Trials underestimate the impact of preventive treatment for household contacts exposed to multidrug-resistant tuberculosis: a simulation study

BackgroundSeveral 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. MethodsWe 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. FindingsDuring 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. InterpretationIf forthcoming trial results demonstrate efficacy, the long-term population impact of MDR-TPT implementation could be much greater than suggested by trial outcomes alone. FundingNIH K01AI138853 and K08AI127908; Johns Hopkins Catalyst Award.