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Dealing with indeterminate outcomes in antimalarial drug efficacy trials

@Oxford

Posted 10/12/2019. In antimalarial efficacy trial, researchers often encounter situation where recurrence due to new infection cannot be differentiated from recrudescence (indeterminate). In this study, Prabin Dahal and colleagues consider indeterminate outcomes as missing and recommend using statistically principled approaches that are more efficient and accurate than current practice of excluding them.

Forest work and its implications for malaria elimination

MORU

Posted 03/12/2019. Malaria transmission in Cambodia is concentrated in forest foci. Nou Sannan, Tom Peto and MORU colleagues interviewed forest workers who had recently been infected with malaria to understand their behaviour and perception of risk, establish the efficacy and feasibility of malaria prophylaxis , and identify potential strategies for malaria elimination in these populations.

Prevalence of vitamin D deficiency in Africa

KWTRP

Posted 29/11/2019. In this systematic review and meta-analysis of African studies, Sarah Atkinson and colleagues show that vitamin D deficiency is prevalent in many African populations. About one in five individuals living in Africa have vitamin D deficiency (<30 nmol/L), with newborns, women, urban residents and populations from northern and southern Africa being at higher risk.

Genetic variation associated with infection and the environment in the accidental pathogen Burkholderia pseudomallei

MORU

Posted 26/11/2019. Claire Chewapreecha and colleagues combined 753 newly sequenced Thai Burkholderia pseudomallei (the bacteria causing melioidosis) isolates with 258 Australian isolates to identify genes associated with either clinical or environmental strains. They found 47 genes that may provide clues to the strategy used by this microbe to adapt to survive in wide range of ecological niches, including human hosts.

Tackling antimicrobial resistance in low-income and middle-income countries

@Oxford

Posted 19/11/2019. Emergence and spread of antimicrobial resistance can lead us to a dead end! It is important to understand factors to its emergence. In this editorial, Bipin Adhikari and colleagues discuss how to broaden our current gaze at tackling the growing antimicrobial resistance in low- and middle- income countries.

Prevalence and correlates of depressive symptoms among adults living with HIV in rural Kilifi, Kenya

KWTRP

Posted 15/11/2019. Depression can co-occur with HIV. Moses Kachama and colleagues found high prevalence of depressive symptoms in adult participants living with HIV from Kilifi (14%). Factors associated with participants being depressed include: additional chronic illness to HIV (one or more), shifting to second-line antiretroviral treatment, HIV clinic being far, and experiencing HIV-related stigma.

Veterinary drug shops as main sources of supply and advice on antimicrobials for animal use in the Mekong Delta of Vietnam

OUCRU

Posted 12/11/2019. Juan Carrique-Mas and colleagues characterize the veterinary drug shop network in two rural districts in the Mekong Delta of Vietnam. This study also describes the linkages between poultry farmers and these drug shops that are the main source of supply of antimicrobials to farmers. Therefore, interventions aimed at reducing excessive antimicrobial usage should include this important stakeholder group.

Clinical REsearch During Outbreaks (CREDO) Training for Low- and Middle-Income Countries

@Oxford

Posted 08/11/2019. Nzelle Delphine Kayem, Peter Horby and colleagues at the University of Oxford report on the first training course specifically designed for clinical research during outbreaks and tailored to low and middle-income countries. Following a very positive evaluation by the first cohort of trainees, the Oxford team plan to franchise out the course through a variety of providers.

Microbiology Investigation Criteria for Reporting Objectively (MICRO): a framework for the reporting and interpretation of clinical microbiology data

MORU

Posted 05/11/19. High quality laboratory data is the cornerstone of antimicrobial resistance surveillance. In this recent article in The Lancet Infectious Diseases, Paul Turner, Elizabeth Ashley and colleagues from COMRU and LOMWRU highlight the problems associated with poor quality data and call for standardised data reporting via the MICRO framework

Patient costs of diabetes mellitus care in public health care facilities in Kenya

KWTRP

Posted 29/10/2019. The unyielding rise in non-communicable diseases like diabetes presents a threat to many resource-constrained health systems. Robinson Oyando and colleagues demonstrate that medicine costs account for more than 50% of diabetes patient costs in Kenya. While hypertension comorbid patients incur higher costs overall, unaffordability of care is intensified by transport costs.

Early life risk factors of motor, cognitive and language development

MORU

Posted 22/10/2019. Rose McGready and SMRU colleagues contributed RCT data from the Thailand-Myanmar border to this large review on low- and middle-income countries (21 studies in 20 882 children). The results suggests targeting parental, environmental and nutritional factors from pre-pregnancy through childhood, as a way forward to improve health and development of children in such settings.

