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Jokinen J.,Finnish National Institute for Health and Welfare | Scott J.A.G.,Wellcome Trust Research Programme | Scott J.A.G.,University of Oxford
Epidemiology | Year: 2010

Background: Community-acquired pneumonia is a common cause of hospitalization among African adults, and Streptococcus pneumoniae is assumed to be a frequent cause. Pneumococcal conjugate vaccine is currently being introduced into childhood immunization programs in Africa. The case for adult vaccination is dependent on the contribution of the pneumococcus to the hospital pneumonia burden. Methods: Pneumococcal diagnosis is complex because there is no gold standard, and culture methods are invalidated by antibiotic use. We used latent class analysis to estimate the proportion of pneumonia episodes caused by pneumococcus. Furthermore, we extended this methodology to evaluate the effect of antimicrobial treatment on test accuracies and the prevalence of the disease. The study combined data from 5 validation studies of pneumococcal diagnostic tests performed on 281 Kenyan adults with pneumonia. Results: The proportion of pneumonia episodes attributable to pneumococcus was 0.46 (95% confidence interval = 0.36-0.57). Failure to account for the effect of antimicrobial exposure underestimates this proportion as 0.32. A history of antibiotic exposure was a poor predictor of antimicrobial activity in patients' urine. Blood culture sensitivity for pneumococcus was estimated at 0.24 among patients with antibiotic exposure, and 0.75 among those without. Conclusions: The large contribution of pneumococcus to adult pneumonia provides a strong case for the investigation of pneumococcal vaccines in African adults. © 2010 by Lippincott Williams & Wilkins.


Feikin D.R.,International Vaccine Access Center | Feikin D.R.,Centers for Disease Control and Prevention | Scott J.A.G.,Wellcome Trust Research Programme | Scott J.A.G.,London School of Hygiene and Tropical Medicine | Gessner B.D.,Voltaire
The Lancet | Year: 2014

Vaccine probe studies have emerged in the past 15 years as a useful way to characterise disease. By contrast, traditional studies of vaccines focus on defining the vaccine effectiveness or efficacy. The underlying basis for the vaccine probe approach is that the difference in disease burden between vaccinated and unvaccinated individuals can be ascribed to the vaccine-specific pathogen. Vaccine probe studies can increase understanding of a vaccine's public health value. For instance, even when a vaccine has a seemingly low efficacy, a high baseline disease incidence can lead to a large vaccine-preventable disease burden and thus that population-based vaccine introduction would be justified. So far, vaccines have been used as probes to characterise disease syndromes caused by Haemophilus influenzae type b, pneumococcus, rotavirus, and early infant influenza. However, vaccine probe studies have enormous potential and could be used more widely in epidemiology, for example, to define the vaccine-preventable burden of malaria, typhoid, paediatric influenza, and dengue, and to identify causal interactions between different pathogens.


Seale A.C.,University College London | Seale A.C.,Imperial College London | Obiero C.W.,Wellcome Trust Research Programme | Berkley J.A.,Wellcome Trust Research Programme | Berkley J.A.,University of Oxford
Current Opinion in Infectious Diseases | Year: 2015

Purpose of review This review discusses the rational development of guidelines for the management of neonatal sepsis in developing countries. Recent findings Diagnosis of neonatal sepsis with high specificity remains challenging in developing countries. Aetiology data, particularly from rural, community-based studies, are very limited, but molecular tests to improve diagnostics are being tested in a community-based study in South Asia. Antibiotic susceptibility data are limited, but suggest reducing susceptibility to first-and second-line antibiotics in both hospital and community-acquired neonatal sepsis. Results of clinical trials in South Asia and sub-Saharan Africa assessing feasibility of simplified antibiotic regimens are awaited. Summary Effective management of neonatal sepsis in developing countries is essential to reduce neonatal mortality and morbidity. Simplified antibiotic regimens are currently being examined in clinical trials, but reduced antimicrobial susceptibility threatens current empiric treatment strategies. Improved clinical and microbiological surveillance is essential, to inform current practice, treatment guidelines, and monitor implementation of policy changes. © 2015 Wolters Kluwer Health, Inc. All rights reserved.


