ARTICLE: The impact of preventive treatment for multidrug- and rifampin-resistant tuberculosis exceeds trial-based estimates
AUTHORS: Parastu Kasaie, Jeff Pennington, Amita Gupta, David W Dowdy, Emily A Kendall
JOURNAL: Clin Infect Dis. 2023 Sep 19:ciad557. doi: 10.1093/cid/ciad557. Online ahead of print.
Abstract
Background: Several clinical trials of tuberculosis preventive treatment (TPT) for household contacts of patients with multidrug- or rifampin-resistant tuberculosis (MDR/RR-TB) are nearing completion. The potential benefits of delivering TPT to MDR/RR-TB contacts extend beyond the outcomes that clinical trials can measure.
Methods: We developed an agent-based, household-structured TB and MDR/RR-TB transmission model, calibrated to an illustrative setting in India. We simulated contact investigation in households of patients with MDR/RR-TB, comparing an MDR/RR-TPT regimen (assuming 6-month duration, 70% efficacy) and associated active case finding against alternatives of contact investigation without TPT or no household intervention. We simulated the TB and MDR/RR-TB incidence averted relative to placebo over two years, as measurable by a typical trial, as well as the incidence averted over a longer time horizon, in the broader population, and relative to no contact investigation.
Results: Observing TPT and placebo recipients for two years as in a typical trial, MDR/RR-TPT was measured to prevent 72% [Interquartile range: 45-100%] of incident MDR/RR-TB among recipients; median number-needed-to-treat to prevent one MDR/RR-TB case was 73, compared to placebo. This number-needed-to-treat decreased to 54 with 13-18 years of observation, to 27 when downstream transmission effects were also considered, and to 12 when the effects of active TB screening were included by comparing to a no-household-contact-intervention scenario.
Conclusions: If forthcoming trial results demonstrate efficacy, the long-term population impact of TPT for MDR/RR-TB - including the large effect of increased active TB detection among MDR/RR-TB contacts - could be much greater than suggested by trial outcomes alone.
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