Young, NeenahBiché, PatrickMohlamonyane, MbaliMorolo, MatshidisoMaholwana, BabalwaAhmed, KhatijaMartinson, NeilHanrahan, Colleen F.Dowdy, David W.2025-06-172025-06-172025-06Young, N., Biché, P., Mohlamonyane, M. et al. 2025, 'Innovative timing strategies for tuberculosis household contact investigation : cost-effectiveness analysis from a randomized trial in rural and urban South Africa (Kharituwe Study)', eClinicalMedicine, vol. 84, art. 103259, pp. 1-10, doi : 10.1016/j.eclinm.2025.103259.2589-5370 (online)10.1016/j.eclinm.2025.103259http://hdl.handle.net/2263/102843DATA SHARING STATEMENT : Datasets generated or analyzed during this study are available upon request by contacting the corresponding author.SUPPLEMENTARY MATERIAL 1 : CHEERS Checklist SUPPLEMENTARY MATERIAL 2 : Supplementary Tables and FiguresBACKGROUND : 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.en© 2025 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).Household contact investigation (HCI)Tuberculosis (TB)South Africa (SA)Economic evaluationArticle