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Genetic variability and consequence of Mycobacterium tuberculosis lineage 3 in Kampala-Uganda

BACKGROUND: Limited data existed exclusively describing Mycobacterium tuberculosis lineage 3 (MTB-L3), sub-lineages, and clinical manifestations in Kampala, Uganda. This study sought to elucidate the circulating MTB-L3 sub-lineages and their corresponding clinical phenotypes. METHOD: A total of 141...

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Autores principales: Wampande, Eddie M., Naniima, Peter, Mupere, Ezekiel, Kateete, David P., Malone, LaShaunda L., Stein, Catherine M., Mayanja-Kizza, Harriet, Gagneux, Sebastien, Boom, W. Henry, Joloba, Moses L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6733460/
https://www.ncbi.nlm.nih.gov/pubmed/31498808
http://dx.doi.org/10.1371/journal.pone.0221644
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author Wampande, Eddie M.
Naniima, Peter
Mupere, Ezekiel
Kateete, David P.
Malone, LaShaunda L.
Stein, Catherine M.
Mayanja-Kizza, Harriet
Gagneux, Sebastien
Boom, W. Henry
Joloba, Moses L.
author_facet Wampande, Eddie M.
Naniima, Peter
Mupere, Ezekiel
Kateete, David P.
Malone, LaShaunda L.
Stein, Catherine M.
Mayanja-Kizza, Harriet
Gagneux, Sebastien
Boom, W. Henry
Joloba, Moses L.
author_sort Wampande, Eddie M.
collection PubMed
description BACKGROUND: Limited data existed exclusively describing Mycobacterium tuberculosis lineage 3 (MTB-L3), sub-lineages, and clinical manifestations in Kampala, Uganda. This study sought to elucidate the circulating MTB-L3 sub-lineages and their corresponding clinical phenotypes. METHOD: A total of 141 M. tuberculosis isolates were identified as M. tuberculosis lineage 3 using Single nucleotide polymorphism (SNP) marker analysis method. To ascertain the sub-lineages/sub-strains within the M. tuberculosis lineage 3, the direct repeat (DR) loci for all the isolates was examined for sub-lineage specific signatures as described in the SITVIT2 database. The infecting sub-strains were matched with patients’ clinical and demographic characteristics to identify any possible association. RESULT: The data showed 3 sub-lineages circulating with CAS 1 Delhi accounting for 55% (77/141), followed by CAS 1-Kili 16% (22/141) and CAS 2/CAS 8% (12/141). Remaining isolates 21% (30/141) were unclassifiable. To explore whether the sub-lineages differ in their ability to cause increased severe disease, we used extent of lung involvement as a proxy for severe disease. Multivariable analysis showed no association between M. tuberculosis lineage 3 sub-lineages with severe disease. The risk factors associated with severe disease include having a positive smear (OR = 9.384; CI 95% = 2.603–33.835), HIV (OR = 0.316; CI 95% = 0.114–0.876), lymphadenitis (OR = 0. 171; CI 95% = 0.034–0.856) and a BCG scar (OR = 0.295; CI 95% = 0.102–0.854). CONCLUSION: In Kampala, Uganda, there are three sub-lineages of M. tuberculosis lineage 3 that cause disease of comparable severity with CAS-Dehli as the most prevalent. Having HIV, lymphadenitis, a BCG scar and a smear negative status is associated with reduced severe disease.
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spelling pubmed-67334602019-09-20 Genetic variability and consequence of Mycobacterium tuberculosis lineage 3 in Kampala-Uganda Wampande, Eddie M. Naniima, Peter Mupere, Ezekiel Kateete, David P. Malone, LaShaunda L. Stein, Catherine M. Mayanja-Kizza, Harriet Gagneux, Sebastien Boom, W. Henry Joloba, Moses L. PLoS One Research Article BACKGROUND: Limited data existed exclusively describing Mycobacterium tuberculosis lineage 3 (MTB-L3), sub-lineages, and clinical manifestations in Kampala, Uganda. This study sought to elucidate the circulating MTB-L3 sub-lineages and their corresponding clinical phenotypes. METHOD: A total of 141 M. tuberculosis isolates were identified as M. tuberculosis lineage 3 using Single nucleotide polymorphism (SNP) marker analysis method. To ascertain the sub-lineages/sub-strains within the M. tuberculosis lineage 3, the direct repeat (DR) loci for all the isolates was examined for sub-lineage specific signatures as described in the SITVIT2 database. The infecting sub-strains were matched with patients’ clinical and demographic characteristics to identify any possible association. RESULT: The data showed 3 sub-lineages circulating with CAS 1 Delhi accounting for 55% (77/141), followed by CAS 1-Kili 16% (22/141) and CAS 2/CAS 8% (12/141). Remaining isolates 21% (30/141) were unclassifiable. To explore whether the sub-lineages differ in their ability to cause increased severe disease, we used extent of lung involvement as a proxy for severe disease. Multivariable analysis showed no association between M. tuberculosis lineage 3 sub-lineages with severe disease. The risk factors associated with severe disease include having a positive smear (OR = 9.384; CI 95% = 2.603–33.835), HIV (OR = 0.316; CI 95% = 0.114–0.876), lymphadenitis (OR = 0. 171; CI 95% = 0.034–0.856) and a BCG scar (OR = 0.295; CI 95% = 0.102–0.854). CONCLUSION: In Kampala, Uganda, there are three sub-lineages of M. tuberculosis lineage 3 that cause disease of comparable severity with CAS-Dehli as the most prevalent. Having HIV, lymphadenitis, a BCG scar and a smear negative status is associated with reduced severe disease. Public Library of Science 2019-09-09 /pmc/articles/PMC6733460/ /pubmed/31498808 http://dx.doi.org/10.1371/journal.pone.0221644 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 (https://creativecommons.org/publicdomain/zero/1.0/) public domain dedication.
spellingShingle Research Article
Wampande, Eddie M.
Naniima, Peter
Mupere, Ezekiel
Kateete, David P.
Malone, LaShaunda L.
Stein, Catherine M.
Mayanja-Kizza, Harriet
Gagneux, Sebastien
Boom, W. Henry
Joloba, Moses L.
Genetic variability and consequence of Mycobacterium tuberculosis lineage 3 in Kampala-Uganda
title Genetic variability and consequence of Mycobacterium tuberculosis lineage 3 in Kampala-Uganda
title_full Genetic variability and consequence of Mycobacterium tuberculosis lineage 3 in Kampala-Uganda
title_fullStr Genetic variability and consequence of Mycobacterium tuberculosis lineage 3 in Kampala-Uganda
title_full_unstemmed Genetic variability and consequence of Mycobacterium tuberculosis lineage 3 in Kampala-Uganda
title_short Genetic variability and consequence of Mycobacterium tuberculosis lineage 3 in Kampala-Uganda
title_sort genetic variability and consequence of mycobacterium tuberculosis lineage 3 in kampala-uganda
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6733460/
https://www.ncbi.nlm.nih.gov/pubmed/31498808
http://dx.doi.org/10.1371/journal.pone.0221644
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