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Molecular characterisation of second-line drug resistance among drug resistant tuberculosis patients tested in Uganda: a two and a half-year’s review

BACKGROUND: Second-line drug resistance (SLD) among tuberculosis (TB) patients is a serious emerging challenge towards global control of the disease. We characterized SLD-resistance conferring-mutations among TB patients with rifampicin and/or isoniazid (RIF and/or INH) drug-resistance tested at the...

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Autores principales: Mujuni, Dennis, Kasemire, Dianah Linda, Ibanda, Ivan, Kabugo, Joel, Nsawotebba, Andrew, Phelan, Jody E., Majwala, Robert Kaos, Tugumisirize, Didas, Nyombi, Abdunoor, Orena, Beatrice, Turyahabwe, Irene, Byabajungu, Henry, Nadunga, Diana, Musisi, Kenneth, Joloba, Moses Lutakoome, Ssengooba, Willy
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9003953/
https://www.ncbi.nlm.nih.gov/pubmed/35410160
http://dx.doi.org/10.1186/s12879-022-07339-w
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author Mujuni, Dennis
Kasemire, Dianah Linda
Ibanda, Ivan
Kabugo, Joel
Nsawotebba, Andrew
Phelan, Jody E.
Majwala, Robert Kaos
Tugumisirize, Didas
Nyombi, Abdunoor
Orena, Beatrice
Turyahabwe, Irene
Byabajungu, Henry
Nadunga, Diana
Musisi, Kenneth
Joloba, Moses Lutakoome
Ssengooba, Willy
author_facet Mujuni, Dennis
Kasemire, Dianah Linda
Ibanda, Ivan
Kabugo, Joel
Nsawotebba, Andrew
Phelan, Jody E.
Majwala, Robert Kaos
Tugumisirize, Didas
Nyombi, Abdunoor
Orena, Beatrice
Turyahabwe, Irene
Byabajungu, Henry
Nadunga, Diana
Musisi, Kenneth
Joloba, Moses Lutakoome
Ssengooba, Willy
author_sort Mujuni, Dennis
collection PubMed
description BACKGROUND: Second-line drug resistance (SLD) among tuberculosis (TB) patients is a serious emerging challenge towards global control of the disease. We characterized SLD-resistance conferring-mutations among TB patients with rifampicin and/or isoniazid (RIF and/or INH) drug-resistance tested at the Uganda National TB Reference Laboratory (NTRL) between June 2017 and December 2019. METHODS: This was a descriptive cross-sectional secondary data analysis of 20,508 M. tuberculosis isolates of new and previously treated patients’ resistant to RIF and/or INH. DNA strips with valid results to characterise the SLD resistance using the commercial Line Probe Assay Genotype MTBDRsl Version 2.0 Assay (Hain Life Science, Nehren, Germany) were reviewed. Data were analysed with STATAv15 using cross-tabulation for frequency and proportions of known resistance-conferring mutations to injectable agents (IA) and fluoroquinolones (FQ). RESULTS: Among the eligible participants, 12,993/20,508 (63.4%) were male and median (IQR) age 32 (24–43). A total of 576/20,508 (2.8%) of the M. tuberculosis isolates from participants had resistance to RIF and/or INH. These included; 102/576 (17.7%) single drug-resistant and 474/576 (82.3%) multidrug-resistant (MDR) strains. Only 102 patients had test results for FQ of whom 70/102 (68.6%) and 01/102 (0.98%) had resistance-conferring mutations in the gyrA locus and gyrB locus respectively. Among patients with FQ resistance, gyrAD94G 42.6% (30.0–55.9) and gyrA A90V 41.1% (28.6–54.3) mutations were most observed. Only one mutation, E540D was detected in the gyrB locus. A total of 26 patients had resistance-conferring mutations to IA in whom, 20/26 77.0% (56.4–91.0) had A1401G mutation in the rrs gene locus. CONCLUSIONS: Our study reveals a high proportion of mutations known to confer high-level fluoroquinolone drug-resistance among patients with rifampicin and/or isoniazid drug resistance. Utilizing routinely generated laboratory data from existing molecular diagnostic methods may aid real-time surveillance of emerging tuberculosis drug-resistance in resource-limited settings.
