Center for Geographic Medicine Research Coast

Medicine, Kenya

Center for Geographic Medicine Research Coast

Medicine, Kenya
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Weinberger D.M.,Harvard University | Harboe Z.B.,Statens Serum Institute | Sanders E.A.M.,University Utrecht | Ndiritu M.,Center for Geographic Medicine Research Coast | And 9 more authors.
Clinical Infectious Diseases | Year: 2010

Background. The 92 capsular serotypes of Streptococcus pneumoniae differ greatly in nasopharyngeal carriage prevalence, invasiveness, and disease incidence. There has been some debate, though, regarding whether serotype independently affects the outcome of invasive pneumococcal disease (IPD). Published studies have shown variable results with regard to case-fatality ratios for specific serotypes and the role of host factors in affecting these relationships. We evaluated whether risk of death due to IPD is a stable serotype-associated property across studies and then compared the pooled effect estimates with epidemiologic and biological correlates. Methods. We performed a systematic review and meta-analysis of serotype-specific disease outcomes for patients with pneumonia and meningitis. Study-specific estimates of risk of death (risk ratio [RR]) were pooled from 9 studies that provided serotype-specific data on pneumonia and meningitis using a random-effects method with serotype 14 as the reference. Pooled RRs were compared with RRs from adults with low comorbidity scores to evaluate potential confounding by host factors. Results. Significant differences were found in the RR estimates among serotypes in patients with bacteremic pneumonia. Overall, serotypes 1, 7F, and 8 were associated with decreased RRs, and serotypes 3, 6A, 6B, 9N, and 19F were associated with increased RRs. Outcomes among meningitis patients did not differ significantly among serotypes. Serotypes with increased RRs had a high carriage prevalence, had low invasiveness, and were more heavily encapsulated in vitro. Conclusions. These results suggest that IPD outcome, like other epidemiologic measures, is a stable serotypeassociated property. © 2010 by the Infectious Diseases Society of America. All rights reserved.

Owino E.A.,University of Pretoria | Sang R.,Kenya Medical Research Institute | Sole C.L.,University of Pretoria | Pirk C.,University of Pretoria | Mbogo C.,Center for Geographic Medicine Research Coast
Parasites and Vectors | Year: 2014

Background: Methods currently used in sampling adult Aedes aegypti, the main vector of dengue and chikungunya viruses are limited for effective surveillance of the vector and accurate determination of the extent of virus transmission during outbreaks and inter - epidemic periods. Here, we document the use of natural human skin odours in baited traps to improve sampling of adult Ae. aegypti in two different endemic areas of chikungunya and dengue in Kenya - Kilifi and Busia Counties. The chemistry of the volatiles released from human odours and the Biogent (BG)-commercial lure were also compared.Methods. Cotton socks and T-shirts were used to obtain natural human skin volatiles from the feet and trunk of three volunteers (volunteers 1 and 2 in Kilifi and volunteers 2 and 3 in Busia). Using Latin square design, we compared the efficacies of BG sentinel traps baited with carbon dioxide plus (a) no bait, (b) human feet volatiles, (c) human trunk volatiles each against (c) a control (Biogent commercial lure) at the two sites. Coupled gas chromatography-mass spectrometry (GC-MS) was used to identify and compare candidate attractants released by the commercial lure and human odours.Results: Ae. aegypti captured in the trap baited with feet odours from volunteer 2 and trunk odours from the same volunteer were significantly higher than in the control trap in Busia and Kilifi respectively, [IRR = 5.63, 95% CI: 1.15 - 28.30, p = 0.030] and [IRR = 3.99, 95% CI: 0.95-16.69, p = 0.049]. At both sites, Ae. aegypti captures in traps baited with either the feet or trunk odours from volunteers 1 and 3 were not significantly different from the control. Major qualitative differences were observed between the chemical profiles of human odours and the commercial BG-lure. Aldehydes, fatty acids and ketones dominated human odour profiles, whereas the BG-lure released mainly hexanoic acid.Conclusions: Our results suggest that additional candidate attractants are present in human skin volatiles which can help to improve the efficacy of lures for trapping and surveillance of Ae. aegypti. © 2014Owino et al.; licensee BioMed Central Ltd.

