Exhaled Mycobacterium tuberculosis output and detection of subclinical disease by face-mask sampling: prospective observational studies

• Published in: The Lancet infectious diseases Vol. 20; no. 5; pp. 607 - 617
• Main Authors: Williams, Caroline M, Abdulwhhab, Mohamad, Birring, Surinder S, De Kock, Elsabe, Garton, Natalie J, Townsend, Eleanor, Pareek, Manish, Al-Taie, Alaa, Pan, Jingzhe, Ganatra, Rakesh, Stoltz, Anton C, Haldar, Pranabashis, Barer, Michael R
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 01.05.2020; Elsevier Limited; Elsevier Science ;, The Lancet Pub. Group
• Subjects: Adult; Aerosols; Bronchoscopy; Chest; Clinical medicine; Coinfection - diagnosis; Coinfection - microbiology; Coinfection - virology; Computed tomography; Concurrent infection; Correlation analysis; Cough; Diagnosis; Diagnostic systems; Diagnostic Tests, Routine - methods; Diurnal; Face; Female; Global health; HIV; HIV Infections - microbiology; HIV Infections - virology; Human immunodeficiency virus; Humans; Infections; Infectious diseases; Longitudinal Studies; Male; Masks - microbiology; Medical research; Middle Aged; Mycobacterium tuberculosis; Mycobacterium tuberculosis - isolation & purification; Observational studies; Patients; Polyvinyl alcohol; Positron emission; Prospective Studies; Public health; Questionnaires; Radiography; Sampling; Sensitivity and Specificity; Signs and symptoms; South Africa; Sputum; Sputum - microbiology; Sputum - virology; Tomography; Tuberculosis; Tuberculosis, Pulmonary - diagnosis; Tuberculosis, Pulmonary - microbiology; Young Adult; South Africa
• ISSN: 1473-3099; 1474-4457
• DOI: 10.1016/S1473-3099(19)30707-8

Tuberculosis remains a global health challenge, with early diagnosis key to its reduction. Face-mask sampling detects exhaled Mycobacterium tuberculosis. We aimed to investigate bacillary output from patients with pulmonary tuberculosis and to assess the potential of face-mask sampling as a diagnostic method in active case-finding. We did a 24-h longitudinal study in patients from three hospitals in Pretoria, South Africa, with microbiologically confirmed pulmonary tuberculosis. Patients underwent 1 h of face-mask sampling eight times over a 24-h period, with contemporaneous sputum sampling. M tuberculosis was detected by quantitative PCR. We also did an active case-finding pilot study in inhabitants of an informal settlement near Pretoria. We enrolled individuals with symptoms of tuberculosis on the WHO screening questionnaire. Participants provided sputum and face-mask samples that were tested with the molecular assay Xpert MTB/RIF Ultra. Sputum-negative and face-mask-positive individuals were followed up prospectively for 20 weeks by bronchoscopy, PET-CT, and further sputum analysis to validate the diagnosis. Between Sept 22, 2015, and Dec 3, 2015, 78 patients with pulmonary tuberculosis were screened for the longitudinal study, of whom 24 completed the study (20 had HIV co-infection). M tuberculosis was detected in 166 (86%) of 192 face-mask samples and 38 (21%) of 184 assessable sputum samples obtained over a 24-h period. Exhaled M tuberculosis output showed no diurnal pattern and did not associate with cough frequency, sputum bacillary content, or chest radiographic disease severity. On May 16, 2018, 45 individuals were screened for the prospective active case-finding pilot study, of whom 20 had tuberculosis symptoms and were willing to take part. Eight participants were diagnosed prospectively with pulmonary tuberculosis, of whom six were exclusively face-mask positive at screening. Four of these participants (three of whom were HIV-positive) had normal findings on chest radiography but had treatment-responsive early tuberculosis-compatible lesions on PET-CT scans, with Xpert-positive sputum samples after 6 weeks. Face-mask sampling offers a highly efficient and non-invasive method for detecting exhaled M tuberculosis, informing the presence of active infection both with greater consistency and at an earlier disease stage than with sputum samples. The approach shows potential for diagnosis and screening, particularly in difficult-to-reach communities. Wellcome Trust, CARA (Council for At-Risk Academics), University of Leicester, the UK Medical Research Council, and the National Institute for Health Research. [Display omitted]