medRxiv. 2023 Feb 8:2023.02.06.23285528. doi: 10.1101/2023.02.06.23285528. Preprint.

ABSTRACT

BACKGROUND: Several clinical trials of tuberculosis preventive treatment (TPT) for household contacts of patients with multidrug-resistant tuberculosis (MDR-TB) are nearing completion. The potential benefits of TPT for MDR-TB contacts extend beyond the outcomes that clinical trials can measure.

METHODS: We developed an agent-based, household-structured TB and MDR-TB transmission model, calibrated to an illustrative setting in India, the country accounting for 26% of global MDR-TB burden. We simulated household contact investigation for contacts of patients with MDR-TB, comparing an MDR-TPT regimen against alternatives of isoniazid preventive treatment, household contact investigation without TPT, or no household contact intervention. We simulated outcomes of a clinical trial and estimated the patient-level and population-level effects over a longer time horizon.

FINDINGS: During two years of follow-up per recipient, a simulated 6-month MDR-TPT regimen with 70% efficacy against both DS- and MDR-TB infection could prevent 72% [Interquartile range (IQR): 45 – 100%] of incident MDR-TB among TPT recipients (number needed to treat (NNT) 73 [44 – 176] to prevent one MDR-TB case), compared to household contact investigation without TPT. This NNT decreased to 54 [30 – 183] when median follow-up was increased from two to 16 years, to 27 [11 – Inf] when downstream transmission effects were also considered, and to 12 [8 – 22] when these effects were compared to a scenario of no household contact intervention.

INTERPRETATION: If forthcoming trial results demonstrate efficacy, the long-term population impact of MDR-TPT implementation could be much greater than suggested by trial outcomes alone.

FUNDING: NIH K01AI138853 and K08AI127908; Johns Hopkins Catalyst Award.

PMID:36798407 | PMC:PMC9934809 | DOI:10.1101/2023.02.06.23285528