Cargando…
Genomic Analysis of Mycobacterium tuberculosis Strains Resistant to Second-Line Anti-Tuberculosis Drugs in Lusaka, Zambia
The emergence of pre-extensively drug-resistant tuberculosis (pre-XDR-TB) is a threat to TB control programs in developing countries such as Zambia. Studies in Zambia have applied molecular techniques to understand drug-resistance-associated mutations, circulating lineages and transmission patterns...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10376136/ https://www.ncbi.nlm.nih.gov/pubmed/37508222 http://dx.doi.org/10.3390/antibiotics12071126 |
_version_ | 1785079196054192128 |
---|---|
author | Chizimu, Joseph Yamweka Solo, Eddie Samuneti Bwalya, Precious Kapalamula, Thoko Flav Mwale, Kaemba Kunkuta Squarre, David Shawa, Misheck Lungu, Patrick Barnes, David Atomanyi Yamba, Kaunda Mufune, Tiza Chambaro, Herman Kamboyi, Harvey Munyeme, Musso Hang’ombe, Bernard Mudenda Kapata, Nathan Mukonka, Victor Chilengi, Roma Thapa, Jeewan Nakajima, Chie Suzuki, Yasuhiko |
author_facet | Chizimu, Joseph Yamweka Solo, Eddie Samuneti Bwalya, Precious Kapalamula, Thoko Flav Mwale, Kaemba Kunkuta Squarre, David Shawa, Misheck Lungu, Patrick Barnes, David Atomanyi Yamba, Kaunda Mufune, Tiza Chambaro, Herman Kamboyi, Harvey Munyeme, Musso Hang’ombe, Bernard Mudenda Kapata, Nathan Mukonka, Victor Chilengi, Roma Thapa, Jeewan Nakajima, Chie Suzuki, Yasuhiko |
author_sort | Chizimu, Joseph Yamweka |
collection | PubMed |
description | The emergence of pre-extensively drug-resistant tuberculosis (pre-XDR-TB) is a threat to TB control programs in developing countries such as Zambia. Studies in Zambia have applied molecular techniques to understand drug-resistance-associated mutations, circulating lineages and transmission patterns of multi-drug-resistant (MDR) Mycobacterium tuberculosis. However, none has reported genotypes and mutations associated with pre-XDR TB. This study characterized 63 drug-resistant M. tuberculosis strains from the University Teaching Hospital between 2018 and 2019 using targeted gene sequencing and conveniently selected 50 strains for whole genome sequencing. Sixty strains had resistance mutations associated to MDR, one polyresistant, and two rifampicin resistant. Among MDR strains, seven percent (4/60) had mutations associated with pre-XDR-TB. While four, one and nine strains had mutations associated with ethionamide, para-amino-salicylic acid and streptomycin resistances, respectively. All 50 strains belonged to lineage 4 with the predominant sub-lineage 4.3.4.2.1 (38%). Three of four pre-XDR strains belonged to sub-lineage 4.3.4.2.1. Sub-lineage 4.3.4.2.1 strains were less clustered when compared to sub-lineages L4.9.1 and L4.3.4.1 based on single nucleotide polymorphism differences. The finding that resistances to second-line drugs have emerged among MDR-TB is a threat to TB control. Hence, the study recommends a strengthened routine drug susceptibility testing for second-line TB drugs to stop the progression of pre-XDR to XDR-TB and improve patient treatment outcomes. |
format | Online Article Text |
id | pubmed-10376136 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-103761362023-07-29 Genomic Analysis of Mycobacterium tuberculosis Strains Resistant to Second-Line Anti-Tuberculosis Drugs in Lusaka, Zambia Chizimu, Joseph Yamweka Solo, Eddie Samuneti Bwalya, Precious Kapalamula, Thoko Flav Mwale, Kaemba Kunkuta Squarre, David Shawa, Misheck Lungu, Patrick Barnes, David Atomanyi Yamba, Kaunda Mufune, Tiza Chambaro, Herman Kamboyi, Harvey Munyeme, Musso Hang’ombe, Bernard Mudenda Kapata, Nathan Mukonka, Victor Chilengi, Roma Thapa, Jeewan Nakajima, Chie Suzuki, Yasuhiko Antibiotics (Basel) Article The emergence of pre-extensively drug-resistant tuberculosis (pre-XDR-TB) is a threat to TB control programs in developing countries such as Zambia. Studies in Zambia have applied molecular techniques to understand drug-resistance-associated mutations, circulating lineages and transmission patterns of multi-drug-resistant (MDR) Mycobacterium tuberculosis. However, none has reported genotypes and mutations associated with pre-XDR TB. This study characterized 63 drug-resistant M. tuberculosis strains from the University Teaching Hospital between 2018 and 2019 using targeted gene sequencing and conveniently selected 50 strains for whole genome sequencing. Sixty strains had resistance mutations associated to MDR, one polyresistant, and two rifampicin resistant. Among MDR strains, seven percent (4/60) had mutations associated with pre-XDR-TB. While four, one and nine strains had mutations associated with ethionamide, para-amino-salicylic acid and streptomycin resistances, respectively. All 50 strains belonged to lineage 4 with the predominant sub-lineage 4.3.4.2.1 (38%). Three of four pre-XDR strains belonged to sub-lineage 4.3.4.2.1. Sub-lineage 4.3.4.2.1 strains were less clustered when compared to sub-lineages L4.9.1 and L4.3.4.1 based on single nucleotide polymorphism differences. The finding that resistances to second-line drugs have emerged among MDR-TB is a threat to TB control. Hence, the study recommends a strengthened routine drug susceptibility testing for second-line TB drugs to stop the progression of pre-XDR to XDR-TB and improve patient treatment outcomes. MDPI 2023-06-29 /pmc/articles/PMC10376136/ /pubmed/37508222 http://dx.doi.org/10.3390/antibiotics12071126 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Chizimu, Joseph Yamweka Solo, Eddie Samuneti Bwalya, Precious Kapalamula, Thoko Flav Mwale, Kaemba Kunkuta Squarre, David Shawa, Misheck Lungu, Patrick Barnes, David Atomanyi Yamba, Kaunda Mufune, Tiza Chambaro, Herman Kamboyi, Harvey Munyeme, Musso Hang’ombe, Bernard Mudenda Kapata, Nathan Mukonka, Victor Chilengi, Roma Thapa, Jeewan Nakajima, Chie Suzuki, Yasuhiko Genomic Analysis of Mycobacterium tuberculosis Strains Resistant to Second-Line Anti-Tuberculosis Drugs in Lusaka, Zambia |
title | Genomic Analysis of Mycobacterium tuberculosis Strains Resistant to Second-Line Anti-Tuberculosis Drugs in Lusaka, Zambia |
title_full | Genomic Analysis of Mycobacterium tuberculosis Strains Resistant to Second-Line Anti-Tuberculosis Drugs in Lusaka, Zambia |
title_fullStr | Genomic Analysis of Mycobacterium tuberculosis Strains Resistant to Second-Line Anti-Tuberculosis Drugs in Lusaka, Zambia |
title_full_unstemmed | Genomic Analysis of Mycobacterium tuberculosis Strains Resistant to Second-Line Anti-Tuberculosis Drugs in Lusaka, Zambia |
title_short | Genomic Analysis of Mycobacterium tuberculosis Strains Resistant to Second-Line Anti-Tuberculosis Drugs in Lusaka, Zambia |
title_sort | genomic analysis of mycobacterium tuberculosis strains resistant to second-line anti-tuberculosis drugs in lusaka, zambia |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10376136/ https://www.ncbi.nlm.nih.gov/pubmed/37508222 http://dx.doi.org/10.3390/antibiotics12071126 |
work_keys_str_mv | AT chizimujosephyamweka genomicanalysisofmycobacteriumtuberculosisstrainsresistanttosecondlineantituberculosisdrugsinlusakazambia AT soloeddiesamuneti genomicanalysisofmycobacteriumtuberculosisstrainsresistanttosecondlineantituberculosisdrugsinlusakazambia AT bwalyaprecious genomicanalysisofmycobacteriumtuberculosisstrainsresistanttosecondlineantituberculosisdrugsinlusakazambia AT kapalamulathokoflav genomicanalysisofmycobacteriumtuberculosisstrainsresistanttosecondlineantituberculosisdrugsinlusakazambia AT mwalekaembakunkuta genomicanalysisofmycobacteriumtuberculosisstrainsresistanttosecondlineantituberculosisdrugsinlusakazambia AT squarredavid genomicanalysisofmycobacteriumtuberculosisstrainsresistanttosecondlineantituberculosisdrugsinlusakazambia AT shawamisheck genomicanalysisofmycobacteriumtuberculosisstrainsresistanttosecondlineantituberculosisdrugsinlusakazambia AT lungupatrick genomicanalysisofmycobacteriumtuberculosisstrainsresistanttosecondlineantituberculosisdrugsinlusakazambia AT barnesdavidatomanyi genomicanalysisofmycobacteriumtuberculosisstrainsresistanttosecondlineantituberculosisdrugsinlusakazambia AT yambakaunda genomicanalysisofmycobacteriumtuberculosisstrainsresistanttosecondlineantituberculosisdrugsinlusakazambia AT mufunetiza genomicanalysisofmycobacteriumtuberculosisstrainsresistanttosecondlineantituberculosisdrugsinlusakazambia AT chambaroherman genomicanalysisofmycobacteriumtuberculosisstrainsresistanttosecondlineantituberculosisdrugsinlusakazambia AT kamboyiharvey genomicanalysisofmycobacteriumtuberculosisstrainsresistanttosecondlineantituberculosisdrugsinlusakazambia AT munyememusso genomicanalysisofmycobacteriumtuberculosisstrainsresistanttosecondlineantituberculosisdrugsinlusakazambia AT hangombebernardmudenda genomicanalysisofmycobacteriumtuberculosisstrainsresistanttosecondlineantituberculosisdrugsinlusakazambia AT kapatanathan genomicanalysisofmycobacteriumtuberculosisstrainsresistanttosecondlineantituberculosisdrugsinlusakazambia AT mukonkavictor genomicanalysisofmycobacteriumtuberculosisstrainsresistanttosecondlineantituberculosisdrugsinlusakazambia AT chilengiroma genomicanalysisofmycobacteriumtuberculosisstrainsresistanttosecondlineantituberculosisdrugsinlusakazambia AT thapajeewan genomicanalysisofmycobacteriumtuberculosisstrainsresistanttosecondlineantituberculosisdrugsinlusakazambia AT nakajimachie genomicanalysisofmycobacteriumtuberculosisstrainsresistanttosecondlineantituberculosisdrugsinlusakazambia AT suzukiyasuhiko genomicanalysisofmycobacteriumtuberculosisstrainsresistanttosecondlineantituberculosisdrugsinlusakazambia |