Scrub typhus and the misconception of doxycycline resistance

MORU

Posted 18/10/2019. Scrub typhus is a major cause of fever across the Asia Pacific region. Doxycycline resistance, the main antibiotic used for treatment, was described in the 1990s but independent verification was neglected, leading to doubts regarding its efficacy. Assessment of historical evidence and recent reports by Tri Wangrangsimakul and colleagues suggest this finding was a misconception.

Short-course primaquine for the radical cure of Plasmodium vivax malaria

MORU

Posted 16/10/2019. Plasmodium vivax is particularly hard to eliminate because it can relapse from dormant liver stages, weeks to months after the initial infection. Bob Taylor and colleagues present a large multicentred clinical trial showing that a 7 day course with double the daily dose of primaquine is as effective as the traditional 14 day primaquine course, with acceptable tolerability in G6PD normal patients. The trial paves the way for safer and more effective treatment of this parasite.

Determinants of dihydroartemisinin-piperaquine treatment failure in Plasmodium falciparum malaria in Cambodia, Thailand, and Vietnam

MORU

Posted 08/10/2019. A rapidly evolving multi-drug resistant lineage of P. falciparum malaria parasites continues to spread in Southeast Asia, leading to alarmingly high treatment failure rates in Cambodia, Thailand and Vietnam for DHA-piperaquine, one of the world’s most important anti-malaria drugs. Rob van der Pluijm and colleagues say that accelerated elimination of P falciparum malaria in this region is urgently needed, to prevent further spread and avoid a potential global health emergency.

Co-trimoxazole or multivitamin multimineral supplement for post-discharge outcomes after severe anaemia in African children

KWTRP

Posted 04/10/2019. Severe anaemia is common and life-threatening for children in sub-Saharan Africa. Previous research found that micronutrient deficiencies might be important causes of severe anaemia. In this trial, Kathryn Maitland and colleagues show that children do not benefit from either antibiotic prophylaxis or vitamin/mineral supplements. Future trials should focus on strategies to prevent the need for readmission.

Quality of medical products for diabetes management

@Oxford MORU

Posted 01/10/2019. In the light of the alarming global increase in diabetes, Kartika Saraswati and colleagues at the LOMWRU-IDDO Medicine Quality team found few investigations on the quality of antidiabetics and supplies for self-monitoring of blood glucose. However, poor quality medical products were identified on four continents. This important public health issue should thus be further investigated.

The ferroportin Q248H mutation protects from anemia, but not malaria or bacteremia

KWTRP

Posted 24/09/2019. Sarah Atkinson and colleagues show that the iron export mutation Q248H that primarily occurs in populations of African ancestry may protect from iron deficiency and anemia. Data from over 18,000 children show little evidence that the mutation protects against malaria, nor is the mutation evolutionary selected in African populations due to malaria exposure. This mutation does not protect from bloodstream bacterial infections either.

A rapid research needs appraisal methodology to identify evidence gaps to inform clinical research priorities in response to outbreaks

@Oxford

Posted 18/09/2019. A protocol for carrying out a systematic rapid research needs appraisal of existing evidence within five days, to rapidly inform clinical research prioritize in response to emerging outbreaks globally. This protocol was developed and successfully piloted by Louise Sigfrid and colleagues using a fictitious Lassa fever outbreak scenario. The protocol is optimized by effective use of global time-zones.

Investigating causal pathways in severe falciparum malaria

MORU

Posted 06/09/2019. A formal causal inference-based analysis of clinical and laboratory data from 9000+ severe falciparum malaria patients from Africa and Asia by James Watson and colleagues suggests that moderate anaemia may be protective against death in severe malaria. The severe anaemia threshold criteria for a definition of severe falciparum malaria should be reconsidered.

Improving the estimation of the global burden of antimicrobial resistant infections

MORU

Posted 03/09/2019. Estimating the global burden of antimicrobial resistance (AMR) is essential for resource allocation and to inform AMR action plans at national and global levels. Direk Limmathurotsakul and colleagues discuss the underlying assumptions, characteristics, limitations, and comparability of the approaches used to quantify mortality from AMR bacterial infections. We define key actions required and call for innovative thinking and solutions to address these problems.

Spatiotemporal epidemiology, environmental correlates, and demography of malaria in Tak Province, Thailand (2012–2015)

MORU

Posted 23/08/2019. Tak Province in western Thailand is a significant target area to help achieve nationwide malaria elimination by 2024, and in the Greater Mekong Subregion by 2030. Integrating routine surveillance and publicly available data, Chris Mercado and colleagues demonstrated Tak’s big decline in malaria from 2012 to 2015, a likely result of elimination activities as opposed to climate or forest change.

