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.

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.

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.

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.

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.

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.

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.

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.

Linkage and association analysis of candidate genes for TB and TNFalpha cytokine expression: evidence for association with IFNGR1, IL-10, and TNF receptor 1 genes.

Tuberculosis (TB) is a growing public health threat globally and several studies suggest a role of host genetic susceptibility in increased TB risk. As part of a household contact study in Kampala, Uganda, we have taken a unique approach to the study of genetic susceptibility to TB by developing an intermediate phenotype model for TB susceptibility, analyzing levels of tumor necrosis factor-alpha (TNFalpha) in response to culture filtrate as the phenotype. In the present study, we analyzed candidate genes related to TNFalpha regulation and found that interleukin (IL)-10, interferon-gamma receptor 1 (IFNGR1), and TNFalpha receptor 1 (TNFR1) genes were linked and associated to both TB and TNFalpha.

Low-cost rapid detection of rifampicin resistant tuberculosis using bacteriophage in Kampala, Uganda.

Background: Resistance to anti-tuberculosis drugs is a serious public health problem. Multi-drug resistant tuberculosis (MDR-TB), defined as resistance to at least rifampicin and isoniazid, has been reported in all regions of the world. Current phenotypic methods of assessing drug susceptibility of M.

Effect of tuberculosis preventive therapy on HIV disease progression and survival in HIV-infected adults.

Purpose: To determine whether tuberculosis (TB) preventive therapies alter the rate of disease progression to AIDS or death and to identify significant prognostic factors for HIV disease progression to AIDS.

Method: In a randomized placebo-controlled trial in Kampala, Uganda, 2,736 purified protein derivative (PPD)-positive and anergic HIV-infected adults were randomly assigned to four and two regimens, respectively. PPD-positive patients were treated with isoniazid (INH) for 6 months (6H; n = 536), INH plus rifampicin for 3 months (3HR; n = 556), INH plus rifampicin plus pyrazinamide for 3 months (3HRZ; n = 462), or placebo for 6 months (n = 464).

Immune correlates of acute Mycobacterium tuberculosis infection in household contacts in Kampala, Uganda.

To determine immunologic and epidemiologic correlates of acute Mycobacterium tuberculosis infection in household contacts of infectious tuberculosis cases, we performed a prospective, community-based cohort study of index cases and their household contacts in Kampala, Uganda. Contacts were evaluated for tuberculin skin test (TST) conversion over two years. Interferon-gamma expression was measured using a whole blood assay after stimulating with M.

Delayed-type hypersensitivity skin test reactivity and survival in HIV-infected patients in Uganda: should anergy be a criterion to start antiretroviral therapy in low-income countries?

Access to antiretroviral (ARV) drugs is improving in sub-Saharan Africa but still constrained by several clinical and logistical obstacles. There is a need to develop affordable markers to guide initiation of treatment. We present a prospective cohort study of 779 patients participating in a TB prophylaxis trial.

Vdelta2+ gammadelta T cell function in Mycobacterium tuberculosis- and HIV-1-positive patients in the United States and Uganda: application of a whole-blood assay.

Background: Vgamma9(+)Vdelta2(+) gammadelta T cells (Vdelta 2(+) T cells) are activated by Mycobacterium tuberculosis and secrete interferon (IFN)-gamma. Vdelta 2(+) T cells recognize phosphoantigens, such as bromohydrin pyrophosphate (BrHPP), and link innate and adaptive immunity.

Methods: A whole-blood assay was developed that used IFN-gamma secretion in response to BrHPP as a measurement of Vdelta2(+) T cell function.

Evidence for a major gene influence on tumor necrosis factor-alpha expression in tuberculosis: path and segregation analysis.

Objective: Tuberculosis (TB) is a growing global public health problem. Several studies suggest a role for host genetics in disease susceptibility, but studies to date have been inconsistent and a comprehensive genetic model has not emerged. A limitation of previous genetic studies is that they only analyzed the binary trait TB, which does not reflect disease heterogeneity.

Mechanisms of apoptosis of T-cells in human tuberculosis.

The role of TGF-beta TNF-alpha FasL and Bcl-2 in apoptosis of CD4 T-cells during active TB was studied. Coculture of PBMC from TB patients with neutralizing antibodies to TGF-beta or TNF-alpha decreased spontaneous (P < or = 0.05) and MTB-induced (P < or = 0.