Browsing by Author "Mayanja-Kizza, H."

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    Polymorphisms in TICAM2 and IL1B are associated with TB
    (Genes & Immunity, 2015) Hall, N. B.; Igo Jr., R. P.; Malone, L. L.; Truitt, B.; Schnell, A.; Tao, L.; Okware, B.; Nsereko, M.; Chervenak, K.; Lancioni, C.; Hawn, T. R.; Mayanja-Kizza, H.; Joloba, M. L.; Boom, W. H.; Stein, C. M.
    Human genetic susceptibility for tuberculosis (TB) has been demonstrated by several studies, but few have examined the multiple innate and adaptive immunity genes comprehensively, age-specific effects and/or resistance to Mycobacterium tuberculosis (Mtb) infection (resistors (RSTRs)). We hypothesized that RSTRs, defined by a persistently negative tuberculin skin test, may have different genetic influences than Mtb disease. We examined 29 candidate genes in pathways that mediate immune responses to Mtb in subjects in a household contact study in Kampala, Uganda. We genotyped 546 haplotype-tagging single-nucleotide polymorphisms (SNPs) in 835 individuals from 481 families; 28.7% had TB, 10.5% were RSTRs, and the remaining 60.8% had latent Mtb infection. Among our most significant findings were SNPs in TICAM2 (P = 3.6 × 10− 6) and IL1B (P = 4.3 × 10− 5) associated with TB. Multiple SNPs in IL4 and TOLLIP were associated with TB (Po0.05). Age–genotype interaction analysis revealed SNPs in IL18 and TLR6 that were suggestively associated with TB in children aged ⩽10 years (P = 2.9 × 10− 3). By contrast, RSTR was associated with SNPs in NOD2, SLC6A3 and TLR4 (nominal Po0.05); these genes were not associated with TB, suggesting distinct genetic influences. We report the first association between TICAM2 polymorphisms and TB and between IL18 and pediatric TB.
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    Predictors of treatment failure among pulmonary tuberculosis patients in Mulago hospital, Uganda
    (African health sciences, 2011) Namukwaya, E.; Nakwagala, F.N.; Mulekya, F.; Mayanja-Kizza, H.; Mugerwa, R.
    Early identification of Tuberculosis (TB) treatment failure using cost effective means is urgently needed in developing nations. The study set out to describe affordable predictors of TB treatment failure in an African setting. Objective: To determine the predictors of treatment failure among patients with sputum smear positive pulmonary TB at Mulago hospital. The study was carried out in the TB clinic of Mulago hospital Kampala, Uganda. This was an unmatched case control study where fifty patients with a diagnosis of TB treatment failure (cases) and 100 patients declared cured after completing anti TB treatment (controls) were recruited into the study. Cases were compared with controls to determine predictors of treatment failure. Results: Significant predictors of treatment failure in this study included a positive sputum smear at 2 months of TB treatment (OR 20.63, 95%CI 5.42- 78.41) and poor adherence to anti TB treatment (OR 14.59, 95%CI 3.04-70.15). Conclusion: This study identified a treatment related and a simple laboratory predictor of TB treatment failure in Mulago hospital which may be used in resource limited settings for early recognition of those at risk and early intervention.
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    A Randomized Trial of Punctuated Antiretroviral Therapy in Ugandan HIV-Seropositive Adults With Pulmonary Tuberculosis and CD41 T-Cell Counts of $350 cells/lL
    (Journal of Infectious Diseases, 2011) Nanteza, M. W.; Mayanja-Kizza, H.; Mupere, E.; Mugyenyi, P.; Mugerwa, R. D.; Havlir, D. V.
    Optimal treatment of human immunodeficiency virus (HIV)–associated tuberculosis in patients with high CD4+ T-cell counts is unknown. Suppression of viral replication during therapy for tuberculosis may block effects of immune activation on T cells and slow HIV disease progression. We conducted a randomized trial in 214 HIV-infected patients with active tuberculosis and CD4+ T-cell counts of ≥350 cells/μL to determine whether 6 months of antiretroviral therapy given during tuberculosis treatment would improve clinical outcomes. Subjects were randomized to receive 6 months of abacavir-lamivudine-zidovudine concurrent with tuberculosis therapy or delayed antiretroviral therapy. Endpoints were CD4+ T-cell counts of <250 cells/μL, AIDS, or death. Intervention and comparison arms had similar median CD4+ counts (517 and 534 cells/μL, respectively) and HIV RNA levels (4.6 and 4.7 log10 copies/μL, respectively). Viral suppression was achieved in 86% of patients allocated to intervention. Seventeen subjects (15.6%) in the intervention arm developed study outcome compared to 25 subjects (22.8%) in the comparison arm (P = .17). Grade 3 or 4 adverse events were less frequent in the intervention arm. By 2 months, 90% of subjects in both arms were culture-negative for tuberculosis.Short-term antiretroviral therapy during tuberculosis treatment in patients with CD4+ T-cell counts of >350 cells/μL was safe and associated with clinical benefits.