A population dynamic model to project the burden of undiagnosed diabetes in Thailand

MORU

Posted 20/08/2019. Demographics changes result in rapid transformation of population structure; together with other factors such as urbanization, household size decreasing and seasonal movement could greatly influence the prediction of disease burden. Wirichada Pan-ngum and colleagues demonstrated this trend using a mathematical modelling approach.

Observational study: 27 years of severe malaria surveillance in Kilifi, Kenya

KWTRP

Posted 30/07/2019. Malaria has been falling in Africa over the last few decades. This reduces the number of children with infection, but the lowered exposure to malaria could change the clinical picture. Work in KEMRI-Wellcome Programme shows this leads to more cerebral malaria and in older children, but fortunately no increase in death rates.

Gastroenteritis aggressive versus slow treatment for rehydration: trial WHO plan versus slow rehydration

KWTRP

Posted 26/07/2019. Although WHO rehydration management guidelines (Plan C) for severe dehydration are widely practiced in resource-poor settings, they have never formally been tested in a clinical trial, despite poor outcomes (mortality). Kathryn Maitland and colleagues evaluated current recommendations versus a slower rehydration regime in Ugandan/Kenyan with severe dehydration secondary to gastroenteritis. We found the slower regime giving rehydration therapy over 8 hours to be safe. For clinicians it was easier to implement than the two-stage Plan C regime. Time correct signs of dehydration and hospital stay was similar in the two groups. Future large trials with mortality as the primary endpoint are warranted.

A systematic review and meta-analysis of patient data from the west Africa (2013-16) Ebola virus disease epidemic

@Oxford

Posted 23/07/2019. Professor Peter Horby and colleagues at the University of Oxford have compiled data from over 6000 patients to provide a comprehensive clinical description of Ebola virus disease. The team also assessed the quality of the published data and found it to be partial, overlapping, and in many instance non-comparable. For high-threat diseases such as Ebola, the authors recommend the establishment of global, anonymised patient registries as a resource for improving patient care.

“We are called the et cetera”: experiences of the poor with health financing reforms that target them in Kenya

KWTRP

Posted 19/07/2019. Pro-poor health financing reforms have the potential to improve access to health services among the poor in Kenya. However, Evelyn Kabia and colleagues show that, for these reforms to be effective, they need to be accompanied by interventions that address barriers across other access dimensions such as geographical accessibility, availability, and acceptability of care.

Nutrition in transition: historical cohort analysis among pregnant women along the Thailand–Myanmar border 1986 - 2016

MORU

Posted 16/07/2019. Worrying nutritional trends in possibly the longest and largest cohort of nearly 50,000 refugee and migrant pregnant women in a LMIC setting. Ahmar Hashmi and colleagues at SMRU summarise trends in under- and over-nutrition among pregnant women, and show a double burden of malnutrition in these marginalised and vulnerable communities from the Myanmar-Thailand border.

Viruses in Vietnamese patients presenting with community acquired sepsis of unknown cause

OUCRU

Posted 12/07/2019. Sepsis is a devastating clinical condition. However, the etiology remains unknown in the majority of the patients. Herein, Dr Tan and colleagues set out to apply metagenomic next generation sequencing to look for viral contents in ~400 Vietnamese patients presenting with sepsis of unknown cause.

Antimicrobial resistance in Cambodia

MORU

Posted 09/07/2019. On behalf of the Cambodian Ministry of Health Technical Working Group on Antimicrobial Resistance, Paul Turner and colleagues at COMRU recently led a review of published data on AMR in Cambodia. Significant AMR was identified in a range of priority pathogens although data were limited. On-going national AMR surveillance will address this data gap.

“I can’t read and don’t understand”: Health literacy and messaging in a migrant population on the Myanmar-Thailand border

MORU

Posted 05/07/2019. Health information can be life-saving, but how can it be conveyed to those who could benefit most? Through analysis of an unsuccessful public health campaign, Mary Ellen Gilder and SMRU colleagues learned from migrant women valuable lessons about health messaging in communities where most women do not complete the fourth grade.

Optimal duration of follow-up antimalarial efficacy in pregnancy on the Thailand–Myanmar border

@Oxford MORU

Posted 02/07/2019. Highly efficacious treatment can limit the cumulative deleterious impact of malaria during pregnancy on the mother and fetus. Correct assessment of treatment efficacy with an adequate length of follow up is required. Makoto Saito and colleagues at the Shoklo Malaria Research Unit (SMRU) on the Thailand-Myanmar border suggest that pregnant women need to be followed up longer than the currently recommended duration of follow-up to assess antimalarial drug efficacy.

