Yirenkyi Stephen Ofori, Taufik Osmanu, Laryea Roger, Acquah-Keelson Amanquador, Opintan Japheth Awuletey, Mensah Gloria Ivy
Laboratory Department, Eastern Regional Hospital, Koforidua, Eastern Region, Ghana.
Department of Medical Microbiology, University of Ghana Medical School, University of Ghana, Accra, Ghana.
PLoS One. 2025 May 20;20(5):e0323527. doi: 10.1371/journal.pone.0323527. eCollection 2025.
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.
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 MTBDRplus, MTBDRsl, line probe assays respectively.
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 katG S315T1 (33, 73.3%) and rpoB 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 gyrAWT3 + gyrAMUT3A and gyrAMUT3A (D94A) (50%) for fluoroquinolone. The other detected mutations with their amino acid changes were gyrA MUT1 (A90V), gyrAWT3 + gyrA MUT3C (D94G) and gyrA MUT2 (S91P) (16.7%) for fluoroquinolones and rrWT2 (position 1484) (33.3%) and rrs MUT2 (G1484T) (16.7%) for aminoglycosides.
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.
广泛耐药（XDR）和准广泛耐药（Pre-XDR）结核病的出现威胁着耐多药结核病（MDR）患者的管理，并对结核病控制项目产生负面影响，尤其是在加纳等发展中国家。加纳于2018年报告了首例XDR-TB病例。然而，关于加纳XDR-TB和Pre-XDR-TB的负担及其相关耐药突变的数据不足。该研究旨在提供加纳MDR-TB病例中Pre-XDR-TB和XDR-TB负担的基线数据。它还确定了导致Pre-XDR/XDR-TB的突变，以便对加纳的Pre-XDR/XDR-TB进行临床和项目管理。
检索了2016年1月至2020年12月期间从加纳各地结核病患者中获得的171份存档临床MDR分离株。分别使用BACTEC MGIT系统和Genotype MTBDRplus、MTBDRsl线探针检测法对分离株进行重新检测，以确认其对一线和二线抗结核药物的表型和基因型敏感性。
171份分离株中的大多数来自7个地区；东部地区的分离株数量最多（39.5%），其次是大阿克拉地区（19.8%）。大多数分离株来自男性结核病患者（78.9%）。在171份存档分离株中，81份（47.4%）被确认为MDR，6份（7.4%）为Pre-XDR-TB，但未检测到XDR-TB。katG S315T1（33份，73.3%）和rpoB S531L（31份，42.5%）分别是在耐异烟肼和利福平的分离株中观察到的主要突变。导致Pre-XDR-TB的许多突变和氨基酸变化为氟喹诺酮类的gyrAWT3 + gyrAMUT3A和gyrAMUT3A（D94A）（50%）。其他检测到的具有氨基酸变化的突变为氟喹诺酮类的gyrA MUT1（A90V）、gyrAWT3 + gyrA MUT3C（D94G）和gyrA MUT2（S91P）（16.7%），以及氨基糖苷类的rrWT2（第1484位）（33.3%）和rrs MUT2（G1484T）（16.7%）。
与Pre-XDR-TB相关的主要突变分别是氟喹诺酮类耐药的D94A和氨基糖苷类耐药的C1402T。加纳MDR-TB患者中Pre-XDR-TB的比例为7.4%；然而，未检测到XDR-TB。建议对Pre-XDR-TB和XDR-TB进行持续监测。
