{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T22:24:51Z","timestamp":1782253491450,"version":"3.54.5"},"reference-count":37,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T00:00:00Z","timestamp":1747699200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec>\n<jats:title>Background<\/jats:title>\n<jats:p>The emergence of Extensively Drug Resistant (XDR) and Pre-extensively drug resistant (Pre-XDR) tuberculosis (TB) threatens the management of multidrug-resistant tuberculosis (MDR) patients and impacts negatively on TB control programs, especially in developing countries like Ghana. The first case of XDR-TB in Ghana was reported in 2018. There is however inadequate data on the burden of XDR-TB and pre-XDR-TB and their associated resistant mutations in Ghana. The study sought to provide baseline data on the burden of pre-XDR-TB and XDR-TB among MDR TB cases in Ghana. It also determined the mutations responsible for pre-XDR\/ XDR-TB, for clinical and programmatic management of pre-XDR\/ XDR-TB in Ghana.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>One hundred and seventy-one (171) archived clinical MDR isolates obtained from TB patients across Ghana between January 2016 and December 2020 were retrieved. The isolates were retested to confirm their phenotypic and genotypic susceptibility to the first and second-line anti-TB drugs using the BACTEC MGIT system and Genotype MTBDR<jats:italic>plus<\/jats:italic>, MTBDR<jats:italic>sl<\/jats:italic>, line probe assays respectively.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>Most of the 171 isolates came from 7 regions; the highest (39.5%) from Eastern, followed by Greater Accra region (19.8%). Most of the isolates were from male TB patients (78.9%). Of the 171 archived isolates, 81 (47.4%) were confirmed to be MDR, 6 (7.4%) were Pre-XDR-TB but no XDR-TB was detected. The <jats:italic>katG<\/jats:italic> S315T1 (33, 73.3%) and <jats:italic>rpoB<\/jats:italic> S531L (31, 42.5%) were the predominant mutations observed among isoniazid and rifampicin resistant isolates respectively. Many of the mutations and amino acid changes that caused pre-XDR-TB were <jats:italic>gyrAWT3\u2009+\u2009gyrAMUT3A<\/jats:italic> and <jats:italic>gyrAMUT3A<\/jats:italic> (D94A) (50%) for fluoroquinolone. The other detected mutations with their amino acid changes were <jats:italic>gyrA<\/jats:italic> MUT1 (A90V), <jats:italic>gyrA<\/jats:italic>WT3\u2009+\u2009<jats:italic>gyrA<\/jats:italic> MUT3C (D94G) and <jats:italic>gyrA<\/jats:italic> MUT2 (S91P) (16.7%) for fluoroquinolones and <jats:italic>rrWT2<\/jats:italic> (position 1484) (33.3%) and <jats:italic>rrs<\/jats:italic> MUT2 (G1484T) (16.7%) for aminoglycosides.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Conclusion<\/jats:title>\n<jats:p>The predominant mutations associated with pre-XDR-TB were D94A and C1402T for fluoroquinolone and aminoglycosides resistance respectively. The proportion of pre-XDR-TB among MDR-TB patients in Ghana was 7.4%; however, no XDR-TB was detected. A sustained surveillance of pre-XDR-TB and XDR-TB is recommended.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0323527","type":"journal-article","created":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T17:29:39Z","timestamp":1747762179000},"page":"e0323527","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Genotypic analysis of drug-resistant tuberculosis in Ghana: Insights into pre-XDR and XDR-TB"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6106-3430","authenticated-orcid":true,"given":"Stephen Ofori","family":"Yirenkyi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osmanu","family":"Taufik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger","family":"Laryea","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanquador","family":"Acquah-Keelson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3928-2116","authenticated-orcid":true,"given":"Japheth Awuletey","family":"Opintan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6499-5946","authenticated-orcid":true,"given":"Gloria Ivy","family":"Mensah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,5,20]]},"reference":[{"key":"pone.0323527.ref001","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1186\/1472-6947-13-56","article-title":"A hybrid seasonal prediction model for tuberculosis incidence in China","volume":"13","author":"S Cao","year":"2013","journal-title":"BMC Med Inform Decis Mak"},{"key":"pone.0323527.ref002","volume-title":"2024 global tuberculosis report","year":"2024"},{"issue":"9","key":"pone.0323527.ref003","doi-asserted-by":"crossref","first-page":"1","DOI":"10.9734\/JAMMR\/2018\/40156","article-title":"Diagnosis and treatment outcome of smear positive pulmonary tuberculosis: retrospective study in Kpando Municipal, Ghana","volume":"25","author":"D Acheampong","year":"2018","journal-title":"J Adv Med Med Res"},{"key":"pone.0323527.ref004","first-page":"1","article-title":"Genetic diversity of multi- and extensively drug-resistant Mycobacterium tuberculosis isolates in the capital of Iran, revealed by whole-genome sequencing","author":"F Vaziri","year":"2019","journal-title":"J Clin Microbiol"},{"issue":"1","key":"pone.0323527.ref005","article-title":"Drug resistance gene mutations and treatment outcomes in MDR-TB: a prospective study in Eastern China","volume":"15","author":"Q Liu","year":"2021","journal-title":"PLoS One"},{"issue":"7","key":"pone.0323527.ref006","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0253826","article-title":"Genotypic diversity of multi- and pre-extremely drug-resistant Mycobacterium tuberculosis isolates from Morocco","volume":"16","author":"A Oudghiri","year":"2021","journal-title":"PLoS One"},{"key":"pone.0323527.ref007","author":"WHO","year":"2022"},{"key":"pone.0323527.ref008","author":"World Health Organization","year":"2014"},{"key":"pone.0323527.ref009","unstructured":"WHO. 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