Genetic Diversity and Drug Resistant Conferring Mutation in Mycobacterium Tuberculosis Isolates from Tuberculosis Lymphadenitis
Abstract
Background: Extra pulmonary tuberculosis (EPTB) is a growing public health concern in Ethiopia, with TB lymphadenitis (TBLN) being the most common. However, there is limited information available on genetic diversity and magnitude of gene mutations conferringdrug resistance in Mycobacterium tuberculosis (MTB) isolates from TBLN patients.
Methods: A cross sectional study was conducted among 91 MTB isolates from culture positive TBLN patients collected between 2016 and 2018. Isolates were typed using spoligotyping thereafter, detection of mutations conferring resistance was carried out using GenoType MTBDRplus.
Result: Spoligotyping of the 91 MTB isolates revealed 28 distinct spoligotype international types (SITs) and 9 orphan or newly identified patterns. The dominantly identified SITs were SIT25, SIT149, and SIT53 respectively; these accounted for 43% of the total number of strains. Our isolates were categorized in to four main lineages, Lineage 4 (49, 53.8%), Lineage 3 (38, 41.7%), Lineage 1 (2, 2.2%) and Lineage 7 (2, 2.2%). Mutations conferring resistance to INH, RIF, and multidrug resistance TB (MDR-TB) were observed in 6 (6.6%), 2(2.2%) and 2(2.2%) isolates, respectively. Both RIF resistant isolates displayed mutations at codon 531 in the rpoB gene with amino acid change of S531L. Among INH resistant strains, four isolates had showed mutation at KatG gene at codon 315 with amino acid change of S315T, one isolates had mutation at inhA gene at codon 15 with amino acid change of C15T and one isolate had mutation at inhA gene with unknown amino acid change. Strains with mutations conferring resistance to any of anti-TB drugs (RIF or INH) were belong to the Lineage 4 (3/6, 50%) and Lineage 3 (3/6, 50%). Four out of six (66.7%) drug resistant isolates were belonged to clustered strains.
Conclusion: Lineage 4 and Lineage 3 were the most prevalent Lineages with high clustering rate of SIT 25, SIT149 and SIT 53. The detection of common gene mutations in all drug resistant strains suggest the feasibility of Genotypes MTBDRplus for rapid detection of drug resistant MTB strains in Ethiopia. Drug resistant isolates were detected among clustered strains which could suggest ongoing resistant strains transmission in the community. This warrants strengthening of the control programs for TBLN in Ethiopia.