Suchdev P.S.,Centers for Disease Control and Prevention | Suchdev P.S.,Emory University | Ruth L.J.,Centers for Disease Control and Prevention | Earley M.,Newborn Screening Quality Assurance Program | And 2 more authors.
Maternal and Child Nutrition | Year: 2014

Although inherited blood disorders are common among children in many parts of Africa, limited data are available about their prevalence or contribution to childhood anaemia. We conducted a cross-sectional survey of 858 children aged 6-35 months who were randomly selected from 60 villages in western Kenya. Haemoglobin (Hb), ferritin, malaria, C-reactive protein (CRP) and retinol binding protein (RBP) were measured from capillary blood. Using polymerase chain reaction (PCR), Hb type, -3.7kb alpha-globin chain deletion, glucose-6-phosphate dehydrogenase (G6PD) genotype and haptoglobin (Hp) genotype were determined. More than 2 out of 3 children had at least one measured blood disorder. Sickle cell trait (HbAS) and disease (HbSS) were found in 17.1% and 1.6% of children, respectively; 38.5% were heterozygotes and 9.6% were homozygotes for α+-thalassaemia. The Hp 2-2 genotype was found in 20.4% of children, whereas 8.2% of males and 6.8% of children overall had G6PD deficiency. There were no significant differences in the distribution of malaria by the measured blood disorders, except among males with G6PD deficiency who had a lower prevalence of clinical malaria than males of normal G6PD genotype (P=0.005). After excluding children with malaria parasitaemia, inflammation (CRP>5mgL-1), iron deficiency (ferritin<12μgL-1) or vitamin A deficiency (RBP<0.7μgL-1), the prevalence of anaemia among those without α+-thalassaemia (43.0%) remained significantly lower than that among children who were either heterozygotes (53.5%) or homozygotes (67.7%, P=0.03). Inherited blood disorders are common among pre-school children in western Kenya and are important contributors to anaemia. © 2012 JohnWiley & Sons Ltd.

Osier F.H.A.,Center for Geographic Medicine Research Coast | Osier F.H.A.,Burnet Institute | Feng G.,Burnet Institute | Boyle M.J.,Burnet Institute | And 10 more authors.
BMC Medicine | Year: 2014

Background: An understanding of the mechanisms mediating protective immunity against malaria in humans is currently lacking, but critically important to advance the development of highly efficacious vaccines. Antibodies play a key role in acquired immunity, but the functional basis for their protective effect remains unclear. Furthermore, there is a strong need for immune correlates of protection against malaria to guide vaccine development.Methods: Using a validated assay to measure opsonic phagocytosis of Plasmodium falciparum merozoites, we investigated the potential role of this functional activity in human immunity against clinical episodes of malaria in two independent cohorts (n = 109 and n = 287) experiencing differing levels of malaria transmission and evaluated its potential as a correlate of protection.Results: Antibodies promoting opsonic phagocytosis of merozoites were cytophilic immunoglobulins (IgG1 and IgG3), induced monocyte activation and production of pro-inflammatory cytokines, and were directed against major merozoite surface proteins (MSPs). Consistent with protective immunity in humans, opsonizing antibodies were acquired with increasing age and malaria exposure, were boosted on re-infection, and levels were related to malaria transmission intensity. Opsonic phagocytosis was strongly associated with a reduced risk of clinical malaria in longitudinal studies in children with current or recent infections. In contrast, antibodies to the merozoite surface in standard immunoassays, or growth-inhibitory antibodies, were not significantly associated with protection. In multivariate analyses including several antibody responses, opsonic phagocytosis remained significantly associated with protection against malaria, highlighting its potential as a correlate of immunity. Furthermore, we demonstrate that human antibodies against MSP2 and MSP3 that are strongly associated with protection in this population are effective in opsonic phagocytosis of merozoites, providing a functional link between these antigen-specific responses and protection for the first time.Conclusions: Opsonic phagocytosis of merozoites appears to be an important mechanism contributing to protective immunity in humans. The opsonic phagocytosis assay appears to be a strong correlate of protection against malaria, a valuable biomarker of immunity, and provides a much-needed new tool for assessing responses to blood-stage malaria vaccines and measuring immunity in populations. © 2014 Osier et al.; licensee BioMed Central Ltd.

