Treatment outcomes of new tuberculosis patients hospitalized in Kampala, Uganda: a prospective cohort study.

Background: In most resource limited settings, new tuberculosis (TB) patients are usually treated as outpatients. We sought to investigate the reasons for hospitalisation and the predictors of poor treatment outcomes and mortality in a cohort of hospitalized new TB patients in Kampala, Uganda.

Methods And Findings: Ninety-six new TB patients hospitalised between 2003 and 2006 were enrolled and followed for two years.

Wasting among Uganda men with pulmonary tuberculosis is associated with linear regain in lean tissue mass during and after treatment in contrast to women with wasting who regain fat tissue mass: prospective cohort study.

Background: Nutritional changes during and after tuberculosis treatment have not been well described. We therefore determined the effect of wasting on rate of mean change in lean tissue and fat mass as measured by bioelectrical impedance analysis (BIA), and mean change in body mass index (BMI) during and after tuberculosis treatment.

Methods: In a prospective cohort study of 717 adult patients, BMI and height-normalized indices of lean tissue (LMI) and fat mass (FMI) as measured by BIA were assessed at baseline, 3, 12, and 24 months.

Variability of infectious aerosols produced during coughing by patients with pulmonary tuberculosis.

Rationale: Mycobacterium tuberculosis is transmitted by infectious aerosols, but assessing infectiousness currently relies on sputum microscopy that does not accurately predict the variability in transmission.

Objectives: To evaluate the feasibility of collecting cough aerosols and the risk factors for infectious aerosol production from patients with pulmonary tuberculosis (TB) in a resource-limited setting.

Methods: We enrolled subjects with suspected TB in Kampala, Uganda and collected clinical, radiographic, and microbiological data in addition to cough aerosol cultures.

Lean tissue mass wasting is associated with increased risk of mortality among women with pulmonary tuberculosis in urban Uganda.

Objectives: We assessed the impact of wasting on survival in patients with tuberculosis by using a precise height-normalized lean tissue mass index (LMI) estimated by bioelectrical impedance analysis and body mass index (BMI).

Methods: In a retrospective cohort study, 747 adult pulmonary patients with tuberculosis who were screened for HIV and nutritional status were followed for survival.

Results: Of 747 patients, 310 had baseline wasting by BMI (kg/m(2)) and 103 by LMI (kg/m(2)).

Clinical spectrum, risk factors and outcome of immune reconstitution inflammatory syndrome in patients with tuberculosis-HIV coinfection.

Background: Here, we aimed to determine the clinical spectrum, predictors and outcomes of paradoxical tuberculosis-immune reconstitution inflammatory syndrome (TB-IRIS) in a resource-limited setting.

Methods: In a prospective cohort, we studied 254 patients with tuberculosis and HIV coinfection commencing antiretroviral therapy (ART). We identified patients with TB-IRIS using the International Network for Studies Against HIV-Associated IRIS (INSHI) case definition.

Incidence and predictors of mortality and the effect of tuberculosis immune reconstitution inflammatory syndrome in a cohort of TB/HIV patients commencing antiretroviral therapy.

Background: Tuberculosis-HIV (TB-HIV) coinfection remains an important cause of mortality in antiretroviral therapy (ART) programs. In a cohort of TB-HIV-coinfected patients starting ART, we examined the incidence and predictors of early mortality.

Methods: Consecutive TB-HIV-coinfected patients eligible for ART were enrolled in a cohort study at the Mulago National Tuberculosis and Leprosy Program clinic in Kampala, Uganda.

Effectiveness of the standard WHO recommended retreatment regimen (category II) for tuberculosis in Kampala, Uganda: a prospective cohort study.

Background: Each year, 10%-20% of patients with tuberculosis (TB) in low- and middle-income countries present with previously treated TB and are empirically started on a World Health Organization (WHO)-recommended standardized retreatment regimen. The effectiveness of this retreatment regimen has not been systematically evaluated.

Methods And Findings: From July 2003 to January 2007, we enrolled smear-positive, pulmonary TB patients into a prospective cohort to study treatment outcomes and mortality during and after treatment with the standardized retreatment regimen.

