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Exhaled Mycobacterium tuberculosis output and detection of subclinical disease by Face-Mask-Sampling in prospective observational studies

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journal contribution
posted on 2020-05-07, 08:07 authored by Caroline Williams, Mohamad Abdulwhhab, Surinder Birring, Elsabe De Kock, Natalie Garton, Eleanor Townsend, Manish Pareek, Alaa Al-Taie, Jingzhe Pan, Rakesh Ganatra, Anton Stoltz, Pranabashis Haldar, Michael Barer

Background

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.

Methods

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.

Findings

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.

Interpretation

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.

Funding

Wellcome Trust, CARA (Council for At-Risk Academics), University of Leicester, the UK Medical Research Council, and the National Institute for Health Research.

Funding

This work was supported by a Wellcome Trust Clinical Fellowship (107302/Z/15/Z, to CMW), a CARA (Council for At-Risk Academics) fellowship (to MA), a University of Leicester international development research fund grant, and a UK Medical Research Council project grant (MR/P023061/1). MP is supported by a National Institute for Health Research Fellowship (PDF-2015-08-102). The views expressed in this publication are those of the authors and not necessarily those of the above funding bodies, the UK National Health Service, or the UK Department of Health. We acknowledge the contributions made by Sherrie Van Zyl, Helen Sithole, and Danie Van Zyl, and all clinical and nursing staff at Kalafong Provincial Tertiary Hospital, Tshwane District Hospital, and Steve Biko Academic Hospital (Pretoria, South Africa), for help with the observational study; we thank Martin Bac, Jannie Hugo, Kate van den Berg, and the Department of Family Medicine at the University of Pretoria for help coordinating the active case-finding pilot study; Ed Nardell for support and critique of the study and comments on this report; and Tahir Hussain for help with compiling the PET-CT images.

History

Citation

The Lancet Infectious Diseases Volume 20, Issue 5, May 2020, Pages 607-617

Published in

Lancet Infectious Diseases

Volume

20

Issue

5

Pagination

607-617

Publisher

Elsevier

issn

1473-3099

Acceptance date

2019-11-04

Copyright date

2020

Available date

2020-02-19

Publisher version

https://www.sciencedirect.com/science/article/pii/S1473309919307078

Language

en

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