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).