Hormonal contraceptive use and HIV disease progression among women in Uganda and Zimbabwe.

Background: HIV-infected women need highly effective contraception to reduce unintended pregnancies and mother-to-child HIV transmission. Previous studies report conflicting results regarding the effect of hormonal contraception on HIV disease progression.

Methods: HIV-infected women in Uganda and Zimbabwe were recruited immediately after seroconversion; CD4 testing and clinical examinations were conducted quarterly.

Secondary attack rate of tuberculosis in urban households in Kampala, Uganda.

Background: Tuberculosis is an ancient disease that continues to threaten individual and public health today, especially in sub-Saharan Africa. Current surveillance systems describe general risk of tuberculosis in a population but do not characterize the risk to an individual following exposure to an infectious case.

Methods: In a study of household contacts of infectious tuberculosis cases (n = 1918) and a community survey of tuberculosis infection (N = 1179) in Kampala, Uganda, we estimated the secondary attack rate for tuberculosis disease and tuberculosis infection.

Evaluation of time to detection of Mycobacterium tuberculosis in broth culture as a determinant for end points in treatment trials.

Time to detection of Mycobacterium tuberculosis in broth culture was examined for utility as a treatment efficacy end point. Of 146 patients in a phase IIB trial, a decreased mean time to detection was found in 5 with treatment failure. Time to detection in an analysis-of-covariance model was associated with lung cavities, less intensive treatment, and differences in the bactericidal effects of treatment regimens.

Hormonal contraception and HIV acquisition: reanalysis using marginal structural modeling.

Hormonal contraceptives are used widely worldwide; their effect on HIV acquisition remains unresolved. We reanalyzed data from the Hormonal Contraception and HIV Study using marginal structural modeling to reduce selection bias due to time-dependent confounding. Replicating our original analysis closely, we found that depo-medroxyprogesterone acetate (DMPA) but not combined oral contraceptive (COC) was associated with increased HIV acquisition.

Mycobacterium tuberculosis microbiologic and clinical treatment outcomes in a randomized trial of immediate versus CD4(+)-initiated antiretroviral therapy in HIV-infected adults with a high CD4(+) cell count.

In a prospective randomized, controlled trial in Uganda comparing the efficacy of antiretroviral therapy during tuberculosis therapy with the efficacy of tuberculosis therapy alone in HIV-infected patients with tuberculosis who have a CD4(+) cell count >350 cells/microL, it was found that antiretroviral therapy did not accelerate microbiologic, radiographic, or clinical responses to tuberculosis therapy: 18% of participants had sputum smears positive for Mycobacterium tuberculosis after 5 months of tuberculosis therapy, despite having had negative culture results. Trial registration. ClinicalTrials.

Tuberculosis treatment in HIV infected Ugandans with CD4 counts>350 cells/mm reduces immune activation with no effect on HIV load or CD4 count.

Background: Both HIV and TB cause a state of heightened immune activation. Immune activation in HIV is associated with progression to AIDS. Prior studies, focusing on persons with advanced HIV, have shown no decline in markers of cellular activation in response to TB therapy alone.

Body composition among HIV-seropositive and HIV-seronegative adult patients with pulmonary tuberculosis in Uganda.

Purpose: We determined whether human immunodeficiency virus (HIV) infection affects body cell mass and fat mass wasting among adults with pulmonary tuberculosis (PTB).

Methods: We screened 967 Ugandan adults for PTB and HIV infection in a cross-sectional study. We compared anthropometric and bioelectric impedance analysis (BIA) body composition parameters among HIV-seropositive and HIV-seronegative men and women with or without PTB by using a non-parametric test.

Rapid detection of Mycobacterium tuberculosis and rifampin resistance by use of on-demand, near-patient technology.

Current nucleic acid amplification methods to detect Mycobacterium tuberculosis are complex, labor-intensive, and technically challenging. We developed and performed the first analysis of the Cepheid Gene Xpert System's MTB/RIF assay, an integrated hands-free sputum-processing and real-time PCR system with rapid on-demand, near-patient technology, to simultaneously detect M. tuberculosis and rifampin resistance.

