KEMRI Wellcome Trust Research Programme

Kilifi, Kenya

KEMRI Wellcome Trust Research Programme

Kilifi, Kenya
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English M.,KEMRI Wellcome Trust Research Programme | Schellenberg J.,London School of Hygiene and Tropical Medicine | Todd J.,London School of Hygiene and Tropical Medicine
Bulletin of the World Health Organization | Year: 2011

Research is needed to help identify interventions that will improve the capacity or functioning of health systems and thereby contribute to achieving global health goals. Well conducted, randomized controlled trials (RCTs), insofar as they reduce bias and confounding, provide the strongest evidence for identifying which interventions delivered directly to individuals are safe and effective. When ethically feasible, they can also help reduce bias and confounding when assessing interventions targeting entire health systems. However, additional challenges emerge when research focuses on interventions that target the multiple units of organization found within health systems. Hence, one cannot complacently assume that randomization can reduce or eliminate bias and confounding to the same degree in every instance. While others have articulated arguments in favour of alternative designs, this paper is intended to help people understand why the potential value afforded by RCTs may be threatened. Specifically, it suggests six points to be borne in mind when exploring the challenges entailed in designing or evaluating RCTs on health system interventions: (i)the number of units available for randomization; (ii)the complexity of the organizational unit under study; (iii)the complexity of the intervention; (iv) the complexity of the cause-effect pathway, (v)contamination; and (vi)outcome heterogeneity. The authors suggest that the latter may be informative and that the reasons behind it should be explored and not ignored. Based on improved understanding of the value and possible limitations of RCTs on health system interventions, the authors show why we need broader platforms of research to complement RCTs.

Wafula F.,Aidspan | Agweyu A.,KEMRI Wellcome Trust Research Programme | Macintyre K.,Aidspan
Journal of Acquired Immune Deficiency Syndromes | Year: 2014

Background: Nearly 40% of Global Fund money goes toward procurement. However, no analyses have been published to show how costs vary across regions and time, despite the availability of procurement data collected through the Global Fund's price and quality reporting system. Methodology: We analyzed data for the 3 most widely procured commodities for the prevention, diagnosis, and treatment of HIV. These were male condoms, HIV rapid tests, and the antiretroviral (ARV) combination of lamivudine/nevirapine/zidovudine. The compared costs, first across time (2005-2012), then across regions, and finally, between individual procurement reported through the price and quality reporting and pooled procurement reported through the Global Fund's voluntary pooled procurement system. All costs were adjusted for inflation and reported in US dollars. Key Findings: There were 2337 entries from 578 grants in 125 countries. The procurement cost for the ARV dropped substantially over the period, whereas those for condoms and HIV tests remained relatively stable. None of the commodity prices increased. Regional variations were pronounced for HIV tests, but minimal for condoms and the ARV. The unit cost for the 3-table ARV combination, for instance, varied between US$0.15 and US$0.23 in South Asia and the Eastern Europe/Central Asia regions, respectively, compared with a range of $0.23 (South Asia)$1.50 (Eastern Europe/Central Asia) for a single diagnostic test. Pooled procurement lowered costs for condoms but not the other commodities. Conclusions: We showed how global procurement costs vary by region and time. Such analyses should be done more often to identify and correct market insufficiencies. © 2013 by Lippincott Williams & Wilkins.

Church J.,Imperial College London | Church J.,KEMRI Wellcome Trust Research Programme | Church J.,Queen Mary, University of London | Maitland K.,Imperial College London | Maitland K.,KEMRI Wellcome Trust Research Programme
BMC Medicine | Year: 2014

