Viable aerosolized Mycobacterium tuberculosis from sputum-positive and sputum-negative TB patients: Treatment effect and secular trends

The potential for bioaerosol release of Mycobacterium tuberculosis (Mtb) during different tuberculosis (TB) disease states is poorly understood. We quantified viable aerosolized Mtb from presumptive TB patients on diagnosis and, thereafter, through six months standard chemotherapy. At presentation, TB clinic attendees (n=102) were classified by laboratory, radiological, and clinical features into Group A: Sputum-GeneXpert-positive TB (n=52), Group B: Sputum-GeneXpert-negative TB (n=20), or Group C: TB not diagnosed (n=30). All were assessed for Mtb bioaerosol release at baseline, and subsequently at two weeks, two months, and six months. In Groups A and B, comprising notified TB cases, Mtb was isolated from 92% and 90% of participants at initial presentation; 87% and 74% at two weeks; 54% and 44% at two months; and 32% and 20% at six months, respectively. Surprisingly, similar numbers were detected in Group C: 93%, 70%, 48%, and 22% at the same timepoints. We also observed a temporal association between Mtb bioaerosol release and TB symptoms in all three groups, with 30% of participants remaining Mtb bioaerosol positive at six months irrespective of TB chemotherapy. Captured Mtb bacilli were predominantly acid-fast stain-negative and poorly culturable; however, following in vitro incubation, one sputum-GeneXpert-positive and two sputum-GeneXpert-negative aerosol samples yielded sufficient biomass for whole-genome sequencing, revealing two different Mtb lineages. The detection of viable aerosolized Mtb in most clinic attendees at presentation, independent of TB diagnosis, suggests that unidentified Mtb transmitters could account for a significant attributable proportion of community exposure. However, longitudinal studies are required to investigate this possibility. One Sentence Summary: M. tuberculosis bacilli are detected in bioaerosols of presumptive tuberculosis (TB) patients irrespective of final TB diagnosis and clear over time.