Infectiousness and social mixing in asymptomatic TB as a driver of population-level transmission

PROJECT SUMMARY/ABSTRACT Achieving substantial reductions in TB incidence will require innovative strategies for halting TB transmission, which have been hampered by a critical knowledge gap of where, when, and by whom transmission is occurring. We and others have shown that only 9-30% of TB cases can be linked to a close contact, suggesting most transmission occurs outside of household settings and with more limited (or casual) contact. Because individuals have more community contacts than household contacts, there is greater opportunity for exposure and infection outside the home, despite a lower intensity of the interactions. Thus, implementing effective measures to prevent transmission requires a comprehensive understanding of when someone becomes infectious and where they are encountering the largest number of susceptible individuals. It is increasingly clear that TB exists along a dynamic spectrum between latent TB infection and active TB disease, with several intervening states characterized by absence of symptoms in the setting of Mtb replication and host response. It is estimated that asymptomatic TB may account for up to half of bacteriologically confirmed TB globally, yet there is limited understanding of infectiousness during this stage. Recent studies have shown that cough may not be necessary for TB to be transmitted. TB bacilli detected in bioaerosols generated by less forceful respiratory maneuvers, such as tidal breathing, are associated with incident TB in close contacts. Since asymptomatic TB remains undiagnosed for an average of two years—during which time people maintain their normal activities and social mixing behaviors—this may explain the large proportion of transmission occurring in community settings. Understanding social contact patterns during early stages of TB has important implications for determining where and when TB is spread. There are limited data on asymptomatic TB transmission; however, research on contact patterns during the COVID-19 pandemic demonstrated community transmission by asymptomatic cases, in part because social contact patterns are unchanged while feeling well. Asymptomatic spread is an established paradigm for several infectious diseases but is yet to be characterized for TB. We will conduct a prospective cohort study of 1,000 close contacts to determine the onset of infectiousness (Aim 1) and measure social contact patterns (Aim 2) along the spectrum of TB disease. Aim 3 will utilize these data to model the proportion of TB transmission that occurs during early-stage disease, particularly in community settings. We have been conducting community-wide TB screening, diagnosis, and transmission research for over two decades, leading to transformative findings that shaped patient care and policy. Our team brings together global leaders in field-based epidemiologic research, transmission science, aerobiology, multi-omics, and modeling to examine fundamental questions in TB transmission science. Together these findings will provide critical information to guide interventions that will more effectively reduce TB incidence