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Use of a modified face mask and liquid-based cough aerosol sampling system to measure the infectiousness of drug-resistant tuberculosis patients

R Venter(1) L Smith(1) J Limberis(2) S Naidoo(3) B Derendinger(1) N Kitchin(6) K Dheda(4) A Esmail(4) K P Fennelly(5) G Theron(1)

1:DST/NRF Centre of Excellence for Biomedical Tuberculosis Research, SA MRC Centre for Molecular and Cellular Biology, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, South Africa; 2:Division of Experimental Medicine, University of California, San Francisco, San Francisco, CA, USA; 3:Institute of Infectious Disease and Molecular Medicine, University of Cape Town, South Africa.; 4:Centre for Lung Infection and Immunity, Department of Medicine and UCT Lung Institute, University of Cape Town, Groote Schuur Hospital, Observatory, South Africa; 5:Pulmonary Branch, Division of Intramural Research, National Institutes of Health, National Heart, Lung and Blood Institute, Bethesda, Maryland; 6:Department of Psychiatry, Stellenbosch University, Cape Town, South Africa; South African Medical Research Council/Stellenbosch University Extramural Unit on the Genomics of Brain Disorders, Department of Psychiatry, Stellenbosch University, Cape Town, South Africa

Understanding tuberculosis (TB) patients’ infectiousness before and during treatment is crucial to control transmission. The traditional use of sputum smears to define infectiousness is severely limited. We compared two novel aerosol sampling systems 1) gMask (containing a gelatine filter) and 2) liquid cough aerosol sampling system (LCASS) against the established cough aerosol sampling system (CASS) for detecting Mycobacterium tuberculosis from aerosols in people with drug-resistant (DR)-TB. gMask sampling times were optimised in ten patients.  Forty-five patients enrolled were sampled a total of130 times.  LCASS (using two reservoirs) was evaluated on a subset of 14 patients, with samples randomly allocated to MGIT960 or most probable number (MPN) assays. The latter was done with or without exponential phase cell-free extract (EPCFE)-supplementation to encourage growth of differentially culturable bacilli (DCTB). gMask sampling of 1hr was sufficient to detect TB. Initial visit positivity rates for CASS, gMask, and LCASS were 6/44 (14%), 10/43 (23%), and 4/14 (29%) respectively. Notably, 30% of gMask-positive cases were sputum culture-negative. Only 1/28 (4%) of patients were CASS-positive one week after treatment. Positive gMasks were detected until week 8 (8/82, 10%), while LCASS readouts were largely negative beyond baseline (one positive MPN at week 8). These alternative aerosol sampling methods are simpler and less expensive that the original CASS and may prove useful for the diagnosis, treatment monitoring and transmission intervention strategies. Moreover, aerosols from patients on treatment may harbour DCTB. These findings underscore the need for improved detection techniques to better understand TB infectivity dynamics.

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