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Sources of multi-drug resistance in patients with previous isoniazid resistant tuberculosis identified using whole genome sequencing

OUCRU

Posted 27/03/2020. Nguyen Thuy Thuong Thuong and colleagues in OUCRU, Vietnam, investigated the sources of multi-drug resistant TB in patients with undiagnosed isoniazid-resistant TB treated with first-line anti-TB therapy. They found that re-infection with a new multi-drug resistant TB strain was just as common as the emergence of rifampicin resistance.

Examining which clinicians provide admission hospital care in a high mortality setting and their adherence to guidelines

KWTRP

Posted 24/03/2020. This study by Morris Ogero and colleagues was based on over 50,000 patients from 13 referral hospitals in Kenya. Results suggest that >85% of admissions are conducted by pre-registration clinicians who are under experiential training. Although clinical assessment was according to guidelines, there was a major challenge in classification of illness severity leading to overuse of treatment.

A trial of lopinavir–ritonavir in adults hospitalized with severe covid-19

@Oxford

Posted 20/03/2020. 199 patients received standard care, of which 99 received lopinavir-ritonavir for 14 days. Lopinavir-ritonavir didn’t induce significant clinical improvement, and mortality was similar in both groups. However, patients treated with lopinavir-ritonavir spent less time in hospital and in intensive care. The trial enrolled severely ill patients and was not big enough to detect modest benefits. Much larger studies are warranted to confirm or exclude if lopinavir-ritonavir treatment can help.

Parenting interventions to prevent violence against children in low- and middle-income countries in East and Southeast Asia

MORU

Posted 17/03/2020. This systematic review and meta-analysis by Amalee McCoy and colleagues synthesizes available evidence on the effectiveness of parenting interventions in preventing violence against children in the East and Southeast Asian region. The results suggest that parenting interventions can reduce rates of particular forms of violence against children, as well as promote positive parent-child interactions.

Mapping the travel patterns of people with malaria in Bangladesh

MORU

Posted 13/06/2020. New research by Ipsita Sinha and colleagues provides a framework for identifying key traveler groups and their origins and destinations of travel combination with knowledge of local epidemiology to inform malaria control and elimination efforts. This publication is based on travel information collected from over 2000 patients from 57 study sites in South-East Bangladesh, in collaboration with the National Malaria Elimination Control programme of Bangladesh.

Estimation of incidence of typhoid and paratyphoid fever in Vientiane, Lao People’s Democratic Republic

MORU

Posted 10/03/2020. Incidence data about infectious diseases are needed to inform decisions about vaccine introduction. Using data from health-seeking behaviour survey for fever and data from hospital bloodstream infection, Mayfong Mayxay and colleagues estimated typhoid and paratyphoid fever incidence in Vientiane, the capital of Laos, and found that the incidence is low, with an annual incidence of 4.7 and 0.5 per 100,000 persons, for typhoid and paratyphoid fever, respectively.

Factors affecting the electrocardiographic QT interval in malaria

MORU

Posted 06/03/2020. Prolongation of the electrocardiographic QT interval is a widely-used marker of the risk of developing abnormal heart rhythms. Several antimalarial drugs are associated with QT interval prolongation. Xin Hui Chan and colleagues found that malaria and fever also affect QT interval. To improve cardiac safety assessments, adjustment for QT interval prolongation occurring after recovery is needed. This would prevent unnecessary withdrawal of lifesaving antimalarial treatment.

Prevalence of group A Streptococcus in primary care patients and the utility of C-reactive protein and clinical scores for its identification in Thailand

MORU

Posted 03/03/2020. It is challenging to know who needs antibiotics for a sore throat and fever. In Thailand, Rachel Greer and colleagues found a bacteria (group A Streptococcus) in less than 1 out 10 patients. These patients had a raised C-reactive protein blood test but it was not able to predict who had the bacteria.

