RESUMEN
While Tanzania is among the high TB burden countries to reach the WHO's End TB 2030 milestones, 41% of the people estimated to have had TB in 2020 were not diagnosed and notified. As part of the response to close the TB treatment coverage gap, SHDEPHA+ Kahama conducted a TB REACH active case-finding (ACF) intervention among rural and mining communities in Northwest Tanzania to increase TB/HIV case notification from July 2017 to June 2020. The intervention successfully linked marginalized mining communities with integrated TB/HIV screening, diagnostic, and referral services, screening 144,707 people for TB of whom 24,200 were tested for TB and 4,478 were tested for HIV, diagnosing 1,499 people with TB and 1,273 people with HIV (including at least 154 people with TB/HIV coinfection). The intervention revealed that community-based ACF can ensure high rates of linkage to care among hard-to-reach populations for TB. Providing integrated TB and HIV screening and diagnostic services during evening hours (Moonlight Events) in and around mining settlements can yield a large number of people with undiagnosed TB and HIV. For TB, this is true not only amongst miners but also FSW living in the same communities, who appear to be at similar or equally high risk of infection. Local NGOs can help to bridge the TB treatment coverage gap and to improve TB and HIV health outcomes by linking these marginalized groups with public sector services. Capturing the number of referrals arriving at CTCs is an important next step to identify how well the integrated TB/HIV outreach services operate and how they can be strengthened.
RESUMEN
In a multiple-dose-ranging trial, we previously evaluated higher doses of rifampin in patients for 2 weeks. The objectives of the current study were to administer higher doses of rifampin for a longer period to compare the pharmacokinetics, safety/tolerability, and bacteriological activity of such regimens. In a double-blind, randomized, placebo-controlled, phase II clinical trial, 150 Tanzanian patients with tuberculosis (TB) were randomized to receive either 600 mg (approximately 10 mg/kg of body weight), 900 mg, or 1,200 mg rifampin combined with standard doses of isoniazid, pyrazinamide, and ethambutol administered daily for 2 months. Intensive pharmacokinetic sampling occurred in 63 patients after 6 weeks of treatment, and safety/tolerability was assessed. The bacteriological response was assessed by culture conversion in liquid and solid media. Geometric mean total exposures (area under the concentration-versus-time curve up to 24 h after the dose) were 24.6, 50.8, and 76.1 mg · h/liter in the 600-mg, 900-mg, and 1,200-mg groups, respectively, reflecting a nonlinear increase in exposure with the dose (P < 0.001). Grade 3 adverse events occurred in only 2 patients in the 600-mg arm, 4 patients in the 900-mg arm, and 5 patients in the 1,200-mg arm. No significant differences in the bacteriological response were observed. Higher daily doses of rifampin (900 and 1,200 mg) resulted in a more than proportional increase in rifampin exposure in plasma and were safe and well tolerated when combined with other first-line anti-TB drugs for 2 months, but they did not result in improved bacteriological responses in patients with pulmonary TB. These findings have warranted evaluation of even higher doses of rifampin in follow-up trials. (This study has been registered at ClinicalTrials.gov under identifier NCT00760149.).
