Drivers of Tuberculosis Transmission

Abstract

Measuring tuberculosis transmission is exceedingly difficult, given the remarkable variability in the timing of clinical disease after Mycobacterium tuberculosis infection; incident disease can result from either a recent (ie, weeks to months) or a remote (ie, several years to decades) infection event. Although we cannot identify with certainty the timing and location of tuberculosis transmission for individuals, approaches for estimating the individual probability of recent transmission and for estimating the fraction of tuberculosis cases due to recent transmission in populations have been developed. Data used to estimate the probable burden of recent transmission include tuberculosis case notifications in young children and trends in tuberculin skin test and interferon γ–release assays. More recently, M. tuberculosis whole-genome sequencing has been used to estimate population levels of recent transmission, identify the distribution of specific strains within communities, and decipher chains of transmission among culture-positive tuberculosis cases. The factors that drive the transmission of tuberculosis in communities depend on the burden of prevalent tuberculosis; the ways in which individuals live, work, and interact (eg, congregate settings); and the capacity of healthcare and public health systems to identify and effectively treat individuals with infectious forms of tuberculosis. Here we provide an overview of these factors, describe tools for measurement of ongoing transmission, and highlight knowledge gaps that must be addressed.

Prevalence and Determinants of QuantiFERON-Diagnosed Tuberculosis Infection in 9810 Mongolian Schoolchildren

“…This figure is similar to that reported from a meta-analysis of ten studies which yielded an estimate of 14.1% (95% confidence interval, 11.6%-16.3%) for the PAF for household transmission [33]. This relatively low figure reflects the fact that tuberculosis disease affects less than 1% of households at any time, even in high incidence settings, making exposure opportunities between a person with tuberculosis and their social network outside the household more numerous [34]. Studies in South Africa have indicated that significant transmission occurs in public transportation [35] and in schools [36].…”

Cell-Mediated Immune Responses to in vivo-Expressed and Stage-Specific Mycobacterium tuberculosis Antigens in Latent and Active Tuberculosis Across Different Age Groups

“…Although one fourth of the global population is estimated to be latently infected (2), none of the current immunodiagnostics can discriminate between recent and past Mtb infection, or predict risk of possible TB progression in LTBI (3)(4)(5). Although neonatal vaccination with Bacillus Calmette-Guérin (BCG), the only licensed TB vaccine, protects infants against severe forms of TB, it is unable to prevent active pulmonary TB in adults and adolescents, such that it has little impact on Mtb transmission (6). To boost or replace BCG, multiple TB vaccine candidates have been proposed and are being evaluated in different higher end preclinical or clinical phase 1 and phase 2 studies (7).…”

Genotypic clustering does not imply recent tuberculosis transmission in a high prevalence setting: A genomic epidemiology study in Lima, Peru

“…Although the dataset used was relatively small, these findings add to the current limited literature on the topic. 44–46 Overall our study highlights the utility of WGS in resolving transmission links particularly in high burden settings where several transmission chains may occur simultaneously. WGS of a well characterized cluster through MIRU-VNTR led to identification of several sub-clusters with further granularity achieved from addition of variants in regions that are routinely excluded from these analyses.…”