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Berkley J.A.,Kenya Medical Research Institute | Berkley J.A.,University of Oxford | Ngari M.,Kenya Medical Research Institute | Thitiri J.,Kenya Medical Research Institute | And 18 more authors.
The Lancet Global Health | Year: 2016

Background: Children with complicated severe acute malnutrition (SAM) have a greatly increased risk of mortality from infections while in hospital and after discharge. In HIV-infected children, mortality and admission to hospital are prevented by daily co-trimoxazole prophylaxis, despite locally reported bacterial resistance to co-trimoxazole. We aimed to assess the efficacy of daily co-trimoxazole prophylaxis on survival in children without HIV being treated for complicated SAM. Methods: We did a multicentre, double-blind, randomised, placebo-controlled study in four hospitals in Kenya (two rural hospitals in Kilifi and Malindi, and two urban hospitals in Mombasa and Nairobi) with children aged 60 days to 59 months without HIV admitted to hospital and diagnosed with SAM. We randomly assigned eligible participants (1:1) to 6 months of either daily oral co-trimoxazole prophylaxis (given as water-dispersible tablets; 120 mg per day for age <6 months, 240 mg per day for age 6 months to 5 years) or matching placebo. Assignment was done with computer-generated randomisation in permuted blocks of 20, stratified by centre and age younger or older than 6 months. Treatment allocation was concealed in opaque, sealed envelopes and patients, their families, and all trial staff were masked to treatment assignment. Children were given recommended medical care and feeding, and followed up for 12 months. The primary endpoint was mortality, assessed each month for the first 6 months, then every 2 months for the second 6 months. Secondary endpoints were nutritional recovery, readmission to hospital, and illness episodes treated as an outpatient. Analysis was by intention to treat. This trial was registered at ClinicalTrials.gov, number NCT00934492. Findings: Between Nov 20, 2009, and March 14, 2013, we recruited and assigned 1778 eligible children to treatment (887 to co-trimoxazole prophylaxis and 891 to placebo). Median age was 11 months (IQR 7-16 months), 306 (17%) were younger than 6 months, 300 (17%) had oedematous malnutrition (kwashiorkor), and 1221 (69%) were stunted (length-for-age Z score <-2). During 1527 child-years of observation, 122 (14%) of 887 children in the co-trimoxazole group died, compared with 135 (15%) of 891 in the placebo group (unadjusted hazard ratio [HR] 0·90, 95% CI 0·71-1·16, p=0·429; 16·0 vs 17·7 events per 100 child-years observed (CYO); difference -1·7 events per 100 CYO, 95% CI -5·8 to 2·4]). In the first 6 months of the study (while participants received study medication), 63 suspected grade 3 or 4 associated adverse events were recorded among 57 (3%) children; 31 (2%) in the co-trimoxazole group and 32 (2%) in the placebo group (incidence rate ratio 0·98, 95% CI 0·58-1·65). The most common adverse events of these grades were urticarial rash (grade 3, equally common in both groups), neutropenia (grade 4, more common in the co-trimoxazole group), and anaemia (both grades equally common in both groups). One child in the placebo group had fatal toxic epidermal necrolysis with concurrent Pseudomonas aeruginosa bacteraemia. Interpretation: Daily co-trimoxazole prophylaxis did not reduce mortality in children with complicated SAM without HIV. Other strategies need to be tested in clinical trials to reduce deaths in this population. Funding: Wellcome Trust, UK. © 2016 Berkley et al. Open Access article distributed under the terms of CC BY.

Joseph Davey D.,University of California at Los Angeles | Myer L.,University of Cape Town | Bukusi E.,Center for Microbiology Research | Kilembe W.,Zambia Emory HIV Research Group | Klausner J.D.,University of California at Los Angeles
Current HIV/AIDS Reports | Year: 2016

Joint United Nations Programme on HIV/AIDS (UNAIDS) established 90–90–90 HIV treatment targets for 2020 including the following: 90 % of HIV-infected people know their HIV status, 90 % of HIV-infected people who know their status are on treatment, and 90 % of people on HIV treatment have a suppressed viral load. Integration of HIV and other programs into the national health system provides an important pathway to reach those targets. We examine the case for integrating HIV and other health services to ensure sustainability and improve health outcomes within national health systems. In this non-systematic review, we examined recent studies on integrating HIV, tuberculosis (TB), maternal-child health (MCH), and sexually transmitted infection (STI) programs. Existing evidence is limited about the effectiveness of integration of HIV and other services. Most studies found that service integration increased uptake of services, but evidence is mixed about the effect on health outcomes or quality of health services. More rigorous studies of different strategies to promote integration over a wider range of services and settings are needed. Research on how best to maximize benefits, including sustainability, of integrated services is necessary to help inform international and national policy. We recommend additional interventions to test how best to integrate HIV and MCH services, HIV and TB services, HIV testing and treatment, and STI testing and treatment. © 2016, Springer Science+Business Media New York.

