Early Bactericidal Activity Trial of Nitazoxanide for Pulmonary Tuberculosis.

This study was conducted in treatment-naive adults with drug-susceptible pulmonary tuberculosis in Port-au-Prince, Haiti, to assess the safety, bactericidal activity, and pharmacokinetics of nitazoxanide (NTZ). This was a prospective phase II clinical trial in 30 adults with pulmonary tuberculosis. Twenty participants received 1 g of NTZ orally twice daily for 14 days. A control group of 10 participants received standard therapy over 14 days. The primary outcome was the change in time to culture positivity (TTP) in an automated liquid culture system. The most common adverse events seen in the NTZ group were gastrointestinal complaints and headache. The mean change in TTP in sputum over 14 days in the NTZ group was 3.2 h ± 22.6 h and was not statistically significant (P = 0.56). The mean change in TTP in the standard therapy group was significantly increased, at 134 h ± 45.2 h (P < 0.0001). The mean NTZ MIC for Mycobacterium tuberculosis isolates was 12.3 µg/ml; the mean NTZ maximum concentration (Cmax) in plasma was 10.2 µg/ml. Negligible NTZ levels were measured in sputum. At the doses used, NTZ did not show bactericidal activity against M. tuberculosis Plasma concentrations of NTZ were below the MIC, and its negligible accumulation in pulmonary sites may explain the lack of bactericidal activity. (This study has been registered at ClinicalTrials.gov under identifier NCT02684240.).

Integration of tuberculosis screening at an HIV voluntary counselling and testing centre in Haiti.

OBJECTIVE: To describe the integration of tuberculosis screening into the activities of an HIV voluntary counselling and testing (VCT) centre in a country with endemic tuberculosis. SETTING: An HIV VCT centre in Port au Prince, Haiti. DESIGN: All patients presenting for HIV VCT who reported cough received same-day evaluation for active tuberculosis. Of the 1327 adults presenting to the centre for the first time between January and April 1997, 263 (20%) reported cough and of these 241 (92%) were evaluated. RESULTS: Of the 241 patients evaluated for cough, 76 (32%) were diagnosed with pulmonary tuberculosis. Of the 76 patients diagnosed with pulmonary tuberculosis, 28 (37%) had a positive smear for acid-fast bacilli (AFB), 14 (18%) had a negative AFB smear but a positive sputum culture for Mycobacterium tuberculosis, and 34 (45%) had culture-negative tuberculosis. Also, 31 out of 241 (13%) VCT clients evaluated for cough were diagnosed with bacterial pneumonia. CONCLUSION: This report confirms that in areas with a high HIV and tuberculosis prevalence, a high proportion of VCT clients have active pulmonary tuberculosis. The integration of tuberculosis screening offers several benefits, including the diagnosis and treatment of large numbers of individuals with tuberculosis, a decreased risk of nosocomial tuberculosis transmission, and the opportunity to provide tuberculosis prophylaxis to HIV-positive patients in whom tuberculosis has been excluded. Future studies are needed to determine the cost-effectiveness of integrated tuberculosis and HIV VCT services, and whether integration should be recommended in all countries with high HIV and tuberculosis rates.

Trimethoprim-sulfamethoxazole compared with ciprofloxacin for treatment and prophylaxis of Isospora belli and Cyclospora cayetanensis infection in HIV-infected patients. A randomized, controlled trial.

BACKGROUND: In developing countries, Isospora belli and Cyclospora cayetanensis frequently cause chronic diarrhea in HIV-infected patients. OBJECTIVE: To compare 1 week of trimethoprim-sulfamethoxazole treatment and 1 week of ciprofloxacin treatment in HIV-infected patients with chronic diarrhea caused by I. belli and C. cayetanensis. DESIGN: Randomized, controlled trial. SETTING: HIV clinic in Port-au-Prince, Haiti. PATIENTS: 42 HIV-infected patients with chronic diarrhea due to I. belli (n = 22) or C cayetanensis (n = 20). INTERVENTIONS: Patients were randomly assigned to receive oral trimethoprim-sulfamethoxazole (160 mg or 800 mg) or ciprofloxacin (500 mg) twice daily for 7 days. Patients who responded clinically and microbiologically received prophylaxis for 10 weeks (1 tablet orally, three times per week). MEASUREMENTS: Treatment success was measured by cessation of diarrhea and negative stool examination at day 7. Prophylaxis success was measured by recurrent disease rate. RESULTS: Diarrhea ceased in all 19 patients treated with trimethoprim-sulfamethoxazole. Eighteen of 19 patients had negative results on stool examination at day 7 (95%). Among the 23 patients who received ciprofloxacin, diarrhea ceased in 20 (87% [CI; 66% to 97%]) and 16 had negative results on stool examination at day 7 (70%). By survival analysis, diarrhea from isosporiasis and cyclosporiasis ceased more rapidly with trimethoprim-sulfamethoxazole than with ciprofloxacin. All patients receiving secondary prophylaxis with trimethoprim-sulfamethoxazole remained disease-free, and 15 of 16 patients receiving secondary prophylaxis with ciprofloxacin remained disease-free. CONCLUSIONS: A 1-week course of trimethoprim-sulfamethoxazole is effective in HIV-infected patients with cyclosporiasis or isosporiasis. Although ciprofloxacin is not as effective, it is acceptable for patients who cannot tolerate trimethoprim-sulfamethoxazole.