriate weight-specific AL pack was in stock (OR = 6.15; 95% CI: 3.43-11.05) and when CQ was absent (OR = 2.16; 95% CI: 1.09-4.28). Routine AL implementation activities were not associated with better performance. CONCLUSION: Although the use of AL was predominant over non-recommended therapies, the quality of AL case-management at the point of care is not yet optimal. There is an urgent need for innovative quality improvement interventions, which should be rigorously tested. Adequate availability of ACTs at the point of care will, however, ultimately determine the success of any performance interventions and ACT policy transitions.

Lairumbi GM, Molyneux S, Snow RW, Marsh K, Peshu N, English M. 2008. Promoting the social value of research in Kenya: examining the practical aspects of collaborative partnerships using an ethical framework. Soc Sci Med, 67 (5), pp. 734-747. | Show Abstract | Read more

The ethics of research continue to attract considerable debate, particularly when that research is sponsored by partners from the North and carried out in the South. Ethical research should contribute to social value in the country where research is being carried out, but there is significant debate around how this might be achieved and who is responsible. The literature suggests that researchers might employ two inter-related strategies to maximise social value: collaborative partnerships with policy makers and communities from the outset of research, and dissemination of research results to participants, policy makers and implementers once the research is over. These areas have received relatively little empirical attention. In this study, we carried out 40 in-depth interviews to explore the role of collaborative partnerships in health research priority setting, and the way in which research findings are disseminated to aid policy making and implementation in Kenya. Interviewees included policy makers, researchers, policy implementers and representatives of organisations funding health reforms in Kenya. Two policy issues were drawn upon as tracers wherever possible: (1) the introduction of Artemesinin-based Combination Therapies (ACTs), an anti-malarial treatment policy; and (2) Haemophilus influenzae (Hib) vaccine for the prevention of pneumococcal diseases among children. The findings point to significant gaps in the 'research to policy to practice' pathway, particularly for national research institutions with a focus on clinical/biomedical research. These gaps reflect poorly effective partnerships among stakeholders and limit the potential social value of much research. While more investment is needed to establish strong structures for promoting and directing collaboration and partnership, how to target this investment is not entirely clear, especially in the context of the considerable power of the global health agenda and the research financing tied to it.

Noor AM, Clements AC, Gething PW, Moloney G, Borle M, Shewchuk T, Hay SI, Snow RW. 2008. Spatial prediction of Plasmodium falciparum prevalence in Somalia. Malar J, 7 (1), pp. 159. | Show Abstract | Read more

BACKGROUND: Maps of malaria distribution are vital for optimal allocation of resources for anti-malarial activities. There is a lack of reliable contemporary malaria maps in endemic countries in sub-Saharan Africa. This problem is particularly acute in low malaria transmission countries such as those located in the horn of Africa. METHODS: Data from a national malaria cluster sample survey in 2005 and routine cluster surveys in 2007 were assembled for Somalia. Rapid diagnostic tests were used to examine the presence of Plasmodium falciparum parasites in finger-prick blood samples obtained from individuals across all age-groups. Bayesian geostatistical models, with environmental and survey covariates, were used to predict continuous maps of malaria prevalence across Somalia and to define the uncertainty associated with the predictions. RESULTS: For analyses the country was divided into north and south. In the north, the month of survey, distance to water, precipitation and temperature had no significant association with P. falciparum prevalence when spatial correlation was taken into account. In contrast, all the covariates, except distance to water, were significantly associated with parasite prevalence in the south. The inclusion of covariates improved model fit for the south but not for the north. Model precision was highest in the south. The majority of the country had a predicted prevalence of < 5%; areas with > or = 5% prevalence were predominantly in the south. CONCLUSION: The maps showed that malaria transmission in Somalia varied from hypo- to meso-endemic. However, even after including the selected covariates in the model, there still remained a considerable amount of unexplained spatial variation in parasite prevalence, indicating effects of other factors not captured in the study. Nonetheless the maps presented here provide the best contemporary information on malaria prevalence in Somalia.

O'Meara WP, Mwangi TW, Williams TN, McKenzie FE, Snow RW, Marsh K. 2008. Relationship between exposure, clinical malaria, and age in an area of changing transmission intensity. Am J Trop Med Hyg, 79 (2), pp. 185-191. | Show Abstract

The relationship between malaria transmission intensity and clinical disease is important for predicting the outcome of control measures that reduce transmission. Comparisons of hospital data between areas of differing transmission intensity suggest that the mean age of hospitalized clinical malaria is higher under relatively lower transmission, but the total number of episodes is similar until transmission drops below a threshold, where the risks of hospitalized malaria decline. These observations have rarely been examined longitudinally in a single community where transmission declines over time. We reconstructed 16 years (1991-2006) of pediatric hospital surveillance data and infection prevalence surveys from a circumscribed geographic area on the Kenyan coast. The incidence of clinical malaria remained high, despite sustained reductions in exposure to infection. However, the age group experiencing the clinical attacks of malaria increased steadily as exposure declined and may precede changes in the number of episodes in an area with declining transmission.

Snow RW, Guerra CA, Mutheu JJ, Hay SI. 2008. International funding for malaria control in relation to populations at risk of stable Plasmodium falciparum transmission. PLoS Med, 5 (7), pp. e142. | Show Abstract | Read more

BACKGROUND: The international financing of malaria control has increased significantly in the last ten years in parallel with calls to halve the malaria burden by the year 2015. The allocation of funds to countries should reflect the size of the populations at risk of infection, disease, and death. To examine this relationship, we compare an audit of international commitments with an objective assessment of national need: the population at risk of stable Plasmodium falciparum malaria transmission in 2007. METHODS AND FINDINGS: The national distributions of populations at risk of stable P. falciparum transmission were projected to the year 2007 for each of 87 P. falciparum-endemic countries. Systematic online- and literature-based searches were conducted to audit the international funding commitments made for malaria control by major donors between 2002 and 2007. These figures were used to generate annual malaria funding allocation (in US dollars) per capita population at risk of stable P. falciparum in 2007. Almost US$1 billion are distributed each year to the 1.4 billion people exposed to stable P. falciparum malaria risk. This is less than US$1 per person at risk per year. Forty percent of this total comes from the Global Fund to Fight AIDS, Tuberculosis and Malaria. Substantial regional and national variations in disbursements exist. While the distribution of funds is found to be broadly appropriate, specific high population density countries receive disproportionately less support to scale up malaria control. Additionally, an inadequacy of current financial commitments by the international community was found: under-funding could be from 50% to 450%, depending on which global assessment of the cost required to scale up malaria control is adopted. CONCLUSIONS: Without further increases in funding and appropriate targeting of global malaria control investment it is unlikely that international goals to halve disease burdens by 2015 will be achieved. Moreover, the additional financing requirements to move from malaria control to malaria elimination have not yet been considered by the scientific or international community.

Zurovac D, Njogu J, Akhwale W, Hamer DH, Larson BA, Snow RW. 2008. Effects of revised diagnostic recommendations on malaria treatment practices across age groups in Kenya. Trop Med Int Health, 13 (6), pp. 784-787. | Show Abstract | Read more

OBJECTIVE: The recent change of treatment policy for uncomplicated malaria from sulfadoxine-pyrime-thamine to artemether-lumefantrine (AL) in Kenya was accompanied by revised malaria diagnosis recommendations promoting presumptive antimalarial treatment in young children and parasitological diagnosis in patients 5 years and older. We evaluated the impact of these age-specific recommendations on routine malaria treatment practices 4-6 months after AL treatment was implemented. METHODS: Cross-sectional, cluster sample survey using quality-of-care assessment methods in all government facilities in four Kenyan districts. Analysis was restricted to the 64 facilities with malaria diagnostics and AL available on the survey day. Main outcome measures were antimalarial treatment practices for febrile patients stratified by age, use of malaria diagnostic tests, and test result. RESULTS: Treatment practices for 706 febrile patients (401 young children and 305 patients > or =5 years) were evaluated. 43.0% of patients > or =5 years and 25.9% of children underwent parasitological malaria testing (87% by microscopy). AL was prescribed for 79.7% of patients > or =5 years with positive test results, for 9.7% with negative results and for 10.9% without a test. 84.6% of children with positive tests, 19.2% with negative tests, and 21.6% without tests were treated with AL. At least one antimalarial drug was prescribed for 75.0% of children and for 61.3% of patients > or =5 years with a negative test result. CONCLUSIONS: Despite different recommendations for patients below and above 5 years of age, malaria diagnosis and treatment practices were similar in the two age groups. Parasitological diagnosis was under-used in older children and adults, and young children were still tested. Use of AL was low overall and alternative antimalarials were commonly prescribed; but AL prescribing largely followed the results of malaria tests. Malaria diagnosis recommendations differing between age groups appear complex to implement; further strengthening of diagnosis and treatment practices under AL policy is required.

Hay SI, Smith DL, Snow RW. 2008. Measuring malaria endemicity from intense to interrupted transmission. Lancet Infect Dis, 8 (6), pp. 369-378. | Show Abstract | Read more

The quantification of malaria transmission for the classification of malaria risk has long been a concern for epidemiologists. During the era of the Global Malaria Eradication Programme, measurements of malaria endemicity were institutionalised by their incorporation into rules outlining defined action points for malaria control programmes. We review the historical development of these indices and their contemporary relevance. This is at a time when many malaria-endemic countries are scaling-up their malaria control activities and reconsidering their prospects for elimination. These considerations are also important to an international community that has recently been challenged to revaluate the prospects for malaria eradication.

Zurovac D, Larson BA, Skarbinski J, Slutsker L, Snow RW, Hamel MJ. 2008. Modeling the financial and clinical implications of malaria rapid diagnostic tests in the case-management of older children and adults in Kenya. Am J Trop Med Hyg, 78 (6), pp. 884-891. | Show Abstract

Using data on clinical practices for outpatients 5 years and older, test accuracy, and malaria prevalence, we model financial and clinical implications of malaria rapid diagnostic tests (RDTs) under the new artemether-lumefantrine (AL) treatment policy in one high and one low malaria prevalence district in Kenya. In the high transmission district, RDTs as actually used would improve malaria treatment (61% less over-treatment but 8% more under-treatment) and lower costs (21% less). Nonetheless, the majority of patients with malaria would not be correctly treated with AL. In the low transmission district, especially because the treatment policy was new and AL was not widely used, RDTs as actually used would yield a minor reduction in under-treatment errors (36% less but the base is small) with 41% higher costs. In both districts, adherence to revised clinical practices with RDTs has the potential to further decrease treatment errors with acceptable costs.

Mwangi TW, Fegan G, Williams TN, Kinyanjui SM, Snow RW, Marsh K. 2008. Evidence for over-dispersion in the distribution of clinical malaria episodes in children. PLoS One, 3 (5), pp. e2196. | Show Abstract | Read more

BACKGROUND: It may be assumed that patterns of clinical malaria in children of similar age under the same level of exposure would follow a Poisson distribution with no over-dispersion. Longitudinal studies that have been conducted over many years suggest that some children may experience more episodes of clinical malaria than would be expected. The aim of this study was to identify this group of children and investigate possible causes for this increased susceptibility. METHODOLOGY AND PRINCIPAL FINDINGS: Using Poisson regression, we chose a group of children whom we designated as 'more susceptible' to malaria from 373 children under 10 years of age who were followed up for between 3 to 5 years from 1998-2003. About 21% of the children were categorized as 'more susceptible' and although they contributed only 23% of the person-time of follow-up, they experienced 55% of total clinical malaria episodes. Children that were parasite negative at all cross-sectional survey were less likely to belong to this group [AOR = 0.09, (95% CI: 0.14-0.61), p = 0.001]. CONCLUSIONS AND SIGNIFICANCE: The pattern of clinical malaria episodes follows a negative binomial distribution. Use of lack of a clinical malaria episode in a certain time period as endpoints for intervention or immunological studies may not adequately distinguish groups who are more or less immune. It may be useful in such studies, in addition to the usual endpoint of the time to first episode, to include end points which take into account the total number of clinical episodes experienced per child.

Noor AM, Moloney G, Borle M, Fegan GW, Shewchuk T, Snow RW. 2008. The use of mosquito nets and the prevalence of Plasmodium falciparum infection in rural South Central Somalia. PLoS One, 3 (5), pp. e2081. | Show Abstract | Read more

BACKGROUND: There have been resurgent efforts in Africa to estimate the public health impact of malaria control interventions such as insecticide treated nets (ITNs) following substantial investments in scaling-up coverage in the last five years. Little is known, however, on the effectiveness of ITN in areas of Africa that support low transmission. This hinders the accurate estimation of impact of ITN use on disease burden and its cost-effectiveness in low transmission settings. METHODS AND PRINCIPAL FINDINGS: Using a stratified two-stage cluster sample design, four cross-sectional studies were undertaken between March-June 2007 across three livelihood groups in an area of low intensity malaria transmission in South Central Somalia. Information on bed net use; age; and sex of all participants were recorded. A finger prick blood sample was taken from participants to examine for parasitaemia. Mantel-Haenzel methods were used to measure the effect of net use on parasitaemia adjusting for livelihood; age; and sex. A total of 10,587 individuals of all ages were seen of which 10,359 provided full information. Overall net use and parasite prevalence were 12.4% and 15.7% respectively. Age-specific protective effectiveness (PE) of bed net ranged from 39% among <5 years to 72% among 5-14 years old. Overall PE of bed nets was 54% (95% confidence interval 44%-63%) after adjusting for livelihood; sex; and age. CONCLUSIONS AND SIGNIFICANCE: Bed nets confer high protection against parasite infection in South Central Somalia. In such areas where baseline transmission is low, however, the absolute reductions in parasitaemia due to wide-scale net use will be relatively small raising questions on the cost-effectiveness of covering millions of people living in such settings in Africa with nets. Further understanding of the progress of disease upon infection against the cost of averting its consequent burden in low transmission areas of Africa is therefore required.

Gething PW, Noor AM, Gikandi PW, Hay SI, Nixon MS, Snow RW, Atkinson PM. 2008. Developing geostatistical space-time models to predict outpatient treatment burdens from incomplete national data. Geogr Anal, 40 (2), pp. 167-188. | Show Abstract | Read more

Basic health system data such as the number of patients utilising different health facilities and the types of illness for which they are being treated are critical for managing service provision. These data requirements are generally addressed with some form of national Health Management Information System (HMIS) which coordinates the routine collection and compilation of data from national health facilities. HMIS in most developing countries are characterised by widespread under-reporting. Here we present a method to adjust incomplete data to allow prediction of national outpatient treatment burdens. We demonstrate this method with the example of outpatient treatments for malaria within the Kenyan HMIS. Three alternative modelling frameworks were developed and tested in which space-time geostatistical prediction algorithms were used to predict the monthly tally of treatments for presumed malaria cases (MC) at facilities where such records were missing. Models were compared by a cross-validation exercise and the model found to most accurately predict MC incorporated available data on the total number of patients visiting each facility each month. A space-time stochastic simulation framework to accompany this model was developed and tested in order to provide estimates of both local and regional prediction uncertainty. The level of accuracy provided by the predictive model, and the accompanying estimates of uncertainty around the predictions, demonstrate how this tool can mitigate the uncertainties caused by missing data, substantially enhancing the utility of existing HMIS data to health-service decision-makers.

Brooker S, Clarke S, Snow RW, Bundy DA. 2008. Malaria in African schoolchildren: options for control. Trans R Soc Trop Med Hyg, 102 (4), pp. 304-305. | Show Abstract | Read more

Intensified malaria control efforts among young African children may increase disease risks among older children who attend school and whose education may be impaired by malaria. However, there is currently no consensus as to the approach to malaria control in schools, with relevant intervention strategies varying according to patterns of malaria transmission. Life skills messages regarding prevention and accessing prompt treatment are important everywhere. Providing free bed nets to schoolchildren may bring individual and community benefits and should be widely promoted. New approaches to school-based chemoprevention and treatment may also be able to play an important role in school-based malaria control, although these require further investigation.

Gitonga CW, Amin AA, Ajanga A, Kangwana BB, Noor AM, Snow RW. 2008. The use of artemether-lumefantrine by febrile children following national implementation of a revised drug policy in Kenya. Trop Med Int Health, 13 (4), pp. 487-494. | Show Abstract | Read more

OBJECTIVES: To examine access to, timing and use of artemisinin-based combination therapy among rural Kenyan febrile children before and following the introduction of artemether-lumefantrine (AL) as first-line antimalarial drug policy. METHODS: In August 2006, a cohort was established within 72 rural clusters in four sentinel districts to monitor the period prevalence of fever and treatment in children aged 0-4 years through four repeat cross-sectional surveys (one prior to introduction of AL and three post-AL introduction: January-June 2007). Mothers/guardians of children were asked about fever in the last 14 days and related treatment actions including the timing, drugs used, dosing and adherence supported by visual aids of commonly available drug products. RESULTS: A total of 2526 child-observations were recorded during the four survey rounds. The period prevalence of fever was between 20% and 26% with little variation between survey rounds. The overall proportion of children with fever receiving antimalarial drugs for their fever was 31 % (95% CI, 26-36%) and the proportion of febrile children receiving antimalarial drugs within 48 h was 23.3% (95% CI, 18.6-28.0%). The proportion of febrile children who received first-line recommended AL within 48 h was 10.2% (95% CI, 7.0-13.4%), compared to only 4.6% (95% CI, 3.8-5.4%) of children receiving sulphadoxine-pyrimethamine first-line therapy in 2001. CONCLUSIONS: Although Kenya was less than a year into the new policy implementation and AL is restricted to the public formal sector, access to antimalarial drugs among children within 48 h and to the first-line therapy has improved. But it remains well below national and international targets. The continued use of amodiaquine and artemisinin monotherapies constrains effective implementation of artemisinin-based combination therapy policy in Kenya.

Aguas R, White LJ, Snow RW, Gomes MG. 2008. Prospects for malaria eradication in sub-Saharan Africa. PLoS One, 3 (3), pp. e1767. | Show Abstract | Read more

BACKGROUND: A characteristic of Plasmodium falciparum infections is the gradual acquisition of clinical immunity resulting from repeated exposures to the parasite. While the molecular basis of protection against clinical malaria remains unresolved, its effects on epidemiological patterns are well recognized. Accumulating epidemiological data constitute a valuable resource that must be intensively explored and interpreted as to effectively inform control planning. METHODOLOGY/PRINCIPAL FINDING: Here we apply a mathematical model to clinical data from eight endemic regions in sub-Saharan Africa. The model provides a quantitative framework within which differences in age distribution of clinical disease are assessed in terms of the parameters underlying transmission. The shorter infectious periods estimated for clinical infections induce a regime of bistability of endemic and malaria-free states in regions of mesoendemic transmission. The two epidemiological states are separated by a threshold that provides a convenient measure for intervention design. Scenarios of eradication and resurgence are simulated. CONCLUSIONS/SIGNIFICANCE: In regions that support mesoendemic transmission, intervention success depends critically on reducing prevalence below a threshold which separates endemic and malaria-free regimes.

Wasunna B, Zurovac D, Goodman CA, Snow RW. 2008. Why don't health workers prescribe ACT? A qualitative study of factors affecting the prescription of artemether-lumefantrine. Malar J, 7 (1), pp. 29. | Show Abstract | Read more

BACKGROUND: Kenya recently changed its antimalarial drug policy to a specific artemisinin-based combination therapy (ACT), artemether-lumefantrine (AL). New national guidelines on the diagnosis, treatment and prevention were developed and disseminated to health workers together with in-service training. METHODS: Between January and March 2007, 36 in-depth interviews were conducted in five rural districts with health workers who attended in-service training and were non-adherent to the new guidelines. A further 20 interviews were undertaken with training facilitators and members of District Health Management Teams (DHMTs) to explore reasons underlying health workers' non-adherence. RESULTS: Health workers generally perceived AL as being tolerable and efficacious as compared to amodiaquine and sulphadoxine-pyremethamine. However, a number of key reasons for non-adherence were identified. Insufficient supply of AL was a major issue and hence fears of stock outs and concern about AL costs was an impediment to AL prescription. Training messages that contradicted the recommended guidelines also led to health worker non-adherence, compounded by a lack of follow-up supervision. In addition, the availability of non-recommended antimalarials such as amodiaquine caused prescription confusion. Some health workers and DHMT members maintained that shortage of staff had resulted in increased patient caseload affecting the delivery of the desirable quality of care and adherence to guidelines. CONCLUSION: The introduction of free efficacious ACTs in the public health sector in Kenya and other countries has major potential public health benefits for Africa. These may not be realized if provider prescription practices do not conform to the recommended treatment guidelines. It is essential that high quality training, drug supply and supervision work synergistically to ensure appropriate case management.

Gikandi PW, Noor AM, Gitonga CW, Ajanga AA, Snow RW. 2008. Access and barriers to measures targeted to prevent malaria in pregnancy in rural Kenya. Trop Med Int Health, 13 (2), pp. 208-217. | Show Abstract | Read more

OBJECTIVES: To evaluate barriers preventing pregnant women from using insecticide-treated nets (ITN) and intermittent presumptive treatment (IPT) with sulphadoxine-pyrimethamine (SP) 5 years after the launch of the national malaria strategy promoting these measures in Kenya. METHODS: All women aged 15-49 years were interviewed during a community survey in four districts between December 2006 and January 2007. Women pregnant in the last 12 months were asked about their age, parity, education, use of nets, ITN, antenatal care (ANC) services and sulphadoxine-pyrimethamine (SP) (overall and for IPT) during pregnancy. Homestead assets were recorded and used to develop a wealth index. Travel time to ANC clinics was computed using a geographic information system algorithm. Predictors of net and IPT use were defined using multivariate logistic regression. RESULTS: Overall 68% of pregnant women used a net; 52% used an ITN; 84% attended an ANC clinic at least once and 74% at least twice. Fifty-three percent of women took at least one dose of IPT-SP, however only 22% took two or more doses. Women from the least poor homesteads (OR = 2.53, 1.36-4.68) and those who used IPT services (OR = 1.73, 1.24-2.42) were more likely to sleep under any net. Women who used IPT were more likely to use ITNs (OR = 1.35, 1.03-1.77), while those who lived more than an hour from an ANC clinic were less likely (OR = 0.61, 0.46-0.81) to use ITN. Women with formal education (1.47, 1.01-2.17) and those who used ITN (OR: 1.68, 1.20-2.36) were more likely to have received at least one dose of IPT-SP. CONCLUSION: Although the use of ITN had increased 10-fold and the use of IPT fourfold since last measured in 2001, coverage remains low. Provider practices in the delivery of protective measures against malaria must change, supported by community awareness campaigns on the importance of mothers' use of IPT.

Chandramohan D, Shibuya K, Setel P, Cairncross S, Lopez AD, Murray CJ, Zaba B, Snow RW, Binka F. 2008. Should data from demographic surveillance systems be made more widely available to researchers? PLoS Med, 5 (2), pp. e57. | Show Abstract | Read more

BACKGROUND TO THE DEBATE: Demographic surveillance--the process of monitoring births, deaths, causes of deaths, and migration in a population over time--is one of the cornerstones of public health research, particularly in investigating and tackling health disparities. An international network of demographic surveillance systems (DSS) now operates, mostly in sub-Saharan Africa and Asia. Thirty-eight DSS sites are coordinated by the International Network for the Continuous Demographic Evaluation of Populations and Their Health (INDEPTH). In this debate, Daniel Chandramohan and colleagues argue that DSS data in the INDEPTH database should be made available to all researchers worldwide, not just to those within the INDEPTH Network. Basia Zaba and colleagues argue that the major obstacles to DSS sites sharing data are technical, managerial, and financial rather than proprietorial concerns about analysis and publication. This debate is further discussed in this month's Editorial.

Guerra CA, Gikandi PW, Tatem AJ, Noor AM, Smith DL, Hay SI, Snow RW. 2008. The limits and intensity of Plasmodium falciparum transmission: implications for malaria control and elimination worldwide. PLoS Med, 5 (2), pp. e38. | Show Abstract | Read more

BACKGROUND: The efficient allocation of financial resources for malaria control using appropriate combinations of interventions requires accurate information on the geographic distribution of malaria risk. An evidence-based description of the global range of Plasmodium falciparum malaria and its endemicity has not been assembled in almost 40 y. This paper aims to define the global geographic distribution of P. falciparum malaria in 2007 and to provide a preliminary description of its transmission intensity within this range. METHODS AND FINDINGS: The global spatial distribution of P. falciparum malaria was generated using nationally reported case-incidence data, medical intelligence, and biological rules of transmission exclusion, using temperature and aridity limits informed by the bionomics of dominant Anopheles vector species. A total of 4,278 spatially unique cross-sectional survey estimates of P. falciparum parasite rates were assembled. Extractions from a population surface showed that 2.37 billion people lived in areas at any risk of P. falciparum transmission in 2007. Globally, almost 1 billion people lived under unstable, or extremely low, malaria risk. Almost all P. falciparum parasite rates above 50% were reported in Africa in a latitude band consistent with the distribution of Anopheles gambiae s.s. Conditions of low parasite prevalence were also common in Africa, however. Outside of Africa, P. falciparum malaria prevalence is largely hypoendemic (less than 10%), with the median below 5% in the areas surveyed. CONCLUSIONS: This new map is a plausible representation of the current extent of P. falciparum risk and the most contemporary summary of the population at risk of P. falciparum malaria within these limits. For 1 billion people at risk of unstable malaria transmission, elimination is epidemiologically feasible, and large areas of Africa are more amenable to control than appreciated previously. The release of this information in the public domain will help focus future resources for P. falciparum malaria control and elimination.

Sipilanyambe N, Simon JL, Chanda P, Olumese P, Snow RW, Hamer DH. 2008. From chloroquine to artemether-lumefantrine: the process of drug policy change in Zambia. Malar J, 7 (1), pp. 25. | Show Abstract | Read more

BACKGROUND: Following the recognition that morbidity and mortality due to malaria had dramatically increased in the last three decades, in 2002 the government of Zambia reviewed its efforts to prevent and treat malaria. Convincing evidence of the failing efficacy of chloroquine resulted in the initiation of a process that eventually led to the development and implementation of a new national drug policy based on artemisinin-based combination therapy (ACT). METHODS: All published and unpublished documented evidence dealing with the antimalarial drug policy change was reviewed. These data were supplemented by the authors' observations of the policy change process. The information has been structured to capture the timing of events, the challenges encountered, and the resolutions reached in order to achieve implementation of the new treatment policy. RESULTS: A decision was made to change national drug policy to artemether-lumefantrine (AL) in the first quarter of 2002, with a formal announcement made in October 2002. During this period, efforts were undertaken to identify funding for the procurement of AL and to develop new malaria treatment guidelines, training materials, and plans for implementation of the policy. In order to avoid a delay in implementation, the policy change decision required a formal adoption within existing legislation. Starting with donated drug, a phased deployment of AL began in January 2003 with initial use in seven districts followed by scaling up to 28 districts in the second half of 2003 and then to all 72 districts countrywide in early 2004. CONCLUSION: Drug policy changes are not without difficulties and demand a sustained international financing strategy for them to succeed. The Zambian experience demonstrates the need for a harmonized national consensus among many stakeholders and a political commitment to ensure that new policies are translated into practice quickly. To guarantee effective policies requires more effort and recognition that this becomes a health system and not a drug issue. This case study attempts to document the successful experience of change to ACT in Zambia and provides a realistic overview of some of the painful experiences and important lessons learnt.

Cited:

25

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Chandramohan D, Shibuya K, Setel P, Cairncross S, Lopez AD, Murray CJL, Zaba B, Snow RW, Binka F. 2008. Should data from demographic surveillance systems be made more widely available to researchers? PLoS Medicine, 5 (2), pp. 0169-0173. | Show Abstract | Read more

Background to the debate: Demographic surveillance - the process of monitoring births, deaths, causes of deaths, and migration in a population over time - is one of the cornerstones of public health research, particularly in investigating and tackling health disparities. An international network of demographic surveillance systems (DSS) now operates, mostly in sub-Saharan Africa and Asia. Thirty-eight DSS sites are coordinated by the International Network for the Continuous Demographic Evaluation of Populations and Their Health (INDEPTH). In this debate, Daniel Chandramohan and colleagues argue that DSS data in the INDEPTH database should be made available to all researchers worldwide, not just to those within the INDEPTH Network. Basia Żaba and colleagues argue that the major obstacles to DSS sites sharing data are technical, managerial, and financial rather than proprietorial concerns about analysis and publication. This debate is further discussed in this month's Editorial. © 2008 Chandramohan et al.

Cited:

248

Scopus

Guerra CA, Gikandi PW, Tatem AJ, Noor AM, Smith DL, Hay SI, Snow RW. 2008. The limits and intensity of Plasmodium falciparum transmission: Implications for malaria control and elimination worldwide PLoS Medicine, 5 (2), pp. 0300-0311. | Show Abstract | Read more

Background: The efficient allocation of financial resources for malaria control using appropriate combinations of interventions requires accurate information on the geographic distribution of malaria risk. An evidence-based description of the global range of Plasmodium falciparum malaria and its endemicity has not been assembled in almost 40 y. This paper aims to define the global geographic distribution of P. falciparum malaria in 2007 and to provide a preliminary description of its transmission intensity within this range. Methods and Findings: The global spatial distribution of P. falciparum malaria was generated using nationally reported case-incidence data, medical intelligence, and biological rules of transmission exclusion, using temperature and aridity limits informed by the bionomics of dominant Anopheles vector species. A total of 4,278 spatially unique cross-sectional survey estimates of P. falciparum parasite rates were assembled. Extractions from a population surface showed that 2.37 billion people lived in areas at any risk of P. falciparum transmission in 2007. Globally, almost 1 billion people lived under unstable, or extremely low, malaria risk. Almost all P. falciparum parasite rates above 50% were reported in Africa in a latitude band consistent with the distribution of Anopheles gambiae s.s. Conditions of low parasite prevalence were also common in Africa, however. Outside of Africa, P. falciparum malaria prevalence is largely hypoendemic (less than 10%), with the median below 5% in the areas surveyed. Conclusions: This new map is a plausible representation of the current extent of P. falciparum risk and the most contemporary summary of the population at risk of P. falciparum malaria within these limits. For 1 billion people at risk of unstable malaria transmission, elimination is epidemiologically feasible, and large areas of Africa are more amenable to control than appreciated previously. The release of this information in the public domain will help focus future resources for P. falciparum malaria control and elimination. © 2008 Guerra et al.

Zurovac D, Njogu J, Akhwale W, Hamer DH, Snow RW. 2008. Translation of artemether-lumefantrine treatment policy into paediatric clinical practice: an early experience from Kenya. Trop Med Int Health, 13 (1), pp. 99-107. | Show Abstract | Read more

OBJECTIVE: To describe the quality of outpatient paediatric malaria case-management approximately 4-6 months after artemether-lumefantrine (AL) replaced sulfadoxine-pyrimethamine (SP) as the nationally recommended first-line therapy in Kenya. METHODS: Cross-sectional survey at all government facilities in four Kenyan districts. Main outcome measures were health facility and health worker readiness to implement AL policy; quality of antimalarial prescribing, counselling and drug dispensing in comparison with national guidelines; and factors influencing AL prescribing for treatment of uncomplicated malaria in under-fives. RESULTS: We evaluated 193 facilities, 227 health workers and 1533 sick-child consultations. Health facility and health worker readiness was variable: 89% of facilities stocked AL, 55% of health workers had access to guidelines, 46% received in-service training on AL and only 1% of facilities had AL wall charts. Of 940 children who needed AL treatment, AL was prescribed for 26%, amodiaquine for 39%, SP for 4%, various other antimalarials for 8% and 23% of children left the facility without any antimalarial prescribed. When AL was prescribed, 92% of children were prescribed correct weight-specific dose. AL dispensing and counselling tasks were variably performed. Higher health worker's cadre, in-service training including AL use, positive malaria test, main complaint of fever and high temperature were associated with better prescribing. CONCLUSIONS: Changes in clinical practices at the point of care might take longer than anticipated. Delivery of successful interventions and their scaling up to increase coverage are important during this process; however, this should be accompanied by rigorous research evaluations, corrective actions on existing interventions and testing cost-effectiveness of novel interventions capable of improving and maintaining health worker performance and health systems to deliver artemisinin-based combination therapy in Africa.

Noor AM, Alegana VA, Gething PW, Tatem AJ, Snow RW. 2008. Using remotely sensed night-time light as a proxy for poverty in Africa. Popul Health Metr, 6 (1), pp. 5. | Show Abstract | Read more

BACKGROUND: Population health is linked closely to poverty. To assess the effectiveness of health interventions it is critical to monitor the spatial and temporal changes in the health indicators of populations and outcomes across varying levels of poverty. Existing measures of poverty based on income, consumption or assets are difficult to compare across geographic settings and are expensive to construct. Remotely sensed data on artificial night time lights (NTL) have been shown to correlate with gross domestic product in developed countries. METHODS: Using national household survey data, principal component analysis was used to compute asset-based poverty indices from aggregated household asset variables at the Administrative 1 level (n = 338) in 37 countries in Africa. Using geographical information systems, mean brightness of and distance to NTL pixels and proportion of area covered by NTL were computed for each Administrative1 polygon. Correlations and agreement of asset-based indices and the three NTL metrics were then examined in both continuous and ordinal forms. RESULTS: At the Administrative 1 level all the NTL metrics distinguished between the most poor and least poor quintiles with greater precision compared to intermediate quintiles. The mean brightness of NTL, however, had the highest correlation coefficient with the asset-based wealth index in continuous (Pearson correlation = 0.64, p < 0.01) and ordinal (Spearman correlation = 0.79, p < 0.01; Kappa = 0.64) forms. CONCLUSION: Metrics of the brightness of NTL data offer a robust and inexpensive alternative to asset-based poverty indices derived from survey data at the Administrative 1 level in Africa. These could be used to explore economic inequity in health outcomes and access to health interventions at sub-national levels where household assets data are not available at the required resolution.

Gething PW, Noor AM, Goodman CA, Gikandi PW, Hay SI, Sharif SK, Atkinson PM, Snow RW. 2007. Information for decision making from imperfect national data: tracking major changes in health care use in Kenya using geostatistics. BMC Med, 5 (1), pp. 37. | Show Abstract | Read more

BACKGROUND: Most Ministries of Health across Africa invest substantial resources in some form of health management information system (HMIS) to coordinate the routine acquisition and compilation of monthly treatment and attendance records from health facilities nationwide. Despite the expense of these systems, poor data coverage means they are rarely, if ever, used to generate reliable evidence for decision makers. One critical weakness across Africa is the current lack of capacity to effectively monitor patterns of service use through time so that the impacts of changes in policy or service delivery can be evaluated. Here, we present a new approach that, for the first time, allows national changes in health service use during a time of major health policy change to be tracked reliably using imperfect data from a national HMIS. METHODS: Monthly attendance records were obtained from the Kenyan HMIS for 1 271 government-run and 402 faith-based outpatient facilities nationwide between 1996 and 2004. A space-time geostatistical model was used to compensate for the large proportion of missing records caused by non-reporting health facilities, allowing robust estimation of monthly and annual use of services by outpatients during this period. RESULTS: We were able to reconstruct robust time series of mean levels of outpatient utilisation of health facilities at the national level and for all six major provinces in Kenya. These plots revealed reliably for the first time a period of steady nationwide decline in the use of health facilities in Kenya between 1996 and 2002, followed by a dramatic increase from 2003. This pattern was consistent across different causes of attendance and was observed independently in each province. CONCLUSION: The methodological approach presented can compensate for missing records in health information systems to provide robust estimates of national patterns of outpatient service use. This represents the first such use of HMIS data and contributes to the resurrection of these hugely expensive but underused systems as national monitoring tools. Applying this approach to Kenya has yielded output with immediate potential to enhance the capacity of decision makers in monitoring nationwide patterns of service use and assessing the impact of changes in health policy and service delivery.

Brooker S, Akhwale W, Pullan R, Estambale B, Clarke SE, Snow RW, Hotez PJ. 2007. Epidemiology of plasmodium-helminth co-infection in Africa: populations at risk, potential impact on anemia, and prospects for combining control. Am J Trop Med Hyg, 77 (6 Suppl), pp. 88-98. | Show Abstract

Human co-infection with Plasmodium falciparum and helminths is ubiquitous throughout Africa, although its public health significance remains a topic for which there are many unknowns. In this review, we adopted an empirical approach to studying the geography and epidemiology of co-infection and associations between patterns of co-infection and hemoglobin in different age groups. Analysis highlights the extensive geographic overlap between P. falciparum and the major human helminth infections in Africa, with the population at coincident risk of infection greatest for hookworm. Age infection profiles indicate that school-age children are at the highest risk of co-infection, and re-analysis of existing data suggests that co-infection with P. falciparum and hookworm has an additive impact on hemoglobin, exacerbating anemia-related malarial disease burden. We suggest that both school-age children and pregnant women--groups which have the highest risk of anemia--would benefit from an integrated approach to malaria and helminth control.