Background: Severe malaria remains a major cause of pediatric hospital admission across Africa. Invasive bacterial infection (IBI) is a recognized complication of Plasmodium falciparum malaria, resulting in a substantially worse outcome. Whether a biological relationship exists between malaria infection and IBI susceptibility remains unclear. We, therefore, examined the extent, nature and evidence of this association.Methods: We conducted a systematic search in August 2012 of three major scientific databases, PubMed, Embase and Africa Wide Information, for articles describing bacterial infection among children with P. falciparum malaria using the search string '(malaria OR plasmodium) AND (bacteria OR bacterial OR bacteremia OR bacteraemia OR sepsis OR septicaemia OR septicemia).' Eligiblity criteria also included studies of children hospitalized with malaria or outpatient attendances in sub-Saharan Africa.Results: A total of 25 studies across 11 African countries fulfilled our criteria. They comprised twenty cohort analyses, two randomized controlled trials and three prospective epidemiological studies. In the meta-analysis of 7,208 children with severe malaria the mean prevalence of IBI was 6.4% (95% confidence interval (CI) 5.81 to 6.98%). In a further meta-analysis of 20,889 children hospitalised with all-severity malaria and 27,641 children with non-malarial febrile illness the mean prevalence of IBI was 5.58 (95% CI 5.5 to 5.66%) in children with malaria and 7.77% (95% CI 7.72 to 7.83%) in non-malaria illness. Ten studies reported mortality stratified by IBI. Case fatality was higher at 81 of 336, 24.1% (95% CI 18.9 to 29.4) in children with malaria/IBI co-infection compared to 585 of 5,760, 10.2% (95% CI 9.3 to 10.98) with malaria alone. Enteric gram-negative organisms were over-represented in malaria cases, non-typhoidal Salmonellae being the most commonest isolate. There was weak evidence indicating IBI was more common in the severe anemia manifestation of severe malaria.Conclusions: The accumulated evidence suggests that children with recent or acute malaria are at risk of bacterial infection, which results in an increased risk of mortality. Characterising the exact nature of this association is challenging due to the paucity of appropriate severity-matched controls and the heterogeneous data. Further research to define those at greatest risk is necessary to target antimicrobial treatment. © 2014 Church and Maitland; licensee BioMed Central Ltd.

English M.,KEMRI Wellcome Trust Research Programme | English M.,University of Oxford
Implementation Science | Year: 2013

Background: District hospital services in Kenya and many low-income countries should deliver proven, effective interventions that could substantially reduce child and newborn mortality. However such services are often of poor quality. Researchers have therefore been challenged to identify intervention strategies that go beyond addressing knowledge, skill, or resource inadequacies to support health systems to deliver better services at scale. An effort to develop a system-oriented intervention tailored to local needs and context and drawing on theory is described.Methods: An intervention was designed to improve district hospital services for children based on four main strategies: a reflective process to distill root causes for the observed problems with service delivery; developing a set of possible intervention approaches to address these problems; a search of literature for theory that provided the most appropriate basis for intervention design; and repeatedly moving backwards and forwards between identified causes, proposed interventions, identified theory, and knowledge of the existing context to develop an overarching intervention that seemed feasible and likely to be acceptable and potentially sustainable.Results and discussion: In addition to human and resource constraints key problems included failures of relevant professionals to take responsibility for or ownership of the challenge of pediatric service delivery; inadequately prepared, poorly supported leaders of service units (mid-level managers) who are often professionally and geographically isolated and an almost complete lack of useful information for routinely monitoring or understanding service delivery practice or outcomes. A system-oriented intervention recognizing the pivotal role of leaders of service units but addressing the outer and inner setting of hospitals was designed to help shape and support an appropriate role for these professionals. It aims to foster a sense of ownership while providing the necessary understanding, knowledge, and skills for mid-level managers to work effectively with senior managers and frontline staff to improve services. The intervention will include development of an information system, feedback mechanisms, and discussion fora that promote positive change. The vehicle for such an intervention is a collaborative network partnering government and national professional associations. This case is presented to promote discussion on approaches to developing context appropriate interventions particularly in international health. © 2013 English; licensee BioMed Central Ltd.

Mackinnon M.J.,KEMRI Wellcome Trust Research Programme | Mackinnon M.J.,University of Oxford
Malaria Journal | Year: 2014

A recent study found that mosquito-transmitted (MT) lines of rodent malaria parasites elicit a more effective immune response than non-transmitted lines maintained by serial blood passage (non-MT), thereby causing lower parasite densities in the blood and less pathology to the host. The authors attribute these changes to higher diversity in expression of antigen-encoding genes in MT cf. non-MT lines. Alternative explanations that are equally parsimonious with these new data, and results from previous studies, suggest that this conclusion may be premature. © 2014 Mackinnon; licensee BioMed Central Ltd.

Chakravorty S.,Imperial College London | Williams T.N.,Imperial College London | Williams T.N.,KEMRI Wellcome Trust Research Programme
Archives of Disease in Childhood | Year: 2015

Sickle cell disease (SCD) is a single gene disorder causing a debilitating systemic syndrome characterised by chronic anaemia, acute painful episodes, organ infarction and chronic organ damage and by a significant reduction in life expectancy. The origin of SCD lies in the malarial regions of the tropics where carriers are protected against death from malaria and hence enjoy an evolutionary advantage. More recently, population migration has meant that SCD now has a worldwide distribution and that a substantial number of children are born with the condition in higher-income areas, including large parts of Europe and North and South America. Newborn screening, systematic clinical followup and prevention of sepsis and organ damage have led to an increased life expectancy among people with SCD in many such countries; however, in resource-limited settings where the majority continue to be born, most affected children continue to die in early childhood, usually undiagnosed, due to the lack of effective programmes for its early detection and treatment. As new therapies emerge, potentially leading to disease amelioration or cure, it is of paramount importance that the significant burden of SCD in resource-poor countries is properly recognised.

