Mycobacterium tuberculosis Beijing Lineage Favors the Spread of Multidrug-Resistant Tuberculosis in the Republic of Georgia

Abstract

High rates and transmission of multidrug-resistant (MDR) tuberculosis (TB) have been associated with theMycobacterium tuberculosis complex (MTBC) Beijing lineage, pointing to the importance of pathogen genetic factors for the modulation of infection outcome and epidemiology. We present here an in-depth analysis of the population structure of MTBC strains from the Republic of Georgia, a high-incidence setting at the Black Sea Coast. Phylogenetic lineages were identified based on 24-locus MIRU-VNTR (for mycobacterial interspersed repetitive unit-variable number tandem repeat) and spoligotyping analysis. Clusters of strains with identical genotyping profiles were determined as an indicator for the rate of recent transmission. Among the 183 M. tuberculosis isolates investigated, the most prominent lineage found was Beijing (26%), followed by the LAM (18%), Ural (12%), and Haarlem (5%) strains. A closely related previously undefined phylogenetic group (62 strains) showed a genotyping pattern similar to laboratory strain H37RV and was denominated as "Georgia-H37RV-like." Although isoniazid resistance was found among strains of different lineages, MDR TB was nearly completely restricted to Beijing strains (P < 0.0001). Approximately 50% of the isolates were grouped in clusters, indicating a high rate of recent transmission. Our data indicate that, in addition to the confirmation of the importance of Beijing genotype strains for the TB epidemiology in former Soviet Union countries, a high-population diversity with strains of the LAM, Ural, Haarlem, and a previously undefined lineage represents nearly two-thirds of the strains found in Georgia. Higher rates among previously treated and MDR TB patients point to a higher potential of lineage Beijing to escape therapy and develop MDR TB.Drug-resistant Mycobacterium tuberculosis complex (MTBC) strains have emerged worldwide as a serious threat for tuberculosis (TB) control. Rates of multidrug-resistant (MDR) strains (i.e., resistance at least to isoniazid [INH] and rifampin [RIF]) have reached levels of up to 14% among patients never treated and up to 40% among previously treated patients in several MDR TB "hot spots" such as such as Karakalpakstan (Uzbekistan) and Kazakhstan in Eastern Europe (10, 37). Every year an estimated 489,000 cases of MDR TB arise globally (36). MDR TB is associated with much poorer treatment outcomes than for drug-susceptible TB, with a much higher risk of developing further resistances (2, 7). Prolonged periods of infectivity result in enhanced transmission of drug-resistant strains, further accelerating the rates of drug resistance (3). Even more worrisome is the emergence of a nearly untreatable form of TB, namely, extensively drug-resistant TB (XDR TB), which is defined as MDR plus additional resistance to any fluoroquinolone and at least one of three injectable drugs (i.e., amikacin, kanamycin, or capreomycin). A recent survey confirmed the worldwide presence of XDR strains, with rates of up 15% of MDR TB cases (30).Considering the difficulti...

Evaluation of Mycobacterium tuberculosis Typing Methods in a 4-Year Study in Schleswig-Holstein, Northern Germany

“…The addition of spoligotyping did not influence the discriminatory power of either of the two other methods but was rather useful for supporting phylogenetic classifications predicted by MIRU-VNTR typing, as previously suggested (1,12). Importantly, all clusters with a confirmed recent transmission link were detected by both MIRU-VNTR and IS6110 RFLP typing.…”

“…The IS6110 fingerprints, spoligotyping patterns, and MIRU-VNTR typing results of the M. tuberculosis complex isolates were analyzed by the BioNumerics program (Windows XP, version 6.5; Applied Maths, Kortrijk, Belgium) as described previously (12,17). The IS6110 patterns were digitized and analyzed for similarity by using the Dice coefficient and a bandmatching tolerance of 1.2%.…”

A surge of MDR and XDR tuberculosis in France among patients born in the Former Soviet Union

“…In the present study, the genotyping analysis revealed four lineages (Beijing, LAM, Haarlem and Ural) already reported in the FSU [17][18][19], although the Beijing family was more frequent (68%) in our study. Of interest, the combination of MIRU-VNTR and antibiotic resistance genotypes and phenotypes suggested that almost all strains defined as clustered by MIRU-VNTR were in fact distinct.…”

Mycobacterium tuberculosis of the RD Rio Genotype Is the Predominant Cause of Tuberculosis and Associated with Multidrug Resistance in Porto Alegre City, South Brazil

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