Evaluation of the GenoType MTBDRplus assay for detection of rifampicin- and isoniazid-resistant Mycobacterium tuberculosis isolates in central Ethiopia

AbstractObjective/Background: Multidrug-resistant tuberculosis (MDR-TB) is growing globally and becoming a major challenge for national TB control programs. Therefore, rapid identification of MDR strains of Mycobacterium tuberculosis and monitoring their transmission could contribute significantly to the control of TB. The GenoType MTBDRplus assay has been recommended by the World Health Organization to identify rifampicin (RIF)- and isoniazid (INH)-resistant M. tuberculosis isolates. This study was carried out to evaluate the performance of the GenoType MTBDRplus assay for the detection of RIF- and INH-resistant M. tuberculosis isolates in central Ethiopia. Methods: A total of 279 M. tuberculosis strains isolated from active TB cases in central Ethiopia were evaluated for their drug sensitivity by the conventional drug-susceptibility test (DST) and compared with data derived from the GenoType MTBDRplus assay. The DST served as the gold standard for evaluating the GenoType MTBDRplus assay. Results: The sensitivity and specificity of the GenoType MTBDRplus assay for the detection of RIF-resistant M. tuberculosis isolates were 80.0% and 99.6%, respectively. Its sensitivity and specificity for the detection of INH-resistant M. tuberculosis isolates were 82.7% and 99.6%, respectively, whereas they were 75.0% and 100%, respectively, for the detection of MDR M. tuberculosis strains. The concordances of the GenoType MTBDRplus assay and the conventional DST for the detection of RIF and INH susceptibility were 80% (8/10) and 86.2% (25/29), respectively. Furthermore, the concordance of the two tests for the detection of MDR M. tuberculosis strains was 75%. Specific mutations were detected in 55.6% (5/9) of the RIF-resistant isolates, with the highest mutation rate (33.3%) for the rpoB gene (Codon S531L). For INH-resistant isolates, the highest mutation rate (88.8%) related to a katG mutation (Codon S315T1). Conclusion: The findings of this study revealed that the GenoType MTBDRplus assay has high sensitivity and specificity for the detection of RIF and INH resistance. These preliminary data support the notion that the assay should be considered as an alternative to the DST for the characterization of MDR in M. tuberculosis isolates and the control of TB

Antibiotic resistance of Mycobacterium tuberculosis complex in Africa: A systematic review of current reports of molecular epidemiology, mechanisms and diagnostics

Figure S1: Frequency of M. tuberculosis Lineages/sub-lineages in Africa, January 2007-December 2018: Frequency of Indo-oceanic lineage/sub-lineages (A); Beijing sublineage (B); CAS-sublineage (C), Euro-American lineage/sub-lineages (D); M. africanum West Africa I & II (E); M. tuberculosis Eth lineage 7 and sub-lineages (F); and proportion of each M. tuberculosis lineage in Africa (G).Table S1: Distribution of M. tuberculosis complex strains, specimen source/s, genotyping method/s, molecular anti-TB drug resistance rate and resistance mechanisms in M. tb across African countries, January 2007 to December 2018Table S2: Resistance mechanisms, molecular diagnosis method/s used, frequency and proportion of gene mutation per total resistant M. tuberculosis complex isolates across African countries, January 2007- December 2018Table S3: Molecular antibiotics resistance rates and resistance mechanisms in M. tuberculosis complex across African countries, January 2007-December 2018.Table S4: Frequency of gene mutation(s) and specific amino acid/nucleotide changes conferring antitubercular drug resistances across African countries January 2007- December 2018Table S5: Distribution of specimen source/s, phenotypic DST method/s used, total number of isolates, and phenotypic antibiotics monoresistance rate, MDR and XDR rate of M. tb complex across African countries, January 2007- December 2018Table S6: Distribution of genotypes/lineages/sub-lineages, frequency and patterns of antibiotics resistance-conferring mutations across African countries, January 2007- December 2018Supplementary dataset 1: Metadata of M. tuberculosis isolates included in phylogenomic analyses.Supplementary dataset 2: Country-by-country frequency of lineage and sub-lineage of M. tuberculosis in Africa: January 2007-December 2018BACKGROUND : Tuberculosis (TB) remains a main global public health problem. However, a systematic review of TB resistance epidemiology in Africa is wanting. METHODS : A comprehensive systematic search of PubMed, Web of Science and ScienceDirect for English research articles reporting on the molecular epidemiology of Mycobacterium tuberculosis complex resistance in Africa from January 2007 to December 2018 was undertaken. RESULTS AND CONCLUSION : Qualitative and quantitative synthesis were, respectively, undertaken with 232 and 186 included articles, representing 32 countries. TB monoresistance rate was highest for isoniazid (59%) and rifampicin (27%), particularly in Zimbabwe (100%), Swaziland (100%), and Sudan (67.9%) whilst multidrug resistance (MDR) rate was substantial in Zimbabwe (100%), Sudan (34.6%), Ivory Coast (24.5%) and Ethiopia (23.9%). Resistance-conferring mutations were commonly found in katG (n = 3694), rpoB (n = 3591), rrs (n = 1272), inhA (n = 1065), pncA (n = 1063) and embB (n = 705) in almost all included countries: S315G/I/N/R/T, V473D/F/G/I, Q471H/Q/R/Y, S303C/L etc. in katG; S531A/F/S/G, H526A/C/D/G, D516A/E/G etc. in rpoB; A1401G, A513C etc. in rrs; -15C→T, -17G→A/T, -16A→G etc. in inhA; Ins456C, Ins 172 G, L172P, C14R, Ins515G etc. in pncA. Commonest lineages and families such as T (n = 8139), LAM (n = 5243), Beijing (n = 5471), Cameroon (n = 3315), CAS (n = 2021), H (n = 1773) etc., with the exception of T, were not fairly distributed; Beijing, Cameroon and CAS were prevalent in South Africa (n = 4964), Ghana (n = 2306), and Ethiopia/Tanzania (n = 799/635), respectively. Resistance mutations were not lineage-specific and sputum (96.2%) were mainly used for diagnosing TB resistance using the LPA (38.5%), GeneXpert (17.2%), whole-genome sequencing (12.3%) and PCR/amplicon sequencing (9%/23%). Intercountry spread of strains was limited while intra-country dissemination was common. TB resistance and its diagnosis remain a major threat in Africa, necessitating urgent action to contain this global menace.http://www.elsevierhealth.com/journals/jinf2020-12-01hj2020Medical Microbiolog