Viable aerosolized Mycobacterium tuberculosis from sputum-positive and sputum-negative TB patients: treatment effect and secular trends. Patterson, B. J., Dinkele, R., Gessner, S., Koch, A., Hoosen, Z., January, V., Leonard, B., McKerry, A., Seldon, R., Vazi, A., Hermans, S., Cobelens, F., Warner, D. F, & Wood, R. medRxiv, jan, 2022.
Viable aerosolized Mycobacterium tuberculosis from sputum-positive and sputum-negative TB patients: treatment effect and secular trends [link]Paper  doi  abstract   bibtex   
Rationale: Knowledge of the potential for aerosol release of Mycobacterium tuberculosis (Mtb) during disease, treatment, recovery, and asymptomatic carriage is fundamental to understanding tuberculosis (TB) transmission. Objectives: To quantify viable aerosolized Mtb from TB clinic attendees. Methods: 102 presumptive TB patients from two informal settlements in Cape Town, South Africa, were classified by laboratory, radiological, and clinical features into three mutually exclusive groups: A. Sputum GeneXpert-positive TB (n=52), B. Sputum GeneXpert-negative TB (n=20), and C. TB not diagnosed (n=30). A respiratory aerosol sampling chamber was used to collect exhaled Mtb organisms over a 15-minute period at baseline, and at 2-months and 6-months post initial presentation. Viable bacilli were enumerated based on incorporation of the fluorescent probe, DMN-trehalose. Measures and Main Results: Mtb was isolated from 92%, 90% and 93% at baseline; 87%, 74%, 71% at 2 weeks; 53%, 47% and 46% at 2 months; and 32%, 25%, 22% at 6-months for groups A, B, and C, respectively. Median Mtb counts (ranges) reduced from baseline to 6 months from 10(1-38), 5(1-31), and 9(1-38) to 3(1-28), 4(3-18), and 2(1-14) for groups A, B, and C, respectively. TB symptoms resolved in all 3 groups. Conclusions: Aerosolized Mtb was isolated from almost all TB patients at baseline and reduced during treatment. Small numbers of viable organisms remained in almost a fifth of patients completing 6-months treatment. Aerosolized Mtb may be a useful metric for modifying standard TB therapy. Aerosolized Mtb in group C may reflect exacerbation of an existing infection or transient Mtb infection not reaching a clinical threshold for TB diagnosis, consistent with recent models proposing cyclic subclinical disease states.Competing Interest StatementThe authors have declared no competing interest.Funding StatementThe National Institutes of Health (NIH) funded this research (R01AI147347 01).Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:This study was approved by the Human Research Ethics Committee (HREC/REF: 529/2019) of the University of Cape Town.I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesAll data produced in the present study are available upon reasonable request to the authors
@article{Patterson2022,
abstract = {Rationale: Knowledge of the potential for aerosol release of Mycobacterium tuberculosis (Mtb) during disease, treatment, recovery, and asymptomatic carriage is fundamental to understanding tuberculosis (TB) transmission. Objectives: To quantify viable aerosolized Mtb from TB clinic attendees. Methods: 102 presumptive TB patients from two informal settlements in Cape Town, South Africa, were classified by laboratory, radiological, and clinical features into three mutually exclusive groups: A. Sputum GeneXpert-positive TB (n=52), B. Sputum GeneXpert-negative TB (n=20), and C. TB not diagnosed (n=30). A respiratory aerosol sampling chamber was used to collect exhaled Mtb organisms over a 15-minute period at baseline, and at 2-months and 6-months post initial presentation. Viable bacilli were enumerated based on incorporation of the fluorescent probe, DMN-trehalose. Measures and Main Results: Mtb was isolated from 92{\%}, 90{\%} and 93{\%} at baseline; 87{\%}, 74{\%}, 71{\%} at 2 weeks; 53{\%}, 47{\%} and 46{\%} at 2 months; and 32{\%}, 25{\%}, 22{\%} at 6-months for groups A, B, and C, respectively. Median Mtb counts (ranges) reduced from baseline to 6 months from 10(1-38), 5(1-31), and 9(1-38) to 3(1-28), 4(3-18), and 2(1-14) for groups A, B, and C, respectively. TB symptoms resolved in all 3 groups. Conclusions: Aerosolized Mtb was isolated from almost all TB patients at baseline and reduced during treatment. Small numbers of viable organisms remained in almost a fifth of patients completing 6-months treatment. Aerosolized Mtb may be a useful metric for modifying standard TB therapy. Aerosolized Mtb in group C may reflect exacerbation of an existing infection or transient Mtb infection not reaching a clinical threshold for TB diagnosis, consistent with recent models proposing cyclic subclinical disease states.Competing Interest StatementThe authors have declared no competing interest.Funding StatementThe National Institutes of Health (NIH) funded this research (R01AI147347 01).Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:This study was approved by the Human Research Ethics Committee (HREC/REF: 529/2019) of the University of Cape Town.I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesAll data produced in the present study are available upon reasonable request to the authors},
author = {Patterson, Benjamin James and Dinkele, Ryan and Gessner, Sophia and Koch, Anastasia and Hoosen, Zeenat and January, Vanessa and Leonard, Bryan and McKerry, Andrea and Seldon, Ronnett and Vazi, Andiswa and Hermans, Sabine and Cobelens, Frank and Warner, Digby F and Wood, Robin},
doi = {10.1101/2022.11.14.22282157},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Patterson et al. - 2022 - Viable aerosolized Mycobacterium tuberculosis from sputum-positive and sputum-negative TB patients treatment e.pdf:pdf},
journal = {medRxiv},
keywords = {OA,fund{\_}not{\_}ack,original},
mendeley-tags = {OA,fund{\_}not{\_}ack,original},
month = {jan},
pages = {2022.11.14.22282157},
title = {{Viable aerosolized Mycobacterium tuberculosis from sputum-positive and sputum-negative TB patients: treatment effect and secular trends}},
url = {http://medrxiv.org/content/early/2022/11/17/2022.11.14.22282157.abstract},
year = {2022}
}

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