Ngugi A.K.,Center for Geographic Medicine Research Coast | Ngugi A.K.,London School of Hygiene and Tropical Medicine | Bottomley C.,London School of Hygiene and Tropical Medicine | Kleinschmidt I.,London School of Hygiene and Tropical Medicine | And 5 more authors.
Epilepsia | Year: 2010

Purpose: To estimate the burden of lifetime epilepsy (LTE) and active epilepsy (AE) and examine the influence of study characteristics on prevalence estimates. Methods: We searched online databases and identified articles using prespecified criteria. Random-effects meta-analyses were used to estimate the median prevalence in developed countries and in urban and rural settings in developing countries. The impact of study characteristics on prevalence estimates was determined using meta-regression models. Results: The median LTE prevalence for developed countries was 5.8 per 1,000 (5th-95th percentile range 2.7-12.4) compared to 15.4 per 1,000 (4.8-49.6) for rural and 10.3 (2.8-37.7) for urban studies in developing countries. The median prevalence of AE was 4.9 per 1,000 (2.3-10.3) for developed countries and 12.7 per 1,000 (3.5-45.5) and 5.9 (3.4-10.2) in rural and urban studies in developing countries. The estimates of burden for LTE and AE in developed countries were 6.8 million (5th-95th percentile range 3.2-14.7) and 5.7 million (2.7-12.2), respectively. In developing countries these were 45 (14-145) million LTE and 17 (10-133) million AE in rural areas and 17 (5-61) million LTE and 10 (5-17) million AE in urban areas. Studies involving all ages or only adults showed higher estimates than pediatric studies. Higher prevalence estimates were also associated with rural location and small study size. Conclusions: This study estimates the global burden of epilepsy and the proportions with AE, which may benefit from treatment. There are systematic differences in reported prevalence estimates, which are only partially explained by study characteristics. © 2010 International League Against Epilepsy.

Barasa E.W.,Center for Geographic Medicine Research Coast | Ayieko P.,Center for Geographic Medicine Research Coast | Cleary S.,University of Cape Town | English M.,Center for Geographic Medicine Research Coast | English M.,University of Oxford
Tropical Medicine and International Health | Year: 2012

Objective To describe out-of-pocket costs of inpatient care for children under 5years of age in district hospitals in Kenya. Methods A total of 256 caretakers of admitted children were interviewed in 2-week surveys conducted in eight hospitals in four provinces in Kenya. Caretakers were asked to report care seeking behaviour and expenditure related to accessing inpatient care. Family socio-economic status was assessed through reported expenditure in the previous month. Results Seventy eight percent of caretakers were required to pay user charges to access inpatient care for children. User charges (mean, US$ 8.1; 95% CI, 6.4-9.7) were 59% of total out-of-pocket costs, while transport costs (mean, US$ 4.9; 95% CI, 3.9-6.0) and medicine costs (mean, US$ 0.7; 95% CI, 0.5-1.0) were 36% and 5%, respectively. The mean total out-of-pocket cost per paediatric admission was US$ 14.1 (95% CI, 11.9-16.2). Out-of-pocket expenditures on health were catastrophic for 25.4% (95% CI, 18.4-33.3) of caretakers interviewed. Out-of-pocket expenditures were regressive, with a greater burden being experienced by households with lower socio-economic status. Conclusion Despite a policy of user fee exemption for children under 5years of age in Kenya, our findings show that high unofficial user fees are still charged in district hospitals. Financing mechanisms that will offer financial risk protection to children seeking care need to be developed to remove barriers to child survival. © 2012 Blackwell Publishing Ltd.

