Dataset Information

Drug-resistant tuberculosis in Eastern Europe: challenges and ways forward.

ABSTRACT: Encouragingly, global rates of new tuberculosis (TB) cases have been falling since 2005, in line with the Millennium Development Goal targets; however, cases of multidrug-resistant (MDR-) and extensively drug-resistant TB (XDR-TB) have been increasing. Fifteen of the world's 27 high MDR- and XDR-TB burden countries are in the World Health Organization (WHO) European Region, of which 10 are in Eastern Europe (including Baltic and Caucasus countries). To address the MDR- and XDR-TB situation in the WHO European Region, a Consolidated Action Plan to Prevent and Combat M/XDR-TB (2011-2015) was developed for all 53 Member States and implemented in 2011. Since the implementation of the Action Plan, the proportion of MDR-TB appears largely to have levelled off among bacteriologically confirmed TB cases in high-burden countries with universal or near universal (>95%) first-line drug susceptibility testing (DST). The treatment success rate, however, continues to decrease. A contributing factor is the substantial proportion of MDR-TB cases that are additionally resistant to either a fluoroquinolone, a second-line injectable agent or both (XDR-TB); high-burden country proportions range from 12.6% to 80.4%. Proportions of XDR-TB range from 5% to 24.8%. Despite much progress in Eastern Europe, critical challenges remain as regards access to appropriate treatment regimens; patient hospitalisation; scale-up of laboratory capacity, including the use of rapid diagnostics and second-line DST; vulnerable populations; human resources; and financing. Solutions to these challenges are aligned with the Post-2015 Global TB strategy. As a first step, the global strategy should be adapted at regional and country levels to serve as a framework for immediate actions as well as longer-term ways forward.

SUBMITTER: Acosta CD

PROVIDER: S-EPMC4547509 | biostudies-other | 2014 Oct

REPOSITORIES: biostudies-other

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Drug-resistant tuberculosis in Eastern Europe: challenges and ways forward.

Acosta C D CD Dadu A A Ramsay A A Dara M M

Public health action 20141001 Suppl 2

Encouragingly, global rates of new tuberculosis (TB) cases have been falling since 2005, in line with the Millennium Development Goal targets; however, cases of multidrug-resistant (MDR-) and extensively drug-resistant TB (XDR-TB) have been increasing. Fifteen of the world's 27 high MDR- and XDR-TB burden countries are in the World Health Organization (WHO) European Region, of which 10 are in Eastern Europe (including Baltic and Caucasus countries). To address the MDR- and XDR-TB situation in th ...[more]

PMID: 26393095

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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.

Project description:IntroductionSexually transmitted infections (STIs) remain prevalent and are increasing in several populations. Appropriate STI diagnosis is crucial to prevent the transmission and sequelae of untreated infection. We reviewed the diagnostic accuracy of syndromic case management and existing point-of-care tests (POCTs), including those in the pipeline, to diagnose STIs in resource-constrained settings.MethodsWe prioritized updating the systematic review and meta-analysis of the diagnostic accuracy of vaginal discharge from 2001 to 2015 to include studies until 2018. We calculated the absolute effects of different vaginal flowcharts and the diagnostic performance of POCTs on important outcomes. We searched the peer-reviewed literature for previously conducted systematic reviews and articles from 1990 to 2018 on the diagnostic accuracy of syndromic management of vaginal and urethral discharge, genital ulcer and anorectal infections. We conducted literature reviews from 2000 to 2018 on the existing POCTs and those in the pipeline.Results and discussionsThe diagnostic accuracy of urethral discharge and genital ulcer disease syndromes is relatively adequate. Asymptomatic Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections limit the use of vaginal discharge and anorectal syndromes. The pooled diagnostic accuracy of vaginal syndromic case management for CT/NG is low, resulting in high numbers of overtreatment and missed treatment. The absolute effect of POCTs was reduced overtreatment and missed treatment. Findings of the reviews on syndromic case management underscored the need for low-cost and accurate POCTs for the identification, first, of CT/NG, and, second, of Mycoplasma genitalium (MG) and Trichomonas vaginalis (TV) and NG and MG resistance/susceptibility testing. Near-patient POCT molecular assays for CT/NG/TV are commercially available. The prices of these POCTs remain the barrier for uptake in resource-constrained settings. This is driving the development of lower cost solutions.ConclusionsThe WHO syndromic case management guidelines should be updated to raise the quality of STI management through the integration of laboratory tests. STI screening strategies are needed to address asymptomatic STIs. POCTs that are accurate, rapid, simple and affordable are urgently needed in resource-constrained settings to support the uptake of aetiological diagnosis and treatment.

Project description:ObjectiveTransmission patterns of drug-resistant Mycobacterium tuberculosis (MTB) may be influenced by differences in socio-demographics, local tuberculosis (TB) endemicity and efficaciousness of TB control programs. This study aimed to investigate the impact of DOTS on the transmission of drug-resistant TB in eastern rural China.MethodsWe conducted a cross-sectional study of all patients diagnosed with drug-resistant TB over a one-year period in two rural Chinese counties with varying lengths of DOTS implementation. Counties included Deqing, with over 11 years' DOTS implementation and Guanyun, where DOTS was introduced 1 year prior to start of this study. We combined demographic, clinical and epidemiologic information with IS6110-based restricted fragment length polymorphism (RFLP) and Spoligotyping analysis of MTB isolates. In addition, we conducted DNA sequencing of resistance determining regions to first-line anti-tuberculosis agents.ResultsOf the 223 drug-resistant isolates, 73(32.7%) isolates were identified with clustered IS6110RFLP patterns. The clustering proportion among total drug-resistant TB was higher in Guanyun than Deqing (26/101.vs.47/122; p,0.04), but not significantly different among the 53 multidrug-resistant isolates (10/18.vs.24/35; p,0.35). Patients with cavitary had increased risk of clustering in both counties. In Guanyun, patients with positive smear test or previous treatment history had a higher clustering proportion. Beijing genotype and isolates resistant to isoniazid and/or rifampicin were more likely to be clustered. Of the 73 patients with clustered drug-resistant isolates, 71.2% lived in the same or neighboring villages. Epidemiological link (household and social contact) was confirmed in 12.3% of the clustered isolates.ConclusionTransmission of drug-resistant TB in eastern rural China is characterized by small clusters and limited geographic spread. Our observations highlight the need for supplementing DOTS with additional strategies, including active case finding at the village level, effective treatment for patients with cavities and drug susceptibility testing for patients at increased risk for drug-resistance.

Dataset Information

Drug-resistant tuberculosis in Eastern Europe: challenges and ways forward.

Publications

Drug-resistant tuberculosis in Eastern Europe: challenges and ways forward.

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