Serum procalcitonin levels in children with clinical syndromes for targeting antibiotic use at an emergency department of a Kenyan hospital

KWTRP

Posted 28/06/2019. Children with severe disease seen at an outpatient department of Kenyan hospital often have elevated procalcitonin, a biomarker for bacterial infection. Samuel Akech and colleagues show that it’s still premature to recommend the use of procalcitonin to guide antibiotic administration unless clinical trials investigating the use of procalcitonin levels to guide antibiotic treatment are done.

Managing health research capacity strengthening consortia

KWTRP

Posted 25/01/2019. As investments in health research capacity strengthening (HRCS) consortia increase, it is essential to consider the role of management approaches used. Nadia Tagoe and colleagues present current evidence and discourse on HRCS consortium management, and show that it is critical to pay attention to both relational and operational aspects of consortia to achieve desired outcomes.

Prevalence, intensity and risk factors of tungiasis in Kilifi County, Kenya II: Results from a school-based observational study

KWTRP

Posted 21/06/2019: Neglected tropical skin disease caused by sand fleas (tungiasis) inflicts misery on millions of children across the Tropics. Lynne Elson and colleagues show that tungiasis could be controlled through strengthening hygiene practices and sealing house and school floor

‘Antibiotic footprint’ as a communication tool to aid reduction of antibiotic consumption

MORU

Posted 18/06/2019. How should we communicate to the public the magnitude of antibiotic use in humans and animals? Led by Direk Limmathurotsakul, our scientists and global partners propose the concept of ‘antibiotic footprint’. It could support individual, national and global actions against superbugs as 'carbon footprint' has done for climate change

Missed nursing care in newborn units: a cross-sectional direct observational study

KWTRP

Posted 14/06/2019. Insufficient nurses caring for sick babies on hospitals’ neonatal units in Kenya seriously undermine efforts to deliver high quality, safe care and make reducing neonatal mortality rates very difficult. Led by David Gathara, the Kenyan and Oxford team conducted the first ever direct observational study of which tasks nurses were able to perform and quantified how much care is missed. Previous work on missed nursing care largely conducted in rich countries has relied on questionnaires so this new work is an important advance.

Novel approaches to control malaria in forested areas of Southeast Asia

MORU

Posted 11/06/2019. Remaining foci of malaria transmission are often in forests, where vectors tend to bite during daytime and outdoors thus reducing the effectiveness of insecticide treated bednets. Limited periods of exposure suggest that chemoprophylaxis could be a promising strategy to protect forest workers against malaria. Lorenz Von Seidlein and colleagues discuss which antimalarial drug regimens are most appropriate, how frequently the chemoprophylaxis should be delivered, and how to motivate forest workers to use and adhere to malaria prophylaxis.

The affordability of antimicrobials for animals and humans at retail in Vietnam: A call for revising pricing policies

OUCRU

Posted 07/06/2019. Juan Carrique-Mas and colleagues quantified the retail prices of the most common antimicrobials used in chicken farms in Vietnam. By comparing these costs with antibiotics for human use, they conclude that extreme low prices of antimicrobials for animal production may be a major factor driving excessive use. The authors advocate for a taxing system that restricts the use of critically important antimicrobials in agriculture.

Malaria morbidity and mortality following introduction of a universal policy of artemisinin-based treatment for malaria in Papua, Indonesia

MORU

Posted 04/06/2019. In Papua, where multidrug resistant P. falciparum and P. vivax are coendemic, the introduction of a universal policy of ACT plus IV artesunate for all patients with malaria halved hospital admissions and malarial deaths. However the reduction in P. vivax was far less than that for P. falciparum. This study by Ric Price and colleagues emphasizes the need for better drug regimens to clear the liver stages of P. vivax.

Antimicrobial-resistant Gram-negative colonization in infants from a neonatal intensive care unit in Thailand

MORU

Posted 31/05/2019. Drug-resistant infections caused by Enterobacteriaceae, a family of Gram-negative bacteria, account for a high and increasing disease burden amongst hospitalised neonates in Southeast Asia; carbapenem-resistant strains are particularly important because of limited antibiotic treatment options. Tamalee Roberts and colleagues found that nearly two thirds of infants in a neonatal unit in Thailand became asymptomatic carriers with carbapenem-resistant Enterobacteriaceae during their hospital stays. This work indicates a critical need for interventions to reduce this usually hidden reservoir of drug-resistant bacteria.