Okiro EA, Hay SI, Gikandi PW, Sharif SK, Noor AM, Peshu N, Marsh K, Snow RW. 2007. The decline in paediatric malaria admissions on the coast of Kenya. Malar J, 6 (1), pp. 151. | Show Abstract | Read more

BACKGROUND: There is only limited information on the health impact of expanded coverage of malaria control and preventative strategies in Africa. METHODS: Paediatric admission data were assembled over 8.25 years from three District Hospitals; Kilifi, Msambweni and Malindi, situated along the Kenyan Coast. Trends in monthly malaria admissions between January 1999 and March 2007 were analysed using several time-series models that adjusted for monthly non-malaria admission rates and the seasonality and trends in rainfall. RESULTS: Since January 1999 paediatric malaria admissions have significantly declined at all hospitals. This trend was observed against a background of rising or constant non-malaria admissions and unaffected by long-term rainfall throughout the surveillance period. By March 2007 the estimated proportional decline in malaria cases was 63% in Kilifi, 53% in Kwale and 28% in Malindi. Time-series models strongly suggest that the observed decline in malaria admissions was a result of malaria-specific control efforts in the hospital catchment areas. CONCLUSION: This study provides evidence of a changing disease burden on the Kenyan coast and that the most parsimonious explanation is an expansion in the coverage of interventions such as the use of insecticide-treated nets and the availability of anti-malarial medicines. While specific attribution to intervention coverage cannot be computed what is clear is that this area of Kenya is experiencing a malaria epidemiological transition.

Smith DL, Guerra CA, Snow RW, Hay SI. 2007. Standardizing estimates of the Plasmodium falciparum parasite rate. Malar J, 6 (1), pp. 131. | Show Abstract | Read more

BACKGROUND: The Plasmodium falciparum parasite rate (PfPR) is a commonly reported index of malaria transmission intensity. PfPR rises after birth to a plateau before declining in older children and adults. Studies of populations with different age ranges generally report average PfPR, so age is an important source of heterogeneity in reported PfPR data. This confounds simple comparisons of PfPR surveys conducted at different times or places. METHODS: Several algorithms for standardizing PfPR were developed using 21 studies that stratify in detail PfPR by age. An additional 121 studies were found that recorded PfPR from the same population over at least two different age ranges; these paired estimates were used to evaluate these algorithms. The best algorithm was judged to be the one that described most of the variance when converting the PfPR pairs from one age-range to another. RESULTS: The analysis suggests that the relationship between PfPR and age is predictable across the observed range of malaria endemicity. PfPR reaches a peak after about two years and remains fairly constant in older children until age ten before declining throughout adolescence and adulthood. The PfPR pairs were poorly correlated; using one to predict the other would explain only 5% of the total variance. By contrast, the PfPR predicted by the best algorithm explained 72% of the variance. CONCLUSION: The PfPR in older children is useful for standardization because it has good biological, epidemiological and statistical properties. It is also historically consistent with the classical categories of hypoendemic, mesoendemic and hyperendemic malaria. This algorithm provides a reliable method for standardizing PfPR for the purposes of comparing studies and mapping malaria endemicity. The scripts for doing so are freely available to all.

Fegan GW, Noor AM, Akhwale WS, Cousens S, Snow RW. 2007. Effect of expanded insecticide-treated bednet coverage on child survival in rural Kenya: a longitudinal study. Lancet, 370 (9592), pp. 1035-1039. | Show Abstract | Read more

BACKGROUND: The potential of insecticide-treated bednets (ITNs) to contribute to child survival has been well documented in randomised controlled trials. ITN coverage has increased rapidly in Kenya from 7% in 2004 to 67% in 2006. We aimed to assess the extent to which this investment has led to improvements in child survival. METHODS: A dynamic cohort of about 3500 children aged 1-59 months were enumerated three times at yearly intervals in 72 rural clusters located in four districts of Kenya. The effect of ITN use on mortality was assessed with Poisson regression to take account of potential effect-modifying and confounding covariates. FINDINGS: 100 children died over 2 years. Overall mortality rates were much the same in the first and second years of the study (14.5 per 1000 person-years in the first year and 15.4 per 1000 person-years in the second). After adjustment for age, time period, and a number of other possible confounding variables, ITN use was associated with a 44% reduction in mortality (mortality rate ratio 0.56, 95% CI 0.33-0.96; p=0.04). This level of protection corresponds to about seven deaths averted for every 1000 ITNs distributed. INTERPRETATION: A combined approach of social marketing followed by mass free distribution of ITNs translated into child survival effects that are comparable with those seen in previous randomised controlled trials.

Noor AM, Amin AA, Akhwale WS, Snow RW. 2007. Increasing coverage and decreasing inequity in insecticide-treated bed net use among rural Kenyan children. PLoS Med, 4 (8), pp. e255. | Show Abstract | Read more

BACKGROUND: Inexpensive and efficacious interventions that avert childhood deaths in sub-Saharan Africa have failed to reach effective coverage, especially among the poorest rural sectors. One particular example is insecticide-treated bed nets (ITNs). In this study, we present repeat observations of ITN coverage among rural Kenyan homesteads exposed at different times to a range of delivery models, and assess changes in coverage across socioeconomic groups. METHODS AND FINDINGS: We undertook a study of annual changes in ITN coverage among a cohort of 3,700 children aged 0-4 y in four districts of Kenya (Bondo, Greater Kisii, Kwale, and Makueni) annually between 2004 and 2006. Cross-sectional surveys of ITN coverage were undertaken coincidentally with the incremental availability of commercial sector nets (2004), the introduction of heavily subsidized nets through clinics (2005), and the introduction of free mass distributed ITNs (2006). The changing prevalence of ITN coverage was examined with special reference to the degree of equity in each delivery approach. ITN coverage was only 7.1% in 2004 when the predominant source of nets was the commercial retail sector. By the end of 2005, following the expansion of heavily subsidized clinic distribution system, ITN coverage rose to 23.5%. In 2006 a large-scale mass distribution of ITNs was mounted providing nets free of charge to children, resulting in a dramatic increase in ITN coverage to 67.3%. With each subsequent survey socioeconomic inequity in net coverage sequentially decreased: 2004 (most poor [2.9%] versus least poor [15.6%]; concentration index 0.281); 2005 (most poor [17.5%] versus least poor [37.9%]; concentration index 0.131), and 2006 with near-perfect equality (most poor [66.3%] versus least poor [66.6%]; concentration index 0.000). The free mass distribution method achieved highest coverage among the poorest children, the highly subsidised clinic nets programme was marginally in favour of the least poor, and the commercial social marketing favoured the least poor. CONCLUSIONS: Rapid scaling up of ITN coverage among Africa's poorest rural children can be achieved through mass distribution campaigns. These efforts must form an important adjunct to regular, routine access to ITNs through clinics, and each complimentary approach should aim to make this intervention free to clients to ensure equitable access among those least able to afford even the cost of a heavily subsidized net.

Baird JK, Snow RW. 2007. Acquired immunity in a holoendemic setting of Plasmodium falciparum and p. Vivax malaria. Am J Trop Med Hyg, 76 (6), pp. 995-996.

Amin AA, Zurovac D, Kangwana BB, Greenfield J, Otieno DN, Akhwale WS, Snow RW. 2007. The challenges of changing national malaria drug policy to artemisinin-based combinations in Kenya. Malar J, 6 (1), pp. 72. | Show Abstract | Read more

BACKGROUND: Sulphadoxine/sulphalene-pyrimethamine (SP) was adopted in Kenya as first line therapeutic for uncomplicated malaria in 1998. By the second half of 2003, there was convincing evidence that SP was failing and had to be replaced. Despite several descriptive investigations of policy change and implementation when countries moved from chloroquine to SP, the different constraints of moving to artemisinin-based combination therapy (ACT) in Africa are less well documented. METHODS: A narrative description of the process of anti-malarial drug policy change, financing and implementation in Kenya is assembled from discussions with stakeholders, reports, newspaper articles, minutes of meetings and email correspondence between actors in the policy change process. The narrative has been structured to capture the timing of events, the difficulties and hurdles faced and the resolutions reached to the final implementation of a new treatment policy. RESULTS: Following a recognition that SP was failing there was a rapid technical appraisal of available data and replacement options resulting in a decision to adopt artemether-lumefantrine (AL) as the recommended first-line therapy in Kenya, announced in April 2004. Funding requirements were approved by the Global Fund to Fight AIDS, Tuberculosis and Malaria (GFATM) and over 60 million US$ were agreed in principle in July 2004 to procure AL and implement the policy change. AL arrived in Kenya in May 2006, distribution to health facilities began in July 2006 coincidental with cascade in-service training in the revised national guidelines. Both training and drug distribution were almost complete by the end of 2006. The article examines why it took over 32 months from announcing a drug policy change to completing early implementation. Reasons included: lack of clarity on sustainable financing of an expensive therapeutic for a common disease, a delay in release of funding, a lack of comparative efficacy data between AL and amodiaquine-based alternatives, a poor dialogue with pharmaceutical companies with a national interest in antimalarial drug supply versus the single sourcing of AL and complex drug ordering, tendering and procurement procedures. CONCLUSION: Decisions to abandon failing monotherapy in favour of ACT for the treatment of malaria can be achieved relatively quickly. Future policy changes in Africa should be carefully prepared for a myriad of financial, political and legislative issues that might limit the rapid translation of drug policy change into action.

Hamer DH, Ndhlovu M, Zurovac D, Fox M, Yeboah-Antwi K, Chanda P, Sipilinyambe N, Simon JL, Snow RW. 2007. Improved diagnostic testing and malaria treatment practices in Zambia. JAMA, 297 (20), pp. 2227-2231. | Show Abstract | Read more

CONTEXT: Improving the accuracy of malaria diagnosis with rapid antigen-detection diagnostic tests (RDTs) has been proposed as an approach for reducing overtreatment of malaria in the current era of widespread implementation of artemisinin-based combination therapy in sub-Saharan Africa. OBJECTIVE: To assess the association between use of microscopy and RDT and the prescription of antimalarials. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional, cluster sample survey, carried out between March and May 2006, of all outpatients treated during 1 working day at government and mission health facilities in 4 sentinel districts in Zambia. MAIN OUTCOME MEASURE: Proportions of patients undergoing malaria diagnostic procedures and receiving antimalarial treatment. RESULTS: Seventeen percent of the 104 health facilities surveyed had functional microscopy, 63% had RDTs available, and 73% had 1 or more diagnostics available. Of patients with fever (suspected malaria), 27.8% (95% confidence interval [CI], 13.1%-42.5%) treated in health facilities with malaria diagnostics were tested and 44.6% had positive test results. Of patients with negative blood smear results, 58.4% (95% CI, 36.7%-80.2%) were prescribed an antimalaria drug, as were 35.5% (95% CI, 16.0%-55.0%) of those with a negative RDT result. Of patients with fever who did not have diagnostic tests done, 65.9% were also prescribed antimalarials. In facilities with artemether-lumefantrine in stock, this antimalarial was prescribed to a large proportion of febrile patients with a positive diagnostic test result (blood smear, 75.0% [95% CI, 51.7%-98.3%]; RDT, 70.4% [95% CI, 39.3%-100.0%]), but also to some of those with a negative diagnostic test result (blood smear, 30.4% [95% CI, 8.0%-52. 9%]; RDT, 26.7% [95% CI, 5.7%-47.7%]). CONCLUSIONS: Despite efforts to expand the provision of malaria diagnostics in Zambia, they continue to be underused and patients with negative test results frequently receive antimalarials. Provision of new tools to reduce inappropriate use of new expensive antimalarial treatments must be accompanied by a major change in clinical treatment of patients presenting with fever but lacking evidence of malaria infection.

Cox J, Hay SI, Abeku TA, Checchi F, Snow RW. 2007. The uncertain burden of Plasmodium falciparum epidemics in Africa. Trends Parasitol, 23 (4), pp. 142-148. | Show Abstract | Read more

Although the control of malaria epidemics has been a priority for the World Health Organization and other agencies for many years, surprisingly little is known about the public health burden of these epidemics. Here, we evaluate the available evidence of the morbidity and mortality impacts of individual epidemics in Africa and examine the problems associated with using these data to estimate the average annual burden of epidemics at national and continental scales. We argue that conventional approaches that are used to assess the burden of epidemics are inadequate, and outline the future steps that are required to produce estimates that are more accurate.

Zurovac D, Ndhlovu M, Sipilanyambe N, Chanda P, Hamer DH, Simon JL, Snow RW. 2007. Paediatric malaria case-management with artemether-lumefantrine in Zambia: a repeat cross-sectional study. Malar J, 6 (1), pp. 31. | Show Abstract | Read more

BACKGROUND: Zambia was the first African country to change national antimalarial treatment policy to artemisinin-based combination therapy--artemether-lumefantrine. An evaluation during the early implementation phase revealed low readiness of health facilities and health workers to deliver artemether-lumefantrine, and worryingly suboptimal treatment practices. Improvements in the case-management of uncomplicated malaria two years after the initial evaluation and three years after the change of policy in Zambia are reported. METHODS: Data collected during the health facility surveys undertaken in 2004 and 2006 at all outpatient departments of government and mission facilities in four Zambian districts were analysed. The surveys were cross-sectional, using a range of quality of care assessment methods. The main outcome measures were changes in health facility and health worker readiness to deliver artemether-lumefantrine, and changes in case-management practices for children below five years of age presenting with uncomplicated malaria as defined by national guidelines. RESULTS: In 2004, 94 health facilities, 103 health workers and 944 consultations for children with uncomplicated malaria were evaluated. In 2006, 104 facilities, 135 health workers and 1125 consultations were evaluated using the same criteria of selection. Health facility and health worker readiness improved from 2004 to 2006: availability of artemether-lumefantrine from 51% (48/94) to 60% (62/104), presence of artemether-lumefantrine dosage wall charts from 20% (19/94) to 75% (78/104), possession of guidelines from 58% (60/103) to 92% (124/135), and provision of in-service training from 25% (26/103) to 41% (55/135). The proportions of children with uncomplicated malaria treated with artemether-lumefantrine also increased from 2004 to 2006: from 1% (6/527) to 27% (149/552) in children weighing 5 to 9 kg, and from 11% (42/394) to 42% (231/547) in children weighing 10 kg or more. In both weight groups and both years, 22% (441/2020) of children with uncomplicated malaria were not prescribed any antimalarial drug. CONCLUSION: Although significant improvements in malaria case-management have occurred over two years in Zambia, the quality of treatment provided at the point of care is not yet optimal. Strengthening weak health systems and improving the delivery of effective interventions should remain high priority in all countries implementing new treatment policies for malaria.

Amin AA, Walley T, Kokwaro GO, Winstanley PA, Snow RW. 2007. Reconciling national treatment policies and drug regulation in Kenya. Health Policy Plan, 22 (2), pp. 111-112. | Read more

Smith DL, McKenzie FE, Snow RW, Hay SI. 2007. Revisiting the basic reproductive number for malaria and its implications for malaria control. PLoS Biol, 5 (3), pp. e42. | Show Abstract | Read more

The prospects for the success of malaria control depend, in part, on the basic reproductive number for malaria, R0. Here, we estimate R0 in a novel way for 121 African populations, and thereby increase the number of R0 estimates for malaria by an order of magnitude. The estimates range from around one to more than 3,000. We also consider malaria transmission and control in finite human populations, of size H. We show that classic formulas approximate the expected number of mosquitoes that could trace infection back to one mosquito after one parasite generation, Z0(H), but they overestimate the expected number of infected humans per infected human, R0(H). Heterogeneous biting increases R0 and, as we show, Z0(H), but we also show that it sometimes reduces R0(H); those who are bitten most both infect many vectors and absorb infectious bites. The large range of R0 estimates strongly supports the long-held notion that malaria control presents variable challenges across its transmission spectrum. In populations where R0 is highest, malaria control will require multiple, integrated methods that target those who are bitten most. Therefore, strategic planning for malaria control should consider R0, the spatial scale of transmission, human population density, and heterogeneous biting.

Cited:

80

Scopus

Guerra CA, Hay SI, Lucioparedes LS, Gikandi PW, Tatem AJ, Noor AM, Snow RW. 2007. Assembling a global database of malaria parasite prevalence for the Malaria Atlas Project MALARIA JOURNAL, 6 | Show Abstract | Read more

Background. Open access to databases of information generated by the research community can synergize individual efforts and are epitomized by the genome mapping projects. Open source models for outputs of scientific research funded by tax-payers and charities are becoming the norm. This has yet to be extended to malaria epidemiology and control. Methods. The exhaustive searches and assembly process for a global database of malaria parasite prevalence as part of the Malaria Atlas Project (MAP) are described. The different data sources visited and how productive these were in terms of availability of parasite rate (PR) data are presented, followed by a description of the methods used to assemble a relational database and an associated geographic information system. The challenges facing spatial data assembly from varied sources are described in an effort to help inform similar future applications. Results. At the time of writing, the MAP database held 3,351 spatially independent PR estimates from community surveys conducted since 1985. These include 3,036 Plasmodium falciparum and 1,347 Plasmodium vivax estimates in 74 countries derived from 671 primary sources. More than half of these data represent malaria prevalence after the year 2000. Conclusion. This database will help refine maps of the global spatial limits of malaria and be the foundation for the development of global malaria endemicity models as part of MAP. A widespread application of these maps is envisaged. The data compiled and the products generated by MAP are planned to be released in June 2009 to facilitate a more informed approach to global malaria control. © 2007 Guerra et al; licensee BioMed Central Ltd.

Guerra CA, Hay SI, Lucioparedes LS, Gikandi PW, Tatem AJ, Noor AM, Snow RW. 2007. Assembling a global database of malaria parasite prevalence for the Malaria Atlas Project. Malar J, 6 pp. 17. | Show Abstract | Read more

BACKGROUND: Open access to databases of information generated by the research community can synergize individual efforts and are epitomized by the genome mapping projects. Open source models for outputs of scientific research funded by tax-payers and charities are becoming the norm. This has yet to be extended to malaria epidemiology and control. METHODS: The exhaustive searches and assembly process for a global database of malaria parasite prevalence as part of the Malaria Atlas Project (MAP) are described. The different data sources visited and how productive these were in terms of availability of parasite rate (PR) data are presented, followed by a description of the methods used to assemble a relational database and an associated geographic information system. The challenges facing spatial data assembly from varied sources are described in an effort to help inform similar future applications. RESULTS: At the time of writing, the MAP database held 3,351 spatially independent PR estimates from community surveys conducted since 1985. These include 3,036 Plasmodium falciparum and 1,347 Plasmodium vivax estimates in 74 countries derived from 671 primary sources. More than half of these data represent malaria prevalence after the year 2000. CONCLUSION: This database will help refine maps of the global spatial limits of malaria and be the foundation for the development of global malaria endemicity models as part of MAP. A widespread application of these maps is envisaged. The data compiled and the products generated by MAP are planned to be released in June 2009 to facilitate a more informed approach to global malaria control.

Cited:

152

Scopus

Smith DL, McKenzie FE, Snow RW, Hay SI. 2007. Revisiting the basic reproductive number for malaria and its implications for malaria control PLoS Biology, 5 (3), pp. 0531-0542. | Show Abstract | Read more

The prospects for the success of malaria control depend, in part, on the basic reproductive number for malaria, R0. Here, we estimate R 0 in a novel way for 121 African populations, and thereby increase the number of R0 estimates for malaria by an order of magnitude. The estimates range from around one to more than 3,000. We also consider malaria transmission and control in finite human populations, of size H. We show that classic formulas approximate the expected number of mosquitoes that could trace infection back to one mosquito after one parasite generation, Z0(H), but they overestimate the expected number of infected humans per infected human, R0(H). Heterogeneous biting increases R0 and, as we show, Z0(H), but we also show that it sometimes reduces R0(H); those who are bitten most both infect many vectors and absorb infectious bites. The large range of R0 estimates strongly supports the long-held notion that malaria control presents variable challenges across its transmission spectrum. In populations where R0 is highest, malaria control will require multiple, integrated methods that target those who are bitten most. Therefore, strategic planning for malaria control should consider R0, the spatial scale of transmission, human population density, and heterogeneous biting.

Larson BA, Amin AA, Noor AM, Zurovac D, Snow RW. 2006. The cost of uncomplicated childhood fevers to Kenyan households: implications for reaching international access targets. BMC Public Health, 6 pp. 314. | Show Abstract | Read more

BACKGROUND: Fever is the clinical hallmark of malaria disease. The Roll Back Malaria (RBM) movement promotes prompt, effective treatment of childhood fevers as a key component to achieving its optimistic mortality reduction goals by 2010. A neglected concern is how communities will access these new medicines promptly and the costs to poor households when they are located in rural areas distant to health services. METHODS: We assemble data developed between 2001 and 2002 in Kenya to describe treatment choices made by rural households to treat a child's fever and the related costs to households. Using a cost-of-illness approach, we estimate the expected cost of a childhood fever to Kenyan households in 2002. We develop two scenarios to explore how expected costs to households would change if more children were treated at a health care facility with an effective antimalarial within 48 hours of fever onset. RESULTS: 30% of uncomplicated fevers were managed at home with modern medicines, 38% were taken to a health care facility (HCF), and 32% were managed at home without the use of modern medicines. Direct household cash expenditures were estimated at $0.44 per fever, while the total expected cost to households (cash and time) of an uncomplicated childhood fever is estimated to be $1.91. An estimated mean of 1.42 days of caretaker time devoted to each fever accounts for the majority of household costs of managing fevers. The aggregate cost to Kenyan households of managing uncomplicated childhood fevers was at least $96 million in 2002, equivalent to 1.00% of the Kenyan GDP. Fewer than 8% of all fevers were treated with an antimalarial drug within 24 hours of fever onset, while 17.5% were treated within 48 hours at a HCF. To achieve an increase from 17.5% to 33% of fevers treated with an antimalarial drug within 48 hours at a HCF (Scenario 1), children already being taken to a HCF would need to be taken earlier. Under this scenario, direct cash expenditures would not change, and total household costs would fall slightly to $1.86 because caretakers also save time with prompt treatment if the child has malaria. CONCLUSION: The management of uncomplicated childhood fevers imposes substantial costs on Kenyan households. Achieving substantial improvements in the numbers of fevers treated within 48 hours at a HCF with an effective antimalarial drug (Scenario 1) will not impose additional costs on households. Achieving additional improvements in fevers treated promptly at a HCF (Scenario 2) will impose additional costs on some households roughly equal to average cash expenses for transportation to a HCF. Additional financing mechanisms that further reduce the costs of accessing care at a HCF and/or that make artemisinin-based combination therapies (ACTs) accessible for home management need to be developed and evaluated as a top priority.

Hay SI, Snow RW. 2006. The malaria Atlas Project: developing global maps of malaria risk. PLoS Med, 3 (12), pp. e473. | Read more

Brooker S, Clements AC, Hotez PJ, Hay SI, Tatem AJ, Bundy DA, Snow RW. 2006. The co-distribution of Plasmodium falciparum and hookworm among African schoolchildren. Malar J, 5 pp. 99. | Show Abstract | Read more

BACKGROUND: Surprisingly little is known about the geographical overlap between malaria and other tropical diseases, including helminth infections. This is despite the potential public health importance of co-infection and synergistic opportunities for control. METHODS: Statistical models are presented that predict the large-scale distribution of hookworm in sub-Saharan Africa (SSA), based on the relationship between prevalence of infection among schoolchildren and remotely sensed environmental variables. Using a climate-based spatial model of the transmission potential for Plasmodium falciparum malaria, adjusted for urbanization, the spatial congruence of populations at coincident risk of infection is determined. RESULTS: The model of hookworm indicates that the infection is widespread throughout Africa and that, of the 179.3 million school-aged children who live on the continent, 50.0 (95% CI: 48.9-51.1) million (27.9% of total population) are infected with hookworm and 45.1 (95% CI: 43.9-46) million are estimated to be at risk of coincident infection. CONCLUSION: Malaria and hookworm infection are widespread throughout SSA and over a quarter of school-aged children in sub-Saharan Africa appear to be at risk of coincident infection and thus at enhanced risk of clinical disease. The results suggest that the control of parasitic helminths and of malaria in school children could be viewed as essential co-contributors to promoting the health of schoolchildren.

Tatem AJ, Snow RW, Hay SI. 2006. Mapping the environmental coverage of the INDEPTH demographic surveillance system network in rural Africa. Trop Med Int Health, 11 (8), pp. 1318-1326. | Show Abstract | Read more

OBJECTIVES: The INDEPTH DSS network was founded in 1998 to provide an international network of field sites for continuous demographic evaluation of populations and their health. Results from the network have been used to derive estimates of mortality, morbidity and health equity. Spatial extrapolation and logical summaries of these findings are dependent on the network covering a representative sample of the environments in a region and their interrelationships being known. Here, we investigate how comprehensive is the coverage of the network of rural DSS sites in Africa in terms of the range of ecological zones found across the continent. METHODS: We used satellite imagery to define an environmental signature for each INDEPTH DSS site, and then calculate Euclidean distances from these signatures to the environmental signatures of every image pixel across Africa. These distances were then mapped and a gridded population surface used to mask uninhabited areas to illustrate the extent of the environmental coverage of the INDEPTH network. Environmental similarities between DSS sites were also calculated, hierarchically clustered and visualized as a dendrogram to examine between site relationships. Finally, an ecozonation of Africa was used to analyse the per-ecozone environmental similarity of the INDEPTH DSS network. RESULTS AND CONCLUSIONS: The current INDEPTH DSS network in Africa spans all the major environmental zones, but within these zones the environmental coverage of the network varies. These variations were mapped by ecozone. These maps provide valuable information in determining the confidence with which relationships derived from rural INDEPTH DSS sites can be extended to other areas. The results also indicate suites of sites that form environmentally cohesive groups and from which data can be logically summarized. Finally, the results highlight areas where the location of new INDEPTH DSS sites would increase significantly the environmental coverage of the network.

Guerra CA, Snow RW, Hay SI. 2006. Mapping the global extent of malaria in 2005. Trends Parasitol, 22 (8), pp. 353-358. | Show Abstract | Read more

Guidelines for travellers on malaria chemoprophylaxis, the altitude limits of dominant vector species, climate suitability for malaria transmission and human population density thresholds have been used to map the crude spatial limits of Plasmodium falciparum and Plasmodium vivax transmission on a global scale. These maps suggest that 2.510 and 2.596 billion people were at possible risk of transmission of P. falciparum and P. vivax, respectively, in 2005. Globally, 75 per cent of humans who are exposed to P. falciparum risk live in only ten countries.

Zurovac D, Larson BA, Akhwale W, Snow RW. 2006. The financial and clinical implications of adult malaria diagnosis using microscopy in Kenya. Trop Med Int Health, 11 (8), pp. 1185-1194. | Show Abstract | Read more

OBJECTIVE: A recent observational study undertaken at 17 health facilities with microscopy in Kenya revealed that potential benefits of malaria microscopy are not realized because of irrational clinical practices and the low accuracy of routine microscopy. Using these data, we modelled financial and clinical implications of revised clinical practices and improved accuracy of malaria microscopy among adult outpatients under the artemether-lumefantrine (AL) treatment policy for uncomplicated malaria in Kenya. METHODS: The cost of AL, antibiotics and malaria microscopy and the expected number of malaria diagnosis errors were estimated per 1,000 adult outpatients presenting at a facility with microscopy under three scenarios: (1) current clinical practice and accuracy of microscopy (option A), (2) revised clinical practice with current accuracy of microscopy (option B) and (3) revised clinical practice with improved accuracy of microscopy (option C). Revised clinical practice was defined as performing a blood slide for all febrile adults and prescribing antimalarial treatment only for positive results. Improved accuracy of routine microscopy was defined as 90% sensitivity and specificity. In the sensitivity analysis, the implications of changes in the cost of drugs and malaria microscopy and changes in background malaria prevalence were examined for each option. RESULTS: The costs of AL, antibiotics and malaria microscopy decreased from 2,154 dollars under option A to 1,254 dollars under option B and 892 dollars under option C. Of the cost savings from option C, 72% was from changes in clinical practice, while 28% was from improvements in the accuracy of microscopy. Compared with 638 malaria overdiagnosis errors per 1,000 adults under option A, 375 and 548 fewer overdiagnosis errors were estimated, respectively, under options B and C. At the same time, the number of missed malaria diagnoses remained generally low under all options. Sensitivity analysis showed that both options B and C are robust to a wide range of assumptions on the costs of drugs, costs of blood slides and malaria prevalence. CONCLUSIONS: Even with the imperfect microscopy conditions at Kenyan facilities, implementation of revised clinical practice (option B) would substantially reduce the costs and errors from malaria overdiagnosis. Additional interventions to improve the accuracy of microscopy (option C) can achieve further benefits; however, improved microscopy in the absence of revised clinical practice is unlikely to generate significant cost savings. Revision of guidelines to state explicitly age-specific indications for the use and interpretation of malaria microscopy is urgently needed. Further prospective studies are required to evaluate the effectiveness and costs of interventions to improve clinical practice and the accuracy of malaria microscopy.

Gething PW, Noor AM, Gikandi PW, Ogara EA, Hay SI, Nixon MS, Snow RW, Atkinson PM. 2006. Improving imperfect data from health management information systems in Africa using space-time geostatistics. PLoS Med, 3 (6), pp. e271. | Show Abstract | Read more

BACKGROUND: Reliable and timely information on disease-specific treatment burdens within a health system is critical for the planning and monitoring of service provision. Health management information systems (HMIS) exist to address this need at national scales across Africa but are failing to deliver adequate data because of widespread underreporting by health facilities. Faced with this inadequacy, vital public health decisions often rely on crudely adjusted regional and national estimates of treatment burdens. METHODS AND FINDINGS: This study has taken the example of presumed malaria in outpatients within the largely incomplete Kenyan HMIS database and has defined a geostatistical modelling framework that can predict values for all data that are missing through space and time. The resulting complete set can then be used to define treatment burdens for presumed malaria at any level of spatial and temporal aggregation. Validation of the model has shown that these burdens are quantified to an acceptable level of accuracy at the district, provincial, and national scale. CONCLUSIONS: The modelling framework presented here provides, to our knowledge for the first time, reliable information from imperfect HMIS data to support evidence-based decision-making at national and sub-national levels.

Rowe AK, Rowe SY, Snow RW, Korenromp EL, Schellenberg JR, Stein C, Nahlen BL, Bryce J, Black RE, Steketee RW. 2006. The burden of malaria mortality among African children in the year 2000. Int J Epidemiol, 35 (3), pp. 691-704. | Show Abstract | Read more

BACKGROUND: Although malaria is a leading cause of child deaths, few well-documented estimates of its direct and indirect burden exist. Our objective was to estimate the number of deaths directly attributable to malaria among children <5 years old in sub-Saharan Africa for the year 2000. METHODS: We divided the population into six sub-populations and, using results of studies identified in a literature review, estimated a malaria mortality rate for each sub-population. Malaria deaths were estimated by multiplying each sub-population by its corresponding rate. Sensitivity analyses were performed to assess the impact of varying key assumptions. RESULTS: The literature review identified 31 studies from 14 countries in middle Africa and 17 studies and reports from four countries in southern Africa. In 2000, we estimated that approximately 100 million children lived in areas where malaria transmission occurs and that 803 620 (precision estimate: 705 821-901 418) children died from the direct effects of malaria. For all of sub-Saharan Africa, including populations not exposed to malaria, malaria accounted for 18.0% (precision estimate: 15.8-20.2%) of child deaths. These estimates were sensitive to extreme assumptions about the causes of deaths with no known cause. CONCLUSIONS: These estimates, based on the best available data and methods, clearly demonstrate malaria's enormous mortality burden. We emphasize that these estimates are an approximation with many limitations and that the estimates do not account for malaria's large indirect burden. We describe information needs that, if filled, might improve the validity of future estimates.

Wambua S, Mwangi TW, Kortok M, Uyoga SM, Macharia AW, Mwacharo JK, Weatherall DJ, Snow RW, Marsh K, Williams TN. 2006. The effect of alpha+-thalassaemia on the incidence of malaria and other diseases in children living on the coast of Kenya. PLoS Med, 3 (5), pp. e158. | Show Abstract | Read more

BACKGROUND: The alpha-thalassaemias are the commonest genetic disorders of humans. It is generally believed that this high frequency reflects selection through a survival advantage against death from malaria; nevertheless, the epidemiological description of the relationships between alpha-thalassaemia, malaria, and other common causes of child mortality remains incomplete. METHODS AND FINDINGS: We studied the alpha+-thalassaemia-specific incidence of malaria and other common childhood diseases in two cohorts of children living on the coast of Kenya. We found no associations between alpha+-thalassaemia and the prevalence of symptomless Plasmodium falciparum parasitaemia, the incidence of uncomplicated P. falciparum disease, or parasite densities during mild or severe malaria episodes. However, we found significant negative associations between alpha+-thalassaemia and the incidence rates of severe malaria and severe anaemia (haemoglobin concentration < 50 g/l). The strongest associations were for severe malaria anaemia (> 10,000 P. falciparum parasites/mul) and severe nonmalaria anaemia; the incidence rate ratios and 95% confidence intervals (CIs) for alpha+-thalassaemia heterozygotes and homozygotes combined compared to normal children were, for severe malaria anaemia, 0.33 (95% CI, 0.15,0.73; p = 0.006), and for severe nonmalaria anaemia, 0.26 (95% CI, 0.09,0.77; p = 0.015). CONCLUSIONS: Our observations suggest, first that selection for alpha+-thalassaemia might be mediated by a specific effect against severe anaemia, an observation that may lead to fresh insights into the aetiology of this important condition. Second, although alpha+-thalassaemia is strongly protective against severe and fatal malaria, its effects are not detectable at the level of any other malaria outcome; this result provides a cautionary example for studies aimed at testing malaria interventions or identifying new malaria-protective genes.

Guerra CA, Snow RW, Hay SI. 2006. A global assessment of closed forests, deforestation and malaria risk. Ann Trop Med Parasitol, 100 (3), pp. 189-204. | Show Abstract | Read more

Global environmental change is expected to affect profoundly the transmission of the parasites that cause human malaria. Amongst the anthropogenic drivers of change, deforestation is arguably the most conspicuous, and its rate is projected to increase in the coming decades. The canonical epidemiological understanding is that deforestation increases malaria risk in Africa and the Americas and diminishes it in South-east Asia. Partial support for this position is provided here, through a systematic review of the published literature on deforestation, malaria and the relevant vector bionomics. By using recently updated boundaries for the spatial limits of malaria and remotely-sensed estimates of tree cover, it has been possible to determine the population at risk of malaria in closed forest, at least for those malaria-endemic countries that lie within the main blocks of tropical forest. Closed forests within areas of malaria risk cover approximately 1.5 million km2 in the Amazon region, 1.4 million km2 in Central Africa, 1.2 million km2 in the Western Pacific, and 0.7 million km2 in South-east Asia. The corresponding human populations at risk of malaria within these forests total 11.7 million, 18.7 million, 35.1 million and 70.1 million, respectively. By coupling these numbers with the country-specific rates of deforestation, it has been possible to rank malaria-endemic countries according to their potential for change in the population at risk of malaria, as the result of deforestation. The on-going research aimed at evaluating these relationships more quantitatively, through the Malaria Atlas Project (MAP), is highlighted.

Zurovac D, Midia B, Ochola SA, English M, Snow RW. 2006. Microscopy and outpatient malaria case management among older children and adults in Kenya. Trop Med Int Health, 11 (4), pp. 432-440. | Show Abstract | Read more

OBJECTIVE: To evaluate the accuracy of routine malaria microscopy, and appropriate use and interpretation of malaria slides under operational conditions in Kenya. METHODS: Cross-sectional survey, using a range of quality of care assessment tools, at government facilities with malaria microscopy in two Kenyan districts of different intensity of malaria transmission. All patients older than 5 years presenting to outpatient departments were enrolled. Two expert microscopists assessed the accuracy of the routine malaria slide results. RESULTS: We analysed 359 consultations performed by 31 clinicians at 17 facilities. Clinical assessment was suboptimal. Blood slide microscopy was performed for 72.7% of patients, who represented 78.5% of febrile patients and 51.3% of afebrile patients. About 95.5% of patients with a positive malaria microscopy result and 79.3% of patients with a negative result received antimalarial treatment. Sulphadoxine-pyremethamine monotherapy was more commonly prescribed for patients with a negative test result (60.7%) than for patients with a positive result (32.4%). Conversely, amodiaquine or quinine were prescribed for only 14.7% of patients with a negative malaria microscopy result compared to 57.7% of patients with a positive result. The prevalence of confirmed malaria was low in both high (10.0%) and low-(16.3%) transmission settings. Combining data from both settings, the sensitivity of routine microscopy was 68.6%; its specificity, 61.5%; its positive predictive value, 21.6% and its negative predictive value, 92.7%. CONCLUSIONS: The potential benefits of microscopy are currently not realised because of the poor quality of routine testing and irrational clinical practices. Ambiguous clinical guidelines permitting treatment of older children and adults with a negative blood slide also undermine rational use of antimalarial drugs.

Snow RW, Hay SI. 2006. Comparing methods of estimating the global morbidity burden from Plasmodium falciparum malaria. Am J Trop Med Hyg, 74 (2), pp. 189-190.

