Genomic Analysis of <i>Mycobacterium tuberculosis</i> 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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MDPI AG
2023-06-01
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| Series: | Antibiotics |
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| Online Access: | https://www.mdpi.com/2079-6382/12/7/1126 |
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| author | Joseph Yamweka Chizimu Eddie Samuneti Solo Precious Bwalya Thoko Flav Kapalamula Kaemba Kunkuta Mwale David Squarre Misheck Shawa Patrick Lungu David Atomanyi Barnes Kaunda Yamba Tiza Mufune Herman Chambaro Harvey Kamboyi Musso Munyeme Bernard Mudenda Hang’ombe Nathan Kapata Victor Mukonka Roma Chilengi Jeewan Thapa Chie Nakajima Yasuhiko Suzuki |
| author_facet | Joseph Yamweka Chizimu Eddie Samuneti Solo Precious Bwalya Thoko Flav Kapalamula Kaemba Kunkuta Mwale David Squarre Misheck Shawa Patrick Lungu David Atomanyi Barnes Kaunda Yamba Tiza Mufune Herman Chambaro Harvey Kamboyi Musso Munyeme Bernard Mudenda Hang’ombe Nathan Kapata Victor Mukonka Roma Chilengi Jeewan Thapa Chie Nakajima Yasuhiko Suzuki |
| author_sort | Joseph Yamweka Chizimu |
| collection | DOAJ |
| 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) <i>Mycobacterium tuberculosis</i>. However, none has reported genotypes and mutations associated with pre-XDR TB. This study characterized 63 drug-resistant <i>M. tuberculosis</i> 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. |
| first_indexed | 2024-03-11T01:22:28Z |
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| institution | Directory Open Access Journal |
| issn | 2079-6382 |
| language | English |
| last_indexed | 2024-03-11T01:22:28Z |
| publishDate | 2023-06-01 |
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| spelling | doaj.art-5fe6dd4cfbbb4f3cb1adb747afffd8202023-11-18T18:02:35ZengMDPI AGAntibiotics2079-63822023-06-01127112610.3390/antibiotics12071126Genomic Analysis of <i>Mycobacterium tuberculosis</i> Strains Resistant to Second-Line Anti-Tuberculosis Drugs in Lusaka, ZambiaJoseph Yamweka Chizimu0Eddie Samuneti Solo1Precious Bwalya2Thoko Flav Kapalamula3Kaemba Kunkuta Mwale4David Squarre5Misheck Shawa6Patrick Lungu7David Atomanyi Barnes8Kaunda Yamba9Tiza Mufune10Herman Chambaro11Harvey Kamboyi12Musso Munyeme13Bernard Mudenda Hang’ombe14Nathan Kapata15Victor Mukonka16Roma Chilengi17Jeewan Thapa18Chie Nakajima19Yasuhiko Suzuki20Division of Bioresources, Hokkaido University International Institute for Zoonosis Control, Sapporo 001-0020, Hokkaido, JapanUniversity Teaching Hospital, Ministry of Health, Lusaka 10101, ZambiaDivision of Bioresources, Hokkaido University International Institute for Zoonosis Control, Sapporo 001-0020, Hokkaido, JapanDepartment of Pathobiology, Faculty of Veterinary Medicine, Lilongwe University of Agriculture and Natural Resources, Lilongwe 207203, MalawiUniversity Teaching Hospital, Ministry of Health, Lusaka 10101, ZambiaDepartment of Veterinary Services, Ministry of Fisheries and Livestock, Lusaka 10101, ZambiaDivision of Bioresources, Hokkaido University International Institute for Zoonosis Control, Sapporo 001-0020, Hokkaido, JapanNational TB Control Program, Ministry of Health, Lusaka 10101, ZambiaDivision of Bioresources, Hokkaido University International Institute for Zoonosis Control, Sapporo 001-0020, Hokkaido, JapanUniversity Teaching