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spelling pubmed-90039532022-04-13 Molecular characterisation of second-line drug resistance among drug resistant tuberculosis patients tested in Uganda: a two and a half-year’s review Mujuni, Dennis Kasemire, Dianah Linda Ibanda, Ivan Kabugo, Joel Nsawotebba, Andrew Phelan, Jody E. Majwala, Robert Kaos Tugumisirize, Didas Nyombi, Abdunoor Orena, Beatrice Turyahabwe, Irene Byabajungu, Henry Nadunga, Diana Musisi, Kenneth Joloba, Moses Lutakoome Ssengooba, Willy BMC Infect Dis Research Article BACKGROUND: Second-line drug resistance (SLD) among tuberculosis (TB) patients is a serious emerging challenge towards global control of the disease. We characterized SLD-resistance conferring-mutations among TB patients with rifampicin and/or isoniazid (RIF and/or INH) drug-resistance tested at the Uganda National TB Reference Laboratory (NTRL) between June 2017 and December 2019. METHODS: This was a descriptive cross-sectional secondary data analysis of 20,508 M. tuberculosis isolates of new and previously treated patients’ resistant to RIF and/or INH. DNA strips with valid results to characterise the SLD resistance using the commercial Line Probe Assay Genotype MTBDRsl Version 2.0 Assay (Hain Life Science, Nehren, Germany) were reviewed. Data were analysed with STATAv15 using cross-tabulation for frequency and proportions of known resistance-conferring mutations to injectable agents (IA) and fluoroquinolones (FQ). RESULTS: Among the eligible participants, 12,993/20,508 (63.4%) were male and median (IQR) age 32 (24–43). A total of 576/20,508 (2.8%) of the M. tuberculosis isolates from participants had resistance to RIF and/or INH. These included; 102/576 (17.7%) single drug-resistant and 474/576 (82.3%) multidrug-resistant (MDR) strains. Only 102 patients had test results for FQ of whom 70/102 (68.6%) and 01/102 (0.98%) had resistance-conferring mutations in the gyrA locus and gyrB locus respectively. Among patients with FQ resistance, gyrAD94G 42.6% (30.0–55.9) and gyrA A90V 41.1% (28.6–54.3) mutations were most observed. Only one mutation, E540D was detected in the gyrB locus. A total of 26 patients had resistance-conferring mutations to IA in whom, 20/26 77.0% (56.4–91.0) had A1401G mutation in the rrs gene locus. CONCLUSIONS: Our study reveals a high proportion of mutations known to confer high-level fluoroquinolone drug-resistance among patients with rifampicin and/or isoniazid drug resistance. Utilizing routinely generated laboratory data from existing molecular diagnostic methods may aid real-time surveillance of emerging tuberculosis drug-resistance in resource-limited settings. BioMed Central 2022-04-11 /pmc/articles/PMC9003953/ /pubmed/35410160 http://dx.doi.org/10.1186/s12879-022-07339-w Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research Article
Mujuni, Dennis
Kasemire, Dianah Linda
Ibanda, Ivan
Kabugo, Joel
Nsawotebba, Andrew
Phelan, Jody E.
Majwala, Robert Kaos
Tugumisirize, Didas
Nyombi, Abdunoor
Orena, Beatrice
Turyahabwe, Irene
Byabajungu, Henry
Nadunga, Diana
Musisi, Kenneth
Joloba, Moses Lutakoome
Ssengooba, Willy
Molecular characterisation of second-line drug resistance among drug resistant tuberculosis patients tested in Uganda: a two and a half-year’s review
title Molecular characterisation of second-line drug resistance among drug resistant tuberculosis patients tested in Uganda: a two and a half-year’s review
title_full Molecular characterisation of second-line drug resistance among drug resistant tuberculosis patients tested in Uganda: a two and a half-year’s review
title_fullStr Molecular characterisation of second-line drug resistance among drug resistant tuberculosis patients tested in Uganda: a two and a half-year’s review
title_full_unstemmed Molecular characterisation of second-line drug resistance among drug resistant tuberculosis patients tested in Uganda: a two and a half-year’s review
title_short Molecular characterisation of second-line drug resistance among drug resistant tuberculosis patients tested in Uganda: a two and a half-year’s review
title_sort molecular characterisation of second-line drug resistance among drug resistant tuberculosis patients tested in uganda: a two and a half-year’s review
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9003953/
https://www.ncbi.nlm.nih.gov/pubmed/35410160
http://dx.doi.org/10.1186/s12879-022-07339-w
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