Estimating the burden of iron deficiency among African children

KWTRP

Posted 28/02/2020. Estimating the burden of iron deficiency in sub-Saharan Africa is challenging because infections influence iron biomarkers. After correcting for the effects of malaria and inflammation on iron biomarkers, Sarah Atkinson and colleagues show that over half of children are iron deficient and transferrin saturation may more accurately estimate the burden of iron deficiency in African children.

Prolonged health worker strikes in Kenya - perspectives and experiences of frontline health managers and local communities in Kilifi County

KWTRP

Posted 25/02/2020. The effects of health worker strikes vary depending on strike duration, alternative healthcare available and responses adopted by management. Most strike-related research has focussed on ethical issues and impacts on mortality. Dennis Waithaka, Nancy Kagwanja, Sassy Molyneux and colleagues explore the experience of health managers and community members during two prolonged strike periods, lasting 250 days.

Estimating hospital catchments from in-patient admission records

KWTRP

Posted 14/02/2020. The delineation of disease-specific hospital catchments is important to identify populations marginalized from health services, but rarely investigated. Victor Alegana and colleagues set out to estimate the extent of malaria catchments and investigate hospitalisation for two severe malaria syndromes in children. Results suggest distinct geographic catchment for malaria and a reduced rate of hospitalisation outside of this catchment. These findings are useful in identifying communities where very sick children may require emergency care.

Neutralizing antibodies against enteroviruses in patients with hand, foot and mouth disease

OUCRU

Posted 11/02/2020. Hand, foot and mouth disease is an emerging infection with pandemic potential. To inform vaccine development, Tan Le Van and colleagues studied the antibody responses in 120 infected patients. Results support previous reports about the potential benefit of enterovirus-A71 vaccine, but emphasize the requirement for multivalent vaccines to control this emerging infection.

Researcher and study participants’ perspectives of consent in clinical studies in four referral hospitals in Vietnam

OUCRU

Posted 07/02/2020. Within the research community, it is generally accepted that consent processes for research should be culturally appropriate and tailored to the context, yet researchers continue to grapple with what valid consent means within specific stakeholder groups. Evelyne Kestelyn and colleagues explored the consent practices and attitudes within hospital-based trial communities from four referral hospitals in Vietnam.

Performance of the Access Bio/CareStart rapid diagnostic test for the detection of glucose-6-phosphate dehydrogenase deficiency

MORU

Posted 04/02/2020. Primaquine radical cure for treatment of Plasmodium vivax is contraindicated in patients with G6PD deficiency. Ric Price, Benedikt Ley and colleagues review evidence from 11 studies of a novel point of care diagnostic (CareStart RDT) and show overall good performance under research conditions. Further feasibility studies are under way to assess its reliability under field conditions.

Transmission dynamics and control of multidrug-resistant Klebsiella pneumoniae in neonates in a developing country

MORU

Posted 31/01/2020. Drug-resistant strains of the bacterial pathogen Klebsiella pneumoniae are an important and increasing cause of infant mortality in developing countries. In this study led by Professor Ben Cooper, researchers used mathematical modelling and whole genome sequencing to quantify the effects of antibiotics and other factors in driving the hidden transmission of this pathogen within a Cambodian neonatal unit.

Barriers in the access, diagnosis and treatment completion for tuberculosis patients in central and western Nepal

@Oxford

Posted 28/01/2020. Delay in access to health services, diagnosis and treatment completion for TB patients is a major problem in Nepal and can contribute to severity of diseases, antimicrobial resistance, and economic burden. In this large qualitative work, Bipin Adhikari and colleagues discuss the factors impeding the access, diagnosis and treatment completion for TB patients in Nepal.

Xpert MTB/RIF Ultra versus Xpert MTB/RIF for the diagnosis of tuberculous meningitis

OUCRU

Posted 24/01/2020. Tuberculous meningitis is the most severe form of tuberculosis. Late diagnosis leads to worse patient outcomes, however currently available diagnostic tests are insufficiently sensitive, and new tests are urgently needed. Joseph Donovan, Guy Thwaites, and colleagues present a randomised diagnostic accuracy study demonstrating that new GeneXpert Ultra is not superior to standard GeneXpert for the diagnosis of tuberculous meningitis in Vietnam.

