Revisiting the Natural History of Pulmonary Tuberculosis: a Bayesian Estimation of Natural Recovery and Mortality rates.

BACKGROUND: Tuberculosis (TB) natural history remains poorly characterised and new investigations are impossible as it would be unethical to follow up TB patients without treatment.

METHODS: We considered the reports identified in a previous systematic review of studies from the pre-chemotherapy era, and extracted detailed data on mortality over time. We used a Bayesian framework to estimate the rates of TB-induced mortality and self-cure. A hierarchical model was employed to allow estimates to vary by cohort. Inference was performed separately for smear-positive TB (SP-TB) and smear-negative TB (SN-TB).

RESULTS: We included 41 cohorts of SP-TB patients and 19 cohorts of pulmonary SN-TB patients in the analysis. The median estimates of the TB-specific mortality rates were 0.389 year-1 (0.335-0.449, 95% credible interval) and 0.025 year-1 (0.017-0.035) for SP-TB and SN-TB patients, respectively. The estimates for self-recovery rates were 0.231year-1 (0.177-0.288) and 0.130 year-1 (0.073-0.209) for SP-TB and SN-TB patients, respectively. These rates correspond to average durations of untreated TB of 1.57 years (1.37-1.81) and 5.35 years (3.42-8.23) for SP-TB and SN-TB, respectively, when assuming a non-TB-related mortality rate of 0.014 year-1 (i.e. a 70-year life expectancy).

CONCLUSIONS: TB-specific mortality rates are around 15 times higher for SP-TB than for SN-TB patients. This difference was underestimated dramatically in previous TB modelling studies, raising concerns about the accuracy of the associated predictions. Despite being less infectious, SN-TB may be responsible for equivalent numbers of secondary infections as SP-TB due to its much longer duration.