Genotypic Characterization of Mycobacterium Tuberculosis Strains Resistant to Rifampicin, Isoniazid and Second-Line Antibiotics in Chad

Abstract

Monitoring drug resistance and identifying the genetic basis of resistance to first- and second-line anti-tuberculosis (anti-TB) drugs provides important information to optimize patient care. The present study was an observational, cross-sectional and analytical study aimed at determining the prevalence of resistance genes to rifampicin, isoniazid and resistant and multi-resistant genes with mutations associated with second-line anti-tuberculosis drugs (Levofloxacin Amikacin, Kanamycin and Capreomycin) among strains of Mycobacterium tuberculosis in nine hospitals in four provinces of Chad with three new molecular techniques. The TB-LAMP molecular technique made it possible to detect 264 (25.14%) strains of Mycobacterium tuberculosis complex among 1050 people referred for tuberculosis research, including 37 cases in relapse and 237 new cases under treatment or not without clinical improvement. The average age of the patients was 34.15 years with the extremes ranging from 12 to 77 years. The sex ratio was 3.33 in favor of men. The GeneXpert made it possible to confirm the 264 positive cases of Mycobacterium tuberculosis (MTB+) of which 76% of men and 24% of women had the MTB+ profile sensitive to rifampicin, and 80% of men and 20% of women harbored the Mycobacterium complex. rifampicin-resistant tuberculosis. The determination of resistance genes including 13% (rpoB) to rifampicin, 4% (inhA) to isoniazid and 8% (rpoB/KatG and/or KatG/inhA) multi-resistant (MDR) genes was carried out using the Line Probe Assay technique. This technique also made it possible to determine resistance genes with associated mutations including 13.6% (gyrA and gyrB), 7.6% (eis), 6.1% (rrs and eis) and 10.6% being mutations affecting the different alleles on the chromosomes of the Mycobacterium tuberculosis complex. This study highlighted the emergence of resistance to rifampicin and isoniazid as well as resistance with mutations associated with second-line anti-tuberculosis drugs. It raises the need to implement an effective surveillance system to detect the resistance of Mycobacterium tuberculosis to anti-tuberculosis drugs in Chad and even in Central Africa.