Innovative timing strategies for tuberculosis household contact investigation: cost-effectiveness analysis from a randomized trial in rural and urban South Africa (Kharituwe Study)

Background Household contact investigation (HCI) for tuberculosis (TB) is recommended but often limited by resource constraints, particularly for individuals unavailable during business hours. Methods We conducted an economic evaluation from January 1, 2022, through December 31, 2022, nested within a randomized trial in South Africa ("Kharituwe") comparing standard HCI for TB and two novel strategies: HCI during holiday periods in a rural setting and off-peak HCI during weekends and evenings in an urban setting. Costs were derived from 2022 expenditures, and secondary TB cases were defined by positive sputum cultures. As a secondary outcome of the Kharituwe Study, we assessed the incremental cost-effectiveness ratio (ICER) of each strategy against a hypothetical no-HCI scenario from the health system perspective in 2022 US dollars. Cost-effectiveness was assessed using a country-specific willingness-to-pay threshold of US$3015 per disability-adjusted life year (DALY) averted. The trial is registered with clincaltrials.gov (NCT04520113). Findings Relative to a hypothetical no-HCI approach, standard HCI was estimated to cost US$1400 [95% uncertainty interval (UI): $1000-$2100] per DALY averted in the urban setting and US$3600 [95% UI: $2500-$5400] in the rural setting. Corresponding cost-effectiveness ratios were US$1900 [95% UI: $1300-$2800] for off-peak (urban) and US$6400 [$3900-$10,000] for holiday-based (rural) HCI. Personnel costs, travel costs (in the rural setting), and TB prevalence among contact persons were primary drivers of cost-effectiveness. Interpretation HCI for TB is likely cost-effective in urban South Africa and may be cost-effective in rural settings, which face barriers including long travel times and lower TB prevalence. Holiday-based HCI was not found to be cost-effective. Integrating HCI for TB into broader home-based interventions may improve cost-effectiveness. Funding Funding was provided by the United States National Institute of Allergy and Infectious Diseases (Grant # 5R01AI147681).