Maitland K.,Imperial College London | Maitland K.,KEMRI Wellcome Trust Research Programme
BMC Medicine | Year: 2015

Over 90% of the world's severe and fatal Plasmodium falciparum malaria is estimated to affect young children in sub-Sahara Africa, where it remains a common cause of hospital admission and inpatient mortality. Few children will ever be managed on high dependency or intensive care units and, therefore, rely on simple supportive treatments and parenteral anti-malarials. There has been some progress on defining best practice for antimalarial treatment with the publication of the AQUAMAT trial in 2010, involving 5,425 children at 11 centres across 9 African countries, showing that in artesunate-treated children, the relative risk of death was 22.5% (95% confidence interval (CI) 8.1 to 36.9) lower than in those receiving quinine. Human trials of supportive therapies carried out on the basis of pathophysiology studies, have so far made little progress on reducing mortality; despite appearing to reduce morbidity endpoints, more often than not they have led to an excess of adverse outcomes. This review highlights the spectrum of complications in African children with severe malaria, the therapeutic challenges of managing these in resource-poor settings and examines in-depth the results from clinical trials with a view to identifying the treatment priorities and a future research agenda. © 2015 Maitland, licensee BioMed Central.

In developing countries referral of severely ill children from primary care to district hospitals is common, but hospital care is often of poor quality. However, strategies to change multiple paediatric care practices in rural hospitals have rarely been evaluated. This cluster randomized trial was conducted in eight rural Kenyan district hospitals, four of which were randomly assigned to a full intervention aimed at improving quality of clinical care (evidence-based guidelines, training, job aides, local facilitation, supervision, and face-to-face feedback; n = 4) and the remaining four to control intervention (guidelines, didactic training, job aides, and written feedback; n = 4). Prespecified structure, process, and outcome indicators were measured at baseline and during three and five 6-monthly surveys in control and intervention hospitals, respectively. Primary outcomes were process of care measures, assessed at 18 months postbaseline. In both groups performance improved from baseline. Completion of admission assessment tasks was higher in intervention sites at 18 months (mean = 0.94 versus 0.65, adjusted difference 0.54 [95% confidence interval 0.05-0.29]). Uptake of guideline recommended therapeutic practices was also higher within intervention hospitals: adoption of once daily gentamicin (89.2% versus 74.4%; 17.1% [8.04%-26.1%]); loading dose quinine (91.9% versus 66.7%, 26.3% [-3.66% to 56.3%]); and adequate prescriptions of intravenous fluids for severe dehydration (67.2% versus 40.6%; 29.9% [10.9%-48.9%]). The proportion of children receiving inappropriate doses of drugs in intervention hospitals was lower (quinine dose >40 mg/kg/day; 1.0% versus 7.5%; -6.5% [-12.9% to 0.20%]), and inadequate gentamicin dose (2.2% versus 9.0%; -6.8% [-11.9% to -1.6%]). Specific efforts are needed to improve hospital care in developing countries. A full, multifaceted intervention was associated with greater changes in practice spanning multiple, high mortality conditions in rural Kenyan hospitals than a partial intervention, providing one model for bridging the evidence to practice gap and improving admission care in similar settings.

Opiyo N.,KEMRI Wellcome Trust Research Programme | English M.,KEMRI Wellcome Trust Research Programme
The Cochrane database of systematic reviews | Year: 2015

