E ach year, approximately half a million new cases of multidrug-resistant (MDR) tuberculosis (TB) challenge global health (1,2). MDR TB is caused by Mycobacterium tuberculosis complex (MTBC) strains, resistant to at least isoniazid and rifampin (3). In Europe, Ukraine is a hotspot of drug-resistant TB, with 6,564 laboratory-confirmed MDR and rifampin-resistant cases (2) and the third highest burden of extensively drug-resistant (XDR) TB (1,097 laboratory confirmed cases) globally in 2017 (2). XDR TB is a complicated form of MDR TB with additional resistances to >1 second-line injectable antimicrobial drug and a fluoroquinolone (1). Treatment of XDR TB can take up to 2 years (4), and treatment of a single XDR TB case has been reported to exceed €100,000 (5,6), even though treatment success rates remain ≈30% in the European region of the World Health Organization (40 countries reported) (7). Improvement of MDR/XDR TB prevention, diagnosis, and treatment is one of the core activities prioritized by WHO and the European Respiratory Society to eliminate TB (6). In addition to shortcomings in TB diagnosis and treatment, bacterial genetic factors might play a role in the epidemiologic success of certain MDR strains, especially of lineage 2 (Beijing) in Eurasia (8-11). Beijing MDR outbreak strains were shown to acquire fitness-enhancing mutations (i.e., mutations that increase in vitro growth rates) that may result in higher virulence and increased transmissibility, thus fostering the MDR TB epidemic in Eastern Europe (8-10). In line with this assumption, recent computational models predict that in many high TB incidence countries, person-to-person transmission but not treatment-related acquisition accounts for almost all (95.9%) incident MDR TB cases (12). Whole-genome sequencing (WGS) coupled with a molecular drug resistance prediction has provided insight into MTBC transmission networks and the transmissibility of MDR/XDR MTBC strains (8-10,13-15). We applied a WGS-based molecular epidemiologic approach to identify molecular resistance patterns, dominant strain types, and Multidrug-and Extensively Drug-Resistant Mycobacterium tuberculosis Beijing Clades,
Objectives and methods: The Xpert® MTB/RIF assay (Cepheid, Sunnyvale, CA, USA) has been in routine use in Odessa Oblast, a region with the highest tuberculosis (TB) incidence in Ukraine, since 2013. We assessed the performance of the assay in routine settings and evaluated its effect on treatment outcomes. Results: The sensitivity of Xpert for TB detection was 93.7% (1165/1243) and 69.5% (448/645) for smearpositive and smear-negative sputum specimens, respectively, and its sensitivity for rifampicin resistance was 93.4% (1212/1298). Median time to TB detection using the Xpert assay was 0 days. Treatment initiation within 1 week increased the proportion of successful outcomes (60.1% versus 25.9%, RR ¼ 1.86, 95%CI ¼ 1.46e2.42), but the introduction of Xpert MTB/RIF has not led to a significant improvement in treatment outcomes (57.2% versus 46.2%; RR ¼ 0.93, 95%CI ¼ 0.77e1.12). Conclusion: Performance characteristics of the Xpert assay demonstrated during its routine implementation in an area of high TB and drug-resistant TB incidence in Ukraine were in line with those demonstrated in similar settings elsewhere. Rollout of rapid molecular testing may lead to better treatment results provided that it is implemented in conjunction with other programmatic improvements.
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