Comparison of rapid tests for detection of rifampicin-resistant Mycobacterium tuberculosis in Kampala, Uganda.

Background: Drug resistant tuberculosis (TB) is a growing concern worldwide. Rapid detection of resistance expedites appropriate intervention to control the disease. Several technologies have recently been reported to detect rifampicin resistant Mycobacterium tuberculosis directly in sputum samples.

Shortening treatment in adults with noncavitary tuberculosis and 2-month culture conversion.

Rationale: Cavitary disease and delayed culture conversion have been associated with relapse. Combining patient characteristics and measures of bacteriologic response might allow treatment shortening with current drugs in some patients.

Objectives: To assess whether treatment could be shortened from 6 to 4 months in patients with noncavitary tuberculosis whose sputum cultures converted to negative after 2 months.

Genome scan of M. tuberculosis infection and disease in Ugandans.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is an enduring public health problem globally, particularly in sub-Saharan Africa. Several studies have suggested a role for host genetic susceptibility in increased risk for TB but results across studies have been equivocal. As part of a household contact study of Mtb infection and disease in Kampala, Uganda, we have taken a unique approach to the study of genetic susceptibility to TB, by studying three phenotypes.

African AIDS vaccine programme for a coordinated and collaborative vaccine development effort on the continent.

The African AIDS Vaccine Programme, formed in 2000, is a network of African HIV vaccine stakeholders, led by Africans across the continent, with a vision of an African continent without AIDS.

Whole blood interferon-gamma responses to mycobacterium tuberculosis antigens in young household contacts of persons with tuberculosis in Uganda.

Background: Due to immunologic immaturity, IFN-gamma-producing T cell responses may be decreased in young children compared to adults, thus we hypothesized that IFN-gamma responses to mycobacterial antigens in household contacts exposed to Mycobacterium tuberculosis (Mtb) would be impaired in young children relative to adults. The objective of this study was to compare whole blood IFN-gamma production in response to mycobacterial antigens between children and adults in Uganda.

Methodology/principal Findings: We studied household contacts of persons with culture-positive pulmonary tuberculosis (TB) enrolled in a cohort study conducted in Kampala, Uganda.

Rate and amplification of drug resistance among previously-treated patients with tuberculosis in Kampala, Uganda.

Background: Drug-resistant Mycobacterium tuberculosis has emerged as a global threat. In resource-constrained settings, patients with a history of tuberculosis (TB) treatment may have drug-resistant disease and may experience poor outcomes. There is a need to measure the extent of and risk factors for drug resistance in such patients.

Trichomonas vaginalis infection and human immunodeficiency virus acquisition in African women.

Background: Trichomoniasis vaginalis is the most common nonviral sexually transmitted infection (STI) worldwide, with a particularly high prevalence in regions of human immunodeficiency virus (HIV) endemicity. However, its impact as a cofactor for HIV acquisition is poorly understood.

Methods: Samples from 213 women who experienced HIV seroconversion (cases) during a longitudinal study involving 4450 women in Uganda and Zimbabwe were matched with samples from HIV-uninfected women (controls).

Early virological response of zidovudine/lamivudine/abacavir for patients co-infected with HIV and tuberculosis in Uganda.

Triple nucleoside reverse transcriptase inhibitors are recommended as an alternative regimen for HIV-infected patients undergoing tuberculosis treatment in resource-limited settings. Few data exist on the efficacy of such regimens in tuberculosis patients. In 34 tuberculosis/HIV-co-infected patients treated with zidovudine/lamivudine/abacavir, 76% achieved HIV RNA less than 50 copies/ml at 24 weeks.

Men's circumcision status and women's risk of HIV acquisition in Zimbabwe and Uganda.

Objective: To assess whether male circumcision of the primary sex partner is associated with women's risk of HIV.

Design: Data were analyzed from 4417 Ugandan and Zimbabwean women participating in a prospective study of hormonal contraception and HIV acquisition. Most were recruited from family planning clinics; some in Uganda were referred from higher-risk settings such as sexually transmitted disease clinics.