Diagnostic performance of the GenoType MTBDRplus VER 2.0 line probe assay for the detection of isoniazid resistant Mycobacterium tuberculosis in Ethiopia.
Shewki Moga, Kidist Bobosha, Dinka Fikadu, Betselot Zerihun, Getu Diriba, Misikir Amare, Russell R Kempker, Henry M Blumberg, Tamrat Abebe
Author Information
Shewki Moga: Ethiopian Public Health Institute (EPHI), Addis Ababa, Ethiopia. ORCID
Kidist Bobosha: Armauer Hansen Research Institute (AHRI), Addis Ababa, Ethiopia.
Dinka Fikadu: Ethiopian Public Health Institute (EPHI), Addis Ababa, Ethiopia.
Betselot Zerihun: Ethiopian Public Health Institute (EPHI), Addis Ababa, Ethiopia. ORCID
Getu Diriba: Ethiopian Public Health Institute (EPHI), Addis Ababa, Ethiopia. ORCID
Misikir Amare: Ethiopian Public Health Institute (EPHI), Addis Ababa, Ethiopia.
Russell R Kempker: Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, Georgia, United States of America.
Henry M Blumberg: Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, Georgia, United States of America.
Tamrat Abebe: Department of Microbiology, Immunology, and Parasitology, School of Medicine, College of Health Sciences, Addis Ababa University (AAU), Addis Ababa, Ethiopia.
BACKGROUND: Isoniazid (INH) resistant Mycobacterium tuberculosis (Hr-TB) is the most common type of drug resistant TB, and is defined as M tuberculosis complex (MTBC) strains resistant to INH but susceptible to rifampicin (RIF). Resistance to INH precedes RIF resistance in almost all multidrug resistant TB (MDR-TB) cases, across all MTBC lineages and in all settings. Therefore, early detection of Hr-TB is critical to ensure rapid initiation of appropriate treatment, and to prevent progression to MDR-TB. We assessed the performance of the GenoType MTBDRplus VER 2.0 line probe assay (LPA) in detecting Isoniazid resistance among MTBC clinical isolates. METHODS: A retrospective study was conducted among M. tuberculosis complex (MTBC) clinical isolates obtained from the third-round Ethiopian national drug resistance survey (DRS) conducted between August 2017 and December 2019. The sensitivity, specificity, positive predictive value, and negative predictive value of the GenoType MTBDRplus VER 2.0 LPA in detecting INH resistance were assessed and compared to phenotypic drug susceptibility testing (DST) using the Mycobacteria Growth Indicator Tube (MGIT) system. Fisher's exact test was performed to compare the performance of LPA between Hr-TB and MDR-TB isolates. RESULTS: A total of 137 MTBC isolates were included, of those 62 were Hr-TB, 35 were MDR-TB and 40 were INH susceptible. The sensitivity of the GenoType MTBDRplus VER 2.0 for detecting INH resistance was 77.4% (95% CI: 65.5-86.2) among Hr-TB isolates and 94.3% (95% CI: 80.4-99.4) among MDR-TB isolates (P = 0.04). The specificity of the GenoType MTBDRplus VER 2.0 for detecting INH resistance was 100% (95% CI: 89.6-100). The katG 315 mutation was observed in 71% (n = 44) of Hr-TB phenotypes and 94.3% (n = 33) of MDR-TB phenotypes. Mutation at position-15 of the inhA promoter region alone was detected in four (6.5%) Hr-TB isolates, and concomitantly with katG 315 mutation in one (2.9%) MDR-TB isolate. CONCLUSIONS: GenoType MTBDRplus VER 2.0 LPA demonstrated improved performance in detecting INH resistance among MDR-TB cases compared to Hr-TB cases. The katG315 mutation is the most common INH resistance conferring gene among Hr-TB and MDR-TB isolates. Additional INH resistance conferring mutations should be evaluated to improve the sensitivity of the GenoType MTBDRplus VER 2.0 for the detection of INH resistance among Hr-TB cases.
