Vahur Hollo

Eligibility for shorter treatment of multidrug-resistant tuberculosis in the European Union

In May 2016, the World Health Organization (WHO) updated its treatment guidelines for drug-resistant tuberculosis (TB) and included a recommendation for the use of the shorter multidrug-resistant (MDR) TB regimen [1]. The WHO update is based on information provided by observational studies coordinated by the International Union Against Tuberculosis and Lung Disease, Médecins sans Frontières and the Damien Foundation which showed that the shorter treatment regimen resulted in a higher likelihood of treatment success compared to the longer conventional treatment in the study settings [2–5]. The shorter MDR-TB regimen consists of a standardised treatment course lasting 9–12 months and includes kanamycin, moxifloxacin, prothionamide, clofazimine, pyrazinamide, isoniazid and ethambutol. It is recommended for patients with rifampicin-resistant (RR) or MDR-TB (cases with TB bacilli resistant to at least isoniazid and rifampicin) who have not been treated previously with second-line drugs and in whom resistance to fluoroquinolones and second-line injectable agents has been excluded or is considered highly unlikely. It is not recommended for pregnant women and patients with extrapulmonary TB. In the European Union, 11% of all MDR-TB cases are eligible for the shorter MDR-TB regimen http://ow.ly/kukg306AcFl

Tuberculosis treatment outcome in the European Union and European Economic Area: an analysis of surveillance data from 2002‒2011

Monitoring the treatment outcome (TO) of tuberculosis (TB) is essential to evaluate the effectiveness of the intervention and to identify potential barriers for TB control. The global target is to reach a treatment success rate (TSR) of at least 85%. We aimed to assess the TB TO in the European Union and European Economic Area (EU/EEA) between 2002 and 2011, and to identify factors associated with unsuccessful treatment. Only 18 countries reported information on TO for the whole observation period accounting for 250,854 new culture-confirmed pulmonary TB cases. The 85% target of TSR was not reached in any year between 2002 and 2011 and was on average 78%. The TSR for multidrug-resistant (MDR)-TB cases at 24-month follow-up was 49%. In the multivariable regression model, unsuccessful treatment was significantly associated with increasing age (odds ratio (OR) = 1.02 per a one-year increase, 95% confidence interval (CI): 1.02-1.02), MDR-TB (OR = 8.7, 95% CI: 5.09-14.97), male sex (OR = 1.40, 95% CI: 1.28-1.52), and foreign origin (OR = 1.32, 95% CI: 1.03-1.70). The data highlight that special efforts are required for patients with MDR-TB and the elderly aged ≥65 years, who have particularly low TSR. To allow for valid monitoring at EU level all countries should aim to report TO for all TB cases.

The effect of migration within the European Union/European Economic Area on the distribution of tuberculosis, 2007 to 2013.

Immigration from tuberculosis (TB) high-incidence countries is known to contribute notably to the TB burden in low-incidence countries. However, the effect of migration enabled by the free movement of persons within the European Union (EU)/European Economic Area (EEA) on TB notification has not been analysed. We analysed TB surveillance data from 29 EU/EEA countries submitted for the years 2007-2013 to The European Surveillance System. We used place of birth and nationality as proxy indicators for native, other EU/EEA and non-EU/EEA origin of the TB cases and analysed the characteristics of the subgroups by origin. From 2007-2013, a total of 527,467 TB cases were reported, of which 129,781 (24.6%) were of foreign origin including 12,566 (2.4%) originating from EU/EEA countries other than the reporting country. The countries reporting most TB cases originating from other EU/EEA countries were Germany and Italy, and the largest proportion of TB cases in individuals came from Poland (n=1,562) and Romania (n=6,285). At EU/EEA level only a small proportion of foreign TB cases originated from other EU/EEA countries, however, the uneven distribution of this presumed importation may pose a challenge to TB programmes in some countries.

Tuberculosis and HIV coinfection in Europe: looking at one reality from two angles.

Objective:To better understand the epidemiology of tuberculosis (TB)/HIV coinfection in the European Union (EU) and European Economic Area (EEA) for planning of prevention and control measures. Design:Analysis of surveillance data. Methods:We performed an analysis of the 2014 TB and AIDS data to assess the burden of TB/HIV coinfection and we applied multivariable logistic regression to evaluate predictors for coinfection. Results:Twenty-one of 31 EU/EEA countries reported HIV testing results for 64.6% of the 32 892 notified TB cases. Of those, 1051 (4.9%) were reported as HIV-positive. Males [adjusted odds ratio (aOR) 1.25; 95% confidence interval (CI) 1.07–1.46] and those in age group 25–44 years were more frequently coinfected. TB cases originating from the WHO African region had the highest proportion of coinfection (aOR 3.28 versus origin in EU/EEA; 95% CI 2.35–4.57). TB treatment was completed successfully by 57.9% of HIV-positive TB cases and 83.5% of HIV-negative cases. In 2014, 3863 cases of AIDS were reported by 29 EU/EEA countries; 691 (17.9%) of these cases presented with TB as an AIDS-defining illness. Persons who had acquired HIV through injecting drug use had higher odds of TB as an AIDS-defining illness (aOR 1.78 versus heterosexual route of transmission; 95% CI 1.37–2.32). Conclusion:TB/HIV coinfection is a substantial problem in the EU/EEA. The occurrence of TB in HIV-positive cases and the low TB treatment success rate suggest that international guidelines for prevention and treatment of TB in HIV-infected adults need to be better implemented.

Impact of HIV infection on treatment outcome of tuberculosis in Europe.