Mbae C.K.,Center for Microbiology Research | Nokes D.J.,KEMRI Wellcome Trust Research Programme | Mulinge E.,Center for Microbiology Research | Nyambura J.,Center for Microbiology Research | And 2 more authors.
BMC Infectious Diseases | Year: 2013

Background: The distribution of and factors associated with intestinal parasitic infections are poorly defined in high risk vulnerable populations such as urban slums in tropical sub-Saharan Africa.Methods: In a cross sectional study, children aged 5 years and below who presented with diarrhoea were recruited from selected outpatient clinics in Mukuru informal settlement, and from Mbagathi District hospital, Nairobi, over a period of two years (2010-2011). Stool samples were examined for the presence of parasites using direct, formal-ether concentration method and the Modified Ziehl Neelsen staining technique.Results: Overall, 541/2112 (25.6%) were positive for at least one intestinal parasite, with the common parasites being; Entamoeba histolytica, 225 (36.7%),Cryptosporidium spp. 187, (30.5%), Giardia lamblia, 98 (16%).The prevalence of intestinal parasites infection was higher among children from outpatient clinics 432/1577(27.4%) than among those admitted in hospital 109/535 (20.1%) p < 0.001. Infections with E. histolytica, and G. lamblia were higher among outpatients than inpatients (13.8% vs 1.3% p < 0.001 and 5.8% vs 1.3% p < 0.049) respectively, while infection with Cryptosporidium spp. was higher among inpatients than outpatients (15.3% vs 6.7%) respectively p < 0.001. Other parasites isolated among outpatients included Isospora belli, 19 (1.2%), Ascaris lumbricoides, 26 (1.6%), and Hymenolepis nana 12 (0.8%), with the remainder detected in less than ten samples each. HIV-infected participants were more likely to be infected with any parasite than uninfected participants, Adjusted Odds Ratio (AOR), 2.04, 95% CI, 1.55-2.67, p < 0.001), and with Cryptosporidium spp. (AOR, 2.96, 95% CI 2.07-4.21, p < 0.001).The inpatients were less likely to be infected with E. histolytica than outpatients (AOR, 0.11, 95% CI, 0.51- 0.24, p < 0.001), but more likely for inpatients to be infected with Cryptosporidium spp. than outpatients (AOR, 1.91, 95% CI, 1.33-2.73, p < 0.001). Mixed parasitic infections were seen in 65 (12.0%) of the 541 infected stool samples.Conclusion: Intestinal parasitic infections are common in urban informal settlements' environment. Routine examinations of stool samples and treatment could benefit both the HIV infected and uninfected children in outpatient and inpatient settings. © 2013 Mbae et al.; licensee BioMed Central Ltd.

Pattacini L.,Fred Hutchinson Cancer Research Center | Fluharty T.R.,Fred Hutchinson Cancer Research Center | Bukusi E.,Center for Microbiology Research | Katabira E.,Makerere University | And 19 more authors.
Journal of Infectious Diseases | Year: 2015

Background. Antiretroviral preexposure prophylaxis (PrEP), using daily oral combination tenofovir disoproxil fumarate plus emtricitabine, is an effective human immunodeficiency virus (HIV) prevention strategy for populations at high risk of HIV acquisition. Although the primary mode of action for the protective effect of PrEP is probably direct antiviral activity, nonhuman primate studies suggest that PrEP may also allow for development of HIV-specific immune responses, hypothesized to result from aborted HIV infections providing a source of immunologic priming. We sought to evaluate whether PrEP affects the development of HIV-specific immune response in humans. Methods and Results. Within a PrEP clinical trial among high-risk heterosexual African men and women, we detected HIV-specific CD4+ and CD8+ peripheral blood T-cell responses in 10%-20% of 247 subjects evaluated. The response rate and magnitude of T-cell responses did not vary significantly between those assigned PrEP versus placebo, and no significant difference between those assigned PrEP and placebo was observed in measures of innate immune function. Conclusions. We found no evidence to support the hypothesis that PrEP alters either the frequency or magnitude of HIV-specific immune responses in HIV-1-exposed seronegative individuals. These results suggest that PrEP is unlikely to serve as an immunologic prime to aid protection by a putative HIV vaccine. © 2014 The Author.

Kariuki S.,Center for Microbiology Research | Onsare R.,Center for Microbiology Research | Mwituria J.,Center for Microbiology Research | Ng'etich R.,Center for Microbiology Research | And 6 more authors.
Food Protection Trends | Year: 2013

Meat production contributes significantly to household food security and domestic and export income in Kenya; thus, managing the safety of meat is essential to protect public health and ensure market access and economic benefit for the country. The management of microbiological risks associated with meat should be based on scientific assessment of health risks, the identification of the critical points through the chain where microbiological contamination occurs and quantitatively increases and at which prevention and control measures can be most effectively applied to protect public health. This is a report of a collaborative study in Kenya aimed to provide risk managers with preliminary data on which to base a risk-based food safety program by undertaking value chain analyses, a microbiological survey of food production and human illness, observations and questionnaires and by bringing stakeholders together to share knowledge and develop management and policy directions. Foodborne bacterial zoonoses and antimicrobial resistance were key hazards for which risk management strategies were required through the value chain, taking into account the diversity of production, slaughter and retail practices and coupled with surveillance and monitoring of disease, food contamination, Antimicrobial Resistance (AMR) and antimicrobial usage.

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