Ibinda F.,Wellcome Trust Research Programme | Wagner R.G.,University of Witwatersrand | Wagner R.G.,Umeå University | Bertram M.Y.,World Health Organization | And 9 more authors.
Epilepsia | Year: 2014

Summary Objectives The burden of epilepsy, in terms of both morbidity and mortality, is likely to vary depending on the etiology (primary [genetic/unknown] vs. secondary [structural/metabolic]) and with the use of antiepileptic drugs (AEDs). We estimated the disability-adjusted life years (DALYs) and modeled the remission rates of active convulsive epilepsy (ACE) using epidemiologic data collected over the last decade in rural Kilifi, Kenya.Methods We used measures of prevalence, incidence, and mortality to model the remission of epilepsy using disease-modeling software (DisMod II). DALYs were calculated as the sum of Years Lost to Disability (YLD) and Years of Life Lost (YLL) due to premature death using the prevalence approach, with disability weights (DWs) from the 2010 Global Burden of Disease (GBD) study. DALYs were calculated with R statistical software with the associated uncertainty intervals (UIs) computed by bootstrapping.Results A total of 1,005 (95% UI 797-1,213) DALYs were lost to ACE, which is 433 (95% UI 393-469) DALYs lost per 100,000 people. Twenty-six percent (113/100,000/year, 95% UI 106-117) of the DALYs were due to YLD and 74% (320/100,000/year, 95% UI 248-416) to YLL. Primary epilepsy accounted for fewer DALYs than secondary epilepsy (98 vs. 334 DALYs per 100,000 people). Those taking AEDs contributed fewer DALYs than those not taking AEDs (167 vs. 266 DALYs per 100,000 people). The proportion of people with ACE in remission per year was estimated at 11.0% in males and 12.0% in females, with highest rates in the 0-5 year age group.Significance The DALYs for ACE are high in rural Kenya, but less than the estimates of 2010 GBD study. Three-fourths of DALYs resulted from secondary epilepsy. Use of AEDs was associated with 40% reduction of DALYs. Improving adherence to AEDs may reduce the burden of epilepsy in this area. © © 2014 The Authors. Epilepsia published by Wiley Periodicals, Inc. on behalf of International League Against Epilepsy.


Hassan A.S.,Wellcome Trust Research Programme | Nabwera H.M.,Wellcome Trust Research Programme | Mwaringa S.M.,Wellcome Trust Research Programme | Obonyo C.A.,Kilifi District Hospital | And 7 more authors.
AIDS Research and Therapy | Year: 2014

Background: An increasing number of people on antiretroviral therapy (ART) in sub-Saharan Africa has led to declines in HIV related morbidity and mortality. However, virologic failure (VF) and acquired drug resistance (ADR) may negatively affect these gains. This study describes the prevalence and correlates of HIV-1 VF and ADR among first-line ART experienced adults at a rural HIV clinic in Coastal Kenya.Methods: HIV-infected adults on first-line ART for ≥6 months were cross-sectionally recruited between November 2008 and March 2011. The primary outcome was VF, defined as a one-off plasma viral load of ≥400 copies/ml. The secondary outcome was ADR, defined as the presence of resistance associated mutations. Logistic regression and Fishers exact test were used to describe correlates of VF and ADR respectively.Results: Of the 232 eligible participants on ART over a median duration of 13.9 months, 57 (24.6% [95% CI: 19.2 - 30.6]) had VF. Fifty-five viraemic samples were successfully amplified and sequenced. Of these, 29 (52.7% [95% CI: 38.8 - 66.3]) had at least one ADR, with 25 samples having dual-class resistance mutations. The most prevalent ADR mutations were the M184V (n = 24), K103N/S (n = 14) and Y181C/Y/I/V (n = 8). Twenty-six of the 55 successfully amplified viraemic samples (47.3%) did not have any detectable resistance mutation. Younger age (15-34 vs. ≥35 years: adjusted odd ratios [95% CI], p-value: 0.3 [0.1-0.6], p = 0.002) and unsatisfactory adherence (<95% vs. ≥95%: 3.0 [1.5-6.5], p = 0.003) were strong correlates of VF. Younger age, unsatisfactory adherence and high viral load were also strong correlates of ADR.Conclusions: High levels of VF and ADR were observed in younger patients and those with unsatisfactory adherence. Youth-friendly ART initiatives and strengthened adherence support should be prioritized in this Coastal Kenyan setting. To prevent unnecessary/premature switches, targeted HIV drug resistance testing for patients with confirmed VF should be considered. © 2014 Hassan et al.; licensee BioMed Central Ltd.


Wafula F.,Aidspan | Agweyu A.,Wellcome Trust Research Programme | Macintyre K.,Aidspan
Malaria Journal | Year: 2013