Noor AM, Amin AA, Gething PW, Atkinson PM, Hay SI, Snow RW. 2006. Modelling distances travelled to government health services in Kenya. Trop Med Int Health, 11 (2), pp. 188-196. | Show Abstract | Read more

OBJECTIVE: To systematically evaluate descriptive measures of spatial access to medical treatment, as part of the millennium development goals to reduce the burden of HIV/AIDS, tuberculosis and malaria. METHODS: We obtained high-resolution spatial and epidemiological data on health services, population, transport network, topography, land cover and paediatric fever treatment in four Kenyan districts to develop access and use models for government health services in Kenya. Community survey data were used to model use of government health services by febrile children. A model based on the transport network was then implemented and adjusted for actual use patterns. We compared the predictive accuracy of this refined model to that of Euclidean distance metrics. RESULTS Higher-order facilities were more attractive to patients (54%, 58% and 60% in three scenarios) than lower-order ones. The transport network model, adjusted for competition between facilities, was most accurate and selected as the best-fit model. It estimated that 63% of the population of the study districts were within the 1 h national access benchmark, against 82% estimated by the Euclidean model. CONCLUSIONS: Extrapolating the results from the best-fit model in study districts to the national level shows that approximately six million people are currently incorrectly estimated to have access to government health services within 1 h. Simple Euclidean distance assumptions, which underpin needs assessments and against which millennium development goals are evaluated, thus require reconsideration.

Noor AM, Omumbo JA, Amin AA, Zurovac D, Snow RW. 2006. Wealth, mother's education and physical access as determinants of retail sector net use in rural Kenya. Malar J, 5 pp. 5. | Show Abstract | Read more

BACKGROUND: Insecticide-treated bed nets (ITN) provide real hope for the reduction of the malaria burden across Africa. Understanding factors that determine access to ITN is crucial to debates surrounding the optimal delivery systems. The influence of homestead wealth on use of nets purchased from the retail sector is well documented, however, the competing influence of mother's education and physical access to net providers is less well understood. METHODS: Between December 2004 and January 2005, a random sample of 72 rural communities was selected across four Kenyan districts. Demographic, assets, education and net use data were collected at homestead, mother and child (aged < 5 years) levels. An assets-based wealth index was developed using principal components analysis, travel time to net sources was modelled using geographic information systems, and factors influencing the use of retail sector nets explored using a multivariable logistic regression model. RESULTS: Homestead heads and guardians of 3,755 children < 5 years of age were interviewed. Approximately 15% (562) of children slept under a net the night before the interview; 58% (327) of the nets used were purchased from the retail sector. Homestead wealth (adjusted OR = 10.17, 95% CI = 5.45-18.98), travel time to nearest market centres (adjusted OR = 0.51, 95% CI = 0.37-0.72) and mother's education (adjusted OR = 2.92, 95% CI = 1.93-4.41) were significantly associated with use of retail sector nets by children aged less than 5 years. CONCLUSION: Approaches to promoting access to nets through the retail sector disadvantage poor and remote communities where mothers are less well educated.

English M, Snow RW. 2006. Iron and folic acid supplementation and malaria risk. Lancet, 367 (9505), pp. 90-91. | Read more

Guerra CA, Snow RW, Hay SI. 2006. Defining the global spatial limits of malaria transmission in 2005. Adv Parasitol, 62 pp. 157-179. | Show Abstract | Read more

There is no accurate contemporary global map of the distribution of malaria. We show how guidelines formulated to advise travellers on appropriate chemoprophylaxis for areas of reported Plasmodium falciparum and Plasmodium vivax malaria risk can be used to generate crude spatial limits. We first review and amalgamate information on these guidelines to define malaria risk at national and sub-national administrative boundary levels globally. We then adopt an iterative approach to reduce these extents by applying a series of biological limits imposed by altitude, climate and population density to malaria transmission, specific to the local dominant vector species. Global areas of, and population at risk from, P. falciparum and often-neglected P. vivax malaria are presented for 2005 for all malaria endemic countries. These results reveal that more than 3 billion people were at risk of malaria in 2005.

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Gething PW, Noor AM, Gikandi PW, Ogara EAA, Hay SI, Nixon MS, Snow RW, Atkinson PM. 2006. Improving imperfect data from health management information systems in Africa using space-time geostatistics PLoS Medicine, 3 (6), pp. 0825-0831. | Show Abstract | Read more

Background: Reliable and timely information on disease-specific treatment burdens within a health system is critical for the planning and monitoring of service provision. Health management information systems (HMIS) exist to address this need at national scales across Africa but are failing to deliver adequate data because of widespread underreporting by health facilities. Faced with this inadequacy, vital public health decisions often rely on crudely adjusted regional and national estimates of treatment burdens. Methods and Findings: This study has taken the example of presumed malaria in outpatients within the largely incomplete Kenyan HMIS database and has defined a geostatistical modelling framework that can predict values for all data that are missing through space and time. The resulting complete set can then be used to define treatment burdens for presumed malaria at any level of spatial and temporal aggregation. Validation of the model has shown that these burdens are quantified to an acceptable level of accuracy at the district, provincial, and national scale. Conclusions: The modelling framework presented here provides, to our knowledge for the first time, reliable information from imperfect HMIS data to support evidence-based decision-making at national and sub-national levels. © 2006 Gething et al.

Mackinnon MJ, Mwangi TW, Snow RW, Marsh K, Williams TN. 2005. Heritability of malaria in Africa. PLoS Med, 2 (12), pp. e340. | Show Abstract | Read more

BACKGROUND: While many individual genes have been identified that confer protection against malaria, the overall impact of host genetics on malarial risk remains unknown. METHODS AND FINDINGS: We have used pedigree-based genetic variance component analysis to determine the relative contributions of genetic and other factors to the variability in incidence of malaria and other infectious diseases in two cohorts of children living on the coast of Kenya. In the first, we monitored the incidence of mild clinical malaria and other febrile diseases through active surveillance of 640 children 10 y old or younger, living in 77 different households for an average of 2.7 y. In the second, we recorded hospital admissions with malaria and other infectious diseases in a birth cohort of 2,914 children for an average of 4.1 y. Mean annual incidence rates for mild and hospital-admitted malaria were 1.6 and 0.054 episodes per person per year, respectively. Twenty-four percent and 25% of the total variation in these outcomes was explained by additively acting host genes, and household explained a further 29% and 14%, respectively. The haemoglobin S gene explained only 2% of the total variation. For nonmalarial infections, additive genetics explained 39% and 13% of the variability in fevers and hospital-admitted infections, while household explained a further 9% and 30%, respectively. CONCLUSION: Genetic and unidentified household factors each accounted for around one quarter of the total variability in malaria incidence in our study population. The genetic effect was well beyond that explained by the anticipated effects of the haemoglobinopathies alone, suggesting the existence of many protective genes, each individually resulting in small population effects. While studying these genes may well provide insights into pathogenesis and resistance in human malaria, identifying and tackling the household effects must be the more efficient route to reducing the burden of disease in malaria-endemic areas.

Amin AA, Snow RW, Kokwaro GO. 2005. The quality of sulphadoxine-pyrimethamine and amodiaquine products in the Kenyan retail sector. J Clin Pharm Ther, 30 (6), pp. 559-565. | Show Abstract | Read more

BACKGROUND AND OBJECTIVE: Malaria is a disease of major public health importance in Kenya killing 26,000 children under 5 years of age annually. This paper seeks to assess the quality of sulphadoxine-pyrimethamine (SP) and amodiaquine (AQ) products available over-the-counter to communities in Kenya as most malaria fevers are self-medicated using drugs from the informal retail sector. METHODS: A retail audit of 880 retail outlets was carried in 2002 in four districts in Kenya, in which antimalarial drug stocks and their primary wholesale sources were noted. In addition, the expiry dates on audited products and the basic storage conditions were recorded on a proforma. The most commonly stocked SP and AQ products were then sampled from the top 10 wholesalers in each district and samples subjected to standard United States Pharmacopoeia (USP) tests of content and dissolution. RESULTS AND DISCUSSION: SP and AQ were the most frequently stocked antimalarial drugs, accounting for approximately 75% of all the antimalarial drugs stocked in the four districts. Of 116 SP and AQ samples analysed, 47 (40.5%) did not meet the USP specifications for content and/or dissolution. Overall, approximately 45.3% of SP and 33.0% of AQ samples were found to be sub-standard. Of the sub-standard SP products, 55.2% were suspensions while 61.1% of the substandard AQ products were tablets. Most SP failures were because of the pyrimethamine component. CONCLUSION: There is a need to strengthen post-marketing surveillance systems to protect patients from being treated with sub-standard and counterfeit antimalarial drugs in Kenya.

Smith DL, Dushoff J, Snow RW, Hay SI. 2005. The entomological inoculation rate and Plasmodium falciparum infection in African children. Nature, 438 (7067), pp. 492-495. | Show Abstract | Read more

Malaria is an important cause of global morbidity and mortality. The fact that some people are bitten more often than others has a large effect on the relationship between risk factors and prevalence of vector-borne diseases. Here we develop a mathematical framework that allows us to estimate the heterogeneity of infection rates from the relationship between rates of infectious bites and community prevalence. We apply this framework to a large, published data set that combines malaria measurements from more than 90 communities. We find strong evidence that heterogeneous biting or heterogeneous susceptibility to infection are important and pervasive factors determining the prevalence of infection: 20% of people receive 80% of all infections. We also find that individual infections last about six months on average, per infectious bite, and children who clear infections are not immune to new infections. The results have important implications for public health interventions: the success of malaria control will depend heavily on whether efforts are targeted at those who are most at risk of infection.

Williams TN, Mwangi TW, Wambua S, Peto TE, Weatherall DJ, Gupta S, Recker M, Penman BS et al. 2005. Negative epistasis between the malaria-protective effects of alpha+-thalassemia and the sickle cell trait. Nat Genet, 37 (11), pp. 1253-1257. | Show Abstract | Read more

The hemoglobinopathies, disorders of hemoglobin structure and production, protect against death from malaria. In sub-Saharan Africa, two such conditions occur at particularly high frequencies: presence of the structural variant hemoglobin S and alpha(+)-thalassemia, a condition characterized by reduced production of the normal alpha-globin component of hemoglobin. Individually, each is protective against severe Plasmodium falciparum malaria, but little is known about their malaria-protective effects when inherited in combination. We investigated this question by studying a population on the coast of Kenya and found that the protection afforded by each condition inherited alone was lost when the two conditions were inherited together, to such a degree that the incidence of both uncomplicated and severe P. falciparum malaria was close to baseline in children heterozygous with respect to the mutation underlying the hemoglobin S variant and homozygous with respect to the mutation underlying alpha(+)-thalassemia. Negative epistasis could explain the failure of alpha(+)-thalassemia to reach fixation in any population in sub-Saharan Africa.

Zurovac D, Ndhlovu M, Rowe AK, Hamer DH, Thea DM, Snow RW. 2005. Treatment of paediatric malaria during a period of drug transition to artemether-lumefantrine in Zambia: cross sectional study. BMJ, 331 (7519), pp. 734. | Show Abstract | Read more

OBJECTIVE: To evaluate treatment practices for uncomplicated malaria after the policy change from chloroquine to sulfadoxine-pyrimethamine and to artemether-lumefantrine in Zambia. DESIGN: Cross sectional survey. SETTING: Outpatient departments of all government and mission facilities in four districts in Zambia. PARTICIPANTS: 944 children with uncomplicated malaria seen by 103 health workers at 94 health facilities. MAIN OUTCOME MEASURES: Antimalarial prescriptions in accordance with national guidelines and influence of factors on health workers' decision to prescribe artemether-lumefantrine. RESULTS: Artemether-lumefantrine, sulfadoxine-pyrimethamine, and chloroquine were available, respectively, at 48 (51%), 94 (100%), and 71 (76%) of the 94 facilities. Of 944 children with uncomplicated malaria, only one child (0.1%) received chloroquine. Among children weighing less than 10 kg, sulfadoxine-pyrimethamine was commonly prescribed in accordance with guidelines (439/550, 79.8%). Among the children weighing 10 kg or more, sulfadoxine-pyrimethamine was commonly prescribed (266/394, 68%), whereas recommended artemether-lumefantrine was prescribed for only 42/394 (11%) children. Among children weighing 10 kg or more seen at facilities where artemether-lumefantrine was available, the same pattern was observed: artemether-lumefantrine was prescribed for only 42/192 (22%) children and sulfadoxine-pyrimethamine remained the drug of choice (103/192, 54%). Programmatic activities such as in-service training and provision of job aids did not seem to influence the prescribing of artemether with lumefantrine. CONCLUSION: Although the use of chloroquine for uncomplicated malaria was successfully discontinued in Zambia, the change of drug policy towards artemether-lumefantrine does not necessarily translate into adequate use of this drug at the point of care.

Snow RW, Guerra CA, Noor AM, Myint HY, Hay SI. 2005. Malaria risk - Reply NATURE, 437 (7056), pp. E4-E5. | Read more

Shanks GD, Hay SI, Omumbo JA, Snow RW. 2005. Malaria in Kenya's western highlands. Emerg Infect Dis, 11 (9), pp. 1425-1432. | Show Abstract | Read more

Records from tea estates in the Kericho district in Kenya show that malaria reemerged in the 1980s. Renewed epidemic activity coincided with the emergence of chloroquine-resistant Plasmodium falciparum malaria and may have been triggered by the failure of antimalarial drugs. Meteorologic changes, population movements, degradation of health services, and changes in Anopheles vector populations are possible contributing factors. The highland malaria epidemics of the 1940s were stopped largely by sporontocidal drugs, and combination chemotherapy has recently limited transmission. Antimalarial drugs can limit the pool of gametocytes available to infect mosquitoes during the brief transmission season.

Amin AA, Snow RW. 2005. Brands, costs and registration status of antimalarial drugs in the Kenyan retail sector. Malar J, 4 pp. 36. | Show Abstract | Read more

BACKGROUND: Although an important source of treatment for fevers, little is known about the structure of the retail sector in Africa with regard to antimalarial drugs. This study aimed to assess the range, costs, sources and registration of antimalarial drugs in the Kenyan retail sector. METHODS: In 2002, antimalarial drug registration and trade prices were established by triangulating national registration lists, government gazettes and trade price indices. Data on registration status and trade prices were compared with similar data generated through a retail audit undertaken among 880 randomly sampled retailers in four districts of Kenya. RESULTS: Two hundred and eighteen antimalarial drugs were in circulation in Kenya in 2002. These included 65 "sulfur"-pyrimethamine (sulfadoxine-pyrimethamine and sulfalene-pyrimethamine (SP), the first-line recommended drug in 2002) and 33 amodiaquine (AQ, the second-line recommended drug) preparations. Only half of SP and AQ products were registered with the Pharmacy and Poisons Board. Of SP and AQ brands at district level, 40% and 44% were officially within legal registration requirements. 29% of retailers at district level stocked SP and 95% stocked AQ. The retail price of adult doses of SP and AQ were on average 0.38 and 0.76 US dollars, 100% and 347% higher than trade prices from manufacturers and importers. Artemether-lumefantrine, the newly announced first-line recommended antimalarial drug in 2004, was found in less than 1% of all retail outlets at a median cost of 7.6 US dollars. CONCLUSION: There is a need to ensure that all antimalarial drugs are registered with the Pharmacy and Poisons Board to facilitate a more stringent post-marketing surveillance system to ensure drugs are safe and of good quality post-registration.

Williams TN, Mwangi TW, Wambua S, Alexander ND, Kortok M, Snow RW, Marsh K. 2005. Sickle cell trait and the risk of Plasmodium falciparum malaria and other childhood diseases. J Infect Dis, 192 (1), pp. 178-186. | Show Abstract | Read more

BACKGROUND: The gene for sickle hemoglobin (HbS) is a prime example of natural selection. It is generally believed that its current prevalence in many tropical populations reflects selection for the carrier form (sickle cell trait [HbAS]) through a survival advantage against death from malaria. Nevertheless, >50 years after this hypothesis was first proposed, the epidemiological description of the relationships between HbAS, malaria, and other common causes of child mortality remains incomplete. METHODS: We studied the incidence of falciparum malaria and other childhood diseases in 2 cohorts of children living on the coast of Kenya. RESULTS: The protective effect of HbAS was remarkably specific for falciparum malaria, having no significant impact on any other disease. HbAS had no effect on the prevalence of symptomless parasitemia but was 50% protective against mild clinical malaria, 75% protective against admission to the hospital for malaria, and almost 90% protective against severe or complicated malaria. The effect of HbAS on episodes of clinical malaria was mirrored in its effect on parasite densities during such episodes. CONCLUSIONS: The present data are useful in that they confirm the mechanisms by which HbAS confers protection against malaria and shed light on the relationships between HbAS, malaria, and other childhood diseases.

Mwangi TW, Ross A, Snow RW, Marsh K. 2005. Case definitions of clinical malaria under different transmission conditions in Kilifi District, Kenya. J Infect Dis, 191 (11), pp. 1932-1939. | Show Abstract | Read more

BACKGROUND: Clear case definitions of malaria are an essential means of evaluating the effectiveness of present and proposed interventions in malaria. The clinical signs of malaria are nonspecific, and parasitemia accompanied by a fever may not be sufficient to define an episode of clinical malaria in endemic areas. We defined and quantified cases of malaria in people of different age groups from 2 areas with different rates of transmission of malaria. METHODS: A total of 1602 people were followed up weekly for 2 years, and all the cases of fever accompanied by parasitemia were identified. Logistic regression methods were used to derive case definitions of malaria. RESULTS: Two case definitions of malaria were derived: 1 for children 1-14 years old and 1 for infants (<1 year old) and older children and adults (> or =15 years old). We also found a higher number of episodes of clinical malaria per person per year in people from an area of low transmission of malaria, compared with the number of episodes in those from an area of higher transmission (0.84 vs. 0.55 episodes/person/year; incidence rate ratio, 0.66 [95% confidence interval, 0.61-0.72]; P<.001). CONCLUSIONS: Case definitions of malaria are bound to be altered by factors that affect immunity, such as age and transmission. Case definitions may, however, be affected by other immunity-altering factors, such as HIV and vaccination status, and this needs to be borne in mind during vaccine trials.

Mwangi TW, Mohammed M, Dayo H, Snow RW, Marsh K. 2005. Clinical algorithms for malaria diagnosis lack utility among people of different age groups. Trop Med Int Health, 10 (6), pp. 530-536. | Show Abstract | Read more

We conducted a study to determine whether clinical algorithms would be useful in malaria diagnosis among people living in an area of moderate malaria transmission within Kilifi District in Kenya. A total of 1602 people of all age groups participated. We took smears and recorded clinical signs and symptoms (prompted or spontaneous) of all those presenting to the study clinic with a history of fever. A malaria case was defined as a person presenting to the clinic with a history of fever and concurrent parasitaemia. A set of clinical signs and symptoms (algorithms) with the highest sensitivity and specificity for diagnosing a malaria case was selected for the age groups </=5 years, 6-14 years and >/=15 years. These age-optimized derived algorithms were able to identify about 66% of the cases among those <15 years of age but only 23% of cases among adults. Were these algorithms to be used as a basis for a decision on treatment among those presenting to the clinic, 16% of children </=5 years, 44% of those 6-14 years of age and 66% of the adults who had a history of fever and parasitaemia >/=5000 parasites/microl of blood would be sent home without treatment. Clinical algorithms therefore appear to have little utility in malaria diagnosis, performing even worse in the older age groups, where avoiding unnecessary use of anti-malarials would make more drugs available to the really needy population of children under 5 years of age.

Omumbo JA, Hay SI, Snow RW, Tatem AJ, Rogers DJ. 2005. Modelling malaria risk in East Africa at high-spatial resolution. Trop Med Int Health, 10 (6), pp. 557-566. | Show Abstract | Read more

OBJECTIVES: Malaria risk maps have re-emerged as an important tool for appropriately targeting the limited resources available for malaria control. In Sub-Saharan Africa empirically derived maps using standardized criteria are few and this paper considers the development of a model of malaria risk for East Africa. METHODS: Statistical techniques were applied to high spatial resolution remotely sensed, human settlement and land-use data to predict the intensity of malaria transmission as defined according to the childhood parasite ratio (PR) in East Africa. Discriminant analysis was used to train environmental and human settlement predictor variables to distinguish between four classes of PR risk shown to relate to disease outcomes in the region. RESULTS: Independent empirical estimates of the PR were identified from Kenya, Tanzania and Uganda (n = 330). Surrogate markers of climate recorded on-board earth orbiting satellites, population settlement, elevation and water bodies all contributed significantly to the predictive models of malaria transmission intensity in the sub-region. The accuracy of the model was increased by stratifying East Africa into two ecological zones. In addition, the inclusion of urbanization as a predictor of malaria prevalence, whilst reducing formal accuracy statistics, nevertheless improved the consistency of the predictive map with expert opinion malaria maps. The overall accuracy achieved with ecological zone and urban stratification was 62% with surrogates of precipitation and temperature being among the most discriminating predictors of the PR. CONCLUSIONS: It is possible to achieve a high degree of predictive accuracy for Plasmodium falciparum parasite prevalence in East Africa using high-spatial resolution environmental data. However, discrepancies were evident from mapped outputs from the models which were largely due to poor coverage of malaria training data and the comparable spatial resolution of predictor data. These deficiencies will only be addressed by more random, intensive small areas studies of empirical estimates of PR.

Williams TN, Mwangi TW, Roberts DJ, Alexander ND, Weatherall DJ, Wambua S, Kortok M, Snow RW, Marsh K. 2005. An immune basis for malaria protection by the sickle cell trait. PLoS Med, 2 (5), pp. e128. | Show Abstract | Read more

BACKGROUND: Malaria resistance by the sickle cell trait (genotype HbAS) has served as the prime example of genetic selection for over half a century. Nevertheless, the mechanism of this resistance remains the subject of considerable debate. While it probably involves innate factors such as the reduced ability of Plasmodium falciparum parasites to grow and multiply in HbAS erythrocytes, recent observations suggest that it might also involve the accelerated acquisition of malaria-specific immunity. METHODS AND FINDINGS: We studied the age-specific protection afforded by HbAS against clinical malaria in children living on the coast of Kenya. We found that protection increased with age from only 20% in the first 2 y of life to a maximum of 56% by the age of 10 y, returning thereafter to 30% in participants greater than 10 y old. CONCLUSIONS: Our observations suggest that malaria protection by HbAS involves the enhancement of not only innate but also of acquired immunity to the parasite. A better understanding of the underlying mechanisms might yield important insights into both these processes.

Zurovac D, Ochola SA, Midia B, Snow RW. 2005. The quality of sulfadoxine-pyrimethamine prescriptions, counselling and drug-dispensing practices, for children in Kenya. Ann Trop Med Parasitol, 99 (3), pp. 321-324. | Read more

Snow RW, Guerra CA, Noor AM, Myint HY, Hay SI. 2005. The global distribution of clinical episodes of Plasmodium falciparum malaria. Nature, 434 (7030), pp. 214-217. | Show Abstract | Read more

Interest in mapping the global distribution of malaria is motivated by a need to define populations at risk for appropriate resource allocation and to provide a robust framework for evaluating its global economic impact. Comparison of older and more recent malaria maps shows how the disease has been geographically restricted, but it remains entrenched in poor areas of the world with climates suitable for transmission. Here we provide an empirical approach to estimating the number of clinical events caused by Plasmodium falciparum worldwide, by using a combination of epidemiological, geographical and demographic data. We estimate that there were 515 (range 300-660) million episodes of clinical P. falciparum malaria in 2002. These global estimates are up to 50% higher than those reported by the World Health Organization (WHO) and 200% higher for areas outside Africa, reflecting the WHO's reliance upon passive national reporting for these countries. Without an informed understanding of the cartography of malaria risk, the global extent of clinical disease caused by P. falciparum will continue to be underestimated.

Hay SI, Shanks GD, Stern DI, Snow RW, Randolph SE, Rogers DJ. 2005. Climate variability and malaria epidemics in the highlands of East Africa. Trends Parasitol, 21 (2), pp. 52-53. | Show Abstract | Read more

Malaria epidemics in the highlands of East Africa garner significant research attention, due, in part, to their proposed sensitivity to climate change. In a recent article, Zhou et al. claim that increases in climate variance, rather than simple increases in climate mean values, have had an important role in the resurgence of malaria epidemics in the East African highlands since the early 1980s. If proven, this would be an interesting result but we believe that the methods used do not test the hypothesis suggested.

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Williams TN, Mwangi TW, Roberts DJ, Alexander ND, Weatherall DJ, Wambua S, Kortok M, Snow RW, Marsh K. 2005. An immune basis for malaria protection by the sickle cell trait PLoS Medicine, 2 (5), pp. 0441-0445. | Show Abstract | Read more

Background: Malaria resistance by the sickle cell trait (genotype HbAS) has served as the prime example of genetic selection for over half a century. Nevertheless, the mechanism of this resistance remains the subject of considerable debate. While it probably involves innate factors such as the reduced ability of Plasmodium falciparum parasites to grow and multiply in HbAS erythrocytes, recent observations suggest that it might also involve the accelerated acquisition of malaria-specific immunity. Methods and Findings: We studied the age-specific protection afforded by HbAS against clinical malaria in children living on the coast of Kenya. We found that protection increased with age from only 20% in the first 2 y of life to a maximum of 56% by the age of 10 y, returning thereafter to 30% in participants greater than 10 y old. Conclusions: Our observations suggest that malaria protection by HbAS involves the enhancement of not only innate but also of acquired immunity to the parasite. A better understanding of the underlying mechanisms might yield important insights into both these processes. © 2005 Williams et al.

Nahlen BL, Korenromp EL, Miller JM, Shibuya K. 2005. Malaria risk: estimating clinical episodes of malaria. Nature, 437 (7056), pp. E3. | Show Abstract | Read more

Estimates of the disease burden caused by malaria are crucial for informing malaria control programmes. Snow and colleagues claim that their estimate of 515 million cases of malaria caused by Plasmodium falciparum globally is up to 50% higher than that reported by the World Health Organization (WHO), and 200% higher for areas outside Africa. However, this comparison refers to the WHO's estimates from 1990 and 1998, and not to the range of 300 million to 500 million that the WHO has used since 2000 (ref. 2). Both groups agree that the burden of malaria disease outside Africa, especially in South Asia, is greater than was estimated in the 1990s.

Omumbo JA, Guerra CA, Hay SI, Snow RW. 2005. The influence of urbanisation on measures of Plasmodium falciparum infection prevalence in East Africa. Acta Trop, 93 (1), pp. 11-21. | Show Abstract | Read more

There is a growing interest in the effects of urbanisation in Africa on Plasmodium falciparum risks and disease outcomes. We undertook a review of published and unpublished literature to identify parasite survey data from communities in East Africa. Data were selected to represent the most reliable and contemporary estimates of infection prevalence and were categorised by urban or rural status using a number of approaches. We identified 329 spatially distinct surveys undertaken since 1980 in the sub-region of which 37 were undertaken in urban settlements and 292 in rural settlements. Overall rural settlements reported significantly higher parasite prevalence among children aged 0-14 than urban settlements (on average 10% higher infection rates; p<0.05). No urban settlements recorded parasite prevalence in excess of 75%. In areas of East Africa where climatic conditions are likely to support higher parasite transmission, the rural-urban difference was most marked. There was a significant trend towards documenting higher classes of parasite prevalence in rural compared to urban settlements (p<0.05) and the mean difference between rural and urban samples was 18% (p<0.001). These results further highlight the need to better define urban extents in Africa in order to capture the non-climatic determinants of infection and disease risk and provide a more informed approach to describing the burden of disease across the continent.

Shanks GD, Biomndo K, Guyatt HL, Snow RW. 2005. Travel as a risk factor for uncomplicated Plasmodium falciparum malaria in the highlands of western Kenya. Trans R Soc Trop Med Hyg, 99 (1), pp. 71-74. | Show Abstract | Read more

In the 1980s, highland malaria returned to the tea estates of western Kenya after an absence of nearly a generation. In order to determine the importance of travel for the spread of malaria in this region, we prospectively collected blood films and travel, demographic and geographic information on well persons and outpatients on tea estates near the western rim of the Rift Valley. Risk factors for malaria asexual parasitaemia included: tribal/ethnic group, home province and home district malaria endemicity. Travel away from the Kericho tea estates within the previous two months showed an odds ratio (OR) for parasitaemia of 1.59 for well persons and 2.38 for outpatients. Sexual stages of malaria parasites (gametocytes) had an OR of 3.14 (well persons) and 2.22 (outpatients) for those who had travelled. Increased risk of malaria parasitaemia with travel was concentrated in children aged <5 years. An increase in population gametocytaemia is possibly due to increased chloroquine resistance and suppressed infections contracted outside of the tea estates.

Hay SI, Guerra CA, Tatem AJ, Atkinson PM, Snow RW. 2005. Urbanization, malaria transmission and disease burden in Africa. Nat Rev Microbiol, 3 (1), pp. 81-90. | Show Abstract | Read more

Many attempts have been made to quantify Africa's malaria burden but none has addressed how urbanization will affect disease transmission and outcome, and therefore mortality and morbidity estimates. In 2003, 39% of Africa's 850 million people lived in urban settings; by 2030, 54% of Africans are expected to do so. We present the results of a series of entomological, parasitological and behavioural meta-analyses of studies that have investigated the effect of urbanization on malaria in Africa. We describe the effect of urbanization on both the impact of malaria transmission and the concomitant improvements in access to preventative and curative measures. Using these data, we have recalculated estimates of populations at risk of malaria and the resulting mortality. We find there were 1,068,505 malaria deaths in Africa in 2000 - a modest 6.7% reduction over previous iterations. The public-health implications of these findings and revised estimates are discussed.

Korenromp EL, Arnold F, Williams BG, Nahlen BL, Snow RW. 2004. Monitoring trends in under-5 mortality rates through national birth history surveys. Int J Epidemiol, 33 (6), pp. 1293-1301. | Show Abstract | Read more

BACKGROUND: We assessed whether Demographic and Health Surveys (DHS), a large and high-quality source of under-5 mortality estimates in developing countries, would be able to detect reductions in under-5 mortality as established in global child health goals. METHODS AND RESULTS: Mortality estimates from 41 DHS conducted in African countries between 1986 and 2002, for the interval of 0-4 years preceding each survey (with a mean time lag of 2.5 years), were reviewed. The median relative error on national mortality rates was 4.4%. In multivariate regression, the relative error decreased with increasing sample size, increasing fertility rates, and increasing mortality rates. The error increased with the magnitude of the survey design effect, which resulted from cluster sampling. With levels of precision observed in previous surveys, reductions in all-cause under-5 mortality rates between two subsequent surveys of 15% or more would be detectable. The detection of smaller mortality reductions would require increases in sample size, from a current median of 7060 to over 20,000 women. Across the actual surveys conducted between 1986 and 2002, varying mortality trends were apparent at a national scale, but only around half of these were statistically significant. CONCLUSIONS: The interpretation of changes in under-5 mortality rates between subsequent surveys needs to take into account statistical significance. DHS birth history surveys with their present sampling design would be able to statistically confirm under-5 mortality reductions in African countries if true reductions were 15% or larger, and are highly relevant to tracking progress towards existing international child health targets.

Omumbo JA, Snow RW. 2004. Plasmodium falciparum parasite prevalence in East Africa: a review. East Afr Med J, 81 (12), pp. 649-656. | Show Abstract

OBJECTIVES: Empirical data on malaria endemicity are rarely available for public domain use to guide effective malaria control. This paper describes the work carried in East Africa since 1997 as part of a pan-African collaboration to map the risk of malaria, Mapping Malaria Risk in Africa (MARA) aimed at redressing deficiency. DATA EXTRACTION: Studies of cross-sectional community estimates of Plasmodium falciparum prevalence among children aged 0-15 years were identified from a variety of sources including electronic searches of published material, manual review of pre-electronic peer reviewed journals and searches of libraries and archives in Kenya, Tanzania and Uganda. Each survey source, infection prevalence, date, longitude and latitude and survey characteristics were recorded. DATA SYNTHESIS: All data were subjected to a number of selection criteria including minimum sample sizes, samples randomly selected, community-based surveys, age ranges of sampled communities within 0-15 years, and surveys that were spatially unique. Of the 2,003 survey data points identified since 1907 in East Africa, only 503 were eligible for inclusion in the analysis dating from 1927 to 2003. The spatial plots of the data demonstrate the paucity of information on malaria prevalence from a number of densely populated areas and highlight the concentration of empirical data in concert with research centres in the sub-region. CONCLUSIONS: Models are required to define malaria risk in areas of East Africa where no empirical data are available so that limited resources can be better targeted to those in greatest need.

English M, Esamai F, Wasunna A, Were F, Ogutu B, Wamae A, Snow RW, Peshu N. 2004. Delivery of paediatric care at the first-referral level in Kenya. Lancet, 364 (9445), pp. 1622-1629. | Show Abstract | Read more

We aimed to investigate provision of paediatric care in government district hospitals in Kenya. We surveyed 14 first-referral level hospitals from seven of Kenya's eight provinces and obtained data for workload, outcome of admission, infrastructure, and resources and the views of hospital staff and caretakers of admitted children. Paediatric admission rates varied almost ten-fold. Basic anti-infective drugs, clinical supplies, and laboratory tests were available in at least 12 hospitals, although these might be charged for on discharge. In at least 11 hospitals, antistaphylococcal drugs, appropriate treatment for malnutrition, newborn feeds, and measurement of bilirubin were rarely or never available. Staff highlighted infrastructure and human and consumable resources as problems. However, a strong sense of commitment, support for the work of the hospital, and a desire for improvement were expressed. Caretakers' views were generally positive, although dissatisfaction with the physical environment in which care took place was common. The capacity of the district hospital in Kenya needs strengthening by comprehensive policies that address real needs if current or new interventions and services at this level of care are to enhance child survival.

Korenromp EL, Armstrong-Schellenberg JR, Williams BG, Nahlen BL, Snow RW. 2004. Impact of malaria control on childhood anaemia in Africa -- a quantitative review. Trop Med Int Health, 9 (10), pp. 1050-1065. | Show Abstract | Read more

OBJECTIVE: To review the impact of malaria control on haemoglobin (Hb) distributions and anaemia prevalences in children under 5 in malaria-endemic Africa. METHODS: Literature review of community-based studies of insecticide-treated bednets, antimalarial chemoprophylaxis and insecticide residual spraying that reported the impact on childhood anaemia. Anaemia outcomes were standardized by conversion of packed cell volumes into Hb values assuming a fixed threefold difference, and by estimation of anaemia prevalences from mean Hb values by applying normal distributions. Determinants of impact were assessed in multivariate analysis. RESULTS: Across 29 studies, malaria control increased Hb among children by, on average, 0.76 g/dl [95% confidence interval (CI): 0.61-0.91], from a mean baseline level of 10.5 g/dl, after a mean of 1-2 years of intervention. This response corresponded to a relative risk for Hb < 11 g/dl of 0.73 (95% CI: 0.64-0.81) and for Hb < 8 g/dl of 0.40 (95% CI: 0.25-0.55). The anaemia response was positively correlated with the impact on parasitaemia (P = 0.005, P = 0.008 and P = 0.01 for the three outcome measures), but no relationship with the type or duration of malaria intervention was apparent. Impact on the prevalence of Hb < 11 g/dl was larger in sites with a higher baseline parasite prevalence. Although no age pattern in impact was apparent across the studies, some individual trials found larger impacts on anaemia in children aged 6-35 months than in older children. CONCLUSION: In malaria-endemic Africa, malaria control reduces childhood anaemia. Childhood anaemia may be a useful indicator of the burden of malaria and of the progress in malaria control.

Guyatt HL, Snow RW. 2004. Impact of malaria during pregnancy on low birth weight in sub-Saharan Africa. Clin Microbiol Rev, 17 (4), pp. 760-769. | Show Abstract | Read more

Malaria during pregnancy can result in low birth weight (LBW), an important risk factor for infant mortality. This article reviews the pathological effects of malaria during pregnancy and the implications for the newborn's development and survival. Empirical data from throughout Africa on associations between placental malaria and birth weight outcome, birth weight outcome and infant mortality, and the rates of LBW in areas with various levels of malaria transmission are evaluated to assess the increased risks of LBW and infant mortality associated with malaria. It is estimated that in areas where malaria is endemic, around 19% of infant LBWs are due to malaria and 6% of infant deaths are due to LBW caused by malaria. These estimates imply that around 100,000 infant deaths each year could be due to LBW caused by malaria during pregnancy in areas of malaria endemicity in Africa.

