Low sensitivity of T-cell based detection of tuberculosis among HIV co-infected Tanzanian in-patients.

OBJECTIVE: To evaluate the performance of QuantiFERON-TB GOLD (QFTG) in a resource-poor setting among patients with and without HIV infection. DESIGN: Cross-sectional study. SETTING: Two hospitals in Northern Tanzania. SUBJECTS: Eighty three adult male and female inpatients. INTERVENTION: All patients were screened for HIV infection and underwent tuberculin skin test (TST) and QFTG. RESULTS: Eighty-three subjects were enrolled, and 29 (35%) of 83 were HIV-infected. QFTG yielded indeterminate results in 12 (22%; 95% CI 12%-34%) of 54 HIV-uninfected and 13 (45%; 95% CI 26%-64%) of 29 HIV-infected subjects (p = 0.0323). Among those with smear-positive pulmonary tuberculosis, TST was positive in 40 (100%; 95% CI 91%-100%) of 40 HIV-uninfected subjects compared with seven (54%; 95% CI 25%-81%) of 13 HIV-infected subjects (p < 0.0001), and QFTG was positive in 28 (70%; 95% CI 53%-83%) of 40 HIV-uninfected subjects compared with three (23%; 95% CI 5%-54%) of 13 HIV-infected subjects (p = 0.0029). Among medical inpatients at risk for latent tuberculosis infection, TST was positive in seven (50%) of 14 HIV-uninfected patients and three (19%) of 16 HIV-infected patients (p = 0.0701) and QFTG was positive among two (14%) of 14 HIV-uninfected patients and three (19%) of 16 HIV-infected patients (p = 0.7437). CONCLUSIONS: The presence of HIV co-infection was associated with a significant reduction in sensitivity of both the TST (p < 0.0001) and QFTG (p = 0.0029) for the diagnosis of active M. tuberculosis infection. The high proportion of indeterminate QFTG and lack of sensitivity, particularly among HIV-infected patients, may limit its applicability in settings like Tanzania. Larger studies in resource-poor settings are required.

Randomized controlled trial of a drug regimen that includes ciprofloxacin for the treatment of pulmonary tuberculosis.

The fluoroquinolones are promising new antituberculous agents. A randomized controlled trial of 200 adult patients with sputum smear-positive pulmonary tuberculosis was conducted in Tanzania. Patients received either a trial regimen (HRC) consisting of isoniazid (300 mg), rifampin (600 mg), and ciprofloxacin (750 mg) or a control regimen (HRZE) consisting of isoniazid (300 mg), rifampin (600 mg), pyrazinamide (25 mg/kg), and ethambutol (15 mg/kg). The 168 evaluable patients all had negative smears and cultures by month 6, but the time to conversion to negativity was longer for the HRC group than for the HRZE group because of the poor response of patients infected with human immunodeficiency virus (HIV) to the HRC regimen. Relapse was more frequent in the HRC group. The sterilizing activity of ciprofloxacin does not appear to be equal to that of the combination of pyrazinamide and ethambutol, but the difference in outcome was significant only among HIV-infected patients.

Early bactericidal and sterilizing activities of ciprofloxacin in pulmonary tuberculosis.

The early bactericidal and sterilizing activities of ciprofloxacin were evaluated in the treatment of adult patients with smear positive pulmonary tuberculosis. Two randomized prospective studies were performed in Northern Tanzania. In study 1, ten patients received either 750 mg ciprofloxacin or 300 ng isoniazid daily for 7 days. Counts of colony-forming units (cfu) of Mycobacterium tuberculosis in early morning sputum were performed. In study 2, twenty patients received either a standard regimen of rifampin (R), isoniazid (H), pyrazinamide (Z), and ethambutol (E) (regimen HRZE) or a trial regimen of ciprofloxacin (C), isoniazid (H), and rifampin (R) (regimen HRC). Sputum colony counts were performed for 8 wk. Patients were tested for antibodies to human immunodeficiency virus (HIV)-1. The results demonstrate that ciprofloxacin alone has useful early bactericidal activity, resulting in a mean daily fall of 0.20 log10cfu/ml/day during 7 days compared with 0.25 log10cfu/ml/day for isoniazid. When HRZE and HRC regimens were compared, the HRC regimen appeared to be inferior in its sterilizing ability, with a culture conversion rate of 67% at 2 months compared with 100% for HRZE. The difference in outcome was most marked in HIV-1 positive patients. The role of ciprofloxacin in combination regimens may be as a bactericidal rather than a sterilizing agent.