Background: Although procurement consumes nearly 40% of Global Fund's money, no analyses have been published to show how costs vary across regions and time. This paper presents an analysis of malaria-related commodity procurement data from 79 countries, as reported through the Global Fund's price and quality reporting (PQR) system for the 2005-2012 period. Methods. Data were analysed for the three most widely procured commodities for prevention, diagnosis and treatment of malaria. These were long-lasting insecticide-treated nets (LLINs), malaria rapid diagnostic tests (RDTs) and the artemether/lumefantrine (AL) combination treatment. Costs were compared across time (2005-2012), regions, and between individual procurement reported through the PQR and pooled procurement reported through the Global Fund's voluntary pooled procurement (VPP) system. All costs were adjusted for inflation and reported in US dollars. Results: The data included 1,514 entries reported from 79 countries over seven years. Of these, 492 entries were for LLINs, 330 for RDTs and 692 for AL. Considerable variations were seen by commodity, although none showed an increase in cost. The costs for LLINs, RDTs and AL all dropped significantly over the period of analysis. Regional variations were also seen, with the cost for all three commodities showing significant variations. The median cost for a single LLIN ranged from USD 4.3 in East Asia to USD 5.0 in West and Central Africa. The cost of a single RDT was lowest in West and Central Africa at US$ 0.57, and highest in the Latin American region at US$ 1.1. AL had the narrowest margin of between US$ 0.06 per tablet in sub-Saharan Africa and South Asia, and US$ 0.08 in the Latin American and Eastern Europe regions. Conclusion: This paper concludes that global procurement costs do vary by region and have reduced overall over time. This suggests a mature market is operating when viewed from the global level, but regional variation needs further attention. Such analyses should be done more often to identify and correct market insufficiencies. © 2013 Wafula et al.; licensee BioMed Central Ltd.


Muinga N.,Wellcome Trust Research Programme | Ayieko P.,Wellcome Trust Research Programme | Opondo C.,Wellcome Trust Research Programme | Ntoburi S.,London School of Hygiene and Tropical Medicine | And 4 more authors.
BMC Health Services Research | Year: 2014

Background: The 'resource readiness' of health facilities to provide effective services is captured in the structure component of the classical Donabedian paradigm often used for assessment of the quality of care in the health sector. Periodic inventories are commonly used to confirm the presence (or absence) of equipment or drugs by physical observation or by asking those in charge to indicate whether an item is present or not. It is then assumed that this point observation is representative of the everyday status. However the availability of an item (consumables) may vary. Arguably therefore a more useful assessment for resources would be one that captures this fluctuation in time. Here we report an approach that may circumvent these difficulties. Methods. We used self-administered questionnaires (SAQ) to seek health worker views of availability of key resources supporting paediatric care linked to a cluster randomized trial of a multifaceted intervention aimed at improving this care conducted in eight rural Kenyan district hospitals. Four hospitals received a full intervention and four a partial intervention. Data were collected pre-intervention and after 6 and 18 months from health workers in three clinical areas asked to score item availability using an 11-point scale. Mean scores for items common to all 3 areas and mean scores for items allocated to domains identified using exploratory factor analysis (EFA) were used to describe availability and explore changes over time. Results: SAQ were collected from 1,156 health workers. EFA identified 11 item domains across the three departments. Mean availability scores for these domains were often <5/10 at baseline reflecting lack of basic resources such as oxygen, nutrition and second line drugs. An improvement in mean scores occurred in 8 out of 11 domains in both control and intervention groups. A calculation of difference in difference of means for intervention vs. control suggested an intervention effect resulting in greater changes in 5 out of 11 domains. Conclusion: Using SAQ data to assess resource availability experienced by health workers provides an alternative to direct observations that provide point prevalence estimates. Further the approach was able to demonstrate poor access to resources, change over time and variability across place. © 2014 Muinga et al.; licensee BioMed Central Ltd.


Sutherland C.J.,London School of Hygiene and Tropical Medicine | Babiker H.,Sultan Qaboos University | Babiker H.,University of Edinburgh | MacKinnon M.J.,Wellcome Trust Research Programme | And 3 more authors.
Parasitology | Year: 2011

Artemisinin-based combination therapy is exerting novel selective pressure upon populations of Plasmodium falciparum across Africa. Levels of resistance to non-artemisinin partner drugs differ among parasite populations, and so the artemisinins are not uniformly protected from developing resistance, already present in South East Asia. Here, we consider strategies for prolonging the period of high level efficacy of combination therapy for two particular endemicities common in Africa. Under high intensity transmission, two alternating first-line combinations, ideally with antagonistic selective effects on the parasite genome, are advocated for paediatric malaria cases. This leaves second-line and other therapies for adult cases, and for intermittent preventive therapy. The drug portfolio would be selected to protect the "premier" combination regimen from selection for resistance, while maximising impact on severe disease and mortality in children. In endemic areas subject to low, seasonal transmission of Plasmodium falciparum, such a strategy may deliver little benefit, as children represent a minority of cases. Nevertheless, the deployment of other drug-based interventions in low transmission and highly seasonal areas, such as mass drug administration aimed to interrupt malaria transmission, or intermittent preventive therapy, does provide an opportunity to diversify drug pressure. We thus propose an integrated approach to drug deployment, which minimises direct selective pressure on parasite populations from any one drug component. This approach is suitable for qualitatively and quantitatively different burdens of malaria, and should be supported by a programme of routine surveillance for emerging resistance. Copyright © 2011 Cambridge University Press.