Zurovac D, Rowe AK, Ochola SA, Noor AM, Midia B, English M, Snow RW. 2004. Predictors of the quality of health worker treatment practices for uncomplicated malaria at government health facilities in Kenya. Int J Epidemiol, 33 (5), pp. 1080-1091. | Show Abstract | Read more

BACKGROUND: When replacing failing drugs for malaria with more effective drugs, an important step towards reducing the malaria burden is that health workers (HW) prescribe drugs according to evidence-based guidelines. Past studies have shown that HW commonly do not follow guidelines, yet few studies have explored with appropriate methods why such practices occur. METHODS: We analysed data from a survey of government health facilities in four Kenyan districts in which HW consultations were observed, caretakers and HW were interviewed, and health facility assessments were performed. The analysis was limited to children 2-59 months old with uncomplicated malaria. Treatment was defined as recommended (antimalarial recommended by national guidelines), a minor error (effective, but non-recommended antimalarial), or inappropriate (no effective antimalarial). RESULTS: We evaluated 1006 consultations performed by 135 HW at 81 facilities: 567 children received recommended treatment, 314 had minor errors, and 125 received inappropriate treatment (weighted percentages: 56.9%, 30.4%, and 12.7%). Multivariate logistic regression analysis revealed that programmatic interventions such as in-service malaria training, provision of guidelines and wall charts, and more frequent supervision were significantly associated with better treatment quality. However, neither in-service training nor possession of the guideline document showed an effect by itself. More qualified HW made more errors: both major and minor errors (but generally more minor errors) when second-line drugs were in stock, and more major errors when second-line drugs were not in stock. Child factors such as age and a main complaint of fever were also associated with treatment quality. CONCLUSIONS: Our results support the use of several programmatic strategies that can redress HW deficiencies in malaria treatment. Targeted cost-effectiveness trials would help refine these strategies and provide more precise guidance on affordable and effective ways to strengthen and maintain HW practices.

Amin AA, Hughes DA, Marsh V, Abuya TO, Kokwaro GO, Winstanley PA, Ochola SA, Snow RW. 2004. The difference between effectiveness and efficacy of antimalarial drugs in Kenya. Trop Med Int Health, 9 (9), pp. 967-974. | Show Abstract | Read more

OBJECTIVE: To demonstrate the difference between effectiveness and efficacy of antimalarial (AM) drugs in Kenya. METHODS: We undertook a series of linked surveys in four districts of Kenya between 2001 and 2002 on (i) community usage of nationally recommended first- and second-line AM drugs; (ii) commonly stocked AM products in the retail and wholesale sectors; and (iii) quality of the most commonly available first- and second-line AM products. These were combined with estimates of adherence and clinical efficacy to derive overall drug effectiveness. RESULTS: The overall modelled effectiveness for sulphadoxine-pyrimethamine (SP) was estimated to be 62% compared with 85% for reported SP clinical efficacy. For amodiaquine the modelled effectiveness was 48% compared with 99% reported efficacy during the same time period. CONCLUSIONS: The quality of AM products and patient adherence to dosage regimens are important determinants of drug effectiveness, and should be measured alongside clinical efficacy. Post-registration measures to regulate drug quality and improve patient adherence would contribute significantly to AM drug performance.

Snow RW. 2004. The invisible victims. Nature, 430 (7002), pp. 934-935. | Read more

Noor AM, Gikandi PW, Hay SI, Muga RO, Snow RW. 2004. Creating spatially defined databases for equitable health service planning in low-income countries: the example of Kenya. Acta Trop, 91 (3), pp. 239-251. | Show Abstract | Read more

Equity is an important criterion in evaluating health system performance. Developing a framework for equitable and effective resource allocation for health depends upon knowledge of service providers and their location in relation to the population they should serve. The last available map of health service providers in Kenya was developed in 1959. We have built a health service provider database from a variety of traditional government and opportunistic non-government sources and positioned spatially these facilities using global positioning systems, hand-drawn maps, topographical maps and other sources. Of 6674 identified service providers, 3355 (50%) were private sector, employer-provided or specialist facilities and only 39% were registered in the Kenyan Ministry of Health database during 2001. Of 3319 public service facilities supported by the Ministry of Health, missions, not-for-profit organizations and local authorities, 84% were registered on a Ministry of Health database and we were able to acquire co-ordinates for 92% of these. The ratio of public health services to population changed from 1:26,000 in 1959 to 1:9300 in 1999-2002. There were 82% of the population within 5 km of a public health facility and resident in 20% of the country. Our efforts to recreate a comprehensive, spatially defined list of health service providers has identified a number of weaknesses in existing national health management information systems, which with an increased commitment and minimal costs can be redressed. This will enable geographic information systems to exploit more fully facility-based morbidity data, population distribution and health access models to target resources and monitor the ability of health sector reforms to achieve equity in service provision.

Gething PW, Noor AM, Zurovac D, Atkinson PM, Hay SI, Nixon MS, Snow RW. 2004. Empirical modelling of government health service use by children with fevers in Kenya. Acta Trop, 91 (3), pp. 227-237. | Show Abstract | Read more

An understanding of spatial patterns of health facility use allows a more informed approach to the modelling of catchment populations. In the absence of patient use data, an intuitive and commonly used approach to the delineation of facility catchment areas is Thiessen polygons. This study presents a series of methods by which the validity of these assumptions can be tested directly and hence the suitability of a Thiessen polygon catchment model explicitly assessed. These methods are applied to paediatric out-patient origin data from a sample of 81 government health facilities in four districts of Kenya. A geographical information system was used to predict the location of the catchment boundary along a transect between each pair of neighbouring facilities based on patient choice patterns. The mean location of boundaries between facilities of different type was found to be significantly displaced from the Thiessen boundary towards the lower-order facility. The affect of distance on within-catchment utilization rate was assessed by using exclusion buffers to remove the effect of neighbouring facilities. Utilization rate was found to exhibit a slight but steady decrease with distance up to 6 km from a facility. The accuracy of the future modelling of unsampled facility catchments can be increased by the incorporation of these trends.

Snow RW, Korenromp EL, Gouws E. 2004. Pediatric mortality in Africa: plasmodium falciparum malaria as a cause or risk? Am J Trop Med Hyg, 71 (2 Suppl), pp. 16-24. | Show Abstract

The disability adjusted life year (DALY) approach of defining cause-specific health burdens is becoming the benchmark for international disease control prioritization. For malaria, this categorical approach may not fully capture its burden that includes chronic anemia, low birth weight, and enhancement of the severity of other childhood diseases. We investigated the extent to which malaria acts as a risk factor for all-cause mortality in African children less than five years of age from 1) ecologic associations between Plasmodium falciparum infection prevalence (PR) and under-five mortality, and 2) reductions in all-cause under-five mortality achieved in malaria intervention trials. Across 48 demographic surveillance studies, when adjusted for secular trends, PR more than doubled all-cause mortality (P = 0.0001). Trials of insecticide-treated mosquito nets generally found smaller population-attributable fractions of pediatric mortality to malaria infection, which may relate to their imperfect coverage and efficacy. In conclusion, the disability and death burden due to malaria in African children could be higher than that detectable from cause-specific DALY estimations.

Mung'Ala-Odera V, Snow RW, Newton CR. 2004. The burden of the neurocognitive impairment associated with Plasmodium falciparum malaria in sub-saharan Africa. Am J Trop Med Hyg, 71 (2 Suppl), pp. 64-70. | Show Abstract

The burden of Plasmodium falciparum malaria has been estimated traditionally in terms of infections and mortality. Neurocognitive sequelae have recently been identified that add to the burden caused by this parasite. We have attempted to provide estimates of the neurocognitive burden based upon more recent estimates of the population at risk and a detailed review of published studies in sub-Saharan Africa. There is little data on which to estimate the burden, and considerable limitations in extracting the data from the published studies to provide these estimates. However, we estimate that at least 1,300-7,800 children will have neurologic sequelae following cerebral malaria in stable endemic areas per year. The figure is likely to be considerably higher, since these estimates do not include neurocognitive impairment following non-cerebral malaria in children or adults in stable endemic areas, or populations in low stable or epidemic areas.

English M, Esamai F, Wasunna A, Were F, Ogutu B, Wamae A, Snow RW, Peshu N. 2004. Assessment of inpatient paediatric care in first referral level hospitals in 13 districts in Kenya. Lancet, 363 (9425), pp. 1948-1953. | Show Abstract | Read more

BACKGROUND: The district hospital is considered essential for delivering basic, cost-effective health care to children in resource poor countries. We aimed to investigate the performance of these facilities in Kenya. METHODS: Government hospitals providing first referral level care were prospectively sampled from 13 Kenyan districts. Workload statistics and data documenting the management and care of admitted children were obtained by specially trained health workers. FINDINGS: Data from 14 hospitals were surveyed with routine statistics showing considerable variation in inpatient paediatric mortality (range 4-15%) and specific case fatality rates (eg, anaemia 3-46%). The value of these routine data is seriously undermined by missing data, apparent avoidance of a diagnosis of HIV/AIDS, and absence of standard definitions. Case management practices are often not in line with national or international guidelines. For malaria, signs defining severity such as the level of consciousness and degree of respiratory distress are often not documented (range per hospital 0-100% and 9-77%, respectively), loading doses of quinine are rarely given (3% of cases) and dose errors are not uncommon. Resource constraints such as a lack of nutritional supplements for malnourished children also restrict the provision of basic, effective care. INTERPRETATION: Even crude performance measures suggest there is a great need to improve care and data quality, and to identify and tackle key health system constraints at the first referral level in Kenya. Appropriate intervention might lead to more effective use of health workers' efforts in such hospitals.

Reitera P, Thomas CJ, Atkinson PM, Hay SI, Randolph SE, Rogers DJ, Shanks GD, Snow RW, Spielman A. 2004. Global warming and malaria: a call for accuracy. Lancet Infect Dis, 4 (6), pp. 323-324. | Read more

Hay SI, Guerra CA, Tatem AJ, Noor AM, Snow RW. 2004. The global distribution and population at risk of malaria: past, present, and future. Lancet Infect Dis, 4 (6), pp. 327-336. | Show Abstract | Read more

The aim of this review was to use geographic information systems in combination with historical maps to quantify the anthropogenic impact on the distribution of malaria in the 20th century. The nature of the cartographic record enabled global and regional patterns in the spatial limits of malaria to be investigated at six intervals between 1900 and 2002. Contemporaneous population surfaces also allowed changes in the numbers of people living in areas of malaria risk to be quantified. These data showed that during the past century, despite human activities reducing by half the land area supporting malaria, demographic changes resulted in a 2 billion increase in the total population exposed to malaria risk. Furthermore, stratifying the present day malaria extent by endemicity class and examining regional differences highlighted that nearly 1 billion people are exposed to hypoendemic and mesoendemic malaria in southeast Asia. We further concluded that some distortion in estimates of the regional distribution of malaria burden could have resulted from different methods used to calculate burden in Africa. Crude estimates of the national prevalence of Plasmodium falciparum infection based on endemicity maps corroborate these assertions. Finally, population projections for 2010 were used to investigate the potential effect of future demographic changes. These indicated that although population growth will not substantially change the regional distribution of people at malaria risk, around 400 million births will occur within the boundary of current distribution of malaria by 2010: the date by which the Roll Back Malaria initiative is challenged to halve the world's malaria burden.

Omumbo JA, Hay SI, Guerra CA, Snow RW. 2004. The relationship between the Plasmodium falciparum parasite ratio in childhood and climate estimates of malaria transmission in Kenya. Malar J, 3 pp. 17. | Show Abstract | Read more

BACKGROUND: Plasmodium falciparum morbid and fatal risks are considerably higher in areas supporting parasite prevalence > or =25%, when compared with low transmission areas supporting parasite prevalence below 25%. Recent descriptions of the health impacts of malaria in Africa are based upon categorical descriptions of a climate-driven fuzzy model of suitability (FCS) for stable transmission developed by the Mapping Malaria Risk in Africa collaboration (MARA). METHODS: An electronic and national search was undertaken to identify community-based parasite prevalence surveys in Kenya. Data from these surveys were matched using ArcView 3.2 to extract spatially congruent estimates of the FCS values generated by the MARA model. Levels of agreement between three classes used during recent continental burden estimations of parasite prevalence (0%, >0-<25% and > or =25%) and three classes of FCS (0, >0-<0.75 and > or =0.75) were tested using the kappa (k) statistic and examined as continuous variables to define better levels of agreement. RESULTS: Two hundred and seventeen independent parasite prevalence surveys undertaken since 1980 were identified during the search. Overall agreement between the three classes of parasite prevalence and FCS was weak although significant (k = 0.367, p < 0.0001). The overall correlation between the FCS and the parasite ratio when considered as continuous variables was also positive (0.364, p < 0.001). The margins of error were in the stable, endemic (parasite ratio > or =25%) class with 42% of surveys represented by an FCS <0.75. Reducing the FCS value criterion to > or =0.6 improved the classification of stable, endemic parasite ratio surveys. Zero values of FCS were not adequate discriminators of zero parasite prevalence. CONCLUSION: Using the MARA model to categorically distinguish populations at differing intensities of malaria transmission in Kenya may under-represent those who are exposed to stable, endemic transmission and over-represent those at no risk. The MARA approach to defining FCS values of suitability for stable transmission represents our only contemporary continental level map of malaria in Africa but there is a need to redefine Africa's population at risk in accordance with both climatic and non-climatic determinants of P. falciparum transmission intensity to provide a more informed approach to estimating the morbid and fatal consequences of infection across the continent.

Guyatt HL, Snow RW. 2004. The management of fevers in Kenyan children and adults in an area of seasonal malaria transmission. Trans R Soc Trop Med Hyg, 98 (2), pp. 111-115. | Show Abstract | Read more

This study investigates the source, timing and types of treatment for fevers across all ages in a low malaria-transmission area of Kenya. The period prevalence for fever, and subsequent treatment seeking behaviour, was similar across all ages. The use of the informal retail sector was common (47% of first actions), though most visits to shops and chemists (77%) resulted in treatment with an antipyretic not an antimalarial. The major source of the first line recommended drug, sulfadoxine-pyrimethamine (SP), was at the formal health sector, and 32% of fevers made at least one visit to a health care facility. Although only 7% of fevers received SP within 24 hours of fever onset, 27% ultimately received treatment with this antimalaria. It is estimated that of the total amount of SP consumed in this population, only 20% is administered to children less than 5 years old. In this area of Kenya disease risks decline with increasing age, however, adult populations consume over 40% of prescribed or purchased anti-malarial drugs. In light of the proposed new, more costly anti-malarial drug combinations these findings have major implications for the effective allocation of limited financial resources at household and government levels.

Guyatt HL, Noor AM, Ochola SA, Snow RW. 2004. Use of intermittent presumptive treatment and insecticide treated bed nets by pregnant women in four Kenyan districts. Trop Med Int Health, 9 (2), pp. 255-261. | Show Abstract | Read more

The roll back malaria (RBM) movement promotes the use of insecticide-treated bednets (ITNs) and intermittent presumptive treatment (IPT) of malaria infection as preventive measures against the adverse effects of malaria among pregnant women in Africa. To determine the use of these preventive measures we undertook a community-based survey of recently pregnant women randomly selected from communities in four districts of Kenya in December 2001. Of the 1814 women surveyed, only 5% had slept under an ITN. More than half of the 13% of women using a bednet (treated or untreated) had bought their nets from shops or markets. Women from rural areas used bednets less than urban women (11% vs. 27%; P < 0.001), and 41% of the bednets used by rural women had been obtained free of charge from a research project in Bondo or a nationwide UNICEF donation through antenatal clinics (ANCs). Despite 96% of ANC providers being aware of IPT with sulphadoxine-pyrimethamine (SP), only 5% of women interviewed had received two or more doses of SP as a presumptive treatment. The coverage of pregnant women with at least one dose of IPT with SP was 14%, though a similar percentage also had received at least a single dose as a curative treatment. The coverage of nationally recommended strategies to prevent malaria during pregnancy during 2001 was low across the diverse malaria ecology of Kenya. Rapid expansion of access to these services is required to meet international and national targets by the year 2005. The scaling up of malaria prevention programmes through ANC services should be possible with 74% of women visiting ANCs at least twice in all four districts. Issues of commodity supply and service costs to clients will be the greatest impediments to reaching RBM targets.

White N, Nosten F, Björkman A, Marsh K, Snow RW. 2004. WHO, the Global Fund, and medical malpractice in malaria treatment. Lancet, 363 (9415), pp. 1160. | Read more

Amin AA, Marsh V, Noor AM, Ochola SA, Snow RW. 2003. The use of formal and informal curative services in the management of paediatric fevers in four districts in Kenya. Trop Med Int Health, 8 (12), pp. 1143-1152. | Show Abstract | Read more

OBJECTIVE: To assess the sources, costs, timing and types of treatment for fevers among children under 5 years of age in four ecologically distinct districts of Kenya. METHODS: Structured questionnaires were administered to caretakers of one randomly selected child aged <5 years per homestead to establish whether the child had had a fever within the last 14 days and the types, sources, costs, and timing of treatment. Drug charts of common proprietary anti-malarial and antipyretic drugs in Kenya were used as visual aids. RESULTS: A total of 2655 fevers were reported among 6287 (42.2%) children with significant differences between the four districts (P<0.01). A substantial number of fevers remained untreated (28.1%) across all districts and more fevers were treated in Greater Kisii than any other district (P<0.01). The median delay to any treatment was 2 days [inter-quartile range (IQR): 2, 4]. The informal retail sector had no transport costs associated with it and charged less for drugs than all the other sectors. Most antimalarial treated fevers occurred in the formal public sector (52.6%). Only 2.3% of fevers were treated within 24 h of onset with a sulphur-pyrimethamine drug, the nationally recommended first-line drug for the management of uncomplicated malaria. CONCLUSIONS: The Abuja target of ensuring that 60% of childhood fevers are treated with appropriate antimalarial drugs within 24 h of onset by 2010 is largely unmet and a major investment in improving prompt access to antimalarial drugs will be required to achieve this.

Noor AM, Zurovac D, Hay SI, Ochola SA, Snow RW. 2003. Defining equity in physical access to clinical services using geographical information systems as part of malaria planning and monitoring in Kenya. Trop Med Int Health, 8 (10), pp. 917-926. | Show Abstract | Read more

Distance is a crucial feature of health service use and yet its application and utility to health care planning have not been well explored, particularly in the light of large-scale international and national efforts such as Roll Back Malaria. We have developed a high-resolution map of population-to-service access in four districts of Kenya. Theoretical physical access, based upon national targets, developed as part of the Kenyan health sector reform agenda, was compared with actual health service usage data among 1668 paediatric patients attending 81 sampled government health facilities. Actual and theoretical use were highly correlated. Patients in the larger districts of Kwale and Makueni, where access to government health facilities was relatively poor, travelled greater mean distances than those in Greater Kisii and Bondo. More than 60% of the patients in the four districts attended health facilities within a 5-km range. Interpolated physical access surfaces across districts highlighted areas of poor access and large differences between urban and rural settings. Users from rural communities travelled greater distances to health facilities than those in urban communities. The implications of planning and monitoring equitable delivery of clinical services at national and international levels are discussed.

East African Network for Monitoring Antimalarial Treatment (EANMAT). 2003. The efficacy of antimalarial monotherapies, sulphadoxine-pyrimethamine and amodiaquine in East Africa: implications for sub-regional policy. Trop Med Int Health, 8 (10), pp. 860-867. | Show Abstract | Read more

Between 1998 and 2001, Kenya, Uganda, Tanzania, Zanzibar, Rwanda and Burundi changed antimalarial drug policy, in the face of widespread chloroquine resistance. The new first-line treatment is either sulphadoxine-pyrimethamine (SP) monotherapy, or a combination of SP with either chloroquine or amodiaquine. Two national malaria control programmes, Burundi and Zanzibar, have decided upon amodiaquine-artesunate as their first-line treatment, although SP will continue to fill this role until the new policy can be implemented. Given the broad uniformity of parasite chemoresistance in the six countries, The East African Network for Monitoring Antimalarial Treatment (EANMAT) has focused attention on, and worked towards, a sub-regional antimalarial drug policy, where the evidence base would be the entire portfolio of network in vivo test results. Currently, there are several different antimalarial drug policies within the EANMAT area: the intention is to eventually replace this plethora of policies with a single, sub-regional policy based upon combination therapy. Currently, successful malaria treatment depends primarily upon the efficacy of SP, and of amodiaquine, which is either a component of first-line treatment, or the second line drug. This report addresses the results of WHO in vivo tests on these two monotherapies within the network. Results are analysed to assess the evidence for change in parasite susceptibility over time; the range of susceptibility to each drug within countries, and the implications of test results on policy.

Hay S, Renshaw M, Ochola SA, Noor AM, Snow RW. 2003. Performance of forecasting, warning and detection of malaria epidemics in the highlands of western Kenya. Trends Parasitol, 19 (9), pp. 394-399. | Show Abstract | Read more

On the 4th July 2002 a leading national newspaper in Kenya, the Daily Nation, ran the headline 'Minister sounds alert on malaria' in an article declaring the onset of epidemics in the highlands of western Kenya. There followed frequent media coverage with quotes from district leaders on the numbers of deaths, and editorials on the failure of the national malaria control strategy. The Ministry of Health made immediate and radical changes to national policy on treatment costs in the highlands by suspending cost-sharing. Development partners and non-governmental organisations also responded with a large increase in the distribution of commodities (approximately 500,000 US dollars) to support preventative strategies across the western highland region. What was conspicuous by its absence was any obvious effort to predict the epidemics in advance of press coverage.

Snow RW, Eckert E, Teklehaimanot A. 2003. Estimating the needs for artesunate-based combination therapy for malaria case-management in Africa. Trends Parasitol, 19 (8), pp. 363-369. | Show Abstract | Read more

Because of inadequacies in national health information systems, the volumes of drugs required to support an effective policy transition toward artesunate-based combination therapy (ACT) are unknown for most African countries. A series of national surveys and population projections have been used to estimate the age-structured fever burden among 41 malaria endemic countries in Africa. Under present fever-management guidelines, commodity costs and internationally agreed coverage targets, the financial resources to meet the needs of ACT in most African countries are huge. Between US$1.6 billion and US$3.4 billion per annum must be found to give Africa the chance to consider a drug policy based on ACT. Substantial reductions in these costs would be achieved through more effective targeting of resources--only 20% of drugs would be required to manage fevers among the most at-risk pediatric patient populations. Better diagnostics would also be an important consideration for a new ACT policy in Africa.

Mwangi TW, Ross A, Marsh K, Snow RW. 2003. The effects of untreated bednets on malaria infection and morbidity on the Kenyan coast. Trans R Soc Trop Med Hyg, 97 (4), pp. 369-372. | Show Abstract | Read more

A study was conducted in order to determine whether children that slept under untreated bednets were protected against both malaria infection and clinical disease compared with children not sleeping under bednets. The study was conducted in Kilifi District, Kenya, during the malaria season (June-August, 2000) and involved 416 children aged < or = 10 years. Data collected from a cross-sectional survey showed evidence of protection against malaria infection among children sleeping under untreated bednets in good condition compared with those not using nets (adjusted odds ratio [AOR] = 0.4, 95% CI 0.22-0.72, P = 0.002). There was no evidence of a protective effect against infection when comparing those that used untreated bednets that were worn and those not using nets (AOR = 0.75, 95% CI 0.34-1.63, P = 0.47). When these same children were followed-up during the malaria season, there was evidence of a lower rate of clinical malaria among those that used untreated nets in good condition (adjusted incidence rate ratio = 0.65, 95% CI 0.45-0.94, P = 0.022), while the rate of clinical malaria among those that used untreated bednets that were worn was similar to that of those that did not use bednets. In the face of persistent failure of communities to take up net retreatment, there is hope that untreated nets will offer some protection against malaria infection and disease compared with not using nets at all.

Korenromp EL, Williams BG, Gouws E, Dye C, Snow RW. 2003. Measurement of trends in childhood malaria mortality in Africa: an assessment of progress toward targets based on verbal autopsy. Lancet Infect Dis, 3 (6), pp. 349-358. | Show Abstract | Read more

Reduction of deaths associated with malaria in children is a primary goal of malaria control programmes in Africa, but there has been little discussion about how changes in mortality will be measured. This paper assesses recent historical changes in the contribution of malaria to child survival in Africa by examining data from demographic surveillance systems (DSS) in 25 mainly rural settings. The data were adjusted for the varying sensitivity and specificity of verbal autopsies (VA) in different ranges of malaria mortality and for varying parasite prevalences. Average malaria mortality in the DSS sites in west Africa was 7.8 per 1000 child-years between 1982 and 1998; the rate did not change significantly over this period. In the sites in east and southern Africa combined, malaria mortality was 6.5 per 1000 child-years between 1982 and 1989, but it increased to 11.9 per 1000 child-years between 1990 and 1998. All-cause child mortality and non-malaria mortality, by contrast, decreased significantly over time in both regions; consequently, the proportion of deaths due to malaria rose from 18% to 23% in west African sites and from 18% to 37% in east and southern African sites between 1982-89 and 1990-98. If malaria mortality fell at a rate consistent with the Roll Back Malaria target of halving malaria mortality by the year 2010, an individual DSS of a total population of 63 500 could with adequate VA adjustment detect this reduction after 7 years.

Hay SI, Were EC, Renshaw M, Noor AM, Ochola SA, Olusanmi I, Alipui N, Snow RW. 2003. Forecasting, warning, and detection of malaria epidemics: a case study. Lancet, 361 (9370), pp. 1705-1706. | Show Abstract | Read more

Our aim was to assess whether a combination of seasonal climate forecasts, monitoring of meteorological conditions, and early detection of cases could have helped to prevent the 2002 malaria emergency in the highlands of western Kenya. Seasonal climate forecasts did not anticipate the heavy rainfall. Rainfall data gave timely and reliable early warnings; but monthly surveillance of malaria out-patients gave no effective alarm, though it did help to confirm that normal rainfall conditions in Kisii Central and Gucha led to typical resurgent outbreaks whereas exceptional rainfall in Nandi and Kericho led to true malaria epidemics. Management of malaria in the highlands, including improved planning for the annual resurgent outbreak, augmented by simple central nationwide early warning, represents a feasible strategy for increasing epidemic preparedness in Kenya.

Makani J, Matuja W, Liyombo E, Snow RW, Marsh K, Warrell DA. 2003. Admission diagnosis of cerebral malaria in adults in an endemic area of Tanzania: implications and clinical description. QJM, 96 (5), pp. 355-362. | Show Abstract | Read more

BACKGROUND: Cerebral malaria is commonly diagnosed in adults in endemic areas in Africa, both in hospitals and in the community. This presents a paradox inconsistent with the epidemiological understanding that the development of immunity during childhood confers protection against severe disease in adult life. AIM: To establish the contribution of Plasmodium falciparum infection in adults admitted with neurological dysfunction in an endemic area, to assess the implications of an admission clinical diagnosis of 'cerebral malaria' on the treatment and clinical outcome, and to describe the clinical features of patients with malaria parasitaemia. DESIGN: Prospective observational study. METHODS: We studied adult patients admitted with neurological dysfunction to Muhimbili National Hospital, Dar-es-Salaam, Tanzania from October 2000 to July 2001. A full blood count was done and serum creatinine, blood glucose and P. falciparum parasite load were measured. RESULTS: Of 199 patients (median age 34.6 years), 38% were diagnosed as 'cerebral malaria' on admission, but only 7.5% had detectable parasitaemia, giving a positive predictive value of 13.3%. Only 1% fulfilled the WHO criteria for cerebral malaria. The prevalence of parasitaemia (7.5%) was less than that observed in a group of asymptomatic controls (9.3%), but distribution of parasite densities was higher in the patients. Mortality was higher in patients with no parasitaemia (22.3%) than in those with parasitaemia (13%). DISCUSSION: Cerebral malaria was grossly overdiagnosed, resulting in unnecessary treatment and insufficient investigation of other possible diagnoses, which could lead to higher mortality. Extension of this misperception to the assessment of cause of death in community surveys may lead to an overestimation of the impact of malaria in adults.

Curtis C, Maxwell C, Lemnge M, Kilama WL, Steketee RW, Hawley WA, Bergevin Y, Campbell CC et al. 2003. Scaling-up coverage with insecticide-treated nets against malaria in Africa: who should pay? Lancet Infect Dis, 3 (5), pp. 304-307. | Show Abstract | Read more

Insecticide-treated nets (ITNs) have been shown to reduce the burden of malaria in African villages by providing personal protection and, if coverage of a community is comprehensive, by reducing the infective mosquito population. We do not accept the view that scaling-up this method should be by making villagers pay for nets and insecticide, with subsidies limited so as not to discourage the private sector. We consider that ITNs should be viewed as a public good, like vaccines, and should be provided via the public sector with generous assistance from donors. Our experience is that teams distributing free ITNs, replacing them after about 4 years when they are torn and retreating them annually, have high productivity and provide more comprehensive and equitable coverage than has been reported for marketing systems. Very few of the free nets are misused or sold. The estimated cost would be an annual expenditure of about US$295 million to provide for all of rural tropical Africa where most of the world's malaria exists. This expenditure is affordable by the world community as a whole, but not by its poorest members. Recently, funding of this order of magnitude has been committed by donor agencies for malaria control.

Hay SJ, Cox J, Rogers DJ, Randolph SE, Stern DL, Shanks GD, Myers MF, Snow RW. 2002. Climate change - Regional warming and malaria resurgence - Reply NATURE, 420 (6916), pp. 628-628. | Read more

Hay SI, Rogers DJ, Randolph SE, Stern DI, Cox J, Shanks GD, Snow RW. 2002. Hot topic or hot air? Climate change and malaria resurgence in East African highlands. Trends Parasitol, 18 (12), pp. 530-534. | Show Abstract | Read more

Climate has a significant impact on malaria incidence and we have predicted that forecast climate changes might cause some modifications to the present global distribution of malaria close to its present boundaries. However, it is quite another matter to attribute recent resurgences of malaria in the highlands of East Africa to climate change. Analyses of malaria time-series at such sites have shown that malaria incidence has increased in the absence of co-varying changes in climate. We find the widespread increase in resistance of the malaria parasite to drugs and the decrease in vector control activities to be more likely driving forces behind the malaria resurgence.

Shanks GD, Hay SI, Stern DI, Biomndo K, Snow RW. 2002. Meteorologic influences on Plasmodium falciparum malaria in the Highland Tea Estates of Kericho, Western Kenya. Emerg Infect Dis, 8 (12), pp. 1404-1408. | Show Abstract | Read more

Recent epidemics of Plasmodium falciparum malaria have been observed in high-altitude areas of East Africa. Increased malaria incidence in these areas of unstable malaria transmission has been attributed to a variety of changes including global warming. To determine whether the reemergence of malaria in western Kenya could be attributed to changes in meteorologic conditions, we tested for trends in a continuous 30-year monthly malaria incidence dataset (1966-1995) obtained from complete hospital registers at a Kenyan tea plantation. Contemporary monthly meteorologic data (1966-1995) that originated from the tea estate meteorologic station and from global climatology records were also tested for trends. We found that total hospital admissions (malaria and nonmalaria) remained unchanged while malaria admissions increased significantly during the period. We also found that all meteorologic variables showed no trends for significance, even when combined into a monthly suitability index for malaria transmission. We conclude that climate changes have not caused the highland malaria resurgence in western Kenya.

Guyatt HL, Ochola SA, Snow RW. 2002. Too poor to pay: charging for insecticide-treated bednets in highland Kenya. Trop Med Int Health, 7 (10), pp. 846-850. | Show Abstract | Read more

WHO has proposed malaria control as a means to alleviate poverty. One of its targets includes a 30-fold increase in insecticide-treated nets (ITNs) in the next 5 years. How this service will be financed remains unclear. In July 2000, 390 homesteads in rural highland Kenya were interviewed on their willingness to pay for ITNs. The costs to a household of protecting themselves with ITNs were compared with current household expenditure. Homesteads expressed a willingness to pay for ITNs, but the amounts offered were not sufficient to cover the costs of providing this service without donor support to meet the difference. Furthermore, as most household expenditure was allocated to basic needs these interventions were 'unaffordable'. The cost of protecting a household with ITNs would be equivalent to sending three children to primary school for a year. The aspiration by poor rural homesteads to protect themselves with ITNs is not compatible with their ability to pay. One option to have an immediate equitable impact on ITN coverage and break the cycle between malaria and poverty is to provide this service free of charge.

Teklehaimanot A, Snow RW. 2002. Will the Global Fund help roll back malaria in Africa? Lancet, 360 (9337), pp. 888-889. | Read more

Guyatt HL, Kinnear J, Burini M, Snow RW. 2002. A comparative cost analysis of insecticide-treated nets and indoor residual spraying in highland Kenya. Health Policy Plan, 17 (2), pp. 144-153. | Show Abstract | Read more

The relative cost of indoor residual house-spraying (IRS) versus insecticide-treated bednets (ITNs) forms part of decisions regarding selective malaria prevention. This paper presents a cost comparison of these two approaches as recently implemented by Merlin, a UK emergency relief organization funded through international donor support and working in the highland districts of Gucha and Kisii in Kenya. The financial costs (cash expenditures) and the economic costs (including the opportunity costs of using existing staff and volunteers, and an annualized cost for capital items) were assessed. The financial cost for IRS was US dollars 0.86 per person protected, compared with 4.21 dollars for ITNs (reducing to 3.42 dollars to the provider assuming cost recovery). The economic cost per person protected for IRS was 0.88 dollars, compared with 2.34 dollars for ITNs. The costs for ITNs were sensitive to the number of nets sold per community group ('efficiency'), as the delivery costs constituted upwards of 40% of the total cost. However, even marked increases in efficiency of these groups could not reduce the costs of ITNs to that comparable with IRS, except if more than one cycle of IRS was needed. The implications of predicted reductions in the cost of insecticide for both IRS and ITNs are also explored. The provision of itemized cost data allows predictions to be made on changes in the design of these programmes. Under almost all design scenarios, IRS would appear to be a more cost-efficient means of vector control in the Kenyan highlands.

Hay SI, Noor AM, Simba M, Busolo M, Guyatt HL, Ochola SA, Snow RW. 2002. Clinical epidemiology of malaria in the highlands of western Kenya. Emerg Infect Dis, 8 (6), pp. 543-548. | Show Abstract | Read more

Malaria in the highlands of Kenya is traditionally regarded as unstable and limited by low temperature. Brief warm periods may facilitate malaria transmission and are therefore able to generate epidemic conditions in immunologically naive human populations living at high altitudes. The adult:child ratio (ACR) of malaria admissions is a simple tool we have used to assess the degree of functional immunity in the catchment population of a health facility. Examples of ACR are collected from inpatient admission data at facilities with a range of malaria endemicities in Kenya. Two decades of inpatient malaria admission data from three health facilities in a high-altitude area of western Kenya do not support the canonical view of unstable transmission. The malaria of the region is best described as seasonal and meso-endemic. We discuss the implications for malaria control options in the Kenyan highlands.

Hay SI, Simba M, Busolo M, Noor AM, Guyatt HL, Ochola SA, Snow RW. 2002. Defining and detecting malaria epidemics in the highlands of western Kenya. Emerg Infect Dis, 8 (6), pp. 555-562. | Show Abstract | Read more

Epidemic detection algorithms are being increasingly recommended for malaria surveillance in sub-Saharan Africa. We present the results of applying three simple epidemic detection techniques to routinely collected longitudinal pediatric malaria admissions data from three health facilities in the highlands of western Kenya in the late 1980s and 1990s. The algorithms tested were chosen because they could be feasibly implemented at the health facility level in sub-Saharan Africa. Assumptions of these techniques about the normal distribution of admissions data and the confidence intervals used to define normal years were also investigated. All techniques identified two "epidemic" years in one of the sites. The untransformed Cullen method with standard confidence intervals detected the two "epidemic" years in the remaining two sites but also triggered many false alarms. The performance of these methods is discussed and comments made about their appropriateness for the highlands of western Kenya.

Guyatt HL, Gotink MH, Ochola SA, Snow RW. 2002. Free bednets to pregnant women through antenatal clinics in Kenya: a cheap, simple and equitable approach to delivery. Trop Med Int Health, 7 (5), pp. 409-420. | Show Abstract | Read more

Kenya's National Malaria Strategy states that insecticide-treated nets (ITNs) would be considered as a free service to pregnant women assuming sufficient financial commitment from donors. In 2001, United Nation's Children's Fund (UNICEF) and the Government of Kenya brokered support to procure and distribute nets and K-O TABs (deltamethrin) to 70 000 pregnant women in 35 districts throughout Kenya around Africa Malaria Day. This intervention represented the single largest operational distribution of ITN services in Kenya to date, and this study evaluates its success, limitations and costs. The tracking process from the central level through to antenatal clinic (ANC) facilities suggests that of the 70 000 nets procured, 37 206 nets (53%) had been distributed to pregnant women throughout the country within 12 weeks. One-fifth of the nets procured (14 117) had gone out to individuals other than pregnant women, most of these at the request of the district teams, with only 2870 nets estimated to have gone astray at the ANC facilities. At 12 weeks, the remaining 18 677 nets were still in storage awaiting distribution, with more than two-thirds having reached the district, and nearly half already being held at ANC facilities. The cost of getting a net and K-O TAB to an ANC facility ready for distribution to a pregnant woman was US$ 3.81. Accounting for the 14 117 nets that had gone to other users, the cost for an ITN received by a pregnant woman was US$ 5.26. Delivering ITNs free to pregnant women through ANCs uses an existing system (with positive spin-offs of low delivery cost and simple logistics), is equitable (as it not only targets those who can afford it) and can have the added benefits of strengthening ANC service, delivery and use.