Digital health Systems in Kenyan Public Hospitals

KWTRP

Posted 21/01/2020. Naomi Muinga and colleagues report on challenges and the progress made in implementing digital health systems in Kenyan public hospitals. Their focus is on systems used primarily for financial management but are also being used for clinical services. They show that the available infrastructure needs to be strengthened to achieve the full benefits of electronic systems.

Economic considerations support C-reactive protein testing alongside malaria rapid diagnostic tests to guide antimicrobial therapy for patients with febrile illness in settings with low malaria endemicity

MORU

Posted 17/01/2020. Malaria is no longer a common cause of febrile illness in many regions of the tropics. Yoel Lubell and colleagues consider the costs and benefits of multiplex malaria/CRP tests that are now commercially available in terms of (i) the improved health outcomes for patients with bacterial illnesses; (ii) the costs of antimicrobial resistance averted; or (iii) the economic benefits of better management of remaining malaria cases and shorter malaria elimination campaigns. They conclude that a multiplexed malaria/CRP test could be highly cost-effective and utilize the well-established funding and distribution systems already in place for malaria RDTs.

An exploration of the gut and environmental resistome in a community in northern Vietnam in relation to antibiotic

OUCRU

Posted 14/01/2020. Vu Thi Ngoc Bich and colleagues analyse the antibiotic resistance gene profiles among humans, animals, and their food and water in a rural Vietnamese community. Colistin resistance genes are predominantly found in both human and animal faeces, and a higher positive proportion of carbapenemase is reported – encoding genes among water and food samples when compared to human and animal faeces. This work is a collaboration between OUCRU and Radboudumc, Maastricht University in the Netherlands and NIHE in Vietnam.

Collective strategies to cope with work related stress among nurses in resource constrained settings

@Oxford KWTRP

Posted 10/01/2020. Our ethnography aimed to describe Nairobi’s inpatient newborn wards and the busy lives of the nurses who work there. They work long hours with little supervision in ill-designed wards, staffed by far too few nurses given the pressing need. Under these difficult conditions, the collective model of nursing that develops reduces nurses’ exposure to stress and anxiety. Jacob McKnight and colleagues describe how these coping methods have implications for the quality of care and limit the potential for a patient-centred approach.

Sensitivity of C‐reactive protein for the identification of bacterial infections in northern Tanzania

MORU

Posted 07/01/2020. Identifying bacterial infections in sub-Saharan Africa is a challenge because of limited access to laboratory infrastructure. Thomas Althaus and colleagues measured high sensitivity of C-reactive protein (CRP) in detecting bacterial blood stream infections and zoonotic bacterial pathogens among febrile patients both in primary levels of care and hospitals in Moshi, northern Tanzania

Feeding practices and risk factors for chronic infant undernutrition among refugees and migrants along the Thailand-Myanmar border

MORU

Posted 20/12/2019. How do birth outcomes, a mother’s nutrition, and how a mother feeds her infant relate to chronic undernutrition among refugee and migrant infants along the Thailand-Myanmar border? Why do these mothers feed their infants as they do? Come learn more from a recent study by Ahmar Hashmi and colleagues at the Shoklo Malaria Research Unit.

Phase 3 Efficacy Analysis of a Typhoid Conjugate Vaccine Trial in Nepal

OUCRU

Posted 17/12/2019. Typhoid fever is rampant in South Asia. This new typhoid vaccine (studied in Kathmandu, Nepal, by Buddha Basnyat and colleagues) appears to be very effective in the prevention of typhoid. Administration of the new vaccine, especially in children, will revolutionize the prevention of this disease. And, crucially, help fight typhoid treatment resistance, a burgeoning problem.

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.

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