Differentially Detectable Mycobacterium tuberculosis Cells in Sputum from Treatment-Naive Subjects in Haiti and Their Proportionate Increase after Initiation of Treatment

Recent reports indicate that the sputum of 80% or more of treatment-naive subjects with tuberculosis recruited in England or South Africa contained more viable Mycobacterium tuberculosis cells detected by limiting dilution (LD) in liquid culture than detected as CFU. Efforts to generate such differe...

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Autores principales: McAulay, Kathrine, Saito, Kohta, Warrier, Thulasi, Walsh, Kathleen Frances, Mathurin, Laurent Daniel, Royal-Mardi, Gertrude, Lee, Myung Hee, Ocheretina, Oksana, Pape, Jean William, Fitzgerald, Daniel W., Nathan, Carl F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6247085/
https://www.ncbi.nlm.nih.gov/pubmed/30459198
http://dx.doi.org/10.1128/mBio.02192-18
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author McAulay, Kathrine
Saito, Kohta
Warrier, Thulasi
Walsh, Kathleen Frances
Mathurin, Laurent Daniel
Royal-Mardi, Gertrude
Lee, Myung Hee
Ocheretina, Oksana
Pape, Jean William
Fitzgerald, Daniel W.
Nathan, Carl F.
author_facet McAulay, Kathrine
Saito, Kohta
Warrier, Thulasi
Walsh, Kathleen Frances
Mathurin, Laurent Daniel
Royal-Mardi, Gertrude
Lee, Myung Hee
Ocheretina, Oksana
Pape, Jean William
Fitzgerald, Daniel W.
Nathan, Carl F.
author_sort McAulay, Kathrine
collection PubMed
description Recent reports indicate that the sputum of 80% or more of treatment-naive subjects with tuberculosis recruited in England or South Africa contained more viable Mycobacterium tuberculosis cells detected by limiting dilution (LD) in liquid culture than detected as CFU. Efforts to generate such differentially detectable (DD) M. tuberculosis populations in vitro have been difficult to reproduce, and the LD assay is prone to artifact. Here, we applied a stringent version of the LD assay to sputum from 33 treatment-naive, HIV-negative Haitian subjects with drug-sensitive tuberculosis (TB) and to a second sputum sample after two weeks of standard treatment with isoniazid, rifampin, pyrazinamide, and ethambutol (HRZE) for 13 of these subjects. Twenty-one percent had statistically defined levels of DD M. tuberculosis in their pretreatment sputum at an average proportional excess over CFU of 3-fold. Sixty-nine percent of those who received HRZE had statistically defined levels of DD M. tuberculosis in their sputum, and of these, the mean proportionate excess over CFU was 7.9-fold. Thus, DD M. tuberculosis is detectable in pretreatment sputum from a significant proportion of subjects in the Western Hemisphere, and certain drugs or drug regimens, while reducing CFU, may at the same time increase the proportional representation of DD M. tuberculosis among the surviving bacilli. Monitoring DD M. tuberculosis may improve our ability to predict the efficacy of efforts to shorten treatment.
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spelling pubmed-62470852018-11-30 Differentially Detectable Mycobacterium tuberculosis Cells in Sputum from Treatment-Naive Subjects in Haiti and Their Proportionate Increase after Initiation of Treatment McAulay, Kathrine Saito, Kohta Warrier, Thulasi Walsh, Kathleen Frances Mathurin, Laurent Daniel Royal-Mardi, Gertrude Lee, Myung Hee Ocheretina, Oksana Pape, Jean William Fitzgerald, Daniel W. Nathan, Carl F. mBio Research Article Recent reports indicate that the sputum of 80% or more of treatment-naive subjects with tuberculosis recruited in England or South Africa contained more viable Mycobacterium tuberculosis cells detected by limiting dilution (LD) in liquid culture than detected as CFU. Efforts to generate such differentially detectable (DD) M. tuberculosis populations in vitro have been difficult to reproduce, and the LD assay is prone to artifact. Here, we applied a stringent version of the LD assay to sputum from 33 treatment-naive, HIV-negative Haitian subjects with drug-sensitive tuberculosis (TB) and to a second sputum sample after two weeks of standard treatment with isoniazid, rifampin, pyrazinamide, and ethambutol (HRZE) for 13 of these subjects. Twenty-one percent had statistically defined levels of DD M. tuberculosis in their pretreatment sputum at an average proportional excess over CFU of 3-fold. Sixty-nine percent of those who received HRZE had statistically defined levels of DD M. tuberculosis in their sputum, and of these, the mean proportionate excess over CFU was 7.9-fold. Thus, DD M. tuberculosis is detectable in pretreatment sputum from a significant proportion of subjects in the Western Hemisphere, and certain drugs or drug regimens, while reducing CFU, may at the same time increase the proportional representation of DD M. tuberculosis among the surviving bacilli. Monitoring DD M. tuberculosis may improve our ability to predict the efficacy of efforts to shorten treatment. American Society for Microbiology 2018-11-20 /pmc/articles/PMC6247085/ /pubmed/30459198 http://dx.doi.org/10.1128/mBio.02192-18 Text en Copyright © 2018 McAulay et al. https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
McAulay, Kathrine
Saito, Kohta
Warrier, Thulasi
Walsh, Kathleen Frances
Mathurin, Laurent Daniel
Royal-Mardi, Gertrude
Lee, Myung Hee
Ocheretina, Oksana
Pape, Jean William
Fitzgerald, Daniel W.
Nathan, Carl F.
Differentially Detectable Mycobacterium tuberculosis Cells in Sputum from Treatment-Naive Subjects in Haiti and Their Proportionate Increase after Initiation of Treatment
title Differentially Detectable Mycobacterium tuberculosis Cells in Sputum from Treatment-Naive Subjects in Haiti and Their Proportionate Increase after Initiation of Treatment
title_full Differentially Detectable Mycobacterium tuberculosis Cells in Sputum from Treatment-Naive Subjects in Haiti and Their Proportionate Increase after Initiation of Treatment
title_fullStr Differentially Detectable Mycobacterium tuberculosis Cells in Sputum from Treatment-Naive Subjects in Haiti and Their Proportionate Increase after Initiation of Treatment
title_full_unstemmed Differentially Detectable Mycobacterium tuberculosis Cells in Sputum from Treatment-Naive Subjects in Haiti and Their Proportionate Increase after Initiation of Treatment
title_short Differentially Detectable Mycobacterium tuberculosis Cells in Sputum from Treatment-Naive Subjects in Haiti and Their Proportionate Increase after Initiation of Treatment
title_sort differentially detectable mycobacterium tuberculosis cells in sputum from treatment-naive subjects in haiti and their proportionate increase after initiation of treatment
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6247085/
https://www.ncbi.nlm.nih.gov/pubmed/30459198
http://dx.doi.org/10.1128/mBio.02192-18
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