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Background: Among all WHO regions, the WHO European Region has the highest proportion of drug-resistant tuberculosis among new and retreated cases. The 18 high-priority countries in eastern Europe and central Asia account for 85% of the tuberculosis incidence and more than 90% of drug-resistant tuberculosis cases emerging in the region. We aimed to analyse time-series trends in notification rates of drug-resistant tuberculosis among new tuberculosis cases in the 18 high-priority countries in the WHO European Region.Methods: We used country data stored in WHO's global tuberculosis database. For each country, we calculated annual notification rates per 100 000 population of new tuberculosis cases and of drug-resistant tuberculosis among new cases reported from Jan 1, 2000, to Dec 31, 2017. We computed annual percentage changes of notification rates and identified time-points of significant change in trends using the joinpoint regression method.Findings: All 17 countries with data (no data available from Turkmenistan) showed a significant decline in new tuberculosis notification rates in the most recent years since the last joinpoint if one was identified. Notification rates of drug-resistant tuberculosis showed diverse trends, with substantial year-to-year variation. In the most recent years, notification rates of drug-resistant tuberculosis among new tuberculosis cases were decreasing in two countries (Estonia and Latvia), increasing in eight countries (Azerbaijan, Kyrgyzstan, Moldova [Republic of Moldova], Romania, Russia [Russian Federation], Tajikistan, Ukraine, and Uzbekistan), and stable in seven countries (Armenia, Belarus, Bulgaria, Georgia, Kazakhstan, Lithuania, and Turkey).Interpretation: Our findings suggest that countries in the WHO European Region are more successful in controlling drug-susceptible tuberculosis than drug-resistant forms, and as a result, the proportion of drug-resistant strains among newly notified patients with tuberculosis is increasing in many settings. Two countries showed that it is possible to decrease incidence of both drug-susceptible and drug-resistant tuberculosis. If no additional efforts are made in prevention and care of patients with drug-resistant tuberculosis, further decline of the tuberculosis burden will be halted. Further studies are needed to investigate the success stories and document the most effective interventions to reach the target to end tuberculosis by 2030.Funding: United States Agency for International Development. [ABSTRACT FROM AUTHOR]

Background: The risk of tuberculosis outbreaks among people fleeing hardship for refuge in Europe is heightened. We describe the cross-border European response to an outbreak of multidrug-resistant tuberculosis among patients from the Horn of Africa and Sudan.Methods: On April 29 and May 30, 2016, the Swiss and German National Mycobacterial Reference Laboratories independently triggered an outbreak investigation after four patients were diagnosed with multidrug-resistant tuberculosis. In this molecular epidemiological study, we prospectively defined outbreak cases with 24-locus mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) profiles; phenotypic resistance to isoniazid, rifampicin, ethambutol, pyrazinamide, and capreomycin; and corresponding drug resistance mutations. We whole-genome sequenced all Mycobacterium tuberculosis isolates and clustered them using a threshold of five single nucleotide polymorphisms (SNPs). We collated epidemiological data from host countries from the European Centre for Disease Prevention and Control.Findings: Between Feb 12, 2016, and April 19, 2017, 29 patients were diagnosed with multidrug-resistant tuberculosis in seven European countries. All originated from the Horn of Africa or Sudan, with all isolates two SNPs or fewer apart. 22 (76%) patients reported their travel routes, with clear spatiotemporal overlap between routes. We identified a further 29 MIRU-VNTR-linked cases from the Horn of Africa that predated the outbreak, but all were more than five SNPs from the outbreak. However all 58 isolates shared a capreomycin resistance-associated tlyA mutation.Interpretation: Our data suggest that source cases are linked to an M tuberculosis clone circulating in northern Somalia or Djibouti and that transmission probably occurred en route before arrival in Europe. We hypothesise that the shared mutation of tlyA is a drug resistance mutation and phylogenetic marker, the first of its kind in M tuberculosis sensu stricto.Funding: The Swiss Federal Office of Public Health, the University of Zurich, the Wellcome Trust, National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC), the Medical Research Council, BELTA-TBnet, the European Union, the German Center for Infection Research, and Leibniz Science Campus Evolutionary Medicine of the Lung (EvoLUNG). [ABSTRACT FROM AUTHOR]

Tuberculosis is over-represented in hard-to-reach (underserved) populations in high-income countries of low tuberculosis incidence. The mainstay of tuberculosis care is early detection of active tuberculosis (case finding), contact tracing, and treatment completion. We did a systematic review with a scoping component of relevant studies published between 1990 and 2015 to update and extend previous National Institute for Health and Care Excellence (NICE) reviews on the effectiveness of interventions for identifying and managing tuberculosis in hard-to-reach populations. The analyses showed that tuberculosis screening by (mobile) chest radiography improved screening coverage and tuberculosis identification, reduced diagnostic delay, and was cost-effective among several hard-to-reach populations. Sputum culture for pre-migration screening and active referral to a tuberculosis clinic improved identification. Furthermore, monetary incentives improved tuberculosis identification and management among drug users and homeless people. Enhanced case management, good cooperation between services, and directly observed therapy improved treatment outcome and compliance. Strong conclusions cannot be drawn because of the heterogeneity of evidence with regard to study population, methodology, and quality. [ABSTRACT FROM AUTHOR]

Tuberculosis disproportionately affects hard-to-reach populations, such as homeless people, migrants, refugees, prisoners, or drug users. These people often face challenges in accessing quality health care. We did a systematic review of the qualitative literature to identify barriers and facilitators to the uptake of tuberculosis diagnostic and treatment services by people from hard-to-reach populations in all European Union (EU), European Economic Area, EU candidate, and Organisation for Economic Co-operation and Development countries. The 12 studies included in this review mainly focused on migrants. Views on perceived susceptibility to and severity of tuberculosis varied widely and included many misconceptions. Stigma and challenges regarding access to health care were identified as barriers to tuberculosis diagnosis and treatment uptake, whereas support from nurses, family, and friends was a facilitator for treatment adherence. Further studies are required to identify barriers and facilitators to the improved identification and management of tuberculosis in hard-to-reach populations to inform recommendations for more effective tuberculosis control programmes. [ABSTRACT FROM AUTHOR]