Timing of household contact investigation for tuberculosis among rural and urban populations in South Africa (Kharituwe study): a pragmatic individually randomized controlled trial.

Background: One major challenge in the implementation of household contact investigation (HCI) for tuberculosis (TB) in high burden settings is finding contact persons in the home for screening. Conducting HCI during evenings, weekends, or holidays, particularly in settings with high levels of poverty, may improve effectiveness and implementation. Methods: We conducted a pragmatic, individually randomized controlled trial of HCI for TB at two sites in South Africa, comparing the effectiveness of two novel strategies for timing (during evenings and weekends in an urban area and during three annual holiday periods in a rural area) to weekday working hours. The primary outcome was the number of secondary cases identified and started on TB treatment per index participant, comparing novel versus standard timing at each site. Clinicaltrials.gov registration: NCT04520113. Findings: From September 2020 to August 2023, we randomized 1335 index participants with TB in Limpopo to receive standard HCI and 666 to receive holiday = based HCI, and 1616 to receive standard HCI and 805 to receive evening/weekend HCI in Soshanguve. In Limpopo, standard HCI and holidy-based HCI and resulted in 0.6 and 0.7 secondary TB diagnoses started on treatment per 100 index participants, respectively (difference: 0.1 [95% CI: -0.7, 0.8, p = 0.84]). In Soshanguve, evening/weekend-based HCI and standard HCI generated 0.4 and 0.6 diagnoses started on TB treatment per 100 index participants, respectively (difference 0.3 [95% CI: -0.8, 0.4, p = 0.54]). Interpretation: HCI conducted either during evenings/weekends or during holiday did not increase effectiveness compared to HCI conducted during weekday working hours. Funding: Funding was provided by the United States National Institute of Allergy and Infectious Diseases (Grant # 5R01AI147681).