Background: Tuberculosis (TB) is transmitted in bioaerosols containing Mycobacterium tuberculosis (Mtb). Despite being central to ongoing TB transmission, no routine diagnostic assay exists to measure Mtb in bioaerosols. Furthermore, published studies of Mtb in bioaerosol samples have been limited to individuals with sputum-positive pulmonary TB. Notably, TB diagnosis is based on clinical symptoms and sputum laboratory findings. This is despite the fact that approximately half of all patients commencing TB treatment are sputum-negative, resulting in a high proportion of presumptive treatments. Here, we propose to use a sensitive air sampling protocol to investigate the prevalence of Mtb-containing bioaerosols in both sputum-positive and sputum-negative TB suspects, at the same time evaluating the potential to identify unrecognized transmitters of TB.
Methods: Our parallel-group design will identify viable Mtb in bioaerosols produced by individuals attending a TB clinic in South Africa. Sampling will be performed on eligible individuals presenting with symptoms indicative of TB and repeated at 14 days if initially positive. Participants will be prospectively classified into three distinct groups based on National TB Control Program (NTBCP) criteria: Group A, TB notification with sputum-based laboratory confirmation; Group B, TB notification with empiric diagnosis; and Group C, individuals not notified. Group C individuals with detectable Mtb bioaerosol will be monitored until resolution of clinical and laboratory status. Collection of bioaerosol specimens will be via two consecutive sampling modalities: (1) direct sampling following a specific respiratory manoeuvre; and (2) indirect sampling during passive respiratory activity. Bioaerosol specimens will be analyzed for viable Mtb using DMN-trehalose staining and live-cell fluorescence microscopy. Mtb genomes and mycobacterial and host lipids will be detected using droplet digital PCR and mass spectrometry analyses, respectively. The primary objective is to determine the prevalence of Mtb bioaerosols in all TB clinic attendees and in each of the groups. Secondary objectives are to investigate differences in prevalence of Mtb bioaerosol by HIV status and current isoniazid preventive therapy (IPT) use; we will also determine the impact of anti-TB chemotherapy on Mtb-containing bioaerosol production.
Discussion: Respiratory bioaerosol has a potential role in non-invasive TB diagnosis, infectivity measurement and treatment monitoring.
Trial Registration: ClinicalTrials.gov: NCT04241809 . Date of Registration: 27/1/2020.
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http://dx.doi.org/10.1186/s12879-020-05278-y | DOI Listing |
Int J Tuberc Lung Dis
October 2024
Department of Basic Mycobacteriosis, Graduate School of Biomedical Science, Nagasaki University, Nagasaki, Japan;, Department of Mycobacterium Reference and Research, Research Institute of Tuberculosis, JATA, Kiyose, Tokyo, Japan.
iScience
September 2024
Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town 7925, South Africa.
Pioneering studies linking symptomatic disease and cough-mediated () release established the infectious origin of tuberculosis (TB), simultaneously informing the notion that pathology is a prerequisite for transmission. Our recent work has challenged this assumption: by sampling TB clinic attendees, we detected equivalent release of -containing bioaerosols by confirmed TB patients and individuals not receiving a TB diagnosis and observed time-dependent reduction in bioaerosol positivity during 6-month follow-up of both cohorts, irrespective of anti-TB chemotherapy. Now, we report widespread release in our TB-endemic setting: of 89 randomly recruited community members, 79.
View Article and Find Full Text PDFmedRxiv
April 2024
Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, 7925, South Africa.
Pioneering studies linking symptomatic disease and cough-mediated release of () established the infectious origin of tuberculosis (TB), simultaneously informing the pervasive notion that pathology is a prerequisite for transmission. Our prior work has challenged this assumption: by sampling TB clinic attendees, we detected equivalent release of -containing bioaerosols by confirmed TB patients and individuals not receiving a TB diagnosis, and we demonstrated a time-dependent reduction in bioaerosol positivity during six-months' follow-up, irrespective of anti-TB chemotherapy. Now, by extending bioaerosol sampling to a randomly selected community cohort, we show that release is common in a TB-endemic setting: of 89 participants, 79.
View Article and Find Full Text PDFInt J Tuberc Lung Dis
April 2024
The Foundation for Medical Research, Mumbai.
Proc Natl Acad Sci U S A
March 2024
Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town 7925, South Africa.
Potential () transmission during different pulmonary tuberculosis (TB) disease states is poorly understood. We quantified viable aerosolized 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).
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