Guyatt HL, Snow RW. 2002. Free insecticide for nets is cost effective - Response TRENDS IN PARASITOLOGY, 18 (5), pp. 205-205. | Read more

Guyatt HL, Corlett SK, Robinson TP, Ochola SA, Snow RW. 2002. Malaria prevention in highland Kenya: indoor residual house-spraying vs. insecticide-treated bednets. Trop Med Int Health, 7 (4), pp. 298-303. | Show Abstract | Read more

This study compares the effectiveness and cost-effectiveness of indoor residual house-spraying (IRS) and insecticide-treated bednets (ITNs) against infection with Plasmodium falciparum as part of malaria control in the highlands of western Kenya. Homesteads operationally targeted for IRS and ITNs during a district-based emergency response undertaken by an international relief agency were selected at random for evaluation. Five hundred and ninety homesteads were selected (200 with no vector control, 200 with IRS and 190 with ITNs). In July 2000, residents in these homesteads were randomly sampled according to three age-groups: 6 months-4 years, 5-15 years, and > 15 years for the presence of P. falciparum antigen (Pf HRP-2) using the rapid whole blood immunochromatographic test (ICT). The prevalence of P. falciparum infection amongst household members not protected by either IRS or ITN was 13%. Sleeping under a treated bednet reduced the risk of infection by 63% (58-68%) and sleeping in a room sprayed with insecticide reduced the risk by 75% (73-76%). The economic cost per infection case prevented by IRS was US$ 9 compared to US$ 29 for ITNs. This study suggests that IRS may be both more effective and cheaper than ITNs in communities subjected to low, seasonal risks of infection and as such should be considered as part of the control armamentarium for malaria prevention.

Molyneux CS, Mung'ala-Odera V, Harpham T, Snow RW. 2002. Maternal mobility across the rural-urban divide: empirical data from coastal Kenya. Environ Urban, 14 (1), pp. 203-217. | Show Abstract | Read more

This paper describes the mobility patterns, rural-urban linkages and household structures for a low-income neighbourhood on the outskirts of Mombasa, Kenya's main port, and a rural settlement 60 kilometres away. Drawing on interviews with a sample of mothers resident in each location, it documents their perceptions of the advantages and disadvantages of rural and urban life, and shows the continuous interchange between the two areas. It also highlights how most rural to urban migrants are familiar with urban environments before moving and how, having moved, many maintain strong rural ties. The ways in which households are split across rural and urban areas is influenced by intra-household relations and by household efforts to balance the income-earning opportunities in town, the relatively low cost of living in rural areas and future family security. This produces dramatic differences between and among rural and urban mothers and suggests a need for policy makers and planners to recognize diversity and to build upon complex livelihood strategies that span the rural-urban divide.

Hay SI, Cox J, Rogers DJ, Randolph SE, Stern DI, Shanks GD, Myers MF, Snow RW. 2002. Climate change and the resurgence of malaria in the East African highlands. Nature, 415 (6874), pp. 905-909. | Show Abstract | Read more

The public health and economic consequences of Plasmodium falciparum malaria are once again regarded as priorities for global development. There has been much speculation on whether anthropogenic climate change is exacerbating the malaria problem, especially in areas of high altitude where P. falciparum transmission is limited by low temperature. The International Panel on Climate Change has concluded that there is likely to be a net extension in the distribution of malaria and an increase in incidence within this range. We investigated long-term meteorological trends in four high-altitude sites in East Africa, where increases in malaria have been reported in the past two decades. Here we show that temperature, rainfall, vapour pressure and the number of months suitable for P. falciparum transmission have not changed significantly during the past century or during the period of reported malaria resurgence. A high degree of temporal and spatial variation in the climate of East Africa suggests further that claimed associations between local malaria resurgences and regional changes in climate are overly simplistic.

Rogers DJ, Randolph SE, Snow RW, Hay SI. 2002. Satellite imagery in the study and forecast of malaria. Nature, 415 (6872), pp. 710-715. | Show Abstract | Read more

More than 30 years ago, human beings looked back from the Moon to see the magnificent spectacle of Earth-rise. The technology that put us into space has since been used to assess the damage we are doing to our natural environment and is now being harnessed to monitor and predict diseases through space and time. Satellite sensor data promise the development of early-warning systems for diseases such as malaria, which kills between 1 and 2 million people each year.

Winstanley PA, Ward SA, Snow RW. 2002. Clinical status and implications of antimalarial drug resistance. Microbes Infect, 4 (2), pp. 157-164. | Show Abstract | Read more

Africa carries the greatest burden of disease caused by Plasmodium falciparum, and we can expect this burden to rise in the near future, mainly because of drug resistance. Although effective drugs are available (such as artemether-lumefantrine, mefloquine, atovaquone-proguanil and halofantrine) they are uniformly too expensive for routine use. Affordable options include chloroquine plus sulfadoxine-pyrimethamine (SP), amodiaquine (alone or in combination with SP) and chlorproguanil-dapsone. Artemisinin combination therapy may offer considerable advantages over alternative therapies, but its introduction faces considerable logistic difficulty.

Omumbo JA, Hay SI, Goetz SJ, Snow RW, Rogers DJ. 2002. Updating Historical Maps of Malaria Transmission Intensity in East Africa Using Remote Sensing. Photogramm Eng Remote Sensing, 68 (2), pp. 161-166. | Show Abstract

Remotely sensed imagery has been used to update and improve the spatial resolution of malaria transmission intensity maps in Tanzania, Uganda, and Kenya. Discriminant analysis achieved statistically robust agreements between historical maps of the intensity of malaria transmission and predictions based on multitemporal meteorological satellite sensor data processed using temporal Fourier analysis. The study identified land surface temperature as the best predictor of transmission intensity. Rainfall and moisture availability as inferred by cold cloud duration (ccd) and the normalized difference vegetation index (ndvi), respectively, were identified as secondary predictors of transmission intensity. Information on altitude derived from a digital elevation model significantly improved the predictions. "Malaria-free" areas were predicted with an accuracy of 96 percent while areas where transmission occurs only near water, moderate malaria areas, and intense malaria transmission areas were predicted with accuracies of 90 percent, 72 percent, and 87 percent, respectively. The importance of such maps for rationalizing malaria control is discussed, as is the potential contribution of the next generation of satellite sensors to these mapping efforts.

Molyneux CS, Murira G, Masha J, Snow RW. 2002. Intra-household relations and treatment decision-making for childhood illness: a Kenyan case study. J Biosoc Sci, 34 (1), pp. 109-131. | Show Abstract

This study, conducted on the Kenyan coast, assesses the effect of intra-household relations on maternal treatment-seeking. Rural and urban Mijikenda mothers' responses to childhood fevers in the last 2 weeks (n=317), and to childhood convulsions in the previous year (n=43), were documented through survey work. The intra-household relations and decision-making dynamics surrounding maternal responses were explored through in-depth individual and group interviews, primarily with women (n=223). Responses to convulsions were more likely than responses to fevers to include a healer consultation (p<0.0001), and less likely to include the purchase of over-the-counter medications (p<0.0001). Mothers received financial or advisory assistance from others in 71% (n=236) of actions taken outside the household in response to fevers. In-depth interviews suggested that general agreement on appropriate therapy results in relatively few intra-household conflicts over the treatment of fevers. Disputes over perceived cause and appropriate therapy of convulsions, however, highlighted the importance of age, gender and relationship to household head in intra-household relations and treatment decision-making. Although mothers' treatment-seeking preferences are often circumscribed by these relations, a number of strategies can be drawn upon to circumvent 'inappropriate' decisions, sometimes with implications for future household responses to similar syndromes. The findings highlight the complexity of intra-household relations and treatment decision-making dynamics. Tentative implications for interventions aimed at improving the home management of malaria, and for further research, are presented.

Hay SI, Cox J, Rogers DJ, Randolph SE, Stern DI, Shanks GD, Myers MF, Snow RW. 2002. Climate change (Communication arising): Regional warming and malaria resurgence Nature, 420 (6916), pp. 628-628. | Read more

Snow RW, Marsh K. 2002. The consequences of reducing transmission of Plasmodium falciparum in Africa. Adv Parasitol, 52 pp. 235-264. | Show Abstract | Read more

Malaria transmission intensity in Africa varies over several log orders, from less than one infected bite per year to more than one thousand. In this review we examine the consequences in terms of age pattern, clinical spectrum and overall burden of disease and discuss the possible implications for interventions that reduce exposure to infected bites. With very low transmission intensity, all age groups are susceptible to severe malaria. With increasing transmission intensities, older children and adults suffer less severe disease and with high transmission rates the majority of severe cases occur in infants under one year of age. This pattern reflects the increasingly rapid acquisition of immune responses that limit the life-threatening effects of malaria with increasing exposure to the parasite. The clinical spectrum of severe malaria varies with transmission: with high transmission, severe malarial anaemia dominates and cerebral malaria is rare. As one moves towards lower transmission rates, cerebral malaria accounts for an increasingly large proportion of cases. Although the population risk of severe disease falls with age, the risk of death at an individual level may rise with age after an initial fall from very high case fatality rates in children aged under 6 months. Of central interest to malaria control is how the overall amount of disease in childhood varies with transmission. Data from a number of sources suggest that, with low transmission, the amount of malarial disease rises with increasing exposure but that this saturates relatively early. A key issue is whether the same pattern obtains for deaths, both those directly due to malaria and those from all causes. The methodological limitations of ecological comparisons between different areas are discussed before presenting a review of attempts to use this approach in Africa. This suggests that children living in areas of low malarial endemicity have all-cause mortality rates about half of those of children living in areas of moderate to high transmission. Deaths in the first year of life rise linearly with increasing exposure to malaria over a wide range of transmission intensities; by contrast all-cause mortality in children aged 0-4 years appears to saturate at relatively low transmission intensities. These data suggest that interventions that reduce exposure to malaria parasites, such as insecticide-treated bed nets (ITNs), will have the greatest chance of a sustained effect when used in areas where disease burdens are high but the frequency of parasite exposure is low-to-moderate. In conditions of high transmission, initial reductions in mortality may prove difficult to sustain as the reduced level of transmission may still lie on the part of the curve where mortality has saturated. However, at all levels of transmission the overall balance of benefits, including reduced load on families and health services from non-life-threatening malaria, favours the widespread introduction of ITNs in endemic areas of Africa.

Guyatt HL, Snow RW. 2002. The cost of not treating bednets. Trends Parasitol, 18 (1), pp. 12-16. | Show Abstract | Read more

For centuries, bednets have been used as a physical barrier against biting insects. Recent epidemiological investigations into their protective effects against malaria were quickly overtaken by studies focusing on the benefits of impregnating bednets with insecticide. The operational problems encountered in re-treating bednets with insecticide are often cited as an impediment to wide-scale implementation. The evidence for a protective effect of untreated nets against malaria is presented here alongside an analysis of how well untreated nets would need to work in order to compete with treated nets within a cost-effectiveness framework.

Snow RW, Trape JF, Marsh K. 2001. The past, present and future of childhood malaria mortality in Africa. Trends Parasitol, 17 (12), pp. 593-597. | Show Abstract | Read more

During the past few years, there has been a historic series of declarations of renewed commitment to malaria control in Africa. Whether the burden of malaria is increasing in Africa is a moot point. This article attempts to re-construct the evidence for the trends in childhood mortality as a result of Plasmodium falciparum infection over the last century in Africa.

Guyatt HL, Snow RW. 2001. Malaria in pregnancy as an indirect cause of infant mortality in sub-Saharan Africa. Trans R Soc Trop Med Hyg, 95 (6), pp. 569-576. | Show Abstract | Read more

Although randomized controlled trials of interventions to reduce malaria in pregnancy have demonstrated an increase in the birthweight of the newborn in primigravidae, the subsequent impact on infant mortality in all-parities has not been assessed. The aim of this paper was to model the possible impact of placental malarial infection on infant mortality through reduced birthweight. An extensive literature search was undertaken to define a series of parameters describing the associations between placental infection, birthweight and premature mortality in sub-Saharan Africa. It was shown that a baby is twice as likely to be born of low birthweight if the mother has an infected placenta at the time of delivery (all-parities: 23% vs 11%, primigravidae only: 32% vs 16%), and that the probability of premature mortality of African newborns in the first year of life is 3 times higher in babies of low birthweight than in those of normal birthweight (16% vs 4.6%). Assuming 25% of pregnant women in malaria-endemic areas of Africa harbour placental malarial infection, it is suggested that 5.7% of infant deaths in malarious areas could be an indirect cause of malaria in pregnancy. This would imply that, in 1997, malaria in pregnancy could have been responsible for around 3700 infant deaths under the diverse epidemiological conditions in Kenya. Placental infection with Plasmodium falciparum appears to have a more significant role in infant survival in Africa than has been previously assumed. This may explain the high reduction in infant mortality rates from interventions aimed at reducing transmission, over and above that expected from a decline in direct malaria-specific mortality alone.

Shanks GD, Hay SI, Snow RW. 2001. Meteorological influences on highland malaria in the tea estates of western Kenya CLINICAL INFECTIOUS DISEASES, 33 (7), pp. 1244-1244.

Shretta R, Walt G, Brugha R, Snow R. 2001. A political analysis of corporate drug donations: the example of Malarone in Kenya. Health Policy Plan, 16 (2), pp. 161-170. | Show Abstract | Read more

This paper describes the introduction of the Malarone Donation Programme in KENYA: Using a policy analysis approach it illustrates the political nature of donation programmes and how they are affected by a large and varied group of national, regional and international stakeholders, with different levels of influence and experience. The paper shows that interaction between these different groups may affect the development and implementation of the donation programme. It ends by raising some more general questions about public/private partnerships and corporate donation programmes, and their potential impact on national drug policies.

Hay SI, Rogers DJ, Shanks GD, Myers MF, Snow RW. 2001. Malaria early warning in Kenya. Trends Parasitol, 17 (2), pp. 95-99. | Show Abstract | Read more

Kenya displays large spatiotemporal diversity in its climate and ecology. It follows that malaria transmission will reflect this environmental heterogeneity in both space and time. In this article, we discuss how such heterogeneity, and its epidemiological consequences, should be considered in the development of early warning systems for malaria epidemics.

Holding PA, Snow RW. 2001. Impact of Plasmodium falciparum malaria on performance and learning: review of the evidence. Am J Trop Med Hyg, 64 (1-2 Suppl), pp. 68-75. | Show Abstract

Despite the growing recognition that Plasmodium falciparum malaria constitutes a major threat to child survival, the indirect consequences of disease and infection on general human development have been less well described. This review suggests that malaria in childhood is likely to have effects on general cognitive and behavioral development, which range from subtle to profound. Nevertheless, our understanding of the numbers of affected children, and the persistence of and recovery from impairment remains ill defined. Only through large long-term studies will we be able to establish the wider consequences of malaria on communities in areas of the world where malaria is endemic.

Guyatt HL, Snow RW. 2001. The epidemiology and burden of Plasmodium falciparum-related anemia among pregnant women in sub-Saharan Africa. Am J Trop Med Hyg, 64 (1-2 Suppl), pp. 36-44. | Show Abstract

The paucity of precise information on the burden of malaria among pregnant women has hampered effective lobbying for the inclusion of preventative strategies against malaria in Safe Motherhood Initiatives. This article reviews the evidence on the coincidental risks of malaria and anemia in Africa and attempts to estimate the probable burden of malaria-related severe anemia in this susceptible group. Twenty-six studies on hemoglobin levels in all-parity pregnant women throughout this region could be matched with a malaria parasite ratio in children < 15 yr old (a measure of the intensity of transmission). In areas with no malaria, the mean hemoglobin levels were markedly higher than those found in areas with stable malaria transmission, though changes with increasing intensity of transmission were unclear. Eighteen studies from areas with stable malaria transmission in sub-Saharan Africa suggested that the median prevalence of severe anemia in all-parity pregnant women is approximately 8.2%. Assuming that 26% of these cases are due to malaria, it is suggested that as many as 400,000 pregnant women may have developed severe anemia as a result of infection with malaria in sub-Saharan Africa in 1995.

Snow RW. 2000. The burden of malaria: understanding the balance between immunity, public health and control. J Med Microbiol, 49 (12), pp. 1053-1055. | Read more

Shretta R, Omumbo J, Rapuoda B, Snow RW. 2000. Using evidence to change antimalarial drug policy in Kenya. Trop Med Int Health, 5 (11), pp. 755-764. | Show Abstract | Read more

Chloroquine resistance was first detected in Kenya in 1978 and escalated during the 1980s. Chloroquine remained the treatment of choice for uncomplicated malaria infections until revised guidelines were launched in 1998 despite a plethora of scientific evidence on failure. This review analyses the range and quality of the evidence base that was used to change the drug policy in Kenya from chloroquine to SP and examines the process of consensus building and decision making. Our review illustrates the difficulties in translating sensitivity data with gross geographical, temporal and methodological variations into national treatment policy. The process was complicated by limited options, unknown adverse effects of replacement therapies, cost, as well as limited guidance on factors pertinent to changing the drug policy for malaria. Although > 50% of the studies showed parasitological failures by 1995, there was a general lack of consensus on the principles for assessing drug failures, the inclusion criteria for the study subjects and the relative benefits of parasitological and clinical assessments. A change in international recommendations for assessment of drug efficacy in 1996 from parasitological to clinical response further perplexed the decisions. There is an urgent need for international standards and evidence-based guidelines to provide a framework to assist the process by which decision-makers in malaria-endemic countries can make rational choices for antimalarial drug policy change.

Hay SI, Myers MF, Burke DS, Vaughn DW, Endy T, Ananda N, Shanks GD, Snow RW, Rogers DJ. 2000. Etiology of interepidemic periods of mosquito-borne disease. Proc Natl Acad Sci U S A, 97 (16), pp. 9335-9339. | Show Abstract | Read more

Dengue viruses and malaria protozoa are of increasing global concern in public health. The diseases caused by these pathogens often show regular seasonal patterns in incidence because of the sensitivity of their mosquito vectors to climate. Between years in endemic areas, however, there can be further significant variation in case numbers for which public health systems are generally unprepared. There is an acute need for reliable predictions of within-year and between-year epidemic events. The prerequisite for developing any system of early warning is a detailed understanding of the factors involved in epidemic genesis. In this report we discuss the potential causes of the interepidemic periods in dengue hemorrhagic fever in Bangkok and of Plasmodium falciparum malaria in a highland area of western Kenya. The alternative causes are distinguished by a retrospective analysis of two unique and contemporaneous 33-year time series of epidemiological and associated meteorological data recorded at these two sites. We conclude that intrinsic population dynamics offer the most parsimonious explanation for the observed interepidemic periods of disease in these locations.

Howard SC, Omumbo J, Nevill C, Some ES, Donnelly CA, Snow RW. 2000. Evidence for a mass community effect of insecticide-treated bednets on the incidence of malaria on the Kenyan coast. Trans R Soc Trop Med Hyg, 94 (4), pp. 357-360. | Show Abstract | Read more

The use of insecticide-treated bednets (ITBNs) has been shown to be effective in reducing mortality and morbidity from malaria. However, there is mixed evidence as to whether or not community-wide use of ITBNs engenders a 'mass effect', such that those not sleeping under bednets are offered protection from widespread ITBN use in the area in which they live. We have analysed data collected in Kilifi, Kenya, from a cohort of children followed from birth to investigate how the degree of net usage in the locality of a child affects the risk of developing malaria. This effect was explored using a Cox proportional hazards model. For those not using ITBNs, we found that an increasing level of ITBN usage within the area surrounding each child was associated with a decreasing risk of developing malaria, thus providing evidence in support of a mass community effect. The size and significance of this effect were found to decrease as non-overlapping areas of increasing distance away from a child's home were considered. The effect was significant for areas at distances of up to 1.5 km away from each child.

Dobson MJ, Malowany M, Snow RW. 2000. Malaria control in East Africa: the Kampala Conference and the Pare-Taveta Scheme: a meeting of common and high ground. Parassitologia, 42 (1-2), pp. 149-166. | Show Abstract

The 1950 Malaria Conference in Equatorial Africa, held in Kampala, Uganda, has been remembered primarily for its decision to control malaria '...by modern methods as soon as feasible, whatever the original degree of endemicity, and without awaiting the outcome of further experiments.' This decision was far from conclusive and, indeed, reflects only one side of the argument which brought two groups of malariologists into direct opposition on the wisdom of malaria control in equatorial Africa, using modern methods such as DDT. Through an examination of the unpublished verbatim transcript of the Kampala Conference, we are able to document the 'furious debates' which took place at Kampala in 1950. We highlight, in particular, the adamant concerns expressed by some of the delegates that intervention in areas of high malaria transmission might lead to a loss of naturally acquired immunity which, in turn, could give rise to a resurgence of malaria, should the control strategies fail to be sustained. As we show, this concern had been expressed by a number of malariologists working in East Africa in the first half of the twentieth century, but it was only with the advent of DDT, as a residual insecticide, that the implications of wide-spread control, in the absence of any knowledge of the long-term consequences, became a serious possibility. While the Kampala Conference gave the 'go ahead' to control malaria in Africa without awaiting the outcome of 'further experiments', a number of participants insisted that a field trial should be set up to evaluate the impact of malaria on areas of high transmission both before and after spraying: to this end, a field trial in Pare-Taveta was carried out in 1954-59. In this paper we look at the Kampala Conference for its scientific debates and the Pare-Taveta Scheme for its field applications. In the final part of the paper, we address a number of questions raised at Kampala which have, once more, become contentious issues, following the recent successful trials of ITBNs. We believe that an understanding of the historical foundations of these issues should provide an important component of the new WHO campaign to Roll Back Malaria.

Shretta R, Brugha R, Robb A, Snow RW. 2000. Sustainability, affordability, and equity of corporate drug donations: the case of Malarone. Lancet, 355 (9216), pp. 1718-1720. | Read more

Shanks GD, Biomndo K, Hay SI, Snow RW. 2000. Changing patterns of clinical malaria since 1965 among a tea estate population located in the Kenyan highlands. Trans R Soc Trop Med Hyg, 94 (3), pp. 253-255. | Show Abstract | Read more

The changing epidemiology of clinical malaria since 1965 among hospitalized patients was studied at a group of tea estates in the western highlands of Kenya. These data indicate recent dramatic increases in the numbers of malaria admissions (6.5 to 32.5% of all admissions), case fatality (1.3 to 6%) and patients originating from low-risk, highland areas (34 to 59%). Climate change, environmental management, population migration, and breakdown in health service provision seem unlikely explanations for this changing disease pattern. The coincident arrival of chloroquine resistance during the late 1980s in the subregion suggests that drug resistance is a key factor in the current pattern and burden of malaria among this highland population.

Snow RW, Howard SC, Mung'Ala-Odera V, English M, Molyneux CS, Waruiru C, Mwangi I, Roberts DJ, Donnelly CA, Marsh K. 2000. Paediatric survival and re-admission risks following hospitalization on the Kenyan coast. Trop Med Int Health, 5 (5), pp. 377-383. | Show Abstract | Read more

The district general hospital (DGH) is a common feature of health service provision in many developing countries. We have used linked demographic and clinical surveillance in a rural community located close to a DGH on the Kenyan coast to define the use and public health significance of essential clinical services provided by it. Of a birth cohort of over 4000 children followed for approximately 6 years, about a third were admitted to hospital at least once. Significantly more children admitted with major infectious diseases such as malaria and acute respiratory tract infections were readmitted with the same condition during the surveillance period than would have been expected by chance. Among surviving admissions, mortality post-discharge was significantly higher than in the cohort which had not been admitted within 3, 6 and 12 months. Most of the patients who died after discharge had been admitted with a diagnosis of gastroenteritis. Most children admitted to the DGH survive hospitalization and the remaining period of childhood. Despite no clinical trial evidence to support the claim, it seems reasonable to assume that in the absence of intensive clinical management provided by a DGH, a significant proportion of these children would not have survived. However, the DGH is able to define a group of at-risk children who re-present with severe complications of infectious disease, and of these several may have underlying conditions not amenable to DGH intervention and continue to have a poor prognosis. Both groups of children represent statistically significant subsets of a rural paediatric community and the future organization and co-ordination of DGH and primary care services need to work in unison to strengthen the service needs of children at risk.

Hay SI, Rogers DJ, Toomer JF, Snow RW. 2000. Annual Plasmodium falciparum entomological inoculation rates (EIR) across Africa: literature survey, Internet access and review. Trans R Soc Trop Med Hyg, 94 (2), pp. 113-127. | Show Abstract | Read more

This paper presents the results of an extensive search of the formal and informal literature on annual Plasmodium falciparum entomological inoculation rates (EIR) across Africa from 1980 onwards. It first describes how the annual EIR data were collated, summarized, geo-referenced and staged for public access on the internet. Problems of data standardization, reporting accuracy and the subsequent publishing of information on the internet follow. The review was conducted primarily to investigate the spatial heterogeneity of malaria exposure in Africa and supports the idea of highly heterogeneous risk at the continental, regional and country levels. The implications for malaria control of the significant spatial (and seasonal) variation in exposure to infected mosquito bites are discussed.

Hay SI, Omumbo JA, Craig MH, Snow RW. 2000. Earth observation, geographic information systems and Plasmodium falciparum malaria in sub-Saharan Africa. Adv Parasitol, 47 pp. 173-215. | Show Abstract

This review highlights the progress and current status of remote sensing (RS) and geographical information systems (GIS) as currently applied to the problem of Plasmodium falciparum malaria in sub-Saharan Africa (SSA). The burden of P. falciparum malaria in SSA is first summarized and then contrasted with the paucity of accurate and recent information on the nature and extent of the disease. This provides perspective on both the global importance of the pathogen and the potential for contribution of RS and GIS techniques. The ecology of P. falciparum malaria and its major anopheline vectors in SSA in then outlined, to provide the epidemiological background for considering disease transmission processes and their environmental correlates. Because RS and GIS are recent techniques in epidemiology, all mosquito-borne diseases are considered in this review in order to convey the range of ideas, insights and innovation provided. To conclude, the impact of these initial studies is assessed and suggestions provided on how these advances could be best used for malaria control in an appropriate and sustainable manner, with key areas for future research highlighted.

Aitman TJ, Cooper LD, Norsworthy PJ, Wahid FN, Gray JK, Curtis BR, McKeigue PM, Kwiatkowski D et al. 2000. Malaria susceptibility and CD36 mutation. Nature, 405 (6790), pp. 1015-1016. | Read more

Molyneux CS, Mung'Ala-Odera V, Harpham T, Snow RW. 1999. Maternal responses to childhood fevers: a comparison of rural and urban residents in coastal Kenya. Trop Med Int Health, 4 (12), pp. 836-845. | Show Abstract | Read more

Urbanization is an important demographic phenomenon in sub-Saharan Africa, and rural-urban migration remains a major contributor to urban growth. In a context of sustained economic recession, these demographic processes have been associated with a rise in urban poverty and ill health. Developments in health service provision need to reflect new needs arising from demographic and disease ecology change. In malaria-endemic coastal Kenya, we compared lifelong rural (n = 248) and urban resident (n = 284) Mijikenda mothers' responses to childhood fevers. Despite marked differences between the rural and urban study areas in demographic structure and physical access to biomedical services, rural and urban mothers' treatment-seeking patterns were similar: most mothers sought only biomedical treatment (88%). Shop-bought medicines were used first or only in 69% of the rural and urban fevers that were treated, and government or private clinics were contacted in 49%. A higher proportion of urban informal vendors stocked prescription-only drugs, and urban mothers more likely to contact a private than a government facility. We conclude that improving self-treatment has enormous potential to reduce morbidity and mortality in low-income urban areas, as has frequently been argued for rural areas. However, because of the underlying socio-economic, cultural and structural differences between rural and urban areas, rural approaches to tackle this may have to be modified in urban environments.

Marsh K, Snow RW. 1999. Malaria transmission and morbidity. Parassitologia, 41 (1-3), pp. 241-246. | Show Abstract

Stable malaria endemicity is maintained over a wide range of transmission intensities in sub-Saharan Africa. This paper considers variations in the clinical manifestations and their consequences with differences in transmission intensity. Epidemiological approaches to malarial disease have concentrated on two clinical syndromes, severe malarial anaemia and cerebral malaria. Within an area the mean age of children with severe malarial anaemia is always lower than that of those with cerebral malaria. In areas of higher malaria transmission children, on average, encounter malaria at a younger age and the mean age of clinical cases is lower. Malarial anaemia tends therefore to be relatively more important under high transmission settings and cerebral malaria tends to gain in importance under lower transmission settings. In a number of studies the total load of malaria morbidity, whether measured as none severe malaria in the community or as severe malaria admitted to hospital, is low under stable low transmission conditions but is at its highest under moderate intensities of transmission. Thereafter it reaches a plateau, or even falls, at the highest transmission intensities. It is not known whether the same is true for mortality in communities living under different transmission settings. Possible implications for changes in patterns of morbidity and mortality following interventions which lower malaria transmission are discussed. It is concluded that such interventions should play an important role in integrated malaria control programmes but that these should involve concomitant introduction of other interventions, in order to minimise the possible risks of a reduced effect as the immune response of the population re-equilibrates in the face of reduced challenge.

White NJ, Nosten F, Looareesuwan S, Watkins WM, Marsh K, Snow RW, Kokwaro G, Ouma J et al. 1999. Averting a malaria disaster. Lancet, 353 (9168), pp. 1965-1967. | Read more

Brooker S, Peshu N, Warn PA, Mosobo M, Guyatt HL, Marsh K, Snow RW. 1999. The epidemiology of hookworm infection and its contribution to anaemia among pre-school children on the Kenyan coast. Trans R Soc Trop Med Hyg, 93 (3), pp. 240-246. | Show Abstract | Read more

Intestinal nematode infections are recognized as a major public health problem, and helminth control is currently being directed towards school-aged children who are known to harbour the heaviest infections and are most likely to suffer from associated morbidity. However, few data are available for the epidemiology of intestinal nematodes in pre-school children in Africa, and the contribution of hookworm infection to the aetiology and severity of anaemia among pre-school children remains poorly understood. This paper investigates the epidemiology of parasitic infections in 460 pre-school children who were part of a larger case-control study of severe malaria in Kilifi on the Kenyan coast. Almost one-third (28.7%) were infected with hookworm, 20.2% with Ascaris lumbricoides and 15.0% with Trichuris trichiura. Infection prevalence of each species rose with age, and the prevalence of heavy infection with hookworm and mean intensity of hookworm were markedly age-dependent. One-third (34.3%) of children had malaria. Overall, 76.3% of children were anaemic (haemoglobin < 110 g/L), with the prevalence decreasing with age. Anaemia was significantly worst in children with heavy hookworm infection (> 200 eggs per gram). This relationship held for all ages, both sexes, and was independent of socioeconomic factors. The application of attributable morbidity methods confirmed the contribution of hookworm infection to anaemia.

Mbogo CN, Kabiru EW, Glass GE, Forster D, Snow RW, Khamala CP, Ouma JH, Githure JI, Marsh K, Beier JC. 1999. Vector-related case-control study of severe malaria in Kilifi District, Kenya. Am J Trop Med Hyg, 60 (5), pp. 781-785. | Show Abstract

A case-control study examined vector-related and environmental parameters associated with severe malaria in Kilifi District along the coast of Kenya. Over an 11-month period, 119 children identified with severe malaria infections at the Kilifi District Hospital were matched by age with control children who reported to the outpatient clinic with nonsevere infections. Intensive mosquito sampling was done in each of the case-control houses over a four-day period, beginning within a week of index case admission. A total of 109 environmental, demographic, behavioral, and animal husbandry variables were characterized for each household. Vector species (Anopheles gambiae s.l. and An. funestus) were detected in 40.1% and 36.1% of case and control houses, respectively. The relative abundance of vectors in individual houses was stable over the two-week resampling periods (r = 0.9). Both the overall abundance of anopheline mosquitoes (odds ratio [OR] = 1.5) and P. falciparum sporozoite rates (OR = 1.5) were not significantly different between case and control houses. In a matched analysis, 11 of 109 house variables associated significantly with severe malaria were also associated with vector abundance, as determined by chi-square linear trend analysis. Under conditions of year-round, low-level transmission on the coast of Kenya, the risk of severe disease in children is multifactorial and not governed strictly by transmission intensity or environmental heterogeneity affecting vector abundance and distributions. This suggests that current interventions that appear to be achievable only in areas where transmission is already low to moderate should be appropriate. However, such interventions should be monitored so that inappropriate and possibly disastrous control activities can be avoided in Africa.

Guyatt HL, Snow RW, Evans DB. 1999. Malaria epidemiology and economics: the effect of delayed immune acquisition on the cost-effectiveness of insecticide-treated bednets. Philos Trans R Soc Lond B Biol Sci, 354 (1384), pp. 827-835. | Show Abstract | Read more

An understanding of the epidemiology of a disease is central in evaluating the health impact and cost-effectiveness of control interventions. The epidemiology of life-threatening malaria is receiving renewed interest, with concerns that the implementation of preventive measures such as insecticide-treated bednets (ITNs) while protecting young children might in fact increase the risks of mortality and morbidity in older ages by delaying the acquisition of functional immunity. This paper aims to illustrate how a combined approach of epidemiology and economics can be used to (i) explore the long-term impact of changes in epidemiological profiles, and (ii) identify those variables that are critical in determining whether an intervention will be an efficient use of resources. The key parameters for determining effectiveness are the protective efficacy of ITNs (reduction in all-cause mortality), the malaria attributable mortality and the increased malaria-specific mortality risk due to delays in the acquisition of functional immunity. In particular, the analysis demonstrates that delayed immune acquisition is not a problem per se, but that the critical issue is whether it occurs immediately following the implementation of an ITN programme or whether it builds up slowly over time. In the 'worst case' scenario where ITNs immediately increase malaria-specific mortality due to reduced immunity, the intervention might actually cost lives. In other words, it might be better to not use ITNs. On the other hand, if reduced immunity takes two years to develop, ITNs would still fall into the category of excellent value for money compared to other health interventions, saving a year of life (YLL) at a cost of between US$25-30. These types of calculations are important in identifying the parameters which field researchers should be seeking to measure to address the important question of the net impact of delaying the acquisition of immunity through preventive control measures.

Craig MH, Snow RW, le Sueur D. 1999. A climate-based distribution model of malaria transmission in sub-Saharan Africa. Parasitol Today, 15 (3), pp. 105-111. | Show Abstract | Read more

Malaria remains the single largest threat to child survival in sub-Saharan Africa and warrants long-term investment for control. Previous malaria distribution maps have been vague and arbitrary. Marlies Craig, Bob Snow and David le Sueur here describe a simple numerical approach to defining distribution of malaria transmission, based upon biological constraints of climate on parasite and vector development. The model compared well with contemporary field data and historical 'expert opinion' maps, excepting small-scale ecological anomalies. The model provides a numerical basis for further refinement and prediction of the impact of climate change on transmission. Together with population, morbidity and mortality data, the model provides a fundamental tool for strategic control of malaria.

Snow RW, Craig MH, Deichmann U, le Sueur D. 1999. A preliminary continental risk map for malaria mortality among African children. Parasitol Today, 15 (3), pp. 99-104. | Show Abstract | Read more

Approaches to global public health are increasingly driven by an understanding of regional patterns of disease-specific mortality and disability. Current estimates of disease risks associated with Plasmodium falciparum in sub-Saharan Africa remain poorly defined. Through the integration of high-resolution population and climate probability models of P. falciparum transmission, geographical information systems have been used to define the spatial limits of populations exposed to the risk of infection in Africa. These estimates were combined with a range of annual malaria-specific mortality rates, derived from a variety of epidemiological approaches, among children aged 0-4 years. The best estimates of malaria-attributable mortality using this approach ranged between 0. 43 million and 0.68 million deaths per annum among an exposed population of approximately 66 million children in 1990. Despite the limitations of modelled transmission and population distributions, these empirical approaches to probabilities of infection risk and epidemiological data on mortality provide a novel approach to present and projected burdens of malaria mortality, as discussed here by Bob Snow, Marlies Craig, Uwe Deichmann and Dave le Sueur.

Gupta S, Snow RW, Donnelly CA, Marsh K, Newbold C. 1999. Immunity to non-cerebral severe malaria is acquired after one or two infections. Nat Med, 5 (3), pp. 340-343. | Show Abstract | Read more

In areas of stable transmission, clinical immunity to mild malaria is acquired slowly, so it is not usually effective until early adolescence. Life-threatening disease is, however, restricted to a much younger age group, indicating that resistance to the severe clinical consequences of infection is acquired more quickly. Understanding how rapidly immunity develops to severe malaria is essential, as severe malaria should be the primary target of intervention strategies, and predicting the result of interventions that reduce host exposure will require consideration of these dynamics. Severe disease in childhood is less frequent in areas where transmission is the greatest. One explanation for this is that infants experience increased exposure to infection while they are protected from disease, possibly by maternal antibody. They therefore emerge from this period of clinical protection with considerably more immunity than those who experience lower transmission intensities. Here we use this data, assuming a period of clinical protection, to estimate the number of prior infections needed to reduce the risk of severe disease to negligible levels. Contrary to expectations, one or two successful infective bites seem to be all that is necessary across a broad range of transmission intensities.