Background:The effect of HIV on tuberculosis (TB) treatment outcomes has not been well established. We aimed to assess the impact of HIV infection on TB treatment outcomes by using data from notifiable disease surveillance in Europe. Methods:We analyzed the treatment outcomes of TB cases reported from nine European countries during 2010–2012. We investigate the effect of HIV on TB treatment outcomes using a multilevel and a multinomial logistic model, and considering the interaction between HIV and multidrug-resistant (MDR) TB. Results:A total of 61 138 TB cases including 5.5% HIV-positive were eligible for our analysis. In the multilevel model adjusted for age and an interaction with MDR TB, HIV was significantly associated with lower treatment success in all MDR strata [non-MDR TB: odds ratio (OR) 0.24 CI (confidence interval) 0.20–0.29; unknown MDR TB status: OR 0.26 CI 0.23–0.30; MDR TB: OR 0.57 CI 0.35–0.91]. In the multinomial regression model, HIV-positive cases had significantly higher relative risk ratio (RRR) for death (non-MDR TB: RRR 4.30 CI 2.31–7.99; unknown MDR TB status: 5.55 CI 3.10–9.92; MDR TB: 3.59 CI 1.56–8.28) and being ‘still on treatment’ (non-MDR TB: RRR 7.27 CI 3.00–17.6; unknown MDR TB status: 5.36 CI 2.44–11.8; MDR TB: 3.76 CI 2.48–5.71). We did not find any significant association between HIV and TB treatment failure (non-MDR TB: RRR 0.50 CI 0.15–1.67; unknown MDR TB status: 1.51 CI 0.86–2.64; MDR TB: 0.51 CI 0.13–1.87). Conclusion:This large study confirms that HIV is a strong risk factor for an adverse TB treatment outcome, which is mainly manifested by an increased risk of death and still being on TB treatment.

Tuberculosis notification rate decreases faster in residents of native origin than in residents of foreign origin in the EU/EEA, 2010 to 2015

To estimate trends in tuberculosis (TB) notification rates by geographical origin, we retrieved surveillance data from 2010 to 2015 for 29 European Union and European Economic Area countries. The TB notification rate decreased at an annual rate of 5.3%. The decrease in notification rate was higher in native residents (7.0%) than in those of foreign origin (3.7%). Targeted screening and facilitated access to care and treatment could help prevent and control TB in migrants.

Is tuberculosis crossing borders at the Eastern boundary of the European Union

Background: The Eastern border of the European Union (EU) consists of 10 countries after the expansion of the EU in 2004 and 2007. These 10 countries border to the East to countries with high tuberculosis (TB) notification rates. We analyzed the notification data of Europe to quantify the impact of cross-border TB at the Eastern border of the EU. Methods: We used TB surveillance data of 2010 submitted by 53 European Region countries to the European Centre for Disease Prevention and Control and the World Health Organization Regional Office for Europe. Notified TB cases were stratified by origin of the case (national/foreign). We calculated the contribution of foreign to overall TB notification. Results: In the 10 EU countries located at the EU Eastern border, 618 notified TB cases (1.7% of all notified TB cases) were of foreign origin. Of those 618 TB cases, 173 (28.0%) were from countries bordering the EU to the East. More specifically, 90 (52.0%) were from Russia, 33 (19.1%) from Belarus, 33 (19.1%) from Ukraine, 13 (7.5%) from Moldova and 4 (2.3%) from Turkey. Conclusions: Currently, migrants contribute little to TB notifications in the 10 EU countries at the Eastern border of the EU, but changes in migration patterns may result in an increasing contribution. Therefore, EU countries at the Eastern border of the EU should strive to provide prompt diagnostic services and adequate treatment of migrants.

Determinants of site of tuberculosis disease: An analysis of European surveillance data from 2003 to 2014

Background We explored host-related factors associated with the site of tuberculosis (TB) disease using variables routinely collected by the 31 EU/EEA countries for national surveillance. Methods Logistic regression models were fitted to case-based surveillance data reported to the European Centre for Disease Prevention and Control for TB cases notified from 2003 to 2014. Missing data on HIV infection and on susceptibility to isoniazid and rifampicin for many patients precluded the inclusion of these variables in the analysis. Records from Finland, Lithuania, Spain and the United Kingdom were excluded for lack of exact details of disease localisation; other records without one or more variable (e.g. previous treatment history, geographical origin) or who had mixed pulmonary and extrapulmonary disease or more than one form of extrapulmonary disease were also removed (total exclusion = 38% of 913,637 notifications). Results 564,916 TB cases reported by 27 EU/EEA countries had exclusive pulmonary (PTB; 83%) or extrapulmonary (EPTB; 17%) disease. EPTB was associated with age <15 years (aOR: 5.50), female sex (aOR: 1.60), no previous TB treatment (aOR: 3.10), and geographic origin (aOR range: 0.52–3.74). Origin from the Indian subcontinent or Africa was most strongly associated with lymphatic, osteo-articular and peritoneal/digestive localization (aOR>3.7), and age <15 years with lymphatic (aOR: 17.96) and central nervous system disease (aOR: 11.41). Conclusions Awareness of host-related determinants of site of TB is useful for diagnosis. The predilection for EPTB among patients originating from countries outside Europe may reflect strain preferences for disease localization, geographic/ethnic differences in disease manifestation and other factors, like HIV.

Complete republication: Epidemiology of tuberculosis in the EU/EEA in 2010 - Monitoring the progress towards tuberculosis elimination.

The 2012 combined tuberculosis (TB) surveillance and monitoring report for the European Union and European Economic Area identifies a mean annual decline in TB notification rate by 4.4% from 2006 to 2010. Culture confirmation for new pulmonary cases and drug susceptibility testing have increased to 65.6% and 70.8%, but remain under their targets of 80% and 100%, respectively. Reporting of treatment outcome and coinfection with human immunodeficiency virus also remain suboptimal. Strengthened control practices are needed to allow progress towards TB elimination.