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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...

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Autores principales: 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
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
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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.
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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
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