The Burden of Extensively Drug Resistant and Pre-Extensively Drug Resistant Tuberculosis among Multidrug-Resistant Mycobacterium Tuberculosis Patients in Ghana.

Abstract

Background The majority of people around the world are at risk because of the rise of extensively drug resistant (XDR) and pre-extensively drug-resistant (Pre-XDR) tuberculosis (TB), especially in developing countries like Ghana. Extensively Drug Resistant Tuberculosis, a considerably more difficult-to-treat type of MDR tuberculosis, had been reported in at least 46 countries as of February 2008. By 2017, 77 countries had reported 11 000 infections of XDR-TB with a treatment success rate of only 34%. In Ghana, the first case of XDR-TB was published in 2018. However, there is insufficient information on the prevalence of XDR-TB, pre-XDR-TB, and their associated resistant mutations in Ghana. The study sought to provide a baseline data on the burden of pre-XDR-TB and XDR-TB 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. Aim of Study: The main aim of the study was to determine the proportion of extensively and pre-extensively Drug Resistant Mycobacterium tuberculosis among multidrug-resistant M. tuberculosis complex patients in Ghana Methods: One hundred and seventy-one (171) archived clinical isolates of MDR-TB collected from patients across Ghana between, January 2016 to December, 2020 were retrieved. The isolates were retested to confirm their phenotypic and genotypic drug susceptibility to the first- and second-line anti-TB drugs using the BACTEC MGIT system and MTBDRplus 96, MTBDRsl 96-line probe assays respectively Results: Of the 171 archival isolates collected, most of the isolates came from 7 regions, Eastern region having the highest (39.5%) followed by Greater Accra (19.8%). Majority of the samples were from males (78.9%). Of the 171 archival isolates collected, 81 (47.4%) were confirmed to be MDR, 6 (7.4%) were Pre-XDR-TB and no XDR-TB was detected. The katG S315T1 (73.3%) and rpoB S531L (42.5%) were the common mutations observed among isoniazid and rifampicin resistant isolates respectively. Majority of the mutations and amino acid changes that caused pre-XDR-TB were gyrAWT3+gyrAMUT3A and gyrAMUT3A (D94A) (50.0%) for fluoroquinolone and (rrsWT1) C1402T (50.0%) for aminoglycosides. The other detected mutations with their amino acid changes were gyrA MUT1 (A90V), gyrAWT3+gyrA MUT3C (D94G) and gyrA MUT2 (S91P) (16.7%) each for fluoroquinolones and rrWT2 (position 1484) (33.3%) and rrs MUT2 (G1484T) (16.7%) for the aminoglycosides. Conclusion: Pre-XDR-TB prevalence was marginally higher amongst MDR-TB patients in Ghana and no XDR-TB was detected. Nonetheless, a sustained surveillance of pre-XDR-TB and XDR-TB is advocated. The most common flouroquinolone mutation associated with pre XDR-TB was D94A