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DRUG RESISTANT TUBERCULOSIS - THE EMERGING SCENARIO.

ABSTRACT: During the period April 1992 to September 1994 a total of 2288 patients of pulmonary tuberculosis were treated at our centre. M. tuberculosis could be isolated from the sputa of 1037 patients (45.3%). All the isolates were subjected to indirect susceptibility testing using drug incorporated Lowenstein-Jensen medium slants. A total of 142 (13.7%) patients showed drug resistance. Single drug resistance was observed in 86 (8.3%) patients whereas resistance to two or more drugs was observed in 56 (5.4%) patients. Patients showing initial drug resistance were more in number (83 cases) than those showing acquired drug resistance (59 cases). Resistance to streptomycin was commonest (8.3% of isolates) followed by isoniazid (5.7%) and rifampicin (5.0%). Multiple drug resistance was mostly acquired (71.4% of drug-resistant isolates).

SUBMITTER: Jena J

PROVIDER: S-EPMC5530262 | biostudies-other | 1996 Apr

REPOSITORIES: biostudies-other

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Project description:BackgroundUral genetic family is a part of the Euro-American lineage of Mycobacterium tuberculosis and is endemic in Northern Eurasia (former Soviet Union [FSU]). These strains were long described as drug susceptible and of low virulence, but recent studies reported an increasing circulation of the multidrug-resistant (MDR) and extensively drug-resistant (XDR) Ural strains. Here, we analyzed all publicly available whole genome sequence data of Ural genotype isolates, in order to elucidate their phylogenomic diversity with a special focus on MDR and potentially epidemic clones.ResultsA total of 149 M. tuberculosis genomes of Ural isolates from FSU countries were mined from the GMTV database and TB-ARC project. We identified 6002 variable amino acid positions that were assessed for functional significance and used to build ML, NJ trees and for Bayesian TMRCA estimation. Three robust monophyletic clades were identified: Clade A (31 isolates from Russia, Belarus, Moldova), Clade B (52 isolates from Russia), and Clade C (37 isolates from Moldova, 2 from Belarus). Clade C was significantly associated with XDR or pre-XDR status compared to the pooled Clades A and B (33/39 versus 5/83, P < 0.0001). Time of origin was estimated for Clade A at 77.7-137 years ago and for Clade B at 56.3-99.2 years ago compared to the significantly more recent origin for Clade C. in silico spoligotyping identified signatures specific of the Clade A (spoligotype SIT35), and Clades B and C (both SIT262).ConclusionsA genetically compact and evolutionarily young Ural Clade C, likely originated after collapse of the Soviet Union, and reached epidemic proportions in Moldova in the last 20 years. This epidemic pre-XDR clone (mostly rifampin, isoniazid and kanamycin resistant) is characterized by a specific combination of mutations: KatG Ser315Thr, fabG1 -15C > T, RpoB Ser450Leu, RpsL Lys88Arg, eis -12G > A and EmbB Ser297Ala/T > G. Its further dissemination may occur towards both Russia and European Union and should be taken into consideration by health authorities. The identified spoligotyping signatures can serve for rapid preliminary detection and surveillance of the more hazardous pre-XDR associated strains of the Ural family, both in populations from countries of their endemic circulation and migrant communities.

Dataset Information

DRUG RESISTANT TUBERCULOSIS - THE EMERGING SCENARIO.

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