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      Aerosolization of Mycobacterium tuberculosis by Tidal Breathing

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          Abstract

          Rationale

          Interrupting tuberculosis (TB) transmission requires an improved understanding of how and when the causative organism, Mycobacterium tuberculosis ( Mtb), is aerosolized. Although cough is commonly assumed to be the dominant source of Mtb aerosols, recent evidence of cough-independent Mtb release implies the contribution of alternative mechanisms.

          Objectives

          To compare the aerosolization of Mtb bacilli and total particulate matter from patients with TB during three separate respiratory maneuvers: tidal breathing (TiBr), FVC, and cough.

          Methods

          Bioaerosol sampling and Mtb enumeration by live-cell, fluorescence microscopy were combined with real-time measurement of CO 2 concentration and total particle counts from 38 patients with GeneXpert-positive TB before treatment initiation.

          Measurements and Main Results

          For all maneuvers, the proportions of particles detected across five size categories were similar, with most particles falling between 0.5–5 μm. Although total particle counts were 4.8-fold greater in cough samples than either TiBr or FVC, all three maneuvers returned similar rates of positivity for Mtb. No correlation was observed between total particle production and Mtb count. Instead, for total Mtb counts, the variability between individuals was greater than the variability between sampling maneuvers. Finally, when modelled using 24-hour breath and cough frequencies, our data indicate that TiBr might contribute more than 90% of the daily aerosolized Mtb among symptomatic patients with TB.

          Conclusions

          Assuming the number of viable Mtb organisms released offers a reliable proxy of patient infectiousness, our observations imply that TiBr and interindividual variability in Mtb release might be significant contributors to TB transmission among active cases.

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          Most cited references26

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          Size distribution and sites of origin of droplets expelled from the human respiratory tract during expiratory activities

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            The role of particle size in aerosolised pathogen transmission: A review

            Summary Understanding respiratory pathogen transmission is essential for public health measures aimed at reducing pathogen spread. Particle generation and size are key determinant for pathogen carriage, aerosolisation, and transmission. Production of infectious respiratory particles is dependent on the type and frequency of respiratory activity, type and site of infection and pathogen load. Further, relative humidity, particle aggregation and mucus properties influence expelled particle size and subsequent transmission. Review of 26 studies reporting particle sizes generated from breathing, coughing, sneezing and talking showed healthy individuals generate particles between 0.01 and 500 μm, and individuals with infections produce particles between 0.05 and 500 μm. This indicates that expelled particles carrying pathogens do not exclusively disperse by airborne or droplet transmission but avail of both methods simultaneously and current dichotomous infection control precautions should be updated to include measures to contain both modes of aerosolised transmission.
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              Tuberculosis.

              Tuberculosis (TB) is an airborne infectious disease caused by organisms of the Mycobacterium tuberculosis complex. Although primarily a pulmonary pathogen, M. tuberculosis can cause disease in almost any part of the body. Infection with M. tuberculosis can evolve from containment in the host, in which the bacteria are isolated within granulomas (latent TB infection), to a contagious state, in which the patient will show symptoms that can include cough, fever, night sweats and weight loss. Only active pulmonary TB is contagious. In many low-income and middle-income countries, TB continues to be a major cause of morbidity and mortality, and drug-resistant TB is a major concern in many settings. Although several new TB diagnostics have been developed, including rapid molecular tests, there is a need for simpler point-of-care tests. Treatment usually requires a prolonged course of multiple antimicrobials, stimulating efforts to develop shorter drug regimens. Although the Bacillus Calmette-Guérin (BCG) vaccine is used worldwide, mainly to prevent life-threatening TB in infants and young children, it has been ineffective in controlling the global TB epidemic. Thus, efforts are underway to develop newer vaccines with improved efficacy. New tools as well as improved programme implementation and financing are necessary to end the global TB epidemic by 2035.
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                Author and article information

                Journal
                Am J Respir Crit Care Med
                Am J Respir Crit Care Med
                ajrccm
                American Journal of Respiratory and Critical Care Medicine
                American Thoracic Society
                1073-449X
                1535-4970
                18 May 2020
                15 July 2022
                18 May 2020
                : 206
                : 2
                : 206-216
                Affiliations
                [ 1 ]South African Medical Research Council/National Health Laboratory Services/University of Cape Town Molecular Mycobacteriology Research Unit & Department of Science and Innovation, National Research Foundation Centre of Excellence for Biomedical Tuberculosis Research, Department of Pathology,
                [ 2 ]Institute of Infectious Diseases and Molecular Medicine,
                [ 4 ]Wellcome Centre for Infectious Diseases Research in Africa, Faculty of Health Sciences, and
                [ 3 ]Desmond Tutu Health Foundation, University of Cape Town, Cape Town, South Africa
                Author notes
                Correspondence and requests for reprints should be addressed to Digby F. Warner, Ph.D., Wolfson Pavilion, Institute of Infectious Disease and Molecular Medicine, UCT Faculty of Health Sciences, Anzio Road, Observatory, 7925, South Africa. E-mail: digby.warner@ 123456uct.ac.za .
                Author information
                https://orcid.org/0000-0001-6456-7530
                https://orcid.org/0000-0002-4146-0930
                Article
                202110-2378OC
                10.1164/rccm.202110-2378OC
                9887416
                35584342
                4ff1a02f-d522-4af8-b8e3-7e9b699a01b8
                Copyright © 2022 by the American Thoracic Society

                This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0. For commercial usage and reprints, please e-mail Diane Gern ( dgern@ 123456thoracic.org ).

                History
                : 21 October 2021
                : 17 March 2022
                Page count
                Figures: 6, Tables: 0, References: 27, Pages: 11
                Funding
                Funded by: South African Medical Research Council, doi 10.13039/501100001322;
                Award ID: MRC-RFA-UFSP-01-2013/CCAMP
                Funded by: Bill and Melinda Gates Foundation, doi 10.13039/100000865;
                Funded by: Bill and Melinda Gates Foundation, doi 10.13039/100000865;
                Award ID: R&D Project 261669
                Funded by: National Institute of Allergy and Infectious Diseases, doi 10.13039/100000060;
                Award ID: R01AI093269
                Funded by: Eunice Kennedy Shriver National Institute of Child Health and Human Development, doi 10.13039/100009633;
                Award ID: U01HD085531
                Categories
                Original Articles
                Tuberculosis and Mycobacterial Disease

                tb transmission,bioaerosol,cough,forced vital capacity
                tb transmission, bioaerosol, cough, forced vital capacity

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