Aerosolization of Mycobacterium tuberculosis by tidal breathing

Abstract

Rationale: Interrupting tuberculosis (TB) transmission requires an improved understanding of how - and when - the causative organism, Mycobacterium tuberculosis (Mtb), is aerosolized. Although Cough is commonly assumed to be the dominant source of Mtb aerosols, recent evidence of Cough-independent Mtb release implies the contribution of alternative mechanisms. Objective: To compare the aerosolization of Mtb and particulate matter from GeneXpert-positive patients during three separate respiratory manoeuvres: Tidal Breathing (TiBr), Forced Vital Capacity (FVC), and Cough. Methodology: Bioaerosol sampling and Mtb detection were combined with real-time assessments of CO2 production and particle counts from 39 confirmed TB patients. Measurements and Main Results: TiBr and FVC produced comparable numbers of particles, with Cough producing >4-fold more. For all manoeuvres, the proportions of particles detected across size categories from 0.5 - 5 µm were similar, with minor differences observed only in particles between 1.5 - 2 µm (p = 0.014) and >5 µm (p = 0.020). Viable Mtb bacilli were detected in 66%, 70%, and 65% of TiBr, FVC, and Cough samples, respectively. Notably, while Cough produced 3-fold more Mtb than TiBr, the relative infrequency of coughing compared to breathing implies that TiBr likely contributes >90% of the daily aerosolised Mtb across a range of Cough frequencies. Conclusions: Our results suggest that, while Cough increases particle aerosolization compared to TiBr, this is not associated with increased Mtb aerosolization. Instead, TiBr produces more Mtb per particle than Cough. Assuming the number of viable Mtb organisms detected provides a proxy measure of patient infectiousness, these observations imply a significant contribution of TiBr to TB transmission.

Aerosolization of viableMycobacterium tuberculosisbacilli by tuberculosis clinic attendees independent of sputum-GeneXpert status

“…Such studies highlight the complexity of the Mtb host-pathogen interaction, and the potential disconnect between symptoms and disease. Furthermore, data reported here and previous bioaerosol sampling studies demonstrate that tidal breathing alone can lead to emission of viable Mtb [10,12,34].…”

PersistentMycobacterium tuberculosisbioaerosol release in a tuberculosis-endemic setting

“…This owes mainly to the challenges inherent in handling extremely paucibacillary samples as well as the assumed importance of pathology for Mtb release -in turn reinforcing the primacy of sputum bacterial burden as key predictor of infectiousness. Insights gained from the COVID-19 pandemic, however, established the plausibility of asymptomatic transmission (Shaikh et al, 2023), with analogous recent results suggesting the cough-independent aerosolization of Mtb (Dinkele et al, 2022, Williams et al, 2020. It seems possible, therefore, that individuals might progress from Mtb infected (often inferred via interferon gamma release assay; IGRA (Cohen et al, 2019)) to infectious before producing sputum.…”

“…1). In the Sirst phase, participants 1-39 underwent bioaerosol collection during three respiratory maneuvers: FVC, TiBr, and induced cough, as previously described (Dinkele et al, 2022). The sequence of these maneuvers remained consistent throughout the study.…”

“…To investigate this possibility, we utilized our bioaerosol sampling platform (Dinkele et al, 2022) to investigate Mtb release in 89 randomly selected participants recruited into two consecutive cohorts: the Sirst was a cross-sectional community survey comprising 39 participants, and the second was a longitudinal observational study in which 50 individuals consented to be sampled at three separate timepoints over two months. As detailed below, our results suggest that earlystage Mtb infection is pervasive and may be an important contributor to the transmission of Mtb in high TB-burden communities.…”

Re-evaluating progression and pathways followingMycobacteria tuberculosisinfection within the spectrum of tuberculosis disease

“…Intermediate disease states between Mtb infection and infectious symptomatic TB disease merit further attention. Infectious subclinical TB is as prevalent as infectious symptomatic disease globally (14) and likely contributes substantially to onward transmission (15)(16)(17). Pathological disease is also highly prevalent (18), and, even when non-infectious, can be severe.…”