The Impact of Preventive Treatment for Multidrug- and Rifampin-Resistant Tuberculosis Exceeds Trial-Based Estimates

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 2 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 2 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; the median number needed to treat (NNT) to prevent 1 MDR/RR-TB case was 73, compared to placebo. This NNT 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.

Keywords: India; antibacterial agents; computer simulation; contact tracing.