Aerosolization of viable <i>Mycobacterium tuberculosis</i> bacilli by tuberculosis clinic attendees independent of sputum-Xpert Ultra status.

Patterson, Benjamin; Dinkele, Ryan; Gessner, Sophia; Koch, Anastasia; Hoosen, Zeenat; January, Vanessa; Leonard, Bryan; McKerry, Andrea et al. · Proc Natl Acad Sci U S A · 2024

cross_sectional · Level IV

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Abstract

Potential <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>) transmission during different pulmonary tuberculosis (TB) disease states is poorly understood. We quantified viable aerosolized <i>Mtb</i> from TB clinic attendees following diagnosis and through six months' follow-up thereafter. Presumptive TB patients (n=102) were classified by laboratory, radiological, and clinical features into Group A: Sputum-Xpert Ultra-positive TB (n=52), Group B: Sputum-Xpert Ultra-negative TB (n=20), or Group C: TB undiagnosed (n=30). All groups were assessed for <i>Mtb</i> bioaerosol release at baseline, and subsequently at 2 wk, 2 mo, and 6 mo. Groups A and B were notified to the national TB program and received standard anti-TB chemotherapy; <i>Mtb</i> was isolated from 92% and 90% at presentation, 87% and 74% at 2 wk, 54% and 44% at 2 mo and 32% and 20% at 6 mo, respectively. Surprisingly, similar numbers were detected in Group C not initiating TB treatment: 93%, 70%, 48% and 22% at the same timepoints. A temporal association was observed between <i>Mtb</i> bioaerosol release and TB symptoms in all three groups. Persistence of <i>Mtb</i> bioaerosol positivity was observed in ~30% of participants irrespective of TB chemotherapy. Captured <i>Mtb</i> bacilli were predominantly acid-fast stain-negative and poorly culturable; however, three bioaerosol samples yielded sufficient biomass following culture for whole-genome sequencing, revealing two different <i>Mtb</i> lineages. Detection of viable aerosolized <i>Mtb</i> in clinic attendees, independent of TB diagnosis, suggests that unidentified <i>Mtb</i> transmitters might contribute a significant attributable proportion of community exposure. Additional longitudinal studies with sputum culture-positive and -negative control participants are required to investigate this possibility.

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