Estimating the contribution to transmission of asymptomatic tuberculosis from population-based genomic epidemiology studies.

Asymptomatic tuberculosis (TB) poses a major challenge to global TB control. Quantifying its contribution to transmission remains a critical question. Although modelling studies have attempted to address this issue, empirical evidence from real-world settings is scarce. In this study, we estimated the contribution of asymptomatic TB to transmission in China using genomic epidemiology data from five population-based studies, encompassing 6,387 TB patients and 1,626 genomic-clustered patients. Transmission were classified as originating from either asymptomatic or symptomatic TB by comparing reported symptom onset dates with phybreak-inferred transmission timings. Across the study regions, 25.0%-51.3% of transmission was attributed to asymptomatic TB, indicating its substantial role in sustaining transmission. However, accurate estimation is hindered by the subjectivity of symptom reporting and reliance on passive case-finding. While this study likely underestimates the true contribution, it establishes a genomic epidemiology-based framework for future refinement. From a public health perspective, the priority should not be precise quantification but rather a shift toward active case-finding to detect both asymptomatic patients and symptomatic patients who have not sought care, thereby disrupting hidden transmission chains and advancing the End TB goals.