LATEBREAKER
Global Health
Duration of effectiveness of preventive treatment for tuberculosis: an individual-participant meta-analysis of 34 contact tracing studies Lauren Linde* Lauren Linde Meredith Brooks C. Robert Horsburgh Leonardo Martinez
Background
Tuberculosis (TB) is an infectious respiratory disease with enormous global impact. Treatment of individuals after TB exposure is widely recommended to prevent disease, however the duration of protection achieved from TB preventive treatment (TPT) is debated. Protection may vary by setting, with shorter protection hypothesized in higher-burden areas. We aimed to assess the effectiveness of TPT over time and among settings of varying TB burden.
Methods
For this individual-participant meta-analysis, we assembled multiple cohorts from TB contact tracing studies published between January 1998 and April 2018. Studies were restricted to those with at least one year of follow-up and individual-level data available for a set list of covariates. We generated Nelson-Aalen cumulative hazard plots to examine comparative hazard by TPT status. Using mixed-effects Cox regression models, we estimated adjusted hazard ratios (aHRs) for incident TB in six-month intervals from six months to four years post-exposure, then for the period from four to 11 years.
Results
We identified 432,589 contacts from 34 studies in 28 countries, with median follow-up time of 2.9 years (range: 0-11 years) and 5,063 incident TB cases. The overall TB incidence rate was 3.7 per 1,000 person-years (PY); 2.0 per 1,000 PY in those who initiated TPT, and 4.0 in those who did not. Receiving TPT was associated with reduced risk of TB for at least 3.5 years (aHR, .31; 95% CI .11-.86 at 36-42 months) overall, with considerable heterogeneity by background TB burden (Fig.). Reduced TB risk was seen among TPT recipients for at least two and three years in low- and medium-burden settings, but only up to the first year of follow-up in high-burden. Contacts given TPT had lower cumulative incidence of TB over follow-up regardless of background burden.
Conclusion
TPT provided sustained protection against TB for at least 2-3 years in low and medium-burden settings, but waned considerably faster in high-burden areas.
