Aerosolization of viable Mycobacterium tuberculosis bacilli by tuberculosis clinic attendees independent of sputum-Xpert Ultra status

Abstract

Potential Mycobacterium tuberculosis ( Mtb ) transmission during different pulmonary tuberculosis (TB) disease states is poorly understood. We quantified viable aerosolized Mtb 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 Mtb 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; Mtb 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 Mtb bioaerosol release and TB symptoms in all three groups. Persistence of Mtb bioaerosol positivity was observed in ~30% of participants irrespective of TB chemotherapy. Captured Mtb 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 Mtb lineages. Detection of viable aerosolized Mtb in clinic attendees, independent of TB diagnosis, suggests that unidentified Mtb 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.

Quantification of tuberculosis exposure in a high-burdened setting: a modelling study

“…Longitudinal bioaerosol sampling indicates that this is a transient state with a rapid rate of loss of detectable Mtb bacilli from the respiratory lining uid in the absence of treatment: the half-life was found to be 83 days as reported in our recent study [2]. We interpret this as a natural process of reversion from a state of Mtb carriage with a gradual reduction in bacillary load leading to clearance that occurs frequently across the healthy population.…”

“…Observational data from symptomatic individuals [2] informed the prior for the rate of reversion, , given by:…”

“…The Aerobiology and TB Research Unit in Cape Town, South Africa has recently published studies demonstrating the detection of Mtb in captured respiratory bioaerosol from a broad range of individuals spanning the TB disease spectrum [2,3]. In brief, the sampling methodology involved a modi ed…”

“…In conjunction, data from a recently published study [2] with longitudinal bioaerosol sampling of TB clinic attendees at baseline and approximately 2-weeks, 2-months and 6-months from the same community were evaluated to determine rates of bioaerosol clearance. Those in the non-TB diagnosed group ("Group C" as described in the aforementioned study [2]) who did not receive treatment (n = 30) were aged between 15-67 (mean age 40 standard deviation 12) and 63% male. The clearance rate was indistinguishable from those on treatment and so the combined result was used to establish a reversion rate.…”

“…TB remains a deadly disease with poorly controlled transmission in many impoverished populations [1]. Ultrasensitive methods of detection have revealed an unexpectedly high prevalence of Mycobacterium tuberculosis (Mtb) bacilli in the respiratory bioaerosol of individuals spanning the tuberculosis (TB) disease spectrum [2,3]. Approximately two-thirds of apparently healthy individuals living in an informal settlement in South Africa were found to have viable Mtb detectable in collected respiratory bioaerosol samples.…”