Snow RW, McCabe E, Mbogo CN, Molyneux CS, Some ES, Mung'ala VO, Nevill CG. 1999. The effect of delivery mechanisms on the uptake of bed net re-impregnation in Kilifi District, Kenya. Health Policy Plan, 14 (1), pp. 18-25. | Show Abstract | Read more

The results of recently completed trials in Africa of insecticide-treated bed nets (ITBN) offer new possibilities for malaria control. These experimental trials aimed for high ITBN coverage combined with high re-treatment rates. Whilst necessary to understand protective efficacy, the approaches used to deliver the intervention provide few indications of what coverage of net re-treatment would be under operational conditions. Varied delivery and financing strategies have been proposed for the sustainable delivery of ITBNs and re-treatment programmes. Following the completion of a randomized, controlled trial on the Kenyan coast, a series of suitable delivery strategies were used to continue net re-treatment in the area. The trial adopted a bi-annual, house-to-house re-treatment schedule free of charge using research project staff and resulted in over 95% coverage of nets issued to children. During the year following the trial, sentinel dipping stations were situated throughout the community and household members informed of their position and opening times. This free re-treatment service achieved between 61-67% coverage of nets used by children for three years. In 1997 a social marketing approach, that introduced cost-retrieval, was used to deliver the net re-treatment services. The immediate result of this transition was that significantly fewer of the mothers who had used the previous re-treatment services adopted this revised approach and coverage declined to 7%. The future of new delivery services and their financing are discussed in the context of their likely impact upon previously defined protective efficacy and cost-effectiveness estimates.

Gupta S, Snow RW, Donnelly C, Newbold C. 1999. Acquired immunity and postnatal clinical protection in childhood cerebral malaria. Proc Biol Sci, 266 (1414), pp. 33-38. | Show Abstract | Read more

By analysing data on the age distribution of cerebral malaria among sites of different transmission intensities, we conclude that the most plausible explanation for the epidemiological patterns seen is that (i) cerebral malaria is caused by a distinct set of Plasmodium falciparum antigenic types; (ii) these antigenic types or 'CM strains' are very common and induce strong strain-specific immunity; and (iii) the postnatal period of protection against cerebral malaria is much longer than the period of protection against other forms of severe disease. The alternative hypothesis that cerebral malaria may be caused by any 'strain' of P. falciparum is compatible with the data only if a single exposure is sufficient to protect against further episodes. This is not consistent with observations on the history of exposure of patients with cerebral malaria. Finally, it is clear that although the delayed peak in incidence of cerebral malaria (with age) can be generated by assuming that subsequent exposures carry a higher risk of disease, such an explanation is not compatible with the observation that severe disease rates are low among infants and young children in areas of high transmissibility.

Snow RW, Craig M, Deichmann U, Marsh K. 1999. Estimating mortality, morbidity and disability due to malaria among Africa's non-pregnant population. Bull World Health Organ, 77 (8), pp. 624-640. | Show Abstract

The contribution of malaria to morbidity and mortality among people in Africa has been a subject of academic interest, political advocacy, and speculation. National statistics for much of sub-Saharan Africa have proved to be an unreliable source of disease-specific morbidity and mortality data. Credible estimates of disease-specific burdens are required for setting global and national priorities for health in order to rationalize the use of limited resources and lobby for financial support. We have taken an empirical approach to defining the limits of Plasmodium falciparum transmission across the continent and interpolated the distributions of projected populations in 1995. By combining a review of the literature on malaria in Africa and models of acquired functional immunity, we have estimated the age-structured rates of the fatal, morbid and disabling sequelae following exposure to malaria infection under different epidemiological conditions.

Snow RW, Gouws E, Omumbo J, Rapuoda B, Craig MH, Tanser FC, le Sueur D, Ouma J. 1998. Models to predict the intensity of Plasmodium falciparum transmission: applications to the burden of disease in Kenya. Trans R Soc Trop Med Hyg, 92 (6), pp. 601-606. | Show Abstract | Read more

There is an increasing need to provide spatial distribution maps of the clinical burden of Plasmodium falciparum malaria in Africa. Recent evidence suggests that risk groups and the clinical spectrum of severe malaria are related to the intensity of P. falciparum transmission. Climate operates to affect the vectorial capacity of P. falciparum transmission and this is particularly important in the Horn of Africa and parts of East Africa. We have used a fuzzy logic climate suitability model to define areas of Kenya unsuitable for stable transmission. Kenya's unstable transmission areas can be divided into areas where transmission potential is limited by low rainfall or low temperature and, combined, encompass over 8 million people. Among areas of stable transmission we have used empirical data on P. falciparum infection rates among 124 childhood populations in Kenya to develop a climate-based statistical model of transmission intensity. This model correctly identified 75% (95% confidence interval CI 70-85) of 3 endemicity classes (low, < 20%; high, > or = 70%; and intermediate parasite prevalences). The model was applied to meteorological and remote sensed data using a geographical information system to provide estimates of endemicity for all of the 1080 populated fourth level administrative regions in Kenya. National census data for 1989 on the childhood populations within each administrative region were projected to provide 1997 estimates. Endemicity-specific estimates of morbidity and mortality were derived from published and unpublished sources and applied to their corresponding exposed-to-risk childhood populations. This combined transmission, population and disease-risk model suggested that every day in Kenya approximately 72 and 400 children below the age of 5 years either die or develop clinical malaria warranting in-patient care, respectively. Despite several limitations, such an approach goes beyond 'best guesses' to provide informed estimates of the geographical burden of malaria and its fatal consequences in Kenya.

Dobson MJ, Malowany M, Ombongi K, Snow RW. 1998. The voice of East Africa: the East African Medical Journal at its 75th anniversary. Trans R Soc Trop Med Hyg, 92 (6), pp. 685-686. | Read more

Hay SI, Snow RW, Rogers DJ. 1998. From predicting mosquito habitat to malaria seasons using remotely sensed data: practice, problems and perspectives. Parasitol Today, 14 (8), pp. 306-313. | Show Abstract | Read more

Remote sensing techniques are becoming increasingly important for identifying mosquito habitats, investigating malaria epidemiology and assisting malaria control. Here, Simon Hay, Bob Snow and David Rogers review the development of these techniques, from aerial photographic identification of mosquito larval habitats on the local scale through to the space-based survey of malaria risk over continental areas using increasingly sophisticated airborne and satellite-sensor technology. They indicate that previous constraints to uptake are becoming less relevant and suggest how future delays in the use of remotely sensed data in malaria control might be avoided.

Snow RW, Peshu N, Forster D, Bomu G, Mitsanze E, Ngumbao E, Chisengwa R, Schellenberg JR, Hayes RJ, Newbold CI, Marsh K. 1998. Environmental and entomological risk factors for the development of clinical malaria among children on the Kenyan coast. Trans R Soc Trop Med Hyg, 92 (4), pp. 381-385. | Show Abstract | Read more

Several malariometric studies have examined the impact on human-vector contact of house construction, demographics, bed net and insect repellent use. However, few studies have documented the significance of these proximate determinants on the risks of clinical disease. We undertook a matched case-control study of the risks of both mild clinical malaria and severe life-threatening malaria according to a range of putative factors which would influence the frequency of child-vector encounters in Kilifi district on the Kenyan coast. Among 394 severe disease cases, 380 age-matched mild disease cases, and their respective location and age-matched community controls, we were unable to demonstrate any statistically significant effect upon disease outcome of house construction, presence of domestic animals, or bed net use. Higher population density within a 250 m radius of the homes conferred significant protection from the risks of developing severe malaria compared to community controls. The risks of developing severe malaria compared to the community controls and the transition from mild to severe disease were statistically significantly lower in those who reported use of mosquito coils, local repellents or aerosol insecticides. We concluded that it is likely that the impact of household features on disease outcome is dependent upon both the density of infecting mosquitoes and acquired immunity within a given locality.

Schellenberg JA, Newell JN, Snow RW, Mung'ala V, Marsh K, Smith PG, Hayes RJ. 1998. An analysis of the geographical distribution of severe malaria in children in Kilifi District, Kenya. Int J Epidemiol, 27 (2), pp. 323-329. | Show Abstract | Read more

BACKGROUND: Although malaria is known to be a major cause of child mortality and morbidity throughout sub-Saharan Africa there are few detailed studies of malaria mortality rates and incidence of severe malarial disease in defined communities. We have studied the geographical pattern of admissions to hospital with severe malaria and the stability of this pattern over time in Kilifi District on the Kenyan Coast. METHODS: Over a 2-year period all children under 5 years of age with severe malaria admitted to the district hospital and living in a rural study population of about 50,000 people were identified. Annual censuses were carried out in the study area, and all households were mapped using a hand-held satellite navigation system. The resulting databases were linked using a geographical information system (GIS). RESULTS: Using methods originally developed for the study of the geographical distribution of childhood leukaemia we assessed the spatial pattern of hospital admission rates for severe malaria. As expected, admission rates were significantly higher in children with easier access to the hospital. For example, those living more than 25 km from the hospital had admission rates which were about one-fifth of those for children living within 5 km of the hospital. Those living more than 2.5 km from the nearest road had admission rates that were about half of those for children living within 0.5 km of a road. We also investigated short-term local fluctuations in severe malaria and found evidence of space-time clustering of severe malaria. CONCLUSIONS: Hospital admission rates for severe malaria are higher in households with better access to hospital than in those further away. The finding of space-time clusters of severe malaria suggests that it would be of value to conduct case-control studies of environmental, genetic and human behavioural factors involved in the aetiology of the disease.

Shulman CE, Dorman EK, Talisuna AO, Lowe BS, Nevill C, Snow RW, Jilo H, Peshu N, Bulmer JN, Graham S, Marsh K. 1998. A community randomized controlled trial of insecticide-treated bednets for the prevention of malaria and anaemia among primigravid women on the Kenyan coast. Trop Med Int Health, 3 (3), pp. 197-204. | Show Abstract | Read more

The effectiveness of insecticide-treated bednets (ITBN) in preventing malaria and anaemia among primigravidae living in Kilifi District, Kenya, was assessed by a randomized controlled trial between September 1994 and November 1995. All residents within 28 community clusters received ITBN in July 1993, whilst residents of another 28 clusters served as contemporaneous controls. All resident primigravid women with singleton pregnancies attending antenatal care at Kilifi District Hospital were eligible for recruitment. 503 primigravidae were recruited. 91.4% were anaemic antenatally (Hb < 11 g/dl): 91.0% from the intervention arm and 92.0% from the control arm. Severe anaemia (Hb < 7 g/dl) was found among 15.1% of intervention women and 20.1% of control women (P = 0.28). No significant differences were observed in reports of febrile illness or the presence of chloroquine in the serum or peripheral parasitaemia during the third trimester between the two groups. In the women delivering in hospital (n = 130), there was no association between placental malaria infection and the intervention: 77.4% of placentas from control women had evidence of past or active infection, compared with 72.0% of placentas from intervention women (P = 0.76). Similarly, in the women delivering in hospital, ITBN did not improve birth weight, and there were no differences in perinatal mortality between the two study groups. Despite ITBN having a great impact on paediatric severe malaria and mortality in this transmission setting, there was very little impact of ITBN on the morbidity associated with malaria infection in primigravidae. Alternative strategies are required to tackle this continued public health problem for pregnant women living in endemic areas similar to the Kenyan Coast.

Snow RW, Nahlen B, Palmer A, Donnelly CA, Gupta S, Marsh K. 1998. Risk of severe malaria among African infants: direct evidence of clinical protection during early infancy. J Infect Dis, 177 (3), pp. 819-822. | Show Abstract | Read more

Little empirical evidence from field-based studies exists on the relative magnitude or duration of clinical protection from Plasmodium falciparum malaria in infancy. A prospective study was undertaken to examine the age distribution of hospital admissions in four geographically and demographically well-defined areas with differing intensities of P. falciparum transmission. Where transmission was perennial, significant clinical protection from severe morbidity was observed up to the third month of life; in the seasonal transmission area, disease rates rose after the sixth month of life. Infants exposed to the highest rates of P. falciparum exposure demonstrated significant declines in the risks of severe malaria from 6 months of age. These data provide direct evidence for the very early acquisition of clinical immunity and for the existence of a period of clinical protection, which together may explain why, in these communities, the cumulative risk of malarial disease throughout childhood appears to decline with increasing transmission intensity.

Kirigia JM, Snow RW, Fox-Rushby J, Mills A. 1998. The cost of treating paediatric malaria admissions and the potential impact of insecticide-treated mosquito nets on hospital expenditure. Trop Med Int Health, 3 (2), pp. 145-150. | Show Abstract | Read more

OBJECTIVE: To calculate the costs at Kilifi District Hospital (KDH) and Malindi Sub-district Hospital (MSH) of treating paediatric malaria admissions including three common presentations of severe paediatric malaria, i.e. cerebral malaria, severe malaria anaemia and malaria-associated seizures; and to estimate the implications for hospital expenditure of a reduction in paediatric malaria admissions. METHODS: Patient data were obtained from hospital records. All costs were allocated to departments that provided direct patient care by a four-stage step-down procedure. Laboratory and drug costs of treating paediatric malaria admissions were separately identified. RESULT: Unit recurrent costs per admission in KDH ranged from US $57 for 'other' paediatric malaria to US $105 for cerebral malaria, and in MSH from US $33 to US $44 for the same categories. The annual recurrent cost of treating all paediatric malaria admissions to KDH prior to the trial was estimated at US $78 900. Adjusting for preintervention differences in malaria admission rates and age between intervention and control areas, the ITBN trial found a 41% reduction in paediatric malaria admissions. The reduction in admissions resulted in an estimated saving of US $6240 in the cost of treating paediatric malaria admissions from the intervention area. CONCLUSION: There would be a substantial reduction in costs of treating paediatric malaria admissions if the intervention were introduced in the whole catchment area of the hospital. Actual savings would depend on the proportion of potential savings that can in practice be realised, and on the effectiveness of the intervention when routinely implemented.

Omumbo J, Ouma J, Rapuoda B, Craig MH, le Sueur D, Snow RW. 1998. Mapping malaria transmission intensity using geographical information systems (GIS): an example from Kenya. Ann Trop Med Parasitol, 92 (1), pp. 7-21. | Show Abstract | Read more

That there are so few examples of the use of epidemiological maps in malaria control may be explained by the lack of suitable, spatially defined data and of an understanding of how epidemiological variables relate to disease outcome. However, recent evidence suggests that the clinical outcomes of infection are determined by the intensity of parasite exposure, and developments in geographical information systems (GIS) provide new ways to represent epidemiological data spatially. In the present study, parasitological data from 682 cross-sectional surveys conducted in Kenya were abstracted and spatially defined. Risks of infection with Plasmodium falciparum among Kenyan children, estimated from combinations of parasitological, geographical, demographic and climatic data in a GIS platform, appear to be low for 2.9 million, stable but low for another 1.3 million, moderate for 3.0 million and high for 0.8 million. (Estimates were not available for 1.4 million children.) Whilst the parasitological data were obtained from a variety of sources across different age-groups and times, these markers of endemicity remained relatively stable within the broad definitions of high, moderate and low transmission intensity. Models relating ecological and climatic features to malaria intensity and improvements in our understanding of the relationships between parasite exposure and disease outcome will hopefully provide a more rational basis for malaria control in the near future.

Snow RW, Marsh K. 1998. New insights into the epidemiology of malaria relevant for disease control. Br Med Bull, 54 (2), pp. 293-309. | Show Abstract | Read more

Despite over 100 years of scientific investigation, malaria remains the leading cause of death among children living in sub-Saharan Africa. Our understanding of the epidemiology of clinical malaria has, until recently, been hampered by a paucity of empirical data from endemic settings. A striking feature of Plasmodium falciparum malaria is that, compared to infection and mild disease, severe complications and death are rare. Perhaps the single most important factor which ameliorates the risk of asymptomatic infection progressing to life-threatening pathology is the development of clinical immunity. Examination of recent epidemiological evidence suggests that the speed with which clinical immunity is acquired is dependent upon the frequency of parasite exposure from birth. Consequently, the age at which disease presentation peaks, the clinical spectrum of disease and the life-time risks of disease appear to be a function of the intensity of transmission within a given community. These observations are discussed in relation to control measures aimed at reducing P. falciparum exposure and the need to understand better the processes by which children naturally acquire clinical immunity before more rational statements can be made about their wide-spread use in Africa.

Hay SI, Snow RW, Rogers DJ. 1998. Predicting malaria seasons in Kenya using multitemporal meteorological satellite sensor data. Trans R Soc Trop Med Hyg, 92 (1), pp. 12-20. | Show Abstract | Read more

This article describes research that predicts the seasonality of malaria in Kenya using remotely sensed images from satellite sensors. The predictions were made using relationships established between long-term data on paediatric severe malaria admissions and simultaneously collected data from the Advanced Very High Resolution Radiometer (AVHRR) on the National Oceanic and Atmospheric Administrations (NOAA) polar-orbiting meteorological satellites and the High Resolution Radiometer (HRR) on the European Organization for the Exploitation of Meteorological Satellites' (EUMETSAT) geostationary Meteosat satellites. The remotely sensed data were processed to provide surrogate information on land surface temperature, reflectance in the middle infra-red, rainfall, and the normalized difference vegetation index (NDVI). These variables were then subjected to temporal Fourier processing and the fitted Fourier data were compared with the mean percentage of total annual malaria admissions recorded in each month. The NDVI in the preceding month correlated most significantly and consistently with malaria presentations across the 3 sites (mean adjusted r2 = 0.71, range 0.61-0.79). Regression analyses showed that an NDVI threshold of 0.35-0.40 was required for more than 5% of the annual malaria cases to be presented in a given month. These thresholds were then extrapolated spatially with the temporal Fourier-processed NDVI data to define the number of months, in which malaria admissions could be expected across Kenya in an average year, at an 8 x 8 km resolution. The resulting maps were compared with the only existing map (Butler's) of malaria transmission periods for Kenya, compiled from expert opinion. Conclusions are drawn on the appropriateness of remote sensing techniques for compiling national strategies for malaria intervention.

Snow RW, Marsh K. 1998. The epidemiology of clinical malaria among African children. Bull Inst Pasteur, 96 (1), pp. 15-23. | Show Abstract | Read more

There is a resurgence of interest in the clinical epidemiology of malaria among African children. This renewed interest follows fifty years of failure to eradicate infection in Africa and redirected efforts toward disease control and prevention. We have a poor understanding of the mechanisms by which clinical immunity is acquired; however, several recent studies have provided new insights into how fast clinical protection is acquired under the varied transmission intensities common to Africa. What is clear is that the frequency with which individuals encounter infection from birth will determine the speed with which they become clinically immune and the patterns of severe pathology they are likely to experience. There remains doubt and concerns over the long-term consequences of reducing natural parasite exposure in several areas of Africa. New field studies are urgently required to tackle these issues so that control may be guided by an improved understanding of malaria as a disease that can lead to death.

Seboxa T, Snow RW. 1997. Epidemiological features of severe paediatric malaria in north western Ethiopia. East Afr Med J, 74 (12), pp. 780-783. | Show Abstract

Malaria remains a major public health challenge in sub-Saharan Africa, yet our knowledge of the epidemiology of malaria in terms of patterns of mortality and morbidity is limited. To examine the clinical and epidemiological presentation of severe life-threatening malaria in Humera, north western Ethiopia studies were conducted among the childhood population in the community, those presenting to out-patient facilities and those admitted to the district hospital. The overall P. falciparum parasite rate among children aged 0-9 years resident within the area was only 12% confirming the low level of endemicity in this area. P. vivax infections were present in 5% of children. Between July 1993 and June 1994 peak out-patient presentation with Plasmodium falciparum coincided with the rains with over 50% of cases occurring between August and October whilst P. vivax infections were predominant during the hot, dry months. Malaria was an important cause of paediatric admission to the local district hospital with an estimated 4.7% of the at-risk childhood community warranting intensive clinical management each year. Case fatality rates were high and the clinical spectrum of severe disease indicated a preponderance of cerebral malaria cases. In addition, respiratory distress was a feature in 12% of the malaria admissions. The suggestion that the coexistence of Plasmodium falciparum and Plasmodium vivax may serve to reduce the severe clinical consequences of P. falciparum malaria is not supported by these observations.

Amukoye E, Winstanley PA, Watkins WM, Snow RW, Hatcher J, Mosobo M, Ngumbao E, Lowe B, Ton M, Minyiri G, Marsh K. 1997. Chlorproguanil-dapsone: effective treatment for uncomplicated falciparum malaria. Antimicrob Agents Chemother, 41 (10), pp. 2261-2264. | Show Abstract

Pyrimethamine-sulfadoxine, the first choice for uncomplicated falciparum malaria in Africa, exerts strong selection pressure for resistance because of its slow elimination. It is likely that resistance will emerge rapidly, and there is no widely affordable replacement. Chlorproguanil-dapsone is cheap, rapidly eliminated, more potent than pyrimethamine-sulfadoxine, and could be introduced in the near future to delay the onset of antifolate resistance and as "salvage therapy" for pyrimethamine-sulfadoxine failure. A total of 448 children were randomly allocated (double blind) to either a single dose of pyrimethamine-sulfadoxine or to one of two chlorproguanil-dapsone regimens: a single dose or three doses at 24-h intervals. Reinfections are clinically indistinguishable from recrudescence and are more likely after treatment with rapidly eliminated drugs; we measured the incidence of parasitemia in 205 initially aparasitemic children to allow comparison with the three treatment groups. The patients and a community surveillance group were followed up for 28 days. At the study end point, 31.2% (95% confidence interval, 24.9-38.0) of the community surveillance group subjects were parasitemic, compared with subjects in the treatment groups, whose rates of parasitemia were 40.8% (32.9-49.0; relative risk [RR], 1.31 [0.99-1.73]) after triple-dose chlorproguanil-dapsone, 19.7% (13.5-27.2; RR, 0.63 [0.43-0.93]) after pyrimethamine-sulfadoxine, and 65.6% (57.5-73.0; RR, 2.10 [1.66-2.65]) after single-dose chlorproguanil-dapsone. Pyrimethamine-sulfadoxine and triple-dose chlorproguanil-dapsone were effective treatments. Pyrimethamine-sulfadoxine provided chemoprophylaxis during follow-up because of its slow elimination. Triple-dose chlorproguanil-dapsone should now be developed in an attempt to reduce the rate of emergence of antifolate resistance in Africa and for affordable salvage therapy in cases of pyrimethamine-sulfadoxine failure.

Fernandez-Reyes D, Craig AG, Kyes SA, Peshu N, Snow RW, Berendt AR, Marsh K, Newbold CI. 1997. A high frequency African coding polymorphism in the N-terminal domain of ICAM-1 predisposing to cerebral malaria in Kenya. Hum Mol Genet, 6 (8), pp. 1357-1360. | Show Abstract | Read more

The malarial parasite Plasmodium falciparum has acted as a potent selective force on the human genome. The particular virulence of this organism is thought to be due to the adherence of parasitised red blood cells to small vessel endothelium through several receptors, including CD36, thrombospondin and intercellular adhesion molecule 1 (ICAM-1, CD54), and parasite isolates differ in their ability to bind to each. Immunohistochemical studies have implicated ICAM-1 as of potential importance in the pathogenesis of cerebral malaria, leading us to reason that if any single receptor were involved in the development of cerebral malaria, then in view of the high mortality of that complication, natural selection should have produced variants with reduced binding capacity. We therefore sequenced the N-terminal domain of ICAM-1 from a number of Africans and discovered a single mutation present at high frequency. Genotypes at this locus from samples from a case-control study indicated an association of the polymorphism with the severity of clinical malaria such that individuals homozygous for the mutation have increased susceptibility to cerebral malaria with a relative risk of two. These counterintuitive results have implications for the mechanism of malaria pathogenesis, resistance to other infectious agents and transplantation immunology.

Newbold CI, Craig AG, Kyes S, Berendt AR, Snow RW, Peshu N, Marsh K. 1997. PfEMP1, polymorphism and pathogenesis. Ann Trop Med Parasitol, 91 (5), pp. 551-557. | Show Abstract | Read more

The virulence of Plasmodium falciparum relative to the other species of malarial parasite which infect humans is thought to be due to this parasite's ability to adhere to endothelial cells lining small blood vessels and, in some cases, to its ability to form rosettes with uninfected erythrocytes. The latter phenotype has been found more frequently in cases of severe disease. The former property means that only the younger, asexual, intra-erythrocytic forms circulate whereas the more mature developmental stages are sequestered in the vasculature of a variety of organs. When large numbers of parasites accumulate in a vulnerable target organ such as the brain, the the life-threatening condition of cerebral malaria may result. While the factors that control whether or not cerebral malaria develops are not clearly defined, one crucial determinant my be the endothelial receptors utilised by the infecting isolate. Many such receptors have been identified, including CD36, thrombospondin, ICAM-1, VCAM, E-selectin and chondroitin-4-sulphate. The results of laboratory, field, post-mortem and direct receptor-binding studies indicate that, of the receptors currently identified, ICAM-1 binding is more likely to be associated with the development of cerebral malaria. The molecule expressed on the surface of the infected erythrocyte which mediates adherence to endothelium belongs to a large family of clonally variable antigens encoded by the var genes. The evidence for this conclusion and progress in defining the regions of var-gene products responsible to receptor-specific binding are discussed. Finally, the organization of the var genes within and between parasites is discussed in relation to the evolution of the var-gene family and its functions of antigenic variation and endothelial adhesion.

Snow RW, Omumbo JA, Lowe B, Molyneux CS, Obiero JO, Palmer A, Weber MW, Pinder M et al. 1997. Relation between severe malaria morbidity in children and level of Plasmodium falciparum transmission in Africa. Lancet, 349 (9066), pp. 1650-1654. | Show Abstract | Read more

BACKGROUND: Malaria remains a major cause of mortality and morbidity in Africa. Many approaches to malaria control involve reducing the chances of infection but little is known of the relations between parasite exposure and the development of effective clinical immunity so the long-term effect of such approaches to control on the pattern and frequency of malaria cannot be predicted. METHODS: We have prospectively recorded paediatric admissions with severe malaria over three to five years from five discrete communities in The Gambia and Kenya. Demographic analysis of the communities exposed to disease risk allowed the estimation of age-specific rates for severe malaria. Within each community the exposure to Plasmodium falciparum infection was determined through repeated parasitological and serological surveys among children and infants. We used acute respiratory-tract infections (ARI) as a comparison. FINDINGS: 3556 malaria admissions were recorded for the five sites. Marked differences were observed in age, clinical spectrum and rates of severe malaria between the five sites. Paradoxically, the risks of severe disease in childhood were lowest among populations with the highest transmission intensities, and the highest disease risks were observed among populations exposed to low-to-moderate intensities of transmission. For severe malaria, for example, admission rates (per 1000 per year) for children up to their 10th birthday were estimated as 3.9, 25.8, 25.9, 16.7, and 18.0 in the five communities; the forces of infection estimated for those communities (new infections per infant per month) were 0.001, 0.034, 0.050, 0.093, and 0.176, respectively. Similar trends were noted for cerebral malaria and for severe malaria anaemia but not for ARI. Mean age of disease decreased with increasing transmission intensity. INTERPRETATION: We propose that a critical determinant of life-time disease risk is the ability to develop clinical immunity early in life during a period when other protective mechanisms may operate. In highly endemic areas measures which reduce parasite transmission, and thus immunity, may lead to a change in both the clinical spectrum of severe disease and the overall burden of severe malaria morbidity.

Marsh K, Snow RW. 1997. 30 years of science and technology: the example of malaria. Lancet, 349 (Suppl 3), pp. 1-2.

Snow RW, Molyneux CS, Njeru EK, Omumbo J, Nevill CG, Muniu E, Marsh K. 1997. The effects of malaria control on nutritional status in infancy. Acta Trop, 65 (1), pp. 1-10. | Show Abstract | Read more

Both malaria and undernutrition are major causes of paediatric mortality and morbidity in sub-Saharan Africa. The introduction of insecticide-treated bed nets (ITBN) during a randomized controlled trial on the Kenyan coast significantly reduced severe, life-threatening malaria and all-cause childhood mortality. This paper describes the effects of the intervention upon the nutritional status of infants aged between 1 and 11 months of age. Seven hundred and eighty seven infants who slept under ITBN and 692 contemporaneous control infants, were seen during one of three cross-sectional surveys conducted during a one year period. Standardized weight-for-age and mid-upper arm circumference measures were significantly higher among infants who used ITBN compared with control infants. Whether these improvements in markers of nutritional status were a direct result of concomitant reductions in clinical malaria episodes remains uncertain. Never-the-less evidence suggests that even moderate increases in weight-for-age scores can significantly reduce the probability of mortality in childhood and ITBN may provide additional gains to child survival beyond their impressive effects upon malaria-specific events.

Newton CR, Warn PA, Winstanley PA, Peshu N, Snow RW, Pasvol G, Marsh K. 1997. Severe anaemia in children living in a malaria endemic area of Kenya. Trop Med Int Health, 2 (2), pp. 165-178. | Show Abstract | Read more

Severe anaemia is an important cause of morbidity and mortality in African children, but the causes, particularly falciparum malaria, are difficult to determine. We assessed the contribution of falciparum malaria to anaemia in Kenyan children by clinical examination and measurement of parasitaemia and haemoglobin (Hb) concentration in 559 children in the community and in 2412 children admitted to Kilifi district hospital during a 2-year period. We also attempted to characterize severe malarial anaemia by examining the causes and pathophysiology of anaemia in 101 children admitted with Hb concentration < or = 50 g/l during a 1-year period. Plasmodium falciparum infection was associated with reduced Hb concentration in children in the community and in those admitted to hospital irrespective of diagnosis. Falciparum malaria was the primary cause in 46 cases (46%) of severe anaemia admitted to hospital. There was no difference in the frequency of haemolysis or dyserythropoiesis in the children with malarial anaemia and those with anaemia from other causes, such as iron deficiency or sickle cell disease. The mortality rate in the children with severe malarial anaemia was 8.6% compared with 3.6% in children with severe anaemia due to other causes. Falciparum malaria does not present with a characteristic clinical or haematological picture, but is a major cause of the morbidity and mortality in children with severe anaemia who live on the Kenyan coast, a malaria endemic area.

Cited:

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Scopus

Snow RW, Marsh K, leSueur D. 1996. The need for maps of transmission intensity to guide malaria control in Africa PARASITOLOGY TODAY, 12 (12), pp. 455-457. | Read more

Shulman CE, Graham WJ, Jilo H, Lowe BS, New L, Obiero J, Snow RW, Marsh K. 1996. Malaria is an important cause of anaemia in primigravidae: evidence from a district hospital in coastal Kenya. Trans R Soc Trop Med Hyg, 90 (5), pp. 535-539. | Show Abstract | Read more

A study was undertaken in order to determine the prevalence and aetiology of anaemia in pregnancy in coastal Kenya, so as to establish locally important causes and enable the development of appropriate intervention strategies. 275 women attending the antenatal clinic at Kilifi district hospital, Kenya, were recruited in November 1993. The prevalence of anaemia (haemoglobin [Hb] < 11 g/dL) was 75.6%, and the prevalence of severe anaemia (Hb < 7g/dL) was 9.8% among all parities; 15.3% of 73 primigravidae were severely anaemic, compared with 7.9% of 202 multigravidae (P = 0.07). In primigravidae, malaria infection (Plasmodium falciparum) was strongly associated with moderate and severe anaemia (chi 2 test for trend, P = 0.003). Severe anaemia was more than twice as common in women with peripheral parasitaemia as in those who were aparasitaemic, and parasitaemia was associated with a 2.2g/dL decrease in mean haemoglobin level (P < 0.001). In multigravidae, iron deficiency and hookworm infection were the dominant risk factors for anaemia. Folate deficiency and human immunodeficiency virus infection were not strongly associated with anaemia. It is suggested that an intervention that can effectively reduce malaria infection in primigravidae could have a major impact on the health of these women and their infants.

Behrens RH, Bradley DJ, Snow RW, Marsh K. 1996. Impact of UK malaria prophylaxis policy on imported malaria. Lancet, 348 (9023), pp. 344-345. | Read more

Snow RW, Molyneux CS, Warn PA, Omumbo J, Nevill CG, Gupta S, Marsh K. 1996. Infant parasite rates and immunoglobulin M seroprevalence as a measure of exposure to Plasmodium falciparum during a randomized controlled trial of insecticide-treated bed nets on the Kenyan coast. Am J Trop Med Hyg, 55 (2), pp. 144-149. | Show Abstract

Repeated cross-sectional surveys among infants sleeping under insecticide-treated bed nets (ITBN) and contemporary control infants were used to estimate changes in Plasmodium falciparum exposure due to ITBN use on the Kenyan coast. Presence of P. falciparum parasites or total P. falciparum Immunoglobulin M (IgM) seropositivity were used independently and in combination in a constant risk catalytic conversion model to estimate the force of infection in ITBN and control communities. Such studies during infancy avoid problems of early saturation of prevalence due to high forces of infection and persistence of infection, minimize problems of self-treatment, and can be conducted among large populations covering a wide geographic area. These contrast previous parasitologic studies of ITBN among older children and the traditional entomologic studies of transmission that are logistically demanding. Our investigations demonstrated that parasite prevalence, IgM seropositivity, and the force of transmission were all significantly reduced by 50%. In addition, more infants under ITBN entered their second year of life without previous exposure to P. falciparum than control infants. These effects upon delayed acquisition of effective immunity require careful monitoring during future vector control programs using ITBN.

Mbogo CN, Baya NM, Ofulla AV, Githure JI, Snow RW. 1996. The impact of permethrin-impregnated bednets on malaria vectors of the Kenyan coast. Med Vet Entomol, 10 (3), pp. 251-259. | Show Abstract | Read more

The effects of introducing permethrin-impregnated bednets on local populations of the malaria vector mosquitoes Anopheles funestus and the An.gambiae complex was monitored during a randomized controlled trial at Kilifi on the Kenyan coast. Pyrethrum spray collections: inside 762 households were conducted between May 1994 and April 1995 after the introduction of bednets in half of the study area. All-night human bait collections were performed in two zones (one control and one intervention) for two nights each month during the same period. PCR identifications of An.gambiae sensu lato showed that proportions of sibling species were An.gambiae sensu stricto > An.merus > An.arabiensis. Indoor-resting densities of An.gambiae s.l. and the proportion of engorged females decreased significantly in intervention zones as compared to control zones. However, the human blood index and Plasmodium falciparum sporozoite rate remained unaffected. Also vector parous rates were unaltered by the intervention, implying that survival rates of malaria vectors were not affected. The human-biting density of An.gambiae s.l., the predominant vector, was consistently higher in the intervention zone compared to the control zone, but showed 8% reduction compared to pre-intervention biting rates-versus 94% increase in the control zone. Bioassay, susceptibility and high-performance liquid chromatography results all indicated that the permethrin content applied to the nets was sufficient to maintain high mortality of susceptible vectors throughout the trial. Increased rates of early outdoor-biting, as opposed to indoor-biting later during the night, were behavioural or vector composition changes associated with this intervention, which would require further monitoring during control programmes employing insecticide-treated bednets.

Nevill CG, Some ES, Mung'ala VO, Mutemi W, New L, Marsh K, Lengeler C, Snow RW. 1996. Insecticide-treated bednets reduce mortality and severe morbidity from malaria among children on the Kenyan coast. Trop Med Int Health, 1 (2), pp. 139-146. | Show Abstract | Read more

New tools to prevent malaria morbidity and mortality are needed to improve child survival in sub-Saharan Africa. Insecticide treated bednets (ITBN) have been shown, in one setting (The Gambia, West Africa), to reduce childhood mortality. To assess the impact of ITBN on child survival under different epidemiological and cultural conditions we conducted a community randomized, controlled trial of permethrin treated bednets (0.5 g/m2) among a rural population on the Kenyan Coast. Between 1991 and 1993 continuous community-based demographic surveillance linked to hospital-based in-patient surveillance identified all mortality and severe malaria morbidity events during a 2-year period among a population of over 11000 children under 5 years of age. In July 1993, 28 randomly selected communities were issued ITBN, instructed in their use and the nets re-impregnated every 6 months. The remaining 28 communities served as contemporaneous controls for the following 2 years, during which continuous demographic and hospital surveillance was maintained until the end of July 1995. The introduction of ITBN led to significant reductions in childhood mortality (PE 33%, CI 7-51%) and severe, life-threatening malaria among children aged 1-59 months (PE 44%, CI 19-62). These findings confirm the value of ITBN in improving child survival and provide the first evidence of their specific role in reducing severe morbidity from malaria.