Weinberger D.M.,Harvard University | Harboe Z.B.,Statens Serum Institute | Flasche S.,Public Health England | Flasche S.,University of Strathclyde | And 3 more authors.
Epidemiology | Year: 2011

INTRODUCTION:: Before the introduction of the heptavalent pneumococcal conjugate vaccine (Prevnar-7), the relative prevalence of serotypes of Streptococcus pneumoniae was fairly stable worldwide. We sought to develop a statistical tool to predict the relative frequency of different serotypes among disease isolates in the pre- and post-Prevnar-7 eras using the limited amount of data that is widely available. Methods: We initially used pre-Prevnar-7 carriage prevalence and estimates of invasiveness derived from case-fatality data as predictors for the relative abundance of serotypes causing invasive pneumococcal disease during the pre- and post-Prevnar-7 eras, using negative binomial regression. We fit the model to pre-Prevnar-7 invasive pneumococcal disease data from England and Wales and used these data to (1) evaluate the performance of the model using several datasets and (2) evaluate the utility of the country-specific carriage data. We then fit an alternative model that used polysaccharide structure, a correlate of prevalence that does not require country-specific information and could be useful in determining the postvaccine population structure, as a predictor. Results: Predictions from the initial model fit data from several pediatric populations in the pre-Prevnar-7 era. After the introduction of Prevnar-7, the model still had a good negative predictive value, though substantial unexplained variation remained. The alternative model had a good negative predictive value but poor positive predictive value. Both models demonstrate that the pneumococcal population follows a somewhat predictable pattern even after vaccination. Conclusions: This approach provides a preliminary framework to evaluate the potential patterns and impact of serotypes causing invasive pneumococcal disease. © 2011 by Lippincott Williams & Wilkins.

Barasa E.W.,Center for Geographic Medicine Research Coast | English M.,Center for Geographic Medicine Research Coast | English M.,University of Oxford
Tropical Medicine and International Health | Year: 2011

Increasingly attention is shifting towards delivering essential packages of care, often based on clinical practice guidelines, as a means to improve maternal, child and newborn survival in low-income settings. Cost effectiveness analysis (CEA), allied to the evaluation of less complex intervention, has become an increasingly important tool for priority setting. Arguably such analyses should be extended to inform decisions around the deployment of more complex interventions. In the discussion, we illustrate some of the challenges facing the extension of CEA to this area. We suggest that there are both practical and methodological challenges to overcome when conducting economic evaluation for packages of care interventions that incorporate clinical guidelines. Some might be overcome by developing specific guidance on approaches, for example clarity in identifying relevant costs. Some require consensus on methods. The greatest challenge, however, lies in how to incorporate, as measures of effectiveness, process measures of service quality. Questions on which measures to use, how multiple measures might be combined, how improvements in one area might be compared with those in another and what value is associated with improvement in health worker practices are yet to be answered. © 2010 Blackwell Publishing Ltd.

Williams T.N.,Center for Geographic Medicine Research Coast | Williams T.N.,University of Oxford | Obaro S.K.,Michigan State University | Obaro S.K.,National Hospital
Trends in Parasitology | Year: 2011

More than 230 000 children are born in Africa with sickle cell disease (SCD) each year: approximately 85% of all affected births worldwide. Although malaria is commonly viewed as a major problem for African patients with this condition, questions still remain about its relative importance as a cause of ill heath and death. In the absence of definitive studies investigating the contribution of malaria to morbidity and mortality in African children with SCD, policy makers will continue to lack the evidence on which to base appropriate management guidelines. © 2011 Elsevier Ltd.

Ngugi A.K.,Center for Geographic Medicine Research Coast | Kariuki S.M.,Center for Geographic Medicine Research Coast | Bottomley C.,Center for Geographic Medicine Research Coast | Kleinschmidt I.,Center for Geographic Medicine Research Coast | And 2 more authors.
Neurology | Year: 2011

Objective: To estimate the pooled incidence of epilepsy from published studies and investigate sources of heterogeneity in the estimates. Methods: We searched online databases for incidence studies and used meta-analytic methods to analyze the data. Results: Thirty-three articles met the entry criteria. The median incidence of epilepsy was 50.4/100,000/year (interquartile range [IQR] 33.6-75.6), while it was 45.0 (IQR 30.3-66.7) for high-income countries and 81.7 (IQR 28.0-239.5) for low- and middle-income countries. Population-based studies had higher incidence estimates than hospital-based studies (p = 0.02) while retrospective study design was associated with lower estimates than prospective studies (p = 0.04). Conclusion: We provide data that could potentially be used to assess the burden and analyze the trends in incidence of epilepsy. Our results support the need for large population-based incidence studies of epilepsy. © 2011 by AAN Enterprises, Inc.

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