Estimating the contribution of subclinical tuberculosis disease to transmission – an individual patient data analysis from prevalence surveys

Abstract

Abstract Background Individuals with bacteriologically confirmed pulmonary tuberculosis disease (TB) that do not report symptoms (subclinical TB) represent around half of all prevalent cases of TB, yet their contribution to Mycobacterium tuberculosis ( Mtb ) transmission is unknown, especially compared to individuals who report symptoms at time of diagnosis (clinical TB). Relative infectiousness can be approximated by cumulative infections in household contacts, but such data are rare. Methods and Findings We reviewed the literature to identify studies where surveys of Mtb infection were linked to population surveys of TB disease. We collated individual population data for analysis and used literature on the relative durations of subclinical and clinical TB to estimate relative infectiousness through a cumulative hazard model, accounting for sputum-smear status. Relative prevalence of subclinical and clinical disease in high burden settings was used to estimate the contribution of subclinical TB to global Mtb transmission. We collated data on 414 index cases and 789 household contacts from three prevalence surveys (Bangladesh, Philippines, Viet Nam) and one case-finding trial in Viet Nam. The odds ratio of household infection prevalence was 1.2 (0.6-2.3, 95% Confidence Interval). Adjusting for duration of disease, we found a per-unit-time infectiousness of subclinical TB relative to clinical TB of 1.93 (0.62-6.18, 95% Prediction Interval (PrI)). 14 countries across Asia and Africa provided data on relative prevalence of subclinical and clinical TB, suggesting an estimated 68% (27-92%, 95% PrI) of global transmission is from subclinical TB. Conclusions Our results suggest that subclinical TB contributes substantially to transmission and needs to be diagnosed and treated for effective progress towards TB elimination.