Waruiru CM, Newton CR, Forster D, New L, Winstanley P, Mwangi I, Marsh V, Winstanley M, Snow RW, Marsh K. 1996. Epileptic seizures and malaria in Kenyan children. Trans R Soc Trop Med Hyg, 90 (2), pp. 152-155. | Show Abstract | Read more

Between October 1990 and November 1991 data were collected on the frequency, causes, and nature of epileptic seizures in children admitted to the paediatric ward at Kilifi District Hospital, Kenya, from a defined study area. During this period, 1324 children were studied, of whom 15.8% had seizures as part of their illness. Malaria was by far the commonest cause of seizures, accounting for 69.0%; no other single condition caused more than 4.4%. The proportion of respiratory infections complicated by seizures was 4.0% compared to 31.3% for malaria. Only 25% of malaria-related epileptic seizures were associated with cerebral malaria; the remainder were associated with otherwise uncomplicated malaria and, in this group, 84% had complex seizures, with 47% being partial and over 70% repetitive. There was no relationship with fever, with 54% of observed seizures occurring at rectal temperatures below 38 degrees C. The minimum community incidence of complex seizures in association with non-cerebral malaria was 5.8 per 1000 per year. Complex epileptic seizures in association with otherwise uncomplicated malaria are common and may be a significant cause of longer term morbidity in malaria endemic areas.

Gupta S, Snow RW. 1996. How do bednets influence the transmissibility of Plasmodium falciparum? Parasitol Today, 12 (3), pp. 89-90. | Read more

Quigley MA, Armstrong Schellenberg JR, Snow RW. 1996. Algorithms for verbal autopsies: a validation study in Kenyan children. Bull World Health Organ, 74 (2), pp. 147-154. | Show Abstract

The verbal autopsy (VA) questionnaire is a widely used method for collecting information on cause-specific mortality where the medical certification of deaths in childhood is incomplete. This paper discusses review by physicians and expert algorithms as approaches to ascribing cause of deaths from the VA questionnaire and proposes an alternative, data-derived approach. In this validation study, the relatives of 295 children who had died in hospital were interviewed using a VA questionnaire. The children were assigned causes of death using data-derived algorithms obtained under logistic regression and using expert algorithms. For most causes of death, the data-derived algorithms and expert algorithms yielded similar levels of diagnostic accuracy. However, a data-derived algorithm for malaria gave a sensitivity of 71% (95% Cl: 58-84%), which was significantly higher than the sensitivity of 47% obtained under an expert algorithm. The need for exploring this and other ways in which the VA technique can be improved are discussed. The implications of less-than-perfect sensitivity and specificity are explored using numerical examples. Misclassification bias should be taken into consideration when planning and evaluating epidemiological studies.

Marsh VM, Mutemi W, Some ES, Haaland A, Snow RW. 1996. Evaluating the community education programme of an insecticide-treated bed net trial on the Kenyan coast. Health Policy Plan, 11 (3), pp. 280-291. | Show Abstract | Read more

Increased interest in the potential contribution of insecticide-impregnated bed nets (ITBN) to malaria control has led to research efforts to determine the impact and sustainability of ITBN programmes in differing environments. There is a need to develop effective, feasible educational strategies that will both inform and motivate community members, and thus maximize the correct usage of ITBN. This is especially true in communities where indigenous usage of bed nets is low. This paper describes the educational component of a randomized controlled community intervention trial of ITBN, with childhood malaria morbidity as an outcome. The educational approach and messages for the ITBN trial were developed from anthropological survey data collected 4 years before the trial, and from community surveys conducted by project researchers. Low levels of understanding amongst mothers of the aetiological link between mosquitos and malaria led to the exclusion of the term 'malaria' from the initial educational messages promoting the use of ITBN. Appropriate individuals within the existing district health care structure were trained as community educators in the project. These educators conducted intensive teaching in the community through public meetings and group teaching in the first 6 months of the trial. The impact of these initial activities was assessed through interviews with a random sample of 100 mothers and 50 household heads. This allowed the identification of messages which had not been well understood and further educational methods were chosen to address the areas pinpointed. The community assessment also demonstrated that, in 1994, over 90% of mothers understood a protective role for bed nets against malaria and the ITBN education messages were changed to take account of this. The school programme was evaluated through determining outreach (the number of households accessed), changes in participant children's knowledge, post-teaching assessment of mothers' knowledge and discussions with parent-teacher associations. It was shown that 40% of intervention homes with children in the target group were accessed, participant children learned the educational messages well (scores increased from a pre-teaching mean of 59% to a post-teaching mean of 92%) and a high level of awareness of the ITBN trial was achieved in these homes (75%). However, specific messages of the education programmed were not well transferred to the home (30%). The discussion emphasises the need for allocation of adequate resources for education in programmes dependent on achieving a change in community practices. We also describe the value of ongoing communication between programme planners and a target population in maximizing the effectiveness of messages and methods used.

Lengeler C, Snow RW. 1996. From efficacy to effectiveness: insecticide-treated bednets in Africa. Bull World Health Organ, 74 (3), pp. 325-332. | Show Abstract

Insecticide-treated bednets and curtains (ITBC) have proven in recent large-scale trials to have a high efficacy in reducing morbidity and mortality from malaria in African children. However, it is unlikely that the efficacy measured in trials can be entirely sustained under programme conditions. This has important implications for the cost-effectiveness of the intervention. Furthermore, there is a need to assess the long-term impact of ITBC. This article traces the history of ITBC and the different phases of their assessment, especially the determination of efficacy in randomized controlled trials (phase III assessment). It then outlines the reasons for continued assessment of their effectiveness under programme conditions (phase IV assessment). The methodologies for measuring effectiveness are discussed, and a critical review of the issues reveals that it is impractical to measure effectiveness directly. A simple effectiveness model, allowing for differentiation between individual and community effectiveness, provides a useful conceptual framework. First, individual effectiveness is measured through a case-control study. This estimate is then combined with a coverage indicator to estimate community effectiveness. This approach could provide programme managers with a powerful tool to monitor the impact of health interventions at the community level.

Greenwood BM, David PH, Otoo-Forbes LN, Allen SJ, Alonso PL, Armstrong Schellenberg JR, Byass P, Hurwitz M, Menon A, Snow RW. 1995. Mortality and morbidity from malaria after stopping malaria chemoprophylaxis. Trans R Soc Trop Med Hyg, 89 (6), pp. 629-633. | Show Abstract | Read more

Gambian children who had received malaria chemoprophylaxis for a variable period of time during their first 5 years of life were followed to determine whether they experienced a rebound in mortality or in morbidity from malaria during the period after chemoprophylaxis was stopped. The risk of dying between the ages of 5 years, when chemoprophylaxis was stopped, and 10 years was no higher among children who had received chemoprophylaxis with Maloprim (pyrimethamine plus dapsone) for some period during their first 5 years of life than among children who had received placebo (21 vs. 24 deaths) and the beneficial effect of chemoprophylaxis on mortality observed during the first 5 years of life was sustained. The incidence of clinical attacks of malaria during the year after medication was stopped was significantly higher among children who had previously received Maloprim for several years than among children who had previously received placebo. However, at the end of this year, there was no significant difference in spleen rate, parasite rate or packed cell volume between the 2 groups of children. Thus, stopping chemoprophylaxis after a period of several years increased the risk of clinical malaria but did not result in a rebound in mortality in Gambian children. However, the number of deaths recorded was small, so a modest effect on mortality cannot be excluded.

Ruwende C, Khoo SC, Snow RW, Yates SN, Kwiatkowski D, Gupta S, Warn P, Allsopp CE, Gilbert SC, Peschu N. 1995. Natural selection of hemi- and heterozygotes for G6PD deficiency in Africa by resistance to severe malaria. Nature, 376 (6537), pp. 246-249. | Show Abstract | Read more

Glucose-6-phosphate dehydrogenase (G6PD) deficiency, the most common enzymopathy of humans, affects over 400 million people. The geographical correlation of its distribution with the historical endemicity of malaria suggests that this disorder has risen in frequency through natural selection by malaria. However, attempts to confirm that G6PD deficiency is protective in case-control studies of malaria have yielded conflicting results. Hence, for this X-linked disorder, it is unclear whether both male hemizygotes and female heterozygotes are protected or, as frequently suggested, only females. Furthermore, how much protection may be afforded is unknown. Here we report that, in two large case-control studies of over 2,000 African children, the common African form of G6PD deficiency (G6PD A-) is associated with a 46-58% reduction in risk of severe malaria for both female heterozygotes and male hemizygotes. A mathematical model incorporating the measured selective advantage against malaria suggests that a counterbalancing selective disadvantage, associated with this enzyme deficiency, has retarded its rise in frequency in malaria-endemic regions. Although G6PD deficiency is now regarded as a generally benign disorder, in earlier environmental conditions it could have been significantly disadvantageous.

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SNOW R, MARSH K. 1995. WILL REDUCING PLASMODIUM-FALCIPARUM TRANSMISSION ALTER MALARIA MORTALITY AMONG AFRICAN CHILDREN PARASITOLOGY TODAY, 11 (5), pp. 188-190. | Show Abstract | Read more

There have been few attempts to examine the relationship between the intensity of transmission and the ensuing burden of disease or mortality from Plasmodium falciparum in Africa Bob Snow and Kevin Marsh here present the available data on malaria-specific mortality and severe morbidity among African children in relation to estimates of annual rates of falciparum inoculation. These data suggest that cohort mortality from malaria may remain similar between areas experiencing over 100-fold differences in transmission pressure. The authors raise doubts about the possible long term benefits to children living in areas of high transmission of control strategies aimed at sustained reduction in human-vector contact, for example insecticide treated bednets.

Mwenesi H, Harpham T, Snow RW. 1995. Child malaria treatment practices among mothers in Kenya. Soc Sci Med, 40 (9), pp. 1271-1277. | Show Abstract | Read more

A study of 883 mothers with children aged 0-9 years was undertaken in Kilifi district on the Kenyan coast in order to examine child malaria treatment practices. Quantitative and qualitative methods were used to investigate: whether complications of childhood malaria were recognized; decision-making dynamics in treatment-seeking; and the extent and reasons for the use of proprietary treatment. Childhood malaria was perceived as a mild, everyday illness, not preventable but treatable. The link between malaria and mosquitoes was not recognized. Mothers recognized convulsions, anaemia and splenomegaly but did not link them to malaria. Antimalarial drugs were not given or were withdrawn from children suffering from these conditions. Ill children were treated promptly by purchase of over-the-counter drugs at retail outlets. The health education implications of these findings are discussed.

Snow RW, Lengeler C, de Savigny D, Cattani J. 1995. Insecticide-treated bed nets in control of malaria in Africa. Lancet, 345 (8956), pp. 1056-1057. | Read more

Mwenesi HA, Harpham T, Marsh K, Snow RW. 1995. Perceptions of symptoms of severe childhood malaria among Mijikenda and Luo residents of coastal Kenya. J Biosoc Sci, 27 (2), pp. 235-244. | Show Abstract | Read more

Effective community based malaria control programmes require an understanding of current perceptions of malaria as a disease and its severe manifestations. Quantitative and qualitative surveys of mothers on the Kenyan Coast suggest that fever is conceptualised in biomedical terms whereas the aetiology of severe malaria is perceived to be of more complex cultural origin. This is reflected in the treatments sought for convulsions. The results are discussed in the context of ethnographic factors. To be effective, future health information programmes must take cultural beliefs into account.

Mbogo CN, Snow RW, Khamala CP, Kabiru EW, Ouma JH, Githure JI, Marsh K, Beier JC. 1995. Relationships between Plasmodium falciparum transmission by vector populations and the incidence of severe disease at nine sites on the Kenyan coast. Am J Trop Med Hyg, 52 (3), pp. 201-206. | Show Abstract

The transmission of Plasmodium falciparum was studied in relation to the incidence of severe malaria infections at nine sites in the Kilifi District in Kenya. Intensive mosquito sampling during a one-year period yielded Anopheles gambiae s. l., An. funestus, An. coustani, An. squamosus, An. nili, and An. pharoensis. Anopheles gambiae s.l. was the predominant vector, comprising 98.4% of the total anophelines collected. Overall, 3.5% of 2,868 An. gambiae s.l. collected indoors and 0.8% of 261 collected outdoors contained P. falciparum sporozoites. Transmission was detected during 10 months, with peak periods from June to August and December to January. In eight of the nine sites, entomologic inoculation rates (EIRs) averaged only four infective bites per year (range 0-18); an annual EIR of 60 was measured for the site with the highest intensity of transmission. The incidence of severe malaria infections, ranging from 8.6 to 38.1 per 1,000 children (0-4 years), was not associated with EIRs. At these sites on the coast of Kenya, a high incidence of severe disease occurs under conditions of very low levels of transmission by vector populations. With respect to conventional approaches for vector control in Africa, decreases in transmission, even to levels barely detectable by standard approaches, may not yield corresponding long-term reductions in the incidence of severe disease.

Snow RW, Bronzan R, Roques T, Nyamawi C, Murphy S, Marsh K. 1994. The prevalence and morbidity of snake bite and treatment-seeking behaviour among a rural Kenyan population. Ann Trop Med Parasitol, 88 (6), pp. 665-671. | Show Abstract

Snake-bite mortality among a rural population in Kenya was estimated to be 6.7/100,000 people each year, representing 0.7% of all deaths. A community-based retrospective survey of 4712 households provided estimates of the incidence of snake bite in this population. Although 151/100,000 people are bitten each year, only 19% of these are bitten by potentially venomous snakes. When those who had been bitten were shown photographs of a range of locally prevalent snakes, most indicated that both venomous and non-venomous snakes were capable of causing death. Most (68%) of bite cases sought treatment from a traditional healer who invariably used local herbal preparations applied to the bite site and/or in a ring around the bitten limb. Local skin incisions were also commonly practised. The use of traditional medicine for snake bite is a feature of most areas of the developing world where venomous snakes are prevalent. Improvements in early referral and appropriate care will only occur when traditional healers are integrated into primary health care and hospital-based health systems.

Mung'ala VO, Snow RW. 1994. Death registration on the Kenyan Coast. East Afr Med J, 71 (11), pp. 747-750. | Show Abstract

District level statistics provide health care planners necessary information for both identifying priority areas and evaluating existing health care programmes. Since 1986 an upgraded civil registration system has been in operation in Kilifi district on the Kenyan Coast. For a one-year period (1992-1993) an independent, prospective surveillance for mortality events in a defined population of approximately 51,000 people was conducted as part of intensive demographic studies. Comparisons between the active surveillance and the civil registration system revealed marked under-reporting of deaths, particularly childhood deaths, to the civil authorities. Consideration needs to be given to methods of increasing the coverage of civil registration or of developing supplementary alternative methods of collecting the same information.

Snow RW, Schellenberg JR, Forster D, Mung'ala VO, Marsh K. 1994. Factors influencing admission to hospital during terminal childhood illnesses in Kenya. Int J Epidemiol, 23 (5), pp. 1013-1019. | Show Abstract | Read more

BACKGROUND: Access to essential clinical services offered by district hospitals or health centres forms an important component of primary health care activities in the developing world. Utilization of hospital facilities during life-threatening childhood illnesses will affect survivorship. METHODS: We have examined clinical, geographical, social, economic and demographic features of families of 49 children who consulted a hospital facility during a terminal illness and 88 who did not during a 1-year prospective demographic and hospital-based surveillance of a rural community on the Kenyan Coast. RESULTS: Of children who died without admission, 15% had symptoms which lasted only 1 day compared to no children who were admitted (P = 0.004). Furthermore, those who died without admission tended to live further away from the nearest bus stage (P = 0.01) and had made greater use of traditional healers (P = 0.08). Mothers' education or household socioeconomic status did not influence admission to hospital. CONCLUSION: Health education is required to improve early recognition of clinical signs warranting hospital care and traditional healers should be included in any community-based education programmes.

Snow RW, Bastos de Azevedo I, Lowe BS, Kabiru EW, Nevill CG, Mwankusye S, Kassiga G, Marsh K, Teuscher T. 1994. Severe childhood malaria in two areas of markedly different falciparum transmission in east Africa. Acta Trop, 57 (4), pp. 289-300. | Show Abstract | Read more

Malaria remains a major public health challenge in sub-Saharan Africa, yet our knowledge of the epidemiology of malaria in terms of patterns of mortality and morbidity is limited. We have examined the presentation of severe, potentially life-threatening malaria to district hospitals in two very different transmission settings: Kilifi, Kenya with low seasonal transmission and Ifakara, Tanzania with high seasonal transmission. The minimum annual rates of severe disease in children below five years in both populations were similar (46 per 1000 children in Kilifi and 51 per 1000 children in Ifakara). However, there were important differences in the age and clinical patterns of severe disease; twice as many patients were under one year of age in Ifakara compared with Kilifi and there was a four fold higher rate of cerebral malaria and three fold lower rate of malaria anaemia among malaria patients at Kilifi compared with Ifakara. Reducing malaria transmission in Ifakara by 95%, for example with insecticide-treated bed nets, would result in a transmission setting comparable to that of Kilifi and although this reduction may yield early successes in reducing severe malaria morbidity and mortality in young, immunologically naive children, place these same children at increased risk at older ages of developing severe and potentially different manifestations of malaria infection hence producing no net cohort gain in survivorship from potentially fatal malaria.

Snow RW, Mung'ala VO, Foster D, Marsh K. 1994. The role of the district hospital in child survival at the Kenyan Coast. Afr J Health Sci, 1 (2), pp. 71-75. | Show Abstract

Strategies for improving child survivorship in sub-Saharan Africa by the year 2000 have focused on low-cost, peripheral preventative and curative activities often with little reference to essential clinical services offered by hospitals at the district level. However, the recent World Bank World Development Report has re-emphasised the potential of district hospitals within selective PHC activities. We have estimated the likely impact of in-patient care offered by a rural district hospital on the Kenyan coast on under 5's mortality through comprehensive demographic and hospital surveillance. Within this population, childhood mortality may have been reduced by 44% as a result of hospital in-patient care. Strengthened referral systems, improvements in hospital accessibility, and better hospital care should be an integral part of PHC and other health promotion activities in sub-Saharan Africa.

Snow RW, Williams RE, Rogers JE, Mung'ala VO, Peshu N. 1994. The prevalence of epilepsy among a rural Kenyan population. Its association with premature mortality. Trop Geogr Med, 46 (3), pp. 175-179. | Show Abstract

During a two year community-based investigation of mortality 3.5% of the deaths to individuals over the age of 5 years were reported by bereaved relatives to have occurred to epileptics and 77% of these deaths were thought to have occurred whilst the patient was in status epilepticus. This prompted us to determine the prevalence of epilepsy in this rural population by interviewing 7,450 residents of a pre-defined study area. The prevalence of 'Kifafa' or 'Vitsala', two local words used to describe epilepsy, but later confirmed through detailed interviews, was 0.4%. This prevalence is clearly an underestimate of the true prevalence of epilepsy in this population but is probably higher than prevalences reported in developed countries. Anti-convulsant prophylaxis is available at the district hospital but this service is only sporadically used by epileptics in this population. Uncontrolled and poorly managed epilepsy may result in an increased risk of premature mortality among epileptics living in this community.

Mbogo CN, Snow RW, Kabiru EW, Ouma JH, Githure JI, Marsh K, Beier JC. 1993. Low-level Plasmodium falciparum transmission and the incidence of severe malaria infections on the Kenyan coast. Am J Trop Med Hyg, 49 (2), pp. 245-253. | Show Abstract

The transmission of Plasmodium falciparum was studied in relation to the incidence of severe malaria infections at Sokoke and Kilifi town, Kilifi District, Kenya. Intensive mosquito sampling during a one-year period yielded Anopheles gambiae s.l., An. funestus, and An. coustani. Anopheles gambiae s.l. was the predominant vector, comprising 87.9% and 97.9% of the total anophelines collected in Sokoke and Kilifi town, respectively. The proportion of An. gambiae s.l. with P. falciparum sporozoite infections was 4.1% (20 of 491) in Sokoke and 2.2% (3 of 138) in Kilifi town; no infections were detected in An. funestus or in An. coustani. Entomologic inoculation rates indicated that residents were exposed to only 8.0 infective bites per year in Sokoke and 1.5 in Kilifi town. Transmission was detected during only six months in Sokoke and three months in Kilifi town despite low-level, year-round vector activity. The yearly incidence of severe P. falciparum infections in children, 1-4 years of age was 24.1 per 1,000 in Sokoke and 4.2 per 1,000 in Kilifi town. Monthly patterns of transmission corresponded closely with the incidence of severe infections. At these sites on the coast of Kenya, the spatial and temporal incidence of severe malaria infections is associated with low-level P. falciparum transmission by vector populations.

Snow RW, Basto de Azevedo I, Forster D, Mwankuyse S, Bomu G, Kassiga G, Nyamawi C, Teuscher T, Marsh K. 1993. Maternal recall of symptoms associated with childhood deaths in rural east Africa. Int J Epidemiol, 22 (4), pp. 677-683. | Show Abstract | Read more

Verbal autopsies (VA) are frequently used to determine causes of death for individuals for whom there is no reliable clinical information regarding the terminal illness. VA interviews are used to note key symptoms and signs recalled by relatives of the deceased and diagnoses ascribed according to the symptom complexes. The VA technique assumes that individual disease entities have discrete symptom complexes and that these can be accurately recognized and recalled by the interviewees. We have examined the accuracy with which specific symptoms are recalled over time by mothers or normal guardians of 491 children who died on the paediatric wards of two district hospitals in East Africa. Kwashiorkor, measles, trauma, generalized convulsions and neonatal tetanus were all reported with a high degree of accuracy for children who died of these conditions and had low false positive rates for children without these conditions. Recall was similar within 1 month of death compared to recall after 6 months for most symptoms and signs except neonatal tetanus where false positive reports by mothers increased with time since death. Symptoms and signs commonly used to describe malaria, respiratory tract and diarrhoea-related deaths were reported by mothers to have been present during the terminal illness in 43% of cases where these features were absent. Recall abilities differed between the two communities studied for some symptoms and signs highlighting the importance of such studies in every setting where VA are applied.

Snow RW, Schellenberg JR, Peshu N, Forster D, Newton CR, Winstanley PA, Mwangi I, Waruiru C, Warn PA, Newbold C. 1993. Periodicity and space-time clustering of severe childhood malaria on the coast of Kenya. Trans R Soc Trop Med Hyg, 87 (4), pp. 386-390. | Show Abstract | Read more

Traditionally malaria epidemiology has focused on factors such as parasite rates and vector dynamics without specific reference to disease. There are limited comprehensive data on malaria as a life-threatening event in African children. We have identified, through hospital surveillance, 581 episodes of severe malaria in residents of a defined area on the Kenya coast over a period of 3 years. This represents an absolute minimum risk of developing severe malaria by the fifth birthday of 1 in 15. The presentation of severe malaria showed marked seasonality, but the timing and magnitude of these fluctuations varied considerably between years. A satellite navigational system was used to define the exact location of the home of each severe malaria case. Space-time clustering of severe malaria was evident in this community. Seasonal peaks in incidence of severe malaria may comprise discrete mini-epidemics. In contrast, parasite rates in the community varied little during the course of the surveillance. The monitoring of disease, as opposed to parasitization, in children may result in more effective targeting of intervention resources.

Greenwood AM, Armstrong JR, Byass P, Snow RW, Greenwood BM. 1992. Malaria chemoprophylaxis, birth weight and child survival. Trans R Soc Trop Med Hyg, 86 (5), pp. 483-485. | Show Abstract | Read more

Study of the effects of malaria chemoprophylaxis given during pregnancy on birthweight and investigation of the influence of birthweight on child survival suggest that, in a rural area of The Gambia, chemoprophylaxis given during pregnancy might reduce infant mortality by about one-fifth in the children of primigravidae but by less than 5% in the children of multigravidae. In malaria endemic areas, primigravidae should be protected against malaria not only for their own sake but also for that of their infants.

Snow RW, Armstrong JR, Forster D, Winstanley MT, Marsh VM, Newton CR, Waruiru C, Mwangi I, Winstanley PA, Marsh K. 1992. Childhood deaths in Africa: uses and limitations of verbal autopsies. Lancet, 340 (8815), pp. 351-355. | Show Abstract | Read more

The verbal autopsy (VA) is an epidemiological tool that is widely used to ascribe causes of death by interviewing bereaved relatives of children who were not under medical supervision at the time of death. This technique was assessed by comparison with a prospective survey of 303 childhood deaths at a district hospital in Kenya where medically confirmed diagnoses were available. Common causes of death were detected by VA with specificities greater than 80%. Sensitivity of the VA technique was greater than 75% for measles, neonatal tetanus, malnutrition, and trauma-related deaths; however, malaria, anaemia, acute respiratory-tract infection, gastroenteritis, and meningitis were detected with sensitivities of less than 50%. There may have been unwarranted optimism in the ability of VAs to detect some of the major causes of death, such as malaria, in African children. VA used in malaria-specific intervention trials should be interpreted with caution and only in the light of known sensitivities and specificities.

Hayes RJ, Marsh K, Snow RW. 1992. Case-control studies of severe malaria. J Trop Med Hyg, 95 (3), pp. 157-166. | Show Abstract

The majority of children infected with Plasmodium falciparum in areas of stable endemicity do not develop severe, life-threatening disease. It is important to identify risk factors for the minority who do. Case-control studies in which children with severe disease are compared with children with non-severe disease and with community controls, avoid some of the ethical and logistical problems inherent in such an undertaking. This paper discusses methodological aspects of case-control studies of severe malaria including case and control definitions, selection of cases and controls, potential risk factors, sample size calculations and analysis. Although specifically concerned with malaria, many of these issues are equally relevant to case-control studies of other infectious and parasitic diseases in a tropical environment.

Snow RW, Peshu N, Forster D, Mwenesi H, Marsh K. 1992. The role of shops in the treatment and prevention of childhood malaria on the coast of Kenya. Trans R Soc Trop Med Hyg, 86 (3), pp. 237-239. | Show Abstract | Read more

A community survey of 388 mothers in a rural and peri-urban population surrounding a district hospital on the coast of Kenya revealed that the preferred choice of treatment for childhood febrile illnesses was with proprietary drugs bought over the counter at shops and kiosks (72% of interviews). 67% of the mothers who reported using shops claimed they would buy chloroquine-based drugs. Preventative measures such as mosquito nets were uncommon (6.2%), but the use of commercial pyrethrum mosquito coils was reported more frequently (46.4%). Separate investigations of treatment given to 394 children before presentation at hospital with severe and mild malaria was consistent with the reports in the community of high usage of shop-bought anti-malarials and anti-pyretics. The involvement of the private sector in peripheral health care delivery for malaria is discussed.

Sisay F, Byass P, Snow RW, Greenwood BM, Perrin LH, Yerly S. 1992. Measurement of serum haptoglobin as an indicator of the efficacy of malaria intervention trials. Trans R Soc Trop Med Hyg, 86 (1), pp. 14-16. | Show Abstract | Read more

Serum haptoglobin levels were measured by an enzyme-linked immunosorbent assay in Gambian children who participated in 3 malaria intervention trials with untreated or impregnated bed nets. In one study, in which a significant effect on clinical malaria was observed, the mean serum haptoglobin level was significantly higher in the intervention than in the control group. In the other 2 studies, in which no significant protection was observed, mean haptoglobin levels were similar in intervention and control groups. Measurement of serum haptoglobin may provide a useful indirect measure of the effectiveness of malaria control programmes.

Snow RW, Byass P, Shenton FC, Greenwood BM. 1991. The relationship between anthropometric measurements and measurements of iron status and susceptibility to malaria in Gambian children. Trans R Soc Trop Med Hyg, 85 (5), pp. 584-589. | Show Abstract | Read more

Anthropometric measurements were made and serum iron and ferritin levels determined in a group of Gambian children at the beginning of the rainy season and these findings were related to the malaria experience of the children during the following malaria transmission season. Susceptibility to malaria was not correlated with prior weight-for-age, height-for-age, weight-for-height or serum albumin, or with serum iron, serum iron binding capacity nor serum ferritin. Thus, our findings do not provide any support for the view that poor nutritional status, as assessed by anthropometric measurements, or iron deficiency protect against malaria infection. Children who developed a clinical attack of malaria accompanied by a high level of parasitaemia tended to have a higher mean weight-for-age at the beginning of the rainy season than did children who had a clinical attack accompanied by a low level of parasitaemia, but the difference between groups was not statistically significant. However, they had a significantly higher mean serum ferritin level (P less than 0.01).

GRAHAM W, BRASS W, SNOW R. 1990. A NOTE ON THE SISTERHOOD ESTIMATOR OF MATERNAL MORTALITY - RESPONSE STUDIES IN FAMILY PLANNING, 21 (6), pp. 346-346. | Read more

Menon A, Snow RW, Byass P, Greenwood BM, Hayes RJ, N'Jie AB. 1990. Sustained protection against mortality and morbidity from malaria in rural Gambian children by chemoprophylaxis given by village health workers. Trans R Soc Trop Med Hyg, 84 (6), pp. 768-772. | Show Abstract | Read more

Mortality and morbidity from malaria were measured in children for a one-year period in a rural area of The Gambia 3-4 years after the introduction of a primary health care programme into some villages in the study area. Among children resident in primary health care villages who received treatment for febrile illnesses from a village health worker resident in their village there was no reduction in overall mortality or in morbidity from malaria compared with levels found in villages without a primary health care worker. However, among children aged 3-59 months who received malaria chemoprophylaxis from a village health worker in addition to treatment there was a 49% reduction in mortality and a 73% reduction in attacks of clinical malaria. The level of protection against malaria achieved by chemoprophylaxis given by village health workers 3-4 years after the chemoprophylaxis programme was started was as high as that obtained shortly after the introduction of the primary health care programme.

Allen SJ, Snow RW, Menon A, Greenwood BM. 1990. Compliance with malaria chemoprophylaxis over a five-year period among children in a rural area of The Gambia. J Trop Med Hyg, 93 (5), pp. 313-322. | Show Abstract

We have reviewed a malaria chemoprophylaxis programme in which Maloprim (pyrimethamine and dapsone) has been administered fortnightly by village health workers (VHWs) to approximately 1500 children each year aged 6-59 months resident in 15 primary health care villages in a rural area of The Gambia over 5 years. Reasonable levels of compliance with chemoprophylaxis have been maintained by many children over this period. this has occurred despite minimal outside supervision and support of the programme. Factors which may have affected the level of compliance in individual villages are identified. Large villages and those where social or political factionalism were evident tended to have low levels of compliance. The attitudes of VHWs and mothers to the programme were determined. Most VHWs cooperated enthusiastically and kept accurate records of compliance, despite receiving no compensation from the villagers for administering chemoprophylaxis. The administration of a drug to prevent illness in children was complementary to the curative service provided by VHWs. The chemoprophylactic was widely acceptable and nearly all mothers stated that the tablets were good for their children's health. However, knowledge of the specific purpose of chemoprophylaxis in the prevention of malaria was limited. Improvements in the programme which may result in higher levels of compliance are discussed.

Greenwood BM, Bradley AK, Byass P, Greenwood AM, Menon A, Snow RW, Hayes RJ, Hatib-N'Jie AB. 1990. Evaluation of a primary health care programme in The Gambia. II. Its impact on mortality and morbidity in young children. J Trop Med Hyg, 93 (2), pp. 87-97. | Show Abstract

Mortality and morbidity in children under 5 years of age were measured in 41 villages and hamlets in a rural area of The Gambia for a 1-year period before and for a 3-year period after the introduction of a primary health care (PHC) programme into 15 of the larger villages in the area. Both infant mortality and child mortality rates fell during the post-intervention period but declines were similar in PHC and in non-PHC villages suggesting that factors such as an up-grading of the Farafenni dispensary, improvements in transport and the survey itself may have played an important part in bringing about these changes. Measurements of morbidity showed a lower prevalence of diarrhoea, vomiting or severe cough in PHC villages after the introduction of the PHC programme. Introduction of the PHC programme had no significant effect on nutritional status or on vaccine coverage. Significant improvements in the health of children in the Farafenni study area have taken place during the past 5 years but the PHC programme is probably only one of the factors that have brought about these changes.

Holmberg M, Vaidya AB, Shenton FC, Snow RW, Greenwood BM, Wigzell H, Pettersson U. 1990. A comparison of two DNA probes, one specific for Plasmodium falciparum and one with wider reactivity, in the diagnosis of malaria. Trans R Soc Trop Med Hyg, 84 (2), pp. 202-205. | Show Abstract | Read more

The sensitivity and specificity of 2 probes for the detection of malarial infection was studied. 399 blood samples from Gambian children were tested in a deoxyribonucleic acid (DNA) hybridization assay, and the results compared with the microscopical findings from thick blood films. 8 additional pure Plasmodium malariae and 14 pure P. vivax samples were also assayed. One probe, containing a 21 base pair tandem repeat and highly specific for P. falciparum, detected this species in all except 2 of 74 samples with a parasitaemia of 250 per microliter or more; the overall sensitivity of the probe was 76%. The other probe, a 6 kilobase pair organelle DNA, is conserved in all Plasmodium species so far tested. Its sensitivity for P. falciparum was lower than the 21 base pair repeat, but it detected P. vivax and P. malariae at low levels of parasitaemia, and thus could be useful in field studies.

Greenwood AM, Bradley AK, Byass P, Greenwood BM, Snow RW, Bennett S, Hatib-N'Jie AB. 1990. Evaluation of a primary health care programme in The Gambia. I. The impact of trained traditional birth attendants on the outcome of pregnancy. J Trop Med Hyg, 93 (1), pp. 58-66. | Show Abstract

In 1983 a primary health care (PHC) programme was introduced into the Farafenni area of The Gambia; an important component of this programme was the identification and training of a traditional birth attendant (TBA) in each village with a population of 400 or greater. The outcome of pregnancy has been documented among women resident in 15 villages which joined the PHC programme and in 26 which were too small to do so, for 1 year before and for 3 years after the start of the programme. In PHC villages 65% of women were assisted at delivery by a trained TBA during the post-implementation period and the proportion of women who delivered in a hospital or health centre increased. Both maternal and neonatal death rates fell in PHC villages during the post-intervention period, declining to about half the levels recorded during pre-intervention surveys during the last year of the study. In non-PHC villages there was also a fall in the maternal death rate but little change in the neonatal death rate. Trained traditional birth attendants probably played some part in improving the outcome of pregnancy in the Farafenni area but other factors, such as improvements in transport, may also have contributed.

Snow RW, Shenton FC, Lindsay SW, Greenwood BM, Bennett S, Wheeler J, Del Giudice G, Verdini AS, Pessi A. 1989. Sporozoite antibodies and malaria in children in a rural area of The Gambia. Ann Trop Med Parasitol, 83 (6), pp. 559-568. | Show Abstract

Sporozoite antibody levels were measured in a group of children aged one to nine years resident in a rural area of The Gambia, using an ELISA to the repeat peptide (NANP)40. The prevalence and titre of antibodies varied with age but not with sex or ethnic group. Significant variations in prevalence were recorded within a group of adjacent villages. Children who were seropositive at the beginning of the dry season had higher spleen and parasite rates both at this time and at the end of the subsequent rainy season than did seronegative children, suggesting that they were exposed more frequently to infection. However, seropositive children had fewer episodes of fever accompanied by high levels of parasitaemia than did seronegative children, suggesting that they had a greater degree of clinical immunity. No differences were found in seroprevalence rates or in mean antibody titres between children who slept under conventional or Permethrin treated bed nets and those who did not, even though bed nets significantly reduced the number of bites by vector mosquitoes.

Lindsay SW, Snow RW, Armstrong JR, Greenwood BM. 1989. Permethrin-impregnated bednets reduce nuisance arthropods in Gambian houses. Med Vet Entomol, 3 (4), pp. 377-383. | Show Abstract | Read more

The prevalence of bedbugs (Cimex hemipterus L.), chicken ticks (Argas persicus Oken) and headlice (Pediculus capitis De Geer) was surveyed in a rural area of The Gambia. At the beginning of the study 37.5% of children's beds were infested with bedbugs and 3.9% with chicken ticks, whilst the prevalence rate of pediculosis in children under 10 years old was 28.8%. Both bedbugs and headlice were clustered within compounds. Headlice prevalence increased with hair length and they were more common on girls than boys. Following this cross-sectional survey all bednets in the sixteen hamlets were either dipped in permethrin or a placebo. About 4 months later it was found that bedbugs and chicken ticks had disappeared from homes in which the bednets had been impregnated with permethrin. There was no reduction in hamlets with placebo-treated bednets. The rate of acquiring headlice between the two surveys was reduced by 91.1% in children who slept under insecticide-treated bednets compared with children with placebo-treated bednets. There were also significantly fewer day-flying and crawling insects, except earwigs, in homes of children who slept under insecticide-treated bednets compared with those with placebo-treated nets. These additional benefits of permethrin-treated bednets should contribute to their widespread acceptance and utilization by the community for personal protection.

Greenwood BM, Byass P, Greenwood AM, Hayes RJ, Menon A, Shenton FC, Stephens J, Snow RW. 1989. Lack of an association between acute gastroenteritis, acute respiratory infections and malaria in young Gambian children. Trans R Soc Trop Med Hyg, 83 (5), pp. 595-598. | Show Abstract | Read more

The incidence of acute gastrointestinal and acute respiratory infections was measured in 2 groups of approximately 750 Gambian children aged 3-59 months during a 3-year period. One group of children was partially protected against malaria by fortnightly chemoprophylaxis with Maloprim whilst children in the other group were infected much more frequently. Mortality from acute gastroenteritis and from acute respiratory infections was similar in the 2 groups. The proportions of children in each group who complained of gastrointestinal or severe respiratory symptoms on morbidity surveillance were also similar. Thus, no evidence was found to suggest that malaria plays either a direct or indirect role in causing acute gastrointestinal or respiratory infections in young children in The Gambia.