Essential guidance on malaria elimination in its history

OUCRU

Posted 28/05/2019. Kevin Baird calls attention to the importance of local expertise in anopheline mosquito ecology as an essential weapon in striving to eliminate malaria. Slight but very specific modifications to environments that disfavour those mosquitoes achieved very significant gains before the advent of DDT insecticide and synthetic antimalarial commodities in the middle of the 20th century. Loss of those commodities, and a lack of alternative strategies, led to the great malaria resurgence of the latter 20th century.

Sustaining pneumococcal vaccination after transitioning from Gavi support: a modelling and cost-effectiveness study in Kenya

KWTRP

Posted 24/05/2019. As low-income countries’ economies grow and financial support from Gavi (the Vaccine Alliance) diminishes, governments need to consider the value of continuing previously-subsidized vaccine programmes at full cost. Anthony Scott and colleagues assess the incremental cost-effectiveness of continuing pneumococcal vaccination use between 2022 and 2032, and found the programme to be highly cost effective.

Spatial heterogeneity and temporal trends in malaria on the Thai–Myanmar border (2012–2017)

MORU

Posted 21/05/2019. Wirichada Pan-ngum and colleagues explore how decreasing trends reflect the achievements of malaria control efforts on the Thai–Myanmar border. However, one of the main challenges facing elimination programs in this low transmission setting is maintaining a strong system for early diagnosis and treatment, even when malaria cases are very close to zero, whilst preventing re-importation of cases.

Biomarkers of post-discharge mortality among children with complicated severe acute malnutrition

KWTRP

Posted 17/05/2019. Undernourished children sustain a high risk of death after discharge from hospital. By examining blood samples taken when children were clinically stable and ready for discharge, Jay Berkley and colleagues found that children who died in the next 60 days had infection-related responses despite following treatment guidelines. Incomplete treatment may underly later mortality.

Intrathecal Immunoglobulin for treatment of adult patients with tetanus

OUCRU

Posted 15/05/2019. Tetanus antitoxin is a vital component of tetanus treatment. In this clinical trial currently running at OUCRU Ho Chi Minh City, Louise Thwaites and colleagues test whether, in addition to standard intramuscular injection of antitoxin, antitoxin given directly into the central nervous system is beneficial in adult patients with tetanus.

Dynamic prediction of death in patients with tuberculous meningitis

OUCRU

Posted 10/05/2019. Previously, Ronald Geskus and colleagues developed a model based on information at diagnosis that provides mortality risk prediction for patients with tuberculosis meningitis. Prediction improves when we use time-updated Glasgow coma score and plasma sodium collected during the disease course. Our model and accompanying app help define patients with poor prognosis.

Microbiology Investigation Criteria for Reporting Objectively (MICRO): a framework for the reporting and interpretation of clinical microbiology data

MORU

Posted 07/05/2019. Developed by Paul Turner and fellow members of the Oxford Tropical Network, the MICRO framework provides the scientific community with clear guidance on reporting and interpretation of clinical microbiology and antimicrobial resistance (AMR) data. Use of the framework will result in publication of better quality data for use in the global fight against AMR. The MICRO guideline is also posted on the EQUATOR website www.equator-network.org/reporting-guidelines

Three phylogenetic groups have driven the recent population expansion of Cryptococcus neoformans

OUCRU

Posted 03/05/2019. Jeremy Day and colleagues sequenced the genomes of 699 Cryptococcus neoformans isolates from meningitis patients from southeast Asia and Africa. The phylogenetic structure demonstrates a recent, exponential, population expansion, driven almost entirely by three sub-clades (VNIa-4, VNIa-5 and VNIa-93). Mitochondrial recombination seen in VNIa-5 may be important in its ability to infect immunocompetent people. VNIa-93, previously associated with poorer outcomes, is in fact associated with a significantly reduced risk of death.

Increasing women's leadership in science in Ho Chi Minh City

OUCRU

Posted 30/04/2019. The Oxford University Clinical Research Unit in Ho Chi Minh City investigated gender-related issues associated with career progression within a LMIC. Ngo Thi Hoa, Louise Thwaites and colleagues surveyed 120 scientists, the majority Vietnamese. They describe barriers to female career progressions such as caring duties and home environments, as well as the specific initiatives launched to increases female leadership.

Clinical characteristics and outcome of children hospitalized with scrub typhus in an area of endemicity

MORU

Posted 25/04/2019. It has been almost 30 years since clinicians from northern Thailand first raised the issue of severe scrub typhus and poor responses to treatment in patients. Tri Wangrangsimakul and colleagues show that paediatric scrub typhus is frequently severe, potentially fatal, and associated with high rates of treatment failure. A lack of awareness leading to delays in treatment may have contributed. Investigating the determinants of treatment failure and raising the awareness of this neglected disease remains a priority.

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