Makerere University

About: Makerere University is a education organization based out in Kampala, Uganda. It is known for research contribution in the topics: Population & Public health. The organization has 7220 authors who have published 12405 publications receiving 366520 citations. The organization is also known as: Makerere University Kampala & MUK.

Tuberculous lymphadenitis associated with human immunodeficiency virus (HIV) in Uganda.

Abstract: Sixteen adults presented with lymphadenopathy which was tuberculous on biopsy; they were all seropositive for human immunodeficiency virus (HIV-1), but none had the clinical criteria of the acquired immunodeficiency syndrome (AIDS). The biopsy specimen showed caseating tuberculosis, with scanty or no visible acid fast bacilli in seven cases; the remaining nine had a poor cellular reactivity with numerous bacilli. Antituberculous chemotherapy for two months reduced the lymphadenopathy. Two patients subsequently developed AIDS. Mycobacterial cultures were not performed, but the infection was almost certainly Mycobacterium tuberculosis. The space-time clustering of tuberculous lymphadenitis now seen in Kampala, and the unusual non-reactive histopathology, are typical of the impairment of cellular immunity induced by HIV infection.

Genomewide Association Study for Determinants of HIV-1 Acquisition and Viral Set Point in HIV-1 Serodiscordant Couples with Quantified Virus Exposure

Abstract: Background Host genetic factors may be important determinants of HIV-1 sexual acquisition. We performed a genome-wide association study (GWAS) for host genetic variants modifying HIV-1 acquisition and viral control in the context of a cohort of African HIV-1 serodiscordant heterosexual couples. To minimize misclassification of HIV-1 risk, we quantified HIV-1 exposure, using data including plasma HIV-1 concentrations, gender, and condom use. Methods We matched couples without HIV-1 seroconversion to those with seroconversion by quantified HIV-1 exposure risk. Logistic regression of single nucleotide polymorphisms (SNPs) for 798 samples from 496 HIV-1 infected and 302 HIV-1 exposed, uninfected individuals was performed to identify factors associated with HIV-1 acquisition. In addition, a linear regression analysis was performed using SNP data from a subset (n = 403) of HIV-1 infected individuals to identify factors predicting plasma HIV-1 concentrations. Results After correcting for multiple comparisons, no SNPs were significantly associated with HIV-1 infection status or plasma HIV-1 concentrations. Conclusion This GWAS controlling for HIV-1 exposure did not identify common host genotypes influencing HIV-1 acquisition. Alternative strategies, such as large-scale sequencing to identify low frequency variation, should be considered for identifying novel host genetic predictors of HIV-1 acquisition.

Effectiveness of artemisinin-based combination therapy used in the context of home management of malaria: A report from three study sites in sub-Saharan Africa

Abstract: The use of artemisinin-based combination therapy (ACT) at the community level has been advocated as a means to increase access to effective antimalarial medicines by high risk groups living in underserved areas, mainly in sub-Saharan Africa. This strategy has been shown to be feasible and acceptable to the community. However, the parasitological effectiveness of ACT when dispensed by community medicine distributors (CMDs) within the context of home management of malaria (HMM) and used unsupervised by caregivers at home has not been evaluated. In a sub-set of villages participating in a large-scale study on feasibility and acceptability of ACT use in areas of high malaria transmission in Ghana, Nigeria and Uganda, thick blood smears and blood spotted filter paper were prepared from finger prick blood samples collected from febrile children between six and 59 months of age reporting to trained CMDs for microscopy and PCR analysis. Presumptive antimalarial treatment with ACT (artesunate-amodiaquine in Ghana, artemether-lumefantrine in Nigeria and Uganda) was then initiated. Repeat finger prick blood samples were obtained 28 days later for children who were parasitaemic at baseline. For children who were parasitaemic at follow-up, PCR analyses were undertaken to distinguish recrudescence from re-infection. The extent to which ACTs had been correctly administered was assessed through separate household interviews with caregivers having had a child with fever in the previous two weeks. Over a period of 12 months, a total of 1,740 children presenting with fever were enrolled across the study sites. Patent parasitaemia at baseline was present in 1,189 children (68.3%) and varied from 60.1% in Uganda to 71.1% in Ghana. A total of 606 children (51% of infected children) reported for a repeat test 28 days after treatment. The crude parasitological failure rate varied from 3.7% in Uganda (C.I. 1.2%–6.2%) to 41.8% in Nigeria (C.I. 35%–49%). The PCR adjusted parasitological cure rate was greater than 90% in all sites, varying from 90.9% in Nigeria (C.I. 86%–95%) to 97.2% in Uganda (C.I. 95%–99%). Reported adherence to correct treatment in terms of dose and duration varied from 81% in Uganda (C.I. 67%–95%) to 97% in Ghana (C.I. 95%–99%) with an average of 94% (C.I. 91%–97%). While follow-up rates were low, this study provides encouraging data on parasitological outcomes of children treated with ACT in the context of HMM and adds to the evidence base for HMM as a public health strategy as well as for scaling-up implementation of HMM with ACTs.

Integrin α4β7 expression on peripheral blood CD4+ T cells predicts HIV acquisition and disease progression outcomes

Abstract: The gastrointestinal (GI) mucosa is central to HIV pathogenesis, and the integrin α4β7 promotes the homing of immune cells to this site, including those that serve as viral targets. Data from simian immunodeficiency virus (SIV) animal models suggest that α4β7 blockade provides prophylactic and therapeutic benefits. We show that pre-HIV infection frequencies of α4β7+ peripheral blood CD4+ T cells, independent of other T cell phenotypes and genital inflammation, were associated with increased rates of HIV acquisition in South African women. A similar acquisition effect was observed in a Kenyan cohort and in nonhuman primates (NHPs) after intravaginal SIV challenge. This association was stronger when infection was caused by HIV strains containing V2 envelope motifs with a preference for α4β7 binding. In addition, pre-HIV α4β7+ CD4+ T cells predicted a higher set-point viral load and a greater than twofold increased rate of CD4+ T cell decline. These results were confirmed in SIV-infected NHPs. Increased frequencies of pre-HIV α4β7+ CD4+ T cells were also associated with higher postinfection expression of lipopolysaccharide binding protein, a microbial translocation marker, suggestive of more extensive gut damage. CD4+ T cells expressing α4β7 were rapidly depleted very early in HIV infection, particularly from the GI mucosa, and were not restored by early antiretroviral therapy. This study provides a link between α4β7 expression and HIV clinical outcomes in humans, in line with observations made in NHPs. Given the availability of a clinically approved anti-α4β7 monoclonal antibody for treatment of inflammatory bowel disease, these data support further evaluation of targeting α4β7 integrin as a clinical intervention during HIV infection.