Greenwood BM, Greenwood AM, Snow RW, Byass P, Bennett S, Hatib-N'Jie AB. 1989. The effects of malaria chemoprophylaxis given by traditional birth attendants on the course and outcome of pregnancy. Trans R Soc Trop Med Hyg, 83 (5), pp. 589-594. | Show Abstract | Read more

A trial of malaria chemoprophylaxis given by traditional birth attendants was undertaken in a rural area of The Gambia where access to antenatal clinics is difficult. Women received one or more doses of Maloprim or placebo from a traditional birth attendant during 1049 of 1208 pregnancies (87%) recorded in 16 villages over a 3-year period. Primigravidae who received Maloprim had a lower parasite rate and a significantly higher mean packed cell volume than primigravidae who received placebo, and their babies were significantly heavier (6% low birth weight vs 22%). In multigravidae chemoprophylaxis reduced malaria parasitaemia but it had no beneficial effect on haemoglobin level and much less effect on birth weight than was observed in primigravidae. However, the mean birth weight of babies born to grandemultigravidae who received chemoprophylaxis was significantly higher than that of babies born to grandemultigravidae who did not.

Lindsay SW, Snow RW, Broomfield GL, Janneh MS, Wirtz RA, Greenwood BM. 1989. Impact of permethrin-treated bednets on malaria transmission by the Anopheles gambiae complex in The Gambia. Med Vet Entomol, 3 (3), pp. 263-271. | Show Abstract | Read more

Malaria vector mosquitoes belonging to the Anopheles gambiae complex were studied in four hamlets in The Gambia. All inhabitants were given bednets treated either with a placebo (milk) in two hamlets or with the pyrethroid insecticide permethrin (500 mg/m2) in two other hamlets. Malaria transmission occurred mainly during a few weeks of the rainy season, in September and October 1987. The indoor resting densities of mosquitoes in permethrin-treated hamlets were reduced, and we estimated over 90% reduction in biting on man by An. gambiae Giles sensu stricto in these hamlets. No mosquitoes were found under permethrin-treated bednets compared with eighty-one recovered from placebo-treated bednets. Mosquitoes exited more readily from rooms where permethrin-treated bednets were used than from rooms with placebo-treated nets. The annual mean probability that a child would receive an infective bite was estimated to be 0.09 in hamlets with insecticide-treated bednets, compared with 1.9 where placebo-treated bednets were used. Permethrin-treated bednets are therefore recommended as a means of effectively reducing the risk of exposure to malaria transmission, particularly in areas of low seasonal transmission.

Lindsay SW, Shenton FC, Snow RW, Greenwood BM. 1989. Responses of Anopheles gambiae complex mosquitoes to the use of untreated bednets in The Gambia. Med Vet Entomol, 3 (3), pp. 253-262. | Show Abstract | Read more

Population dynamics of the Anopheles gambiae complex of malaria vector mosquitoes were studied in four small hamlets in The Gambia. Bednets were used to reduce man/vector contact in two of the hamlets. High densities of An. gambiae, sensu lato, were present for only 3-8 weeks during the rainy season, depending on the position of the hamlet within the study area. The proportions of blood-fed mosquitoes caught indoors (83.0%) and existing from houses (11.6%) were lower in hamlets where bednets were used than in hamlets without (96.5% and 33.1% respectively). Fewer of the blood-fed mosquitoes had fed on man in houses where people slept under bednets (68.2%) than in those without (81.5%). However, the average number of infective bites received by children was still greater than one a year in hamlets where bednets were used. Consequently bednets are considered unlikely to be an effective malaria control measure so long as they are untreated with insecticide.

Stephens J, Alonso PL, Byass P, Snow RW. 1989. Tropical epidemiology: a system for continuous demographic monitoring of a study population. Methods Inf Med, 28 (3), pp. 155-159. | Show Abstract

Epidemiologists in many developing countries, where official demographic services are unavailable, have to include some demographic functions in their work. The usual method of documenting a study population for epidemiological research in a developing country consists of three stages: mapping, enumeration and vital registration. This paper considers the last element of this process, detailing the development of a suitable data system and explaining how its implementation using microcomputers and a database management system can help in the creation of an on-line continuous vital registration system for a study population as an epidemiological tool. The issues covered are data collection, entry and analysis, and the advantages of such a system for use in epidemiological research in developing countries are also discussed.

Snow RW, Menon A, Greenwood BM. 1989. Measuring morbidity from malaria. Ann Trop Med Parasitol, 83 (3), pp. 321-323.

Graham W, Brass W, Snow RW. 1989. Estimating maternal mortality: the sisterhood method. Stud Fam Plann, 20 (3), pp. 125-135. | Show Abstract | Read more

This paper describes a new indirect technique for deriving population-based estimates of maternal mortality. The technique, called the "sisterhood method," is relevant to developing countries where the alternative data sources and approaches to estimation are often inadequate and inappropriate. The sisterhood method uses the proportions of adult sisters dying during pregnancy, childbirth, or the puerperium reported by adults during a census or survey, to derive a variety of indicators of maternal mortality. The first field trial of the method was carried out in the North Bank Division of The Gambia, West Africa, in 1987. The results indicate a lifetime risk of maternal mortality of 0.0584, or 1 in 17, approximating a maternal mortality ratio of 1,005 per 100,000 live births, which is consistent with previous estimates for this region.

Greenwood BM, Greenwood AM, Smith AW, Menon A, Bradley AK, Snow RW, Sisay F, Bennett S, Watkins WM, N'Jie AB. 1989. A comparative study of Lapudrine (chlorproguanil) and Maloprim (pyrimethamine and dapsone) as chemoprophylactics against malaria in Gambian children. Trans R Soc Trop Med Hyg, 83 (2), pp. 182-188. | Show Abstract | Read more

A comparison has been made of Lapudrine (chlorproguanil) and Maloprim (pyrimethamine +dapsone) as malaria chemoprophylactics when given every two weeks for 3 years to Gambian children under the age of 5 years. Both drugs produced falls in spleen and malaria parasite rates and an increase in packed cell volume. Maloprim, but not chlorproguanil, significantly reduced the incidence of episodes of fever accompanied by malaria parasitaemia. Children who received Maloprim, but not those who received chlorproguanil, grew better than children in the placebo group. This finding suggests that brief clinical episodes of malaria are more important in impairing growth than more prolonged periods of asymptomatic parasitaemia. No serious side-effect attributable to either drug was observed. After chemoprophylaxis had been given for 3 malaria transmission seasons the level of resistance of Plasmodium falciparum to pyrimethamine and to chlorproguanil was about 10%.

MacCormack CP, Snow RW, Greenwood BM. 1989. Use of insecticide-impregnated bed nets in Gambian primary health care: economic aspects. Bull World Health Organ, 67 (2), pp. 209-214. | Show Abstract

Village-wide use of permethrin-impregnated bed nets, compared with placebo-treated nets, has reduced clinical attacks of malaria by 63% in the Gambia. Costs were calculated for nets made by local tailors and for their treatment with insecticide in the villages, as well as for targeted chemoprophylaxis and back-up treatment for fever, in a comprehensive malaria control strategy through primary health care. The villagers' preferences for bed net fabrics and willingness to pay for them, and their preferences for various items of expenditure by ranked order, age group, and sex are given. Ethnic differences in the use of bed nets are also discussed.

Troye-Blomberg M, Kabilan L, Riley EM, Ortlund J, Andersson G, Perlmann H, Olerup O, Högh B, Petersen E, Snow RW. 1988. T cell reactivity of defined peptides from a major Plasmodium falciparum vaccine candidate: the Pf155/RESA antigen. Immunol Lett, 19 (3), pp. 229-233. | Show Abstract | Read more

Several immunodominant B-cell epitopes of the P. falciparum antigen blood stage Pf155/RESA, a major vaccine candidate antigen, are located in the molecular regions containing amino acid repeats. We started to map Pf155/RESA for T cell reactive epitopes. For this purpose, short synthetic peptides corresponding to the 3'- and 5' repeat regions of the molecule as well as to non-repeated sequences outside these regions were prepared. T cells from P. falciparum primed donors from two highly endemic areas of Africa were tested for their responsiveness to the peptides by thymidine incorporation and/or interferon gamma (IFN-gamma) release. There was a considerable variation in the response to the different peptides. However, the strongest and most frequent responses were seen with a few peptides from the 3'- and 5'-repeat regions. Thus, the immunodominant B cell epitope regions of Pf155/RESA, contain several T cell epitopes. Since the repeat regions are known to be conserved in different P. falciparum strains, the T cell epitopes reported here may be suitable constituents of a P. falciparum subunit vaccine.

Greenwood BM, Greenwood AM, Bradley AK, Snow RW, Byass P, Hayes RJ, N'Jie AB. 1988. Comparison of two strategies for control of malaria within a primary health care programme in the Gambia. Lancet, 1 (8595), pp. 1121-1127. | Show Abstract | Read more

Two drug strategies for the control of malaria in children aged 3-59 months have been compared in a rural area of The Gambia--treatment of presumptive episodes of clinical malaria with chloroquine by village health workers, and treatment combined with fortnightly chemoprophylaxis with 'Maloprim' (pyrimethamine/dapsone) which was also given by village health workers. Treatment alone did not have any significant effect on mortality or morbidity from malaria. In contrast, treatment and chemoprophylaxis reduced overall mortality in children aged 1-4 years, mortality from probable malaria, and episodes of fever associated with malaria parasitaemia. A high level of compliance with chemoprophylaxis was obtained and no harmful consequences of chemoprophylaxis were observed.

Snow RW, Rowan KM, Lindsay SW, Greenwood BM. 1988. A trial of bed nets (mosquito nets) as a malaria control strategy in a rural area of The Gambia, West Africa. Trans R Soc Trop Med Hyg, 82 (2), pp. 212-215. | Show Abstract | Read more

An intervention trial was undertaken in a rural area of The Gambia to assess the impact on malaria morbidity of the use of bed nets. Bed nets were allocated at random among a group of 16 Fula hamlets, where they were previously rarely used. The incidence of febrile episodes with associated malaria parasitaemias throughout the rainy season and the prevalence of splenomegaly and parasitaemia at the end of the rainy season were determined in 233 children aged 1-9 years who slept under bed nets and in 163 children who did not. Bed nets were used correctly by the children in the study cohort, but direct observations showed that a significant number of children left their nets for a period during the night. There was no significant difference in the incidence of clinical attacks of malaria or in any other malariometric measurement between the 2 groups. Thus, bed nets were not effective in reducing malaria morbidity in this group of children. The apparent protection from bed nets demonstrated in previous retrospective surveys may have been due to an increased number of infective bites being received by exposed individuals sleeping close to users of bed nets.

Snow RW, Phillips A, Lindsay SW, Greenwood BM. 1988. How best to treat bed nets with insecticide in the field. Trans R Soc Trop Med Hyg, 82 (4), pp. 647-648. | Read more

Otoo LN, Snow RW, Menon A, Byass P, Greenwood BM. 1988. Immunity to malaria in young Gambian children after a two-year period of chemoprophylaxis. Trans R Soc Trop Med Hyg, 82 (1), pp. 59-65. | Show Abstract | Read more

A cohort of 48 Gambian children was protected against malaria by fortnightly administration of Maloprim (pyrimethamine and dapsone) for 2 years between their 3 and 5 birthdays. A matched cohort of 47 children received placebo. During the year following the termination of prophylaxis there was no increase in the frequency of clinical attacks of malaria in the protected children compared with the control children. Antibody levels to circumsporozoite protein were measured by a radioimmunoassay and that to blood-stage antigens by a variety of techniques including an ELISA to whole blood-stage Plasmodium falciparum antigen, immunofluorescent assays (IFAT) to acetone fixed, glutaraldehyde fixed and unfixed parasites, a merozoite inhibition test and an opsonizing assay. Antibody levels were, in general, lower in protected than in control children and several differences between the two groups were statistically significant. When antibody levels were measured by ELISA and IFAT at the end of the following rainy season, when malaria transmission was intense, those in protected children had increased to comparable levels to those found in control children. Our findings suggest that chemoprophylaxis given for 2 years lowers malaria antibody levels but that it does not interfere with the development of protective immunity.

Snow RW, Lindsay SW, Hayes RJ, Greenwood BM. 1988. Permethrin-treated bed nets (mosquito nets) prevent malaria in Gambian children. Trans R Soc Trop Med Hyg, 82 (6), pp. 838-842. | Show Abstract | Read more

The incidence of clinical attacks of malaria was significantly less in Gambian children aged 1-9 years who slept in villages where all the bed nets (mosquito nets) were treated with permethrin than in children who slept in control villages with placebo-treated nets. Significant differences in changes in spleen size and in packed cell volume were also observed between the 2 groups during the course of a rainy season. No side effect was noted. Treatment of bed nets with insecticide is a form of malaria control that is well suited to community participation and can readily be incorporated into primary health care programmes. Insecticide-treated nets may be more effective in areas of seasonal or low intensity transmission than in areas with heavy perennial challenge.

Lindsay SW, Snow RW. 1988. The trouble with eaves; house entry by vectors of malaria. Trans R Soc Trop Med Hyg, 82 (4), pp. 645-646. | Read more

Holmberg M, Shenton FC, Franzén L, Janneh K, Snow RW, Pettersson U, Wigzell H, Greenwood BM. 1987. Use of a DNA hybridization assay for the detection of Plasmodium falciparum in field trials. Am J Trop Med Hyg, 37 (2), pp. 230-234. | Show Abstract

A DNA probe consisting of 21 base pair repeats obtained from a Tanzanian isolate of Plasmodium falciparum, cloned in pBR322 and labeled with 32P by nick translation was used to detect malaria parasitemia in samples obtained during a malaria survey undertaken in The Gambia. In an initial trial the hybridization assay had a specificity for P. falciparum of 100% and a sensitivity of 68%. False negative results were obtained only on samples with low parasitemia. Assay of red cells collected during an earlier malaria survey which had been stored for 1 year at -20 degrees C gave a higher level of sensitivity (85%), suggesting a beneficial effect from freezing and thawing. This was confirmed by examining in the same assay red cells processed immediately after collection and after 2 weeks of storage at -20 degrees C. Freezing and thawing gave a 21% increase in positivity, and a sensitivity of 100% was achieved with the frozen samples. Quantitation of autoradiographs by visual inspection and by scintillation counting gave a reasonable correlation with parasite counts. The DNA hybridization assay has considerable promise as an epidemiological tool.

Snow RW, Bradley AK, Hayes R, Byass P, Greenwood BM. 1987. Does woodsmoke protect against malaria? Ann Trop Med Parasitol, 81 (4), pp. 449-451.

Snow RW. 1987. Bed-nets and protection against malaria. Lancet, 1 (8548), pp. 1493-1494. | Read more

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SNOW R, JAWARA M, CURTIS C. 1987. OBSERVATIONS ON ANOPHELES-GAMBIAE GILES SL (DIPTERA, CULICIDAE) DURING A TRIAL OF PERMETHRIN-TREATED BED NETS IN THE GAMBIA BULLETIN OF ENTOMOLOGICAL RESEARCH, 77 (2), pp. 279-286.

Menon A, Snow RW, Otoo L, Greenwood BM. 1987. Decline in sensitivity of Plasmodium falciparum to chloroquine in The Gambia. Lancet, 1 (8540), pp. 1029-1030. | Read more

Rowan KM, Byass P, Snow RW. 1987. On-line tropical epidemiology--a case-study from The Gambia. Methods Inf Med, 26 (2), pp. 73-76.

Snow RW, Rowan KM, Greenwood BM. 1987. A trial of permethrin-treated bed nets in the prevention of malaria in Gambian children. Trans R Soc Trop Med Hyg, 81 (4), pp. 563-567. | Show Abstract | Read more

A trial was undertaken in a rural area of The Gambia to investigate the impact of permethrin-treated bed nets on malaria. Two groups of children, matched for age, sex, and malaria exposure, were followed through the rainy season of 1985 for illness and febrile episodes. One group of 205 children slept under permethrin-treated bed nets (0.5 g/m2); 184 children who slept under placebo-treated nets formed the control group. At the end of the rains the children were examined for splenomegaly and blood samples were taken for determination of packed cell volume (PCV) and parasitaemia. Permethrin treatment of bed nets was well accepted and was without side-effects. Children who slept under treated nets had significantly fewer episodes of clinical malaria than control children. However, at the end of the rains there was no significant difference in the prevalence of splenomegaly or parasitaemia or in the mean PCV between the groups. It is suggested that permethrin treatment of nets may have a greater effect on the duration of probing by mosquitoes for a blood meal than on the number of bites received.

MacCormack CP, Snow RW. 1986. Gambian cultural preferences in the use of insecticide-impregnated bed nets. J Trop Med Hyg, 89 (6), pp. 295-302. | Show Abstract

In field trials of permethrin-treated bed nets in a large Mandinka village, 95% of people were already sleeping under locally-made nets. They lasted about 6 years and cost about US$9.00 ($1.50 per year). Two permethrin dips per year added a further $0.60 per year (1985 prices). Non-immune children slept in beds shared with adults, and people wanted nets for many reasons, not just malaria protection. Fifty-eight per cent of people preferred opaque sheeting to open netting; sheeting gave more privacy, lasted longer, gave better protection from very small insects, dust, rats, etc. White was the colour preferred by 90% of interviewees. Comparing Mandinka with Wolof and Fula, there were ethnic differences in net owning and the proportion of children sleeping in beds with a mattress.

Greenwood BM, Greenwood AM, Bradley AK, Shenton FC, Smith AW, Snow RW, Williams K, Eggelte TA, Huikeshoven H, de Wit M. 1986. ELISA tests for dapsone and pyrimethamine and their application in a malaria chemoprophylaxis programme. Bull World Health Organ, 64 (6), pp. 909-916. | Show Abstract

Enzyme-linked immunosorbent asays (ELISAs) are described for determining levels of dapsone and pyrimethamine in urine. Both assays have a sensitivity of about 20 mug/l and are reproducible, but each produces some false positives. The problem of false positive reactions was partially obviated by requiring positive results in both assays. In a pilot study involving 50 children aged 3 months to 4 years who were given a single dose of Maloprim (pyrimethamine + dapsone), 75% were positive for dapsone 7 days after administration of the drug, while 25% were still positive 15 days after its administration. The corresponding proportions for pyrimethamine were 73% and 30%, respectively. Comparison of the results obtained in a larger chemoprophylaxis trial with those from the pilot study indicated that the assays described could be used to investigate whether antimalarials had been taken.

MacCormack CP, Snow RW. 1985. What do people think of bednets? Parasitol Today, 1 (5), pp. 147-148. | Read more

Kabaria CW, Molteni F, Mandike R, Chacky F, Noor AM, Snow RW, Linard C. 2016. Mapping intra-urban malaria risk using high resolution satellite imagery: a case study of Dar es Salaam. Int J Health Geogr, 15 (1), pp. 26. | Show Abstract | Read more

BACKGROUND: With more than half of Africa's population expected to live in urban settlements by 2030, the burden of malaria among urban populations in Africa continues to rise with an increasing number of people at risk of infection. However, malaria intervention across Africa remains focused on rural, highly endemic communities with far fewer strategic policy directions for the control of malaria in rapidly growing African urban settlements. The complex and heterogeneous nature of urban malaria requires a better understanding of the spatial and temporal patterns of urban malaria risk in order to design effective urban malaria control programs. In this study, we use remotely sensed variables and other environmental covariates to examine the predictability of intra-urban variations of malaria infection risk across the rapidly growing city of Dar es Salaam, Tanzania between 2006 and 2014. METHODS: High resolution SPOT satellite imagery was used to identify urban environmental factors associated malaria prevalence in Dar es Salaam. Supervised classification with a random forest classifier was used to develop high resolution land cover classes that were combined with malaria parasite prevalence data to identify environmental factors that influence localized heterogeneity of malaria transmission and develop a high resolution predictive malaria risk map of Dar es Salaam. RESULTS: Results indicate that the risk of malaria infection varied across the city. The risk of infection increased away from the city centre with lower parasite prevalence predicted in administrative units in the city centre compared to administrative units in the peri-urban suburbs. The variation in malaria risk within Dar es Salaam was shown to be influenced by varying environmental factors. Higher malaria risks were associated with proximity to dense vegetation, inland water and wet/swampy areas while lower risk of infection was predicted in densely built-up areas. CONCLUSIONS: The predictive maps produced can serve as valuable resources for municipal councils aiming to shrink the extents of malaria across cities, target resources for vector control or intensify mosquito and disease surveillance. The semi-automated modelling process developed can be replicated in other urban areas to identify factors that influence heterogeneity in malaria risk patterns and detect vulnerable zones. There is a definite need to expand research into the unique epidemiology of malaria transmission in urban areas for focal elimination and sustained control agendas.

Atta H, Barwa C, Zamani G, Snow RW. 2016. Malaria and complex emergencies in the eastern mediterranean region Eastern Mediterranean Health Journal, 22 (4), pp. 235-236.

Snow RW. 2014. Sixty years trying to define the malaria burden in Africa: have we made any progress? BMC Med, 12 (1), pp. 227. | Show Abstract | Read more

Controversy surrounds the precise numbers of malaria deaths and clinical episodes in Africa. This would not have surprised malariologists working in Africa 60 years ago as they began to unravel the enigma that is 'malaria'. Malaria is a complex disease manifesting as a multitude of symptoms, degrees of severity and indirect morbid consequences. Clinical immunity develops quickly and the presence of infection cannot always be used to distinguish between malaria and other illnesses. During the 1950s and 1960s parasite prevalence was used in preference to statistics on malaria mortality and morbidity. An argument is made for a resurrection of this measure of the quantity of malaria across Africa as a more reliable means to understand the impact of control.

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Scopus

Noor AM, Kinyoki DK, Mundia CW, Kabaria CW, Mutua JW, Alegana VA, Fall IS, Snow RW. 2014. The changing risk of Plasmodium falciparum malaria infection in Africa: 2000-10: A spatial and temporal analysis of transmission intensity The Lancet, 383 (9930), pp. 1739-1747. | Show Abstract | Read more

Background Over a decade ago, the Roll Back Malaria Partnership was launched, and since then there has been unprecedented investment in malaria control. We examined the change in malaria transmission intensity during the period 2000-10 in Africa. Methods We assembled a geocoded and community Plasmodium falciparum parasite rate standardised to the age group 2-10 years (PfPR2-10) database from across 49 endemic countries and territories in Africa from surveys undertaken since 1980. The data were used within a Bayesian space-time geostatistical framework to predict PfPR2-10 in 2000 and 2010 at a 1 × 1 km spatial resolution. Population distribution maps at the same spatial resolution were used to compute populations at risk by endemicity class and estimate population-adjusted PfPR2-10 (PAPfPR2-10) for each of the 44 countries for which predictions were possible for each year. Findings Between 2000 and 2010, the population in hyperendemic (>50% to 75% PfPR2-10) or holoendemic (>75% PfPR2-10) areas decreased from 218·6 million (34·4%) of 635·7 million to 183·5 million (22·5%) of 815·7 million across 44 malaria-endemic countries. 280·1 million (34·3%) people lived in areas of mesoendemic transmission (>10% to 50% PfPR 2-10) in 2010 compared with 178·6 million (28·1%) in 2000. Population in areas of unstable or very low transmission (<5% PfPR 2-10) increased from 131·7 million people (20·7%) in 2000 to 219·0 million (26·8%) in 2010. An estimated 217·6 million people, or 26·7% of the 2010 population, lived in areas where transmission had reduced by at least one PfPR2-10 endemicity class. 40 countries showed a reduction in national mean PAPfPR2-10. Only ten countries contributed 87·1% of the population living in areas of hyperendemic or holoendemic transmission in 2010. Interpretation Substantial reductions in malaria transmission have been achieved in endemic countries in Africa over the period 2000-10. However, 57% of the population in 2010 continued to live in areas where transmission remains moderate to intense and global support to sustain and accelerate the reduction of transmission must remain a priority. Funding Wellcome Trust. Copyright © Noor et al.

Zurovac D, Githinji S, Memusi D, Kigen S, Machini B, Muturi A, Otieno G, Snow RW, Nyandigisi A. 2014. Major improvements in the quality of malaria case-management under the "test and treat" policy in Kenya. PLoS One, 9 (3), pp. e92782. | Show Abstract | Read more

BACKGROUND: Monitoring implementation of the "test and treat" case-management policy for malaria is an important component of all malaria control programmes in Africa. Unfortunately, routine information systems are commonly deficient to provide necessary information. Using health facility surveys we monitored health systems readiness and malaria case-management practices prior to and following implementation of the 2010 "test and treat" policy in Kenya. METHODS/FINDINGS: Between 2010 and 2013 six national, cross-sectional, health facility surveys were undertaken. The number of facilities assessed ranged between 172 and 176, health workers interviewed between 216 and 237 and outpatient consultations for febrile patients evaluated between 1,208 and 2,408 across six surveys. Comparing baseline and the last survey results, all readiness indicators showed significant (p<0.005) improvements: availability of parasitological diagnosis (55.2% to 90.7%); RDT availability (7.5% to 69.8%); total artemether-lumefantrine (AL) stock-out (27.2% to 7.0%); stock-out of one or more AL packs (59.5% to 21.6%); training coverage (0 to 50.2%); guidelines access (0 to 58.1%) and supervision (17.9% to 30.8%). Testing increased by 34.0% (23.9% to 57.9%; p<0.001) while testing and treatment according to test result increased by 34.2% (15.7% to 49.9%; p<0.001). Treatment adherence for test positive patients improved from 83.3% to 90.3% (p = 0.138) and for test negative patients from 47.9% to 83.4% (p<0.001). Significant testing and treatment improvements were observed in children and adults. There was no difference in practices with respect to the type and result of malaria test (RDT vs microscopy). Of eight dosing, dispensing and counseling tasks, improvements were observed for four tasks. Overall AL use for febrile patients decreased from 63.5% to 35.6% (p<0.001). CONCLUSIONS: Major improvements in the implementation of "test and treat" policy were observed in Kenya. Some gaps towards universal targets still remained. Other countries facing similar needs and challenges may consider health facility surveys to monitor malaria case-management.

Noor AM, Uusiku P, Kamwi RN, Katokele S, Ntomwa B, Alegana VA, Snow RW. 2013. The receptive versus current risks of Plasmodium falciparum transmission in northern Namibia: implications for elimination. BMC Infect Dis, 13 (1), pp. 184. | Show Abstract | Read more

BACKGROUND: Countries aiming for malaria elimination need to define their malariogenic potential, of which measures of both receptive and current transmission are major components. As Namibia pursues malaria elimination, the importation risks due to cross-border human population movements with higher risk neighboring countries has been identified as a major challenge. Here we used historical and contemporary Plasmodium falciparum prevalence data for Namibia to estimate receptive and current levels of malaria risk in nine northern regions. We explore the potential of these risk maps to support decision-making for malaria elimination in Namibia. METHODS: Age-corrected geocoded community P. falciparum rate PfPR2-10 data from the period 1967-1992 (n = 3,260) and 2009 (n = 120) were modeled separately within a Bayesian model-based geostatistical (MBG) framework. A full Bayesian space-time MBG model was implemented using the 1967-1992 data to make predictions for every five years from 1969 to 1989. These maps were used to compute the maximum mean PfPR2-10 at 5 x 5 km locations in the northern regions of Namibia to estimate receptivity. A separate spatial Bayesian MBG was fitted to the 2009 data to predict current risk of malaria at similar spatial resolution. Using a high-resolution population map for Namibia, population at risk by receptive and current endemicity by region and population adjusted PfPR2-10 by health district were computed. Validations of predictions were undertaken separately for the historical and current risk models. RESULTS: Highest receptive risks were observed in the northern regions of Caprivi, Kavango and Ohangwena along the border with Angola and Zambia. Relative to the receptive risks, over 90% of the 1.4 million people across the nine regions of northern Namibia appear to have transitioned to a lower endemic class by 2009. The biggest transition appeared to have occurred in areas of highest receptive risks. Of the 23 health districts, 12 had receptive PAPfPR2-10 risks of 5% to 18% and accounted for 57% of the population in the north. Current PAPfPR2-10 risks was largely <5% across the study area. CONCLUSIONS: The comparison of receptive and current malaria risks in the northern regions of Namibia show health districts that are most at risk of importation due to their proximity to the relatively higher transmission northern neighbouring countries, higher population and modeled receptivity. These health districts should be prioritized as the cross-border control initiatives are rolled out.

Noor AM, Alegana VA, Kamwi RN, Hansford CF, Ntomwa B, Katokele S, Snow RW. 2013. Malaria control and the intensity of Plasmodium falciparum transmission in Namibia 1969-1992. PLoS One, 8 (5), pp. e63350. | Show Abstract | Read more

BACKGROUND: Historical evidence of the levels of intervention scale up and its relationships to changing malaria risks provides important contextual information for current ambitions to eliminate malaria in various regions of Africa today. METHODS: Community-based Plasmodium falciparum prevalence data from 3,260 geo-coded time-space locations between 1969 and 1992 were assembled from archives covering an examination of 230,174 individuals located in northern Namibia. These data were standardized the age-range 2 to less than 10 years and used within a Bayesian model-based geo-statistical framework to examine the changes of malaria risk in the years 1969, 1974, 1979, 1984 and 1989 at 5×5 km spatial resolution. This changing risk was described against rainfall seasons and the wide-scale use of indoor-residual house-spraying and mass drug administration. RESULTS: Most areas of Northern Namibia experienced low intensity transmission during a ten-year period of wide-scale control activities between 1969 and 1979. As control efforts waned, flooding occurred, drug resistance emerged and the war for independence intensified the spatial extent of moderate-to-high malaria transmission expanded reaching a peak in the late 1980s. CONCLUSIONS: Targeting vectors and parasite in northern Namibia was likely to have successfully sustained a situation of low intensity transmission, but unraveled quickly to a peak of transmission intensity following a sequence of events by the early 1990s.

Snow RW, Amratia P, Zamani G, Mundia CW, Noor AM, Memish ZA, Al Zahrani MH, Al Jasari A, Fikri M, Atta H. 2013. The malaria transition on the Arabian Peninsula: progress toward a malaria-free region between 1960-2010. Adv Parasitol, 82 pp. 205-251. | Show Abstract | Read more

The transmission of malaria across the Arabian Peninsula is governed by the diversity of dominant vectors and extreme aridity. It is likely that where malaria transmission was historically possible it was intense and led to a high disease burden. Here, we review the speed of elimination, approaches taken, define the shrinking map of risk since 1960 and discuss the threats posed to a malaria-free Arabian Peninsula using the archive material, case data and published works. From as early as the 1940s, attempts were made to eliminate malaria on the peninsula but were met with varying degrees of success through to the 1970s; however, these did result in a shrinking of the margins of malaria transmission across the peninsula. Epidemics in the 1990s galvanised national malaria control programmes to reinvigorate control efforts. Before the launch of the recent global ambition for malaria eradication, countries on the Arabian Peninsula launched a collaborative malaria-free initiative in 2005. This initiative led a further shrinking of the malaria risk map and today locally acquired clinical cases of malaria are reported only in Saudi Arabia and Yemen, with the latter contributing to over 98% of the clinical burden.

Talisuna AO, Karema C, Ogutu B, Juma E, Logedi J, Nyandigisi A, Mulenga M, Mbacham WF et al. 2012. Mitigating the threat of artemisinin resistance in Africa: improvement of drug-resistance surveillance and response systems. Lancet Infect Dis, 12 (11), pp. 888-896. | Show Abstract | Read more

Artemisinin-resistant Plasmodium falciparum malaria has emerged in western Cambodia and has been detected in western Thailand. The situation is ominously reminiscent of the emergence of resistance to chloroquine and to sulfadoxine-pyrimethamine several decades ago. Artemisinin resistance is a major threat to global public health, with the most severe potential effects in sub-Saharan Africa, where the disease burden is highest and systems for monitoring and containment of resistance are inadequate. The mechanisms that underlie artemisinin resistance are not fully understood. The main phenotypic trait associated with resistance is a substantial delay in parasite clearance, so far reported in southeast Asia but not in Africa. One of the pillars of the WHO global plan for artemisinin resistance containment is to increase monitoring and surveillance. In this Personal View, we propose strategies that should be adopted by malaria-endemic countries in Africa: resource mobilisation to reactivate regional surveillance networks, establishment of baseline parasite clearance profiles to serve as benchmarks to track emerging artemisinin resistance, improved data sharing to allow pooled analyses to identify rare events, modelling of risk factors for drug resistance, and development and validation of new approaches to monitor resistance.

Noor AM, ElMardi KA, Abdelgader TM, Patil AP, Amine AA, Bakhiet S, Mukhtar MM, Snow RW. 2012. Malaria risk mapping for control in the republic of Sudan. Am J Trop Med Hyg, 87 (6), pp. 1012-1021. | Show Abstract | Read more

Evidence shows that malaria risk maps are rarely tailored to address national control program ambitions. Here, we generate a malaria risk map adapted for malaria control in Sudan. Community Plasmodium falciparum parasite rate (PfPR) data from 2000 to 2010 were assembled and were standardized to 2-10 years of age (PfPR(2-10)). Space-time Bayesian geostatistical methods were used to generate a map of malaria risk for 2010. Surfaces of aridity, urbanization, irrigation schemes, and refugee camps were combined with the PfPR(2-10) map to tailor the epidemiological stratification for appropriate intervention design. In 2010, a majority of the geographical area of the Sudan had risk of < 1% PfPR(2-10). Areas of meso- and hyperendemic risk were located in the south. About 80% of Sudan's population in 2011 was in the areas in the desert, urban centers, or where risk was < 1% PfPR(2-10). Aggregated data suggest reducing risks in some high transmission areas since the 1960s.

Zurovac D, Talisuna AO, Snow RW. 2012. Mobile phone text messaging: tool for malaria control in Africa. PLoS Med, 9 (2), pp. e1001176. | Read more

Noor AM, Alegana VA, Patil AP, Moloney G, Borle M, Yusuf F, Amran J, Snow RW. 2012. Mapping the receptivity of malaria risk to plan the future of control in Somalia. BMJ Open, 2 (4), pp. e001160-e001160. | Show Abstract | Read more

OBJECTIVES: To measure the receptive risks of malaria in Somalia and compare decisions on intervention scale-up based on this map and the more widely used contemporary risk maps. DESIGN: Cross-sectional community Plasmodium falciparum parasite rate (PfPR) data for the period 2007-2010 corrected to a standard age range of 2 to <10 years (PfPR(2-10)) and used within a Bayesian space-time geostatistical framework to predict the contemporary (2010) mean PfPR(2-10) and the maximum annual mean PfPR(2-10) (receptive) from the highest predicted PfPR(2-10) value over the study period as an estimate of receptivity. SETTING: Randomly sampled communities in Somalia. PARTICIPANTS: Randomly sampled individuals of all ages. MAIN OUTCOME MEASURE: Cartographic descriptions of malaria receptivity and contemporary risks in Somalia at the district level. RESULTS: The contemporary annual PfPR(2-10) map estimated that all districts (n=74) and population (n=8.4 million) in Somalia were under hypoendemic transmission (≤10% PfPR(2-10)). Of these, 23% of the districts, home to 13% of the population, were under transmission of <1% PfPR(2-10). About 58% of the districts and 55% of the population were in the risk class of 1% to <5% PfPR(2-10). In contrast, the receptivity map estimated 65% of the districts and 69% of the population were under mesoendemic transmission (>10%-50% PfPR(2-10)) and the rest as hypoendemic. CONCLUSION: Compared with maps of receptive risks, contemporary maps of transmission mask disparities of malaria risk necessary to prioritise and sustain future control. As malaria risk declines across Africa, efforts must be invested in measuring receptivity for efficient control planning.

Wesolowski A, Eagle N, Tatem AJ, Smith DL, Noor AM, Snow RW, Buckee CO. 2012. Quantifying the impact of human mobility on malaria. Science, 338 (6104), pp. 267-270. | Show Abstract | Read more

Human movements contribute to the transmission of malaria on spatial scales that exceed the limits of mosquito dispersal. Identifying the sources and sinks of imported infections due to human travel and locating high-risk sites of parasite importation could greatly improve malaria control programs. Here, we use spatially explicit mobile phone data and malaria prevalence information from Kenya to identify the dynamics of human carriers that drive parasite importation between regions. Our analysis identifies importation routes that contribute to malaria epidemiology on regional spatial scales.

Snow RW, Amratia P, Kabaria CW, Noor AM, Marsh K. 2012. The changing limits and incidence of malaria in Africa: 1939-2009. Adv Parasitol, 78 pp. 169-262. | Show Abstract | Read more

Understanding the historical, temporal changes of malaria risk following control efforts in Africa provides a unique insight into what has been and might be archived towards a long-term ambition of elimination on the continent. Here, we use archived published and unpublished material combined with biological constraints on transmission accompanied by a narrative on malaria control to document the changing incidence of malaria in Africa since earliest reports pre-second World War. One result is a more informed mapped definition of the changing margins of transmission in 1939, 1959, 1979, 1999 and 2009.

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