Abstract
BackgroundTuberculosis (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.MethodsOur 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.DiscussionRespiratory bioaerosol has a potential role in non-invasive TB diagnosis, infectivity measurement and treatment monitoring.Trial registrationClinicalTrials.gov: NCT04241809. Date of Registration: 27/1/2020.
Highlights
Tuberculosis (TB) is transmitted in bioaerosols containing Mycobacterium tuberculosis (Mtb)
As others have highlighted [2], it remains unclear when source cases become infectious, how long after effective treatment they remain infectious, what are the respiratory mechanisms of aerosolization, and how long Mtb bioaerosols remain viable in the environment
The implications of bioaerosol positivity in people with suspected pulmonary TB differ depending on the subgroup sampled
Summary
Tuberculosis (TB) is transmitted in bioaerosols containing Mycobacterium tuberculosis (Mtb). Persistence of the TB epidemic is driven by successive cycles of infection, pulmonary disease, Mtb bioaerosol expulsion and inhalation by susceptible individuals Interventions to interrupt this cycle are critical to curb the TB epidemic, knowledge of the physical process of Mtb transmission is limited. While sputum Mtb positivity and presence of lung cavitation predict infectiousness, prediction is partial (and based on retrospective, epidemiological analyses) limiting accurate risk stratification for contact screening. To address these knowledge gaps, tools to facilitate direct detection of viable aerosolized Mtb bacilli in exhaled breath are urgently required
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