Tuberculosis and human immunodeficiency virus co-infections and their predictors at a hospital-based HIV/AIDS clinic in Uganda.

SETTING: Mulago Hospital, Uganda. OBJECTIVE: 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 throughout 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 confirmed 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/m(2) (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 antiretroviral 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.

Severity of human immunodeficiency virus infection is associated with decreased phase angle, fat mass and body cell mass in adults with pulmonary tuberculosis infection in Uganda.

Although coinfection with tuberculosis and human immunodeficiency virus (HIV) is emerging as a major problem in many developing countries, nutritional status has not been well characterized in adults with tuberculosis and HIV infection. We compared nutritional status between 261 HIV-positive and 278 HIV-negative adults with pulmonary tuberculosis in Kampala, Uganda, using anthropometry and bioelectrical impedance analysis. Among 163 HIV-positive and 199 HIV-negative men, intracellular water-to-extracellular water (ICW:ECW) ratio was 1.48 +/- 0.26 and 1.59 +/- 0.48 (P = 0.006) and phase angle was 5.42 +/- 1.05 and 5.76 +/- 1.30 (P = 0.009), respectively. Among 98 HIV-positive and 79 HIV-negative women, ICW:ECW was 1.19 +/- 0.16 and 1.23 +/- 0.15 (P = 0.11) and phase angle was 5.35 +/- 1.27 and 5.43 +/- 0.93 (P = 0.61), respectively. There were no significant differences in BMI, body cell mass, fat mass or fat-free mass between HIV-positive and HIV-negative adults. Among HIV-positive subjects, BMI, ICW:ECW, body cell mass, fat mass and phase angle were significantly lower among those with CD4(+) lymphocytes < or = 200 cells/microL compared with those who had > 200 cells/microL. In sub-Saharan Africa, coinfection with pulmonary tuberculosis and HIV is associated with smaller body cell mass and intracellular water, but not fat-free mass, and by large differences in ICW:ECW and phase angle alpha.

Quantitative bacillary response to treatment in Mycobacterium tuberculosis infected and M. africanum infected adults with pulmonary tuberculosis.

Data regarding possible differences in microbiological response to therapy of disease caused by Mycobacterium tuberculosis and M. africanum are limited. Presenting clinical characteristics and sputum bacillary load during standard short-course chemotherapy in patients with newly-diagnosed pulmonary tuberculosis due to M. tuberculosis (n = 7) and M. africanum (n = 6) were compared. Changes in sputum bacillary load were measured using quantitative acid-fast bacilli smears, colony forming unit assay, and time until positive culture in the BACTEC radiometric system. Presentation and response to short course chemotherapy were comparable between patients infected with M. tuberculosis and those infected with M. africanum.

Quantitative sputum bacillary load during rifampin-containing short course chemotherapy in human immunodeficiency virus-infected and non-infected adults with pulmonary tuberculosis.

SETTING: National Tuberculosis (TB) Treatment Centre, Mulago Hospital and Joint Clinical Research Centre, Kampala, Uganda. OBJECTIVE: To compare the quantitative sputum bacillary load between TB patients infected with the human immunodeficiency virus (HIV) and those non-infected, during treatment with standard short course chemotherapy (SCC). DESIGN: To compare clinical characteristics and quantitative sputum bacillary load as measured by quantitative acid-fast bacilli (AFB) smears, colony forming unit (cfu) assay and time until positive culture in the BACTEC radiometric liquid system between 14 HIV-infected and 22 non-HIV-infected adults with initial episodes of smear-positive pulmonary TB at baseline and during treatment with standard four-drug SCC. RESULTS: Other than cavitation (P = 0.042) and adenopathy (P = 0.03), which were more common among non-HIV-infected and HIV-infected patients, respectively, there were no significant differences in baseline demographic, clinical, radiological and laboratory characteristics between the groups. Mean pretreatment sputum bacillary burden (6.5+/-0.51 log10 AFB/ml, 5.91+/-0.91 log10 cfu/ml and 1.8+/-1.7 days until positive BACTEC culture for HIV-infected patients and 6.32+/-0.85 log10 AFB/ml, 5.58+/-0.68 log10 cfu/ml and 1+/-1.2 days until positive BACTC culture for non-HIV-infected patients) were comparable between HIV-infected and non-HIV-infected patients. Clinical and bacteriological responses to standard SCC and treatment outcome did not differ between the groups. CONCLUSION: Quantitative sputum bacillary load at baseline and during SCC did not differ significantly between HIV-infected and non-HIV-infected adults with initial episodes of smear-positive TB.

Predicting the outcome of therapy for pulmonary tuberculosis.

Patients vary considerably in their response to treatment of pulmonary tuberculosis. Although several studies have indicated that adverse outcomes are more likely in those patients with delayed sputum sterilization, few tools are available to identify those patients prospectively. In this study, multivariate models were developed to predict the response to therapy in a prospectively recruited cohort of 42 HIV-uninfected subjects with drug-sensitive tuberculosis. The cohort included 2 subjects whose initial response was followed by drug-sensitive relapse. The total duration of culture positivity was best predicted by a model that included sputum M. tuberculosis antigen 85 concentration on Day 14 of therapy, days-to-positive in BACTEC on Day 30, and the baseline radiographic extent of disease (R = 0.63). A model in which quantitative AFB microscopy replaced BACTEC also performed adequately (R = 0.58). Both models predicted delayed clearance of bacilli in both relapses (> 85th percentile of all subjects) using information collected during the first month of therapy. Stratification of patients according to anticipated response to therapy may allow TB treatment to be individualized, potentially offering superior outcomes and greater efficiency in resource utilization, and aiding in the conduct of clinical trials.

