We completed subculturing and WGS on a subset of culture isolates obtained at the clinical laboratory during the study period. Indeed, the implementation of rapid Xpert MTB/RIF diagnostics (Cepheid) in the Odessa region has not resulted in substantially improved MDR TB treatment outcomes (32).
Strains of the 3 outbreak clades acquired putative compensatory mutations, e.g., in rpoB or rpoC previously suggested to mitigate the growth deficit of rifampin-resistant strains (10,11). ~20 to 25% of patients with MDR-TB and XDR-TB treated2 1. 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). 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). These Beijing clades showed a lower median pairwise SNP distance of 25 (interquartile range [IQR] 20.0–32.5) for Central Asia outbreak, 39 (IQR 25.0–48.0) for Europe/Russia W148 outbreak, and 14 (IQR 11.5–18.0) for Ukraine outbreak, contrasting with a distance of 122 (IQR 170.8–139.0) for other Beijing strains (p<0.05, one-way ANOVA, Bonferroni multiple comparison test) (Appendix 2 Figure 1). Multiple errors have probably contributed to the development of XDR disease in South Africa. 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). Though not representative, the data showed that 10% of MDR tuberculosis isolates were in fact XDR tuberculosis. Centers for Disease Control and Prevention. received the Gertrud Meissner Award sponsored by HAIN Lifescience, outside the submitted work; S.N. However, because of limitations of the contact tracing review, it is possible that we overlooked some contacts connected to prisons in Ukraine. There was 1 case of XDR TB in the United States in 2018. In contrast, first-line drug resistance rates among all other Beijing and non-Beijing strains were reduced (8%–33% for individual drugs). Effective implementation of these regulations requires much more effective national surveillance and response systems — and therefore the mobilization of resources.
Branches are color-coded according to the... We classified a total of 177 clinical isolates based on WGS data from 10,339 variable positions, according to a recently proposed SNP barcode (22). Tuberculosis has now surpassed AIDS as the world’s leading infectious cause of death, and the so-called XDR strain is the ultimate in lethality. We prepared a box plot of pairwise genomic distances of MTBC strains from defined strain groups with R version 3.3 using the ggplot2 package version 2.2 (Appendix 2 Figure 1). The global threat of XDR tuberculosis has great significance for the public health field. In most countries, this ideal is not achieved because of insufficient primary care services and the lack of adequate laboratories and of tools permitting easy, prompt detection of drug resistance.
Because Ukraine lacks resources for contact tracing and TB is stigmatized, we anticipated that the journal information would yield few contacts.
An effective vaccine would be the most powerful tool for preventing tuberculosis and drug resistance, but a vaccine is not anticipated anytime soon. We created an association plot in R version 3.3 (https://www.r-project.org) using the vcd package version 1.4.
We conducted a retrospective review of epidemiologic contact tracing for patients infected with a Ukraine outbreak strain through patient records. This study demonstrates that MDR/XDR TB patients in southern Ukraine are infected predominantly with strains belonging to 3 distinct MTBC Beijing outbreak clades. Well-trained laboratory technicians are also of paramount importance for ensuring proper diagnosis.
We combined all remaining SNP positions that had a clear base call for all strains and matched the threshold levels in >95% of all strains in one FASTA alignment, further excluding repetitive regions and resistance-associated genes. XDR Tuberculosis — Implications for Global Public Health.
And if tuberculosis isolates are not tested for drug susceptibility from the outset, resistance may be detected too late to permit a cure. XDR tuberculosis also has major implications for the care of patients with HIV and for HIV control, because a high prevalence of HIV predicts extreme vulnerability to tuberculosis. Multidrug-resistant TB (MDR TB) is resistant to at least isoniazid (INH) and rifampin (RIF).
In 2017, the most recent data available, 515 deaths in the United States were attributed to TB.
Limited benefit of the new shorter multidrug-resistant tuberculosis regimen in Europe.
Similar patterns can be observed for the other 2 outbreaks: shared first-line resistance mediating mutations; unique mutations mediating resistance to kanamycin (eis −8 del c, −10 g/a, −12 c/t, −14 c/t, −15 c/g, −35 g/a, −37 g/t); cross-resistance to all injectable drugs (rrs 1401 a/g); and resistance to the fluoroquinolones (gyrA A90V, S91P, D94G, D94N, D94Y, D94A) (Figure 4; Appendix 1 Table 1). You will be subject to the destination website's privacy policy when you follow the link. The 3 Beijing outbreak strains all harbored high rates of first-line drug resistances to isoniazid (93%–100%), rifampin (93%–100%), streptomycin (93%–100%), ethambutol (86%–100%), and pyrazinamide (75%–100%) (Table 2). Multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) is an emerging threat to TB control in Ukraine, a country with the third highest XDR TB burden globally. Prevention, however, is insufficient once drug-resistant tuberculosis has spread. CDC twenty four seven. 2020;26(3):481-490. https://dx.doi.org/10.3201/eid2603.190525. Concise summaries and expert physician commentary that busy clinicians need to enhance patient care.
The neighborhood contact had also been detected by applying the strict SNP threshold. Genotyping analysis revealed that 85% of the 46 isolates tested belonged to the KwaZulu-Natal (KZN) family of tuberculosis strains, which had been recognized in the province for a decade.1, These alarming findings attracted much attention at the International AIDS Society conference in Toronto in August 2006. If TB disease is present, cough and feverwould be the predominant symptoms. We excluded known and newly identified phylogenetic, non–resistance-related variants (8,24,25) from the genotypic drug resistance prediction (Appendix 1 Table 3). WHO places prevention and care of XDR-TB as a priority through the strengthening of basic TB control and the necessary interventions to cure existing cases. We applied a WGS-based molecular epidemiologic approach to identify molecular resistance patterns, dominant strain types, and patient-related factors associated with MDR/XDR TB in a convenience sample from southern Ukraine. There was 1 case of XDR TB in the United States in 2018. TB is one of the most common infections in people living with HIV/AIDS.
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