AUTHORS' CONCLUSIONS: In-service neonatal emergency care courses probably improve health professionals' treatment of seriously ill babies in the short term. Further multi-centre randomised trials evaluating the effects of in-service emergency care training on long-term outcomes (health professional practice and patient outcomes) are needed.BACKGROUND: A variety of in-service emergency care training courses are currently being promoted as a strategy to improve the quality of care provided to seriously ill newborns and children in low-income countries. Most courses have been developed in high-income countries. However, whether these courses improve the ability of health professionals to provide appropriate care in low-income countries remains unclear. This is the first update of the original review.OBJECTIVES: To assess the effects of in-service emergency care training on health professionals' treatment of seriously ill newborns and children in low-income countries.SEARCH METHODS: For this update, we searched the Cochrane Database of Systematic Reviews, part of The Cochrane Library (; MEDLINE, Ovid SP; EMBASE, Ovid SP; the Cochrane Central Register of Controlled Trials (CENTRAL), part of The Cochrane Library ( (including the Cochrane Effective Practice and Organisation of Care (EPOC) Group Specialised Register); Science Citation Index and Social Sciences Citation Index, Institute for Scientific Information (ISI) Web of Knowledge/Science and eight other databases. We performed database searches in February 2015. We also searched clinical trial registries, websites of relevant organisations and reference lists of related reviews. We applied no date, language or publication status restrictions when conducting the searches.SELECTION CRITERIA: Randomised trials, non-randomised trials, controlled before and after studies and interrupted-time-series studies that compared the effects of in-service emergency care training versus usual care were eligible for inclusion. We included only hospital-based studies and excluded community-based studies. Two review authors independently screened and selected studies for inclusion.DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed study risk of bias and confidence in effect estimates (certainty of evidence) for each outcome using GRADE (Grades of Recommendation, Assessment, Development and Evaluation). We described results and presented them in GRADE tables.MAIN RESULTS: We identified no new studies in this update. Two randomised trials (which were included in the original review) met the review eligibility criteria. In the first trial, newborn resuscitation training compared with usual care improved provider performance of appropriate resuscitation (trained 66% vs usual care 27%, risk ratio 2.45, 95% confidence interval (CI) 1.75 to 3.42; moderate certainty evidence) and reduced inappropriate resuscitation (trained mean 0.53 vs usual care 0.92, mean difference 0.40, 95% CI 0.13 to 0.66; moderate certainty evidence). Effect on neonatal mortality was inconclusive (trained 28% vs usual care 25%, risk ratio 0.77, 95% CI 0.40 to 1.48; N = 27 deaths; low certainty evidence). Findings from the second trial suggest that essential newborn care training compared with usual care probably slightly improves delivery room newborn care practices (assessment of breathing, preparedness for resuscitation) (moderate certainty evidence).

Agency: GTR | Branch: MRC | Program: | Phase: Research Grant | Award Amount: 95.39K | Year: 2016

For the first time, in 2013, the WHO guidelines for treating children with Severe Acute Malnutrition (SAM) included guidance on how to diagnose and treat SAM in infants aged below 6 months. The treatment guidelines for infants under 6 months focused on inpatient treatment and recommended that admitted infants with SAM be supported to re-establish exclusive breastfeeding before they can be discharged. The recommendation was based mainly on programmatic reports and a few studies that had shown that lactation failure is common among infants with SAM, and that re-establishing breastfeeding among infants being treated for SAM is possible using re-lactation techniques such as supplementary suckling. However, since none of the studies followed infants up after discharge, we still do not know i) if exclusive breastfeeding was retained after discharge; ii) if retaining exclusive breastfeeding after discharge is sufficient for nutritional recovery and iii) if additional breastfeeding support offered to mothers of discharged infants would be beneficial. The proposed study is aimed at generating important information to develop a trial to establish the effectiveness of home-based breastfeeding support to mothers of infants discharged from SAM treatment on survival and growth. The main aim of the proposed study is to i) establish the breastfeeding retention rate among infants under 6 months discharged from SAM treatment within the current strategies that are without a specific post discharge breastfeeding support; and ii) establish whether among infants retaining exclusive breastfeeding, breastmilk alone is sufficient for nutritional recovery. This information will form the baseline data from where any success of any applied intervention will be measured. Hence the findings from this study will strengthen the calculations of the sample size required to show an improvement in the outcomes due to an intervention. In addition, the study will provide insight on the acceptability and sustainability of using peer breastfeeding supporters commonly used to encourage breastfeeding in preterm neonates for infants with SAM. It will also provide information on the optimal trial follow-up strategy that could be applied successfully for this group of participants. Apart from providing information for trial development, the study findings will by themselves provide data to previously identified research gap. Within the 2013 updated WHO guidelines on management of SAM in children, (page 66) the question of how breastfeeding is most effectively established is raised. Our study intends to optimize the WHO inpatient treatment guidelines and will in the process develop a step-by-step re-lactation protocol that would be applicable for resource poor settings. Recently, using the well developed and highly recommended Child Health and Nutrition Research Initiative (CHNRI) methodology, researchers, developmental partners and other stakeholders including UN agencies identified that research into the components of a package care for outpatient care as one of the top research priorities for infants with SAM (Angood, McGrath et al. 2015). Findings from the proposed study will provide baseline information useful in designing and testing a package for outpatient care.

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