Sullivan P.S.,Emory University | Carballo-Dieguez A.,Columbia University | Coates T.,University of California at Los Angeles | Goodreau S.M.,University of Washington | And 6 more authors.
The Lancet | Year: 2012

Men who have sex with men (MSM) have been substantially affected by HIV epidemics worldwide. Epidemics in MSM are re-emerging in many high-income countries and gaining greater recognition in many low-income and middle-income countries. Better HIV prevention strategies are urgently needed. Our review of HIV prevention strategies for MSM identified several important themes. At the beginning of the epidemic, stand-alone behavioural interventions mostly aimed to reduce unprotected anal intercourse, which, although somewhat efficacious, did not reduce HIV transmission. Biomedical prevention strategies reduce the incidence of HIV infection. Delivery of barrier and biomedical interventions with coordinated behavioural and structural strategies could optimise the effectiveness of prevention. Modelling suggests that, with sufficient coverage, available interventions are sufficient to avert at least a quarter of new HIV infections in MSM in diverse countries. Scale-up of HIV prevention programmes for MSM is difficult because of homophobia and bias, suboptimum access to HIV testing and care, and financial constraints.


News Article | November 22, 2016
Site: www.eurekalert.org

Giving preventive antimalarial drugs to children up to age 10 during active malaria season reduced the cases of malaria in that age group and lowered the malaria incidence in adults, according to a randomized trial carried out in Senegal and published in PLOS Medicine by researchers from the Université Cheikh Anta Diop, Senegal, the London School of Hygiene & Tropical Medicine, UK, and other collaborators. In 2012, the World Health Organization recommended that children under 5 years of age living in central Africa receive Seasonal Malaria Chemoprevention (SMC) with sulfadoxine-pyrimethamine and amodiaquine for up to 4 months of the year to prevent malaria. However, in many areas there is a substantial burden of disease in older children. The investigators designed a study in which 54 health posts in central Senegal were randomized to provide SMC to children up to age 10, or act as controls. For the years of the study, between 2008 and 2011, malaria cases and deaths in each community were monitored at outpatient clinics and hospitals. Over three years, 780,000 SMC treatments were given to children. Mortality, the primary study endpoint, was similar between the test and control areas (4.6 and 4.5 per 1000 respectively in children under 5 years and 1.3 and 1.2 per 1000 in children 5-9 years of age, with a mortality rate ratio 0.90; 95 percent confidence interval 0.68-1.2, p=0.496). However, SMC was found to reduce the incidence of malaria in those under age 10 by 60% (95 percent confidence interval 54-64%, p "Apart from in Senegal, SMC is currently being provided only for children up to 5 years of age, but in many areas the burden in older children may justify extending this range," says author Paul Milligan of the London School of Hygiene & Tropical Medicine. "Our study shows that in some areas expanding the age range for SMC could have a substantial impact on the malaria burden and could contribute to reducing malaria transmission." In an accompanying Perspective, Robert Snow of the Kenya Medical Research Institute/Wellcome Trust Research Programme discusses the history of SMC in Africa and compares the costs and benefits of expanding the targeted age range. "[Seasonal malaria chemoprevention] is notable for incorporating the idea that different approaches may be appropriate in different settings," he notes. "Even if a fraction of the costs of delivering SMC were dedicated to intensive surveillance and a sustained research agenda, national malaria programmes could adapt to a changing epidemiology, parasite resistance and community acceptability." This study was funded by the Bill and Melinda Gates Foundation, grant number 40099. MC received support through a Population Health Scientist Fellowship jointly funded by the UK Medical Research Council (MRC) and the UK Department for International Development (DFID). JLN is supported by a Wellcome Trust Intermediate Fellowship in Public Health and Tropical Medicine. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors have declared that no competing interests exist. Cissé B, Ba EH, Sokhna C, NDiaye JL, Gomis JF, Dial Y, et al. (2016) Effectiveness of Seasonal Malaria Chemoprevention in Children under Ten Years of Age in Senegal: A Stepped-Wedge Cluster-Randomised Trial. PLoS Med 13(11): e1002175. doi:10.1371/journal.pmed.1002175 IN YOUR COVERAGE PLEASE USE THIS URL TO PROVIDE ACCESS TO THE FREELY AVAILABLE PAPER:http://journals. RWS is funded as a Principal Research Fellow by the Wellcome Trust wellcome.ac.uk (# 103602). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The author has declared that no competing interests exist. KEMRI-Wellcome Trust Collaborative Programme, Nairobi, Kenya Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom IN YOUR COVERAGE PLEASE USE THIS URL TO PROVIDE ACCESS TO THE FREELY AVAILABLE PAPER:http://journals.

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