Hidden spread: asymptomatic tuberculosis transmits as much as symptomatic cases

Tuberculosis remains a major public health challenge in places with high disease burden, and control programs typically focus on people who show symptoms. Jason R. Andrews and colleagues set out to test whether people without symptoms nonetheless contribute substantially to ongoing spread. To do this they used samples collected in Mato Grosso do Sul, Brazil, over a long period (2008–2024). From 2017 to 2022 they carried out active case finding in three of the state’s largest prisons, collecting sputum from people regardless of whether they had symptoms and testing those samples with GeneXpert and by culture. The aim was to compare multiple genetic measures of recent transmission between symptomatic and asymptomatic tuberculosis cases identified in that prison screening and in the broader collection of isolates. Using whole-strain data and population-level sampling, the researchers investigated whether asymptomatic infections were less likely to belong to recent transmission chains or to seed secondary cases than symptomatic infections, or whether they played a comparable role in maintaining transmission at the population level.

The study analyzed 2,362 strains of Mycobacterium tuberculosis. Most strains belonged to lineage 4, and 78.2% of all isolates were part of a genomic cluster, indicating recent transmission. Drug resistance was uncommon: 3.5% (115/2,362) of strains were resistant to at least one drug and 0.6% (16/2,362) were multi-drug resistant. Among the 2,362 people with tuberculosis, 1,137 were incarcerated at diagnosis; 505 of those were identified through active case finding in the prisons, with 277 classified as symptomatic and 228 as asymptomatic. The team compared several phylogenetic and transmission metrics: phylogenetic clustering proportion (77% symptomatic vs. 85% asymptomatic; p = 0.816), Time-scaled Haplotype Density (THD; median 0.50 vs. 0.39; p = 0.120), and Local Branching Index (LBI; median 0.00863 vs. 0.00871; p = 0.086). They also inferred transmission probabilities using Bayesian Reconstruction and Evolutionary Analysis of Transmission Histories (BREATH), which showed no significant difference in the number of secondary infections from symptomatic versus asymptomatic individuals (p = 0.56). These comparisons held across genomic clusters and were robust to model assumptions.

The results point to an important conclusion: asymptomatic tuberculosis cases can be as involved in recent transmission as symptomatic cases. Using multiple genomic measures and a Bayesian approach, the investigators found no meaningful differences between symptomatic and asymptomatic people in indicators that signal recent spread or the number of likely secondary infections. That finding matters for control strategies that rely primarily on identifying people who report symptoms. In settings like the prisons studied here, routine screening that tests people regardless of symptoms—using tools such as GeneXpert and culture—can uncover infections that might otherwise be missed but that appear capable of sustaining transmission chains. Although the study observed relatively low levels of drug resistance, the high proportion of clustered strains (78.2%) underscores active transmission. Policymakers and public health programs may need to broaden screening approaches and include active case finding and genomic surveillance to better interrupt transmission driven in part by asymptomatic infections.