Quantitative sputum bacillary load during rifampin-containing short course chemotherapy in human immunodeficiency virus-infected and non-infected adults with pulmonary tuberculosis

Setting: National Tuberculosis (TB) Treatment Centre; Mulago Hospital and Joint Clinical Research Centre; Kampala; Uganda. Objective: To compare the quantitative sputum bacillary load between TB patients infected with the human immunodeficiency virus (HIV) and those non-infected; during treatment with standard short course chemotherapy (SCC). Design: To comapre clinical characteristics and quantitative sputum bacillary load as measured by quantitative acid-fast bacilli (AFB) smears; colony forming unit (cfu) assay and time until positive culture in the BACTEC radiometric liquid system between 14 HIV-infected and 22 non-HIV-Infected adults with initial episodes of smear-positive polmunary TB at baseline and during treatment with standard four-drug SCC. Results: Other than cavitation (P=0.042) and adenopathy (P=0.03); which were more common among non-HIV-infected patients; respectively; there were no significant differences in baseline demographics; clinical; radiological and laboratory characteristics between the groups. Mean pretreatment sputum bacillary burden (6.5+/-0.51 log 10 AFB/ml; 5.91+/-0.91 log 10 cfu/ml and 1.8+/-1.7 days until positive BACTEC culture for HIV-infected patients and 6.32+/-0.85 log 10 AFB/ml; 5.58+/-0.68 log 10 cfu/ml and 1+/-1.2 days until positive BACTEC culture for non-HIV-infected patients) were comparable between HIV-infected and non-HIV-infected patients. Clinical bacteriological responses to standard SCC and treatment outcome did not differ between the groups. Conclusion: Quantitative sputum bacillary load at baseline and during SCC did not differ significantly between HIV-infected and non-HIV-Infected adults with initial episodes of smear - positive TB

Drug tolerance in Mycobacterium tuberculosis.

Although Mycobacterium tuberculosis is eradicated rapidly during therapy in some patients with pulmonary tuberculosis, it can persist for many months in others. This study examined the relationship between mycobacterial drug tolerance (delayed killing in vitro), persistence, and relapse. It was performed with 39 fully drug-susceptible isolates from a prospective trial of standard short-course antituberculous therapy with sputum smear-positive, human immunodeficiency virus-uninfected subjects with pulmonary tuberculosis in Brazil and Uganda. The rate of killing in vitro was determined by monitoring the growth index (GI) in BACTEC 12B medium after addition of drug to established cultures and was measured as the number of days required for 99% sterilization. Drugs differed significantly in bactericidal activity, in the following order from greatest to least, rifampin > isoniazid-ethambutol > ethambutol (P < 0.001). Isolates from subjects who had relapses (n = 2) or in whom persistence was prolonged (n = 1) were significantly more tolerant of isoniazid-ethambutol and rifampin than isolates from other subjects (P < 0.01). More generally, the duration of persistence during therapy was predicted by strain tolerance to isoniazid and rifampin (P = 0.012 and 0.026, respectively). Tolerance to isoniazid-ethambutol and tolerance to rifampin were highly correlated (P < 0.001). Tolerant isolates did not differ from others with respect to the MIC of isoniazid; the rate of killing of a tolerant isolate by isoniazid-ethambutol was not increased at higher drug concentrations. These observations suggest that tolerance may not be due to drug-specific mechanisms. Tolerance was of the phenotypic type, although increased tolerance appeared to emerge after prolonged drug exposure in vivo. This study suggests that drug tolerance may be an important determinant of the outcome of therapy for tuberculosis.

Induction of the antigen 85 complex of Mycobacterium tuberculosis in sputum: a determinant of outcome in pulmonary tuberculosis treatment.

Sputum quantitative culture, acid-fast smear, days-to-positive by BACTEC, and Mycobacterium tuberculosis antigen 85 complex were monitored during therapy in 42 patients with pulmonary tuberculosis (TB). By BACTEC, 4 patients were persistently positive on days 90-180, and treatment ultimately failed in 2 of these. Antigen 85 expression increased in subjects in whom disease persisted (persisters) from days 0 to 14 when the difference between persisters and nonpersisters was statistically significant (P = .002). Only antigen 85 complex values at day 14 suggested TB persistence at or after day 90. All subjects with day 14 antigen 85 complex values < 60 pg/mL responded rapidly to treatment and were cured. Of those with values > 60 pg/mL, in 33% TB persisted at or after day 90 and treatment failed in 17%. Biologic factors expressed early in therapy, not related to compliance or resistance, may exert a substantial influence on outcome. The antigen 85 complex is critical in cell wall biosynthesis and is induced by isoniazid in vitro. Its induction may represent an adaptive transition to a persistent state during therapy.