Potential limitations of community-wide strategy to treat Mycobacterium tuberculosis infection

A quarter of the world's population has immunologic evidence of past or present Mycobacterium tuberculosis (Mtb) infection (MTBI) detected as TST or IGRA positivity. Community-based preventive treatment of individuals with MTBI has resulted in transient decreases in TB cases, but its long-term effectiveness has been controversial. Due to the likelihood that many of those with immune responses to Mtb antigens may no longer harbor Mtb, widespread treatment of all such individuals may result in unnecessary exposure to antibiotics. We raise an additional concern that preventive treatment of individuals with MTBI, who are not at the risk of disease progression, may result in loss of protective immunity, provided by the persistent infection, and enhanced risk of TB upon re-exposure to Mtb. There is evidence from human cohorts and animal studies that prior exposure to Mtb confers protection against TB development upon re-exposure, and that treatment of Mtb-infected animals often results in loss of this protection. We build a novel epidemiological model of Mtb dynamics and progression to TB in a community allowing for protection afforded by MTBI against exogenous reinfection-driven disease progression. We show that implementation of treatment of MTBI in the whole community will result in reduction of TB cases but stopping the program may result in an increase in new TB cases that may offset (or even exceed) benefits of the preventive treatment program. Our results suggest that better understanding protective effects provided by MTBI against progression to TB upon Mtb re-exposure and identification of Mtb-infected individuals who most benefit from preventive treatment must be a priority before preventive treatment of asymptomatic MTBI is widely implemented.