Is cough really necessary for TB transmission?

Cough has long been implicated in the production of infectious aerosol leading to transmission of tuberculosis (TB). However, prevalence studies frequently identify radiographic evidence of TB in subclinical individuals in the absence of reported coughing. Elucidating the role of cough in transmission depends on understanding the physical process of aerosolizing and expelling mycobacterium tuberculosis (Mtb) bacilli. In the last decade, human aerosol studies have progressed with improved precision of particle detection and greater sophistication of experimental protocols. Combining principles of respiratory physiology, the site and mechanism of aerosolization of respiratory lining fluids during phases of the respiratory cycle has been investigated in detail. Additionally, recent success in the direct detection of naturally generated Mtb aerosols has allowed more detailed characterization in terms of their rate of production and size distribution. We propose that TB transmission depends on the coincidence of the site of aerosol generation with the presence of Mtb bacilli. This review will examine the evidence for site of aerosol production during cough and respiratory activities in conjunction with the characteristics of detectable Mtb aerosols and locations of tuberculosis infection. Furthermore, we propose respiratory activities that are likely to optimise aerosol sampling for investigation of transmission.