Hospital, Ministry of Health, Lusaka 10101, ZambiaProvincial Health Office, Central Province, Ministry of Health, Kabwe 10101, ZambiaDepartment of Veterinary Services, Ministry of Fisheries and Livestock, Lusaka 10101, ZambiaDivision of Bioresources, Hokkaido University International Institute for Zoonosis Control, Sapporo 001-0020, Hokkaido, JapanDepartment of Disease Control, School of Veterinary Medicine, The University of Zambia, Lusaka 10101, ZambiaDepartment of Para-Clinical Studies, School of Veterinary Medicine, The University of Zambia, Lusaka 10101, ZambiaZambia National Public Health Institute, Ministry of Health, Lusaka 10101, ZambiaSchool of Public Health and Environmental Sciences, Levy Mwanawasa Medical University, Ministry of Health, Lusaka 10101, ZambiaZambia National Public Health Institute, Ministry of Health, Lusaka 10101, ZambiaDivision of Bioresources, Hokkaido University International Institute for Zoonosis Control, Sapporo 001-0020, Hokkaido, JapanDivision of Bioresources, Hokkaido University International Institute for Zoonosis Control, Sapporo 001-0020, Hokkaido, JapanDivision of Bioresources, Hokkaido University International Institute for Zoonosis Control, Sapporo 001-0020, Hokkaido, JapanThe 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) <i>Mycobacterium tuberculosis</i>. However, none has reported genotypes and mutations associated with pre-XDR TB. This study characterized 63 drug-resistant <i>M. tuberculosis</i> 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.https://www.mdpi.com/2079-6382/12/7/1126<i>Mycobacterium tuberculosis</i>pre-extensively drug resistancerecent transmissionwhole-genome sequencingZambia |
| spellingShingle | Joseph Yamweka Chizimu Eddie Samuneti Solo Precious Bwalya Thoko Flav Kapalamula Kaemba Kunkuta Mwale David Squarre Misheck Shawa Patrick Lungu David Atomanyi Barnes Kaunda Yamba Tiza Mufune Herman Chambaro Harvey Kamboyi Musso Munyeme Bernard Mudenda Hang’ombe Nathan Kapata Victor Mukonka Roma Chilengi Jeewan Thapa Chie Nakajima Yasuhiko Suzuki Genomic Analysis of <i>Mycobacterium tuberculosis</i> Strains Resistant to Second-Line Anti-Tuberculosis Drugs in Lusaka, Zambia Antibiotics <i>Mycobacterium tuberculosis</i> pre-extensively drug resistance recent transmission whole-genome sequencing Zambia |
| title | Genomic Analysis of <i>Mycobacterium tuberculosis</i> Strains Resistant to Second-Line Anti-Tuberculosis Drugs in Lusaka, Zambia |
| title_full | Genomic Analysis of <i>Mycobacterium tuberculosis</i> Strains Resistant to Second-Line Anti-Tuberculosis Drugs in Lusaka, Zambia |
| title_fullStr | Genomic Analysis of <i>Mycobacterium tuberculosis</i> Strains Resistant to Second-Line Anti-Tuberculosis Drugs in Lusaka, Zambia |
| title_full_unstemmed | Genomic Analysis of <i>Mycobacterium tuberculosis</i> Strains Resistant to Second-Line Anti-Tuberculosis Drugs in Lusaka, Zambia |
| title_short | Genomic Analysis of <i>Mycobacterium tuberculosis</i> Strains Resistant to Second-Line Anti-Tuberculosis Drugs in Lusaka, Zambia |
| title_sort | genomic analysis of i mycobacterium tuberculosis i strains resistant to second line anti tuberculosis drugs in lusaka zambia |
| topic | <i>Mycobacterium tuberculosis</i> pre-extensively drug resistance recent transmission whole-genome sequencing Zambia |
| url | https://www.mdpi.com/2079-6382/12/7/1126 |
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