Assessing infectiousness and the impact of effective treatment to guide isolation recommendations for people with pulmonary tuberculosis

Abstract Determining the extent and duration of infectiousness of individuals with pulmonary tuberculosis (TB) is critical for various aspects of TB care, including decisions regarding isolation. Studies suggest considerable heterogeneity in infectiousness of people with pulmonary TB. Pre-treatment, measures of bacillary burden including sputum smear microscopy, culture time-to-positivity, and Xpert MTB/RIF cycle threshold (Ct) value, predict the risk of transmission to contacts. Index patients with smear negative disease pose lower infectious risk than those who have smear-positive disease, and household contact infection is more likely with index patients who have lower Xpert Ct values. Newer tools that enable detection of Mycobacterium tuberculosis complex (Mtb complex) from cough aerosol sampling and face mask sampling may be better predictors of contact infection risk. Clinical factors such as cough strength and frequency, and presence of cavitation on chest imaging, may also assist with risk prediction. Post-treatment, smear and culture status are poor predictors of infectiousness. While the exact duration of infectiousness post treatment initiation remains uncertain, data from human-to-guinea pig transmission studies and clinical studies suggest effective treatment results in a rapid decline in infectiousness, irrespective of smear or culture conversion. This is largely supported by early bactericidal activity and transcriptomic studies, and cough aerosol sampling studies, although a subset of patients may have persistent cough aerosol positivity. These findings can enable a more nuanced approach to isolation decision making, while further research studies are awaited.