Phenotypic and genotypic analyses to guide selection of reverse transcriptase inhibitors in second-line HIV therapy following extended virological failure in Uganda

Objectives We investigated phenotypic and genotypic resistance after 2 years of first-line therapy with two HIV treatment regimens in the absence of virological monitoring. Methods NORA [Nevirapine OR Abacavir study, a sub-study of the Development of AntiRetroviral Therapy in Africa (DART) trial] randomized 600 symptomatic HIV-infected Ugandan adults (CD4 cell count <200 cells/mm3) to receive zidovudine/lamivudine plus abacavir (cABC arm) or nevirapine (cNVP arm). All virological tests were performed retrospectively, including resistance tests on week 96 plasma samples with HIV RNA levels ≥1000 copies/mL. Phenotypic resistance was expressed as fold-change in IC50 (FC) relative to wild-type virus. Results HIV-1 RNA viral load ≥1000 copies/mL at week 96 was seen in 58/204 (28.4%) cABC participants and 21/159 (13.2%) cNVP participants. Resistance results were available in 35 cABC and 17 cNVP participants; 31 (89%) cABC and 16 (94%) cNVP isolates had a week 96 FC below the biological cut-off for tenofovir (2.2). In the cNVP arm, 16/17 participants had resistance mutations synonymous with high-level resistance to nevirapine and efavirenz; FC values for etravirine were above the biological cut-off in 9 (53%) isolates. In multivariate regression models, K65R, Y115F and the presence of thymidine analogue-associated mutations were associated with increased susceptibility to etravirine in the cABC arm. Conclusions Our data support the use of tenofovir following failure of a first-line zidovudine-containing regimen and shed further light on non-nucleoside reverse transcriptase inhibitor hypersusceptibility

No evidence for association with APOL1 kidney disease risk alleles and Human African Trypanosomiasis in two Ugandan populations:

Human African trypanosomiasis (HAT) manifests as an acute form caused by Trypanosoma brucei rhodesiense (Tbr) and a chronic form caused by Trypanosoma brucei gambiense (Tbg). Previous studies have suggested a host genetic role in infection outcomes, particularly for APOL1. We have undertaken a candidate gene association studies (CGAS) in a Ugandan Tbr and a Tbg HAT endemic area, to determine whether polymorphisms in IL10, IL8, IL4, HLAG, TNFA, TNX4LB, IL6, IFNG, MIF, APOL1, HLAA, IL1B, IL4R, IL12B, IL12R, HP, HPR, and CFH have a role in HAT

The Association of Falciparum Malaria and HIV/AIDS Infection in Relation to Parasitaemia and Anti- Malarial Treatment Outcome as seen at the Moi Teaching and Referral Hospital in Eldoret, Kenya

This paper examines the effect of HIV infection on falciparum malaria parasitaemia based on a study conducted at the Moi Teaching and Referral Hospital in Eldoret, Kenya. One hundred consenting patients with malaria were recruited into the study, malaria parasitaemia levels, HIV status and CD4 counts were determined for each patient, and the outcome of antimalarial drug treatment with quinine or artemisinin derivative drugs observed. Malaria parasitaemia was monitored for each patient after antimalarial drug administration, for up to 7 days. Of the 100 patients recruited with falciparum malaria, 60% were children (&lt;18 years) and 40% were adults. Of the total admitted subjects to study, 17% (5 children and 12 adults) were HIV positive. Malaria parasitaemia levels were higher in HIV positive patients than in HIV negative individuals.and that HIV-negative individuals had a better parasitaemia clearance outcome by day seven (pday7) compared to HIV-positive ones whose parasitaemia clearance went beyond seven-day treatment period. This study strongly recommends investigative work to be done in view of the recent Kenya Government launch of ACT as a first line course of treatment for uncomplicated malaria

Social Mobilization and Compliance with Mass Treatment for Lymphatic Filariasis Elimination in Kenya

SUMMARY This study aimed to establish the role of social mobilization in mass drug administration (MDA) uptake during the National Programme to Eliminate Lymphatic Filariasis (LF) in Kenya. MDA for LF based on diethylcarbamazine (DEC) and albendazole using community-based treatment approach has been conducted for three years (2003, 2005 and 2008) in Kwale and Malindi districts. In each district, one high and one low, compliance locations were selected based on 2008 MDA data. From the four locations, nine villages were systematically sampled and a total of 965 randomly selected household heads interviewed. Sixteen focus group discussions with adult and youth male and female groups and separate in-depth interviews with eighty opinion leaders and eighty LF patients with clinical manifestations, purposively selected were conducted. Semi-structured interviews were held separately with fifteen community drug distributors, five health personnel and four LF coordinators also purposively selected. The results showed that knowledge about MDA for LF was not significantly associated with compliance (P&gt;0.05). Seventy three percent in low and 78% in high compliance villages knew about MDA. The most common source of MDA information given by 49% of respondents in high and 40% in low compliance villages were the community drug distributors (CDDs). The content of MDA information received influenced compliance (P&lt; 0.001), 71% in high compared to 61% in low compliance villages received correct information. The frequency of receiving MDA information also influenced compliance (P&lt; 0.001), 65.5% in high compared to 50% in low compliance villages received the correct information at least once before treatment. Opinion towards the source of MDA information was also associated with compliance, 46% in high compared to 43% in low compliance villages considered the source as adequate (P&lt; 0.001). The study results show that for MDA to be successful, information dissemination should be done by all stakeholders with the health personnel taking the lead role so that more adequate and factual content is relayed. Community sensitization and mobilization should be done repeatedly for all to get the information in good time to comply with treatment

Gross and Histopathological Findings in Cercopithecus Aethiops with Experimental Cyclospora Infection in Kenya

Journal ArticleIn 2009, experimental Cyclospora infections were established in two juvenile female and two adult male Cercopithecus aethiops (African green monkeys) at Nairobi’s Institute of Primate Research (IPR). The study animals were humanely sacrificed, and gross and histopathological evaluation was done at seven weeks post-infection. On gross examination, the juveniles had no abnormalities except for a slight enlargement of the mesenteric lymph nodes, while the adults displayed more pathology of enlarged lymph nodes, hemorrhagic gastrointestinal tracts, widespread necrotic foci of the liver, and enlarged spleens. Significant histopathological findings were observed in both the juveniles and adults, which ranged from mild inflammatory reactions in the stomach and intestines to intense cellular infiltrations with mitotic activity and lymphocytic infiltrations around the periportal area of the livers. The lymph nodes had extensive hyperplasia with many mitotic cells

Home Parenteral Nutrition (HPN): An international benchmarking exercise

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Cystic echinococcosis in Mundari tribe-members of South Sudan.

Many neglected tropical diseases, including the zoonotic disease cystic echinococcosis (hydatidosis), are endemic to East Africa. However, their geographical distribution is heterogenous and incompletely characterized. The aim of this study was to determine if Mundari pastoralists harbor endemic human hydatidosis. The survey was conducted in cattle camps randomly selected from accessible sites provided by officials in Terekeka, South Sudan. Following informed consent, a questionnaire collected demographic data and hydatid exposure risk. A systematic sonographic abdominal exam was performed using General Electric's LOGIQ Book XP with a 3C-RS 2-5 MHz curvilinear transducer. Six hundred and ten individuals were screened from 13 camps. Four infections were identified, all in women. The prevalence of abdominal hydatid disease in the Mundari tribe-members in cattle camps was 0·7% and all individuals reporting at least one high-risk exposure to hydatid disease. Cystic echinococcosis is endemic among Mundari pastoralists; however, it would appear to be less endemic than in neighboring tribes