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    Relationship of immunodiagnostic assays for tuberculosis and numbers of circulating CD4+ T-cells in HIV infection
    (European Respiratory Journal, 2010) Leidl, L.; Mayanja-Kizza, H.; Sotgiu, G.; Baseke, J.; Ernst, M.; Hirsch, C.; Golettie, D.; Toossi, Z.; Lange, C.
    Infection with HIV is the greatest risk factor for tuberculosis (TB) in Africa. Tuberculin skin test (TST), QuantiFERON-TB Gold In-Tube (QFT-G-IT) and T-Spot.TB assays were performed in newly diagnosed HIV-infected individuals with and without active TB and in HIV-uninfected subjects at a university outpatient clinic in Kampala, Uganda. A total of 135 individuals were enrolled: 109 with a new diagnosis of HIV-1 infection but no active TB, 19 with HIV-1 infection and active TB, and seven HIV-uninfected healthy subjects. In control subjects immune responses were positive in 57.2% by TST and in 100% by at least one interferon-γ release assay.In HIV-1 infected patients without active TB, induration in the TST (mm) (rho = 0.41, p-value <0.0001) and concentration of interferon (IFN)-γ in the QFT-G-IT tube with Mycobacterium tuberculosis-specific antigens (rho = 0.38; p = 0.0001) were negatively correlated to numbers of circulating CD4+ T-cells, while numbers of IFN-γ producing cells (rho = 0.03–0.13; p-value = 0.21–0.77) and frequencies of positive test results for the T-Spot.TB test among groups of patients with different levels of immunodeficiency remained constant (p-value = 0.46).In HIV-1 infection, TST and QFT-G-IT immune responses are both strongly related to the degree of immunodeficiency, while results of the T-Spot.TB are independent of the level of CD4+ T-cell depletion.
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    Tuberculosis and human immunodeficiency virus co-infections and their predictors at a hospital-based HIV/AIDS clinic in Uganda
    (The International journal of tuberculosis and lung disease, 2010) Nakanjako, D.; Mayanja-Kizza, H.; Ouma, J.; Wanyenze, R.; Mwesigire, D.; Namale, A.; Ssempiira, J.; Senkusu, J.; Colebunders, R.; Kamya, M. R.
    To evaluate the burden of TB-HIV (tuberculosis-human immunodeficiency virus) co-infections and their predictors in an urban hospital-based HIV programme. DESIGN: Prospective observational study. METHODS: Clinicians screened all patients with HIV/ AIDS (acquired immune-deficiency syndrome) for previous and current TB treatment at enrolment and through- out follow-up. RESULTS: Of 10 924 patients enrolled between August 2005 and February 2009, co-prevalent TB was 157/10 924 (1.4%), which included 88/157 (56%) with TB con- firmed at enrolment and 65/157 (41%) with TB diagnoses established during follow-up in whom symptoms were present at enrolment. Male sex (adjusted odds ratio [aOR] 2.3, 95%CI 1.6–3.2) and body mass index (BMI) ⩽20 kg/m2 (aOR 3.8, 95%CI 2.5–5.4) were associated with co-prevalent TB. Overall, 749/10 767 (7%) were diagnosed with incident TB at a higher rate among anti- retroviral treatment (ART) patients (8/100 patient years of observation [PYO]) than non-ART patients (5/100 PYO, log rank P < 0.001). Female sex (adjusted hazard ratio [aHR] 1.4, 95%CI 1.2–1.7) and baseline BMI ⩽ 20 (aHR 1.9, 95%CI 1.6–2.2) predicted incident TB. CONCLUSION: Routine TB screening in the HIV/AIDS care programme identified a significant number of TB- HIV co-infections among patients with and without ART, and is therefore a potential strategy to improve HIV treatment outcomes in resource-limited settings.