A Cluster-Randomized Trial of DOTS vs DOTS Plus Active Case Finding

Tuberculosis (TB) continues to be a major cause of morbidity and mortality worldwide, particularly in developing countries. The World Health Organization (WHO) has estimated that one-third of the world's population is infected with Mycobacterium tuberculosis. Tuberculosis remains a major public health problem in Brazil, being the 15th highest TB burden in the world. The goal of this project is to determine whether TB active case finding (ACF) in conjunction with directly observed therapy (DOTS) results in lower incidence of TB compared with routine DOTS alone. This community-randomized trial will be conducted in 20 Rio de Janeiro communities within 2 APs with high rates of TB where community health workers and health units are undergoing intensive training to implement DOTS programs. This will be a collaborative effort between the Municipal Health Secretariat of Rio de Janeiro and the Johns Hopkins University Center for Tuberculosis Research. A cluster-randomized trial will be conducted to compare the impact of 2 case detection and treatment strategies on the community incidence of TB. The 20 communities within 2 planning areas (APs) will be randomly assigned to routine DOTS based on passive case detection or DOTS+ACF, where TB cases are actively detected by community outreach. In all communities, cases of TB will be identified through the existing TB clinics using identical procedures for subjects reporting to the TB clinics on their own accord. These subjects will be identified through traditional methods of passive case finding (PCF). In DOTS+ACF communities, all households will be surveyed by community health workers to identify individuals with cough for greater than or equal to 3 weeks, and all symptomatic subjects will provide a spot sputum specimen for acid-fast bacilli smear at the time of their household survey. Results will be returned to the subject at their home and appropriate follow-up measures will be provided to confirm TB diagnoses and provide treatment. The primary objective of the study is to compare TB incidence in communities randomized to DOTS+ACF and DOTS alone over the 18-month period following ACF campaign. The study hypothesizes that the average TB incidence in these 18 months will be 42% less in the DOTS+ACF arm compared with the DOTS-arm. The study has two secondary objectives. The first secondary objective will be to compare case notification rates of TB in the 2 arms of the study during the ACF campaign. Researchers hypothesize that TB notification rates will be at least 40% greater in the DOTS+ACF communities during the ACF period of the study. The second secondary objective will be to compare treatment completion rates between the 2 arms of the study. Researchers hypothesize that subjects detected through ACF will have equal treatment completion rates (+/- 5%) as subjects in the DOTS-arm. Tuberculosis diagnosis is the primary outcome measure. Treatment completion is the secondary outcome measure. The study population will be residents of the 20 communities selected, approximately 200,000 people with no restriction on age. Diagnosing subjects earlier will ensure that they are treated earlier and have less time to spread the disease to their contacts.