Bioaerosol Sampling in Suspected Pulmonary Tuberculosis

Overview

Tuberculosis (TB) is transmitted in bioaerosols containing Mycobacterium tuberculosis (Mtb). Mtb-containing bioaerosols are likely related to host infectiousness and 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. Currently TB diagnosis is based on clinical symptoms and sputum laboratory findings. However, approximately half of all patients commencing TB treatment are sputum negative resulting in a high proportion of presumptive treatments. We therefore propose to use a sensitive sampling protocol to investigate the prevalence of Mtb-containing bioaerosols in both sputum-positive and sputum-negative TB suspects.

Our pragmatic, parallel-group design is aimed at identifying viable Mtb in bioaerosols produced by individuals attending a TB clinic in Cape Town, South Africa. Bioaerosol sampling will be performed on all eligible individuals presenting with symptoms indicative of TB and repeated at 14 days if initially positive for viable Mtb. Participants will be classified into three distinct groups based on the 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 of a specific respiratory manoeuvre; and (2) indirect sampling following passive respiratory activity and environmental sampling. 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 mutually exclusive groups A, B and C. Secondary objectives are to investigate differences in prevalence of Mtb bioaerosol by HIV status, current isoniazid preventive therapy (IPT) use and pre and post initiation of anti-TB chemotherapy.