A pilot sentinel surveillance system to monitor treatment and treatment outcomes of chronic hepatitis B and C infections in clinical centres in three European countries, 2019.

BackgroundThe World Health Organization European Action Plan 2020 targets for the elimination of viral hepatitis are that > 75% of eligible individuals with chronic hepatitis B (HBV) or hepatitis C (HCV) are treated, of whom > 90% achieve viral suppression.AimTo report the results from a pilot sentinel surveillance to monitor chronic HBV and HCV treatment uptake and outcomes in 2019.MethodsWe undertook retrospective enhanced data collection on patients with a confirmed chronic HBV or HCV infection presenting at one of seven clinics in three countries (Croatia, Romania and Spain) for the first time between 1 January 2019 and 30 June 2019. Clinical records were reviewed from date of first attendance to 31 December 2019 and data on sociodemographics, clinical history, laboratory results, treatment and treatment outcomes were collected. Treatment eligibility, uptake and case outcome were assessed.ResultsOf 229 individuals with chronic HBV infection, treatment status was reported for 203 (89%). Of the 80 individuals reported as eligible for treatment, 51% (41/80) were treated of whom 89% (33/37) had achieved viral suppression. Of 240 individuals with chronic HCV infection, treatment status was reported for 231 (96%). Of 231 eligible individuals, 77% (179/231) were treated, the majority of whom had received direct acting antivirals (99%, 174/176) and had achieved sustained virological response (98%, 165/169).ConclusionTreatment targets for global elimination were missed for HBV but not for HCV. A wider European implementation of sentinel surveillance with a representative sample of sites could help monitor progress towards achieving hepatitis control targets.

Effect of neuraminidase inhibitor (oseltamivir) treatment on outcome of hospitalised influenza patients, surveillance data from 11 EU countries, 2010 to 2020.

BackgroundTimely treatment with neuraminidase inhibitors (NAI) can reduce severe outcomes in influenza patients.AimWe assessed the impact of antiviral treatment on in-hospital deaths of laboratory-confirmed influenza patients in 11 European Union countries from 2010/11 to 2019/20.MethodsCase-based surveillance data from hospitalised patients with known age, sex, outcome, ward, vaccination status, timing of antiviral treatment, and hospitalisation were obtained. A mixed effect logistic regression model using country as random intercept was applied to estimate the adjusted odds ratio (aOR) for in-hospital death in patients treated with NAIs vs not treated.ResultsOf 19,937 patients, 31% received NAIs within 48 hours of hospital admission. Older age (60-79 years aOR 3.0, 95% CI: 2.4-3.8; 80 years 8.3 (6.6-10.5)) and intensive care unit admission (3.8, 95% CI: 3.4-4.2) increased risk of dying, while early hospital admission after symptom onset decreased risk (aOR 0.91, 95% CI: 0.90-0.93). NAI treatment initiation within 48 hours and up to 7 days reduced risk of dying (0-48 hours aOR 0.51, 95% CI: 0.45-0.59; 3-4 days 0.59 (0.51-0.67); 5-7 days 0.64 (0.56-0.74)), in particular in patients 40 years and older (e.g. treatment within 48 hours: 40-59 years aOR 0.43, 95% CI: 0.28-0.66; 60-79 years 0.50 (0.39-0.63); ≥80 years 0.51 (0.42-0.63)).ConclusionNAI treatment given within 48 hours and possibly up to 7 days after symptom onset reduced risk of in-hospital death. NAI treatment should be considered in older patients to prevent severe outcomes.

A joint cross-border investigation of a cluster of multidrug-resistant tuberculosis in Austria, Romania and Germany in 2014 using classic, genotyping and whole genome sequencing methods: lessons learnt.

Molecular surveillance of multidrug-resistant tuberculosis (MDR-TB) using 24-loci MIRU-VNTR in the European Union suggests the occurrence of international transmission. In early 2014, Austria detected a molecular MDR-TB cluster of five isolates. Links to Romania and Germany prompted the three countries to investigate possible cross-border MDR-TB transmission jointly. We searched genotyping databases, genotyped additional isolates from Romania, used whole genome sequencing (WGS) to infer putative transmission links, and investigated pairwise epidemiological links and patient mobility. Ten isolates from 10 patients shared the same 24-loci MIRU-VNTR pattern. Within this cluster, WGS defined two subgroups of four patients each. The first comprised an MDR-TB patient from Romania who had sought medical care in Austria and two patients from Austria. The second comprised patients, two of them epidemiologically linked, who lived in three different countries but had the same city of provenance in Romania. Our findings strongly suggested that the two cases in Austrian citizens resulted from a newly introduced MDR-TB strain, followed by domestic transmission. For the other cases, transmission probably occurred in the same city of provenance. To prevent further MDR-TB transmission, we need to ensure universal access to early and adequate therapy and collaborate closely in tuberculosis care beyond administrative borders.

Surveillance for severe acute respiratory infections (SARI) in hospitals in the WHO European region - an exploratory analysis of risk factors for a severe outcome in influenza-positive SARI cases.

BACKGROUND: The 2009 H1N1 pandemic highlighted the need to routinely monitor severe influenza, which lead to the establishment of sentinel hospital-based surveillance of severe acute respiratory infections (SARI) in several countries in Europe. The objective of this study is to describe characteristics of SARI patients and to explore risk factors for a severe outcome in influenza-positive SARI patients. METHODS: Data on hospitalised patients meeting a syndromic SARI case definition between 2009 and 2012 from nine countries in Eastern Europe (Albania, Armenia, Belarus, Georgia, Kazakhstan, Kyrgyzstan, Romania, Russian Federation and Ukraine) were included in this study. An exploratory analysis was performed to assess the association between risk factors and a severe (ICU, fatal) outcome in influenza-positive SARI patients using a multivariate logistic regression analysis. RESULTS: Nine countries reported a total of 13,275 SARI patients. The majority of SARI patients reported in these countries were young children. A total of 12,673 SARI cases (95%) were tested for influenza virus and 3377 (27%) were laboratory confirmed. The majority of tested SARI cases were from Georgia, the Russian Federation and Ukraine and the least were from Kyrgyzstan. The proportion positive varied by country, season and age group, with a tendency to a higher proportion positive in the 15+ yrs age group in six of the countries. ICU admission and fatal outcome were most often recorded for influenza-positive SARI cases aged > 15 yrs. An exploratory analysis using pooled data from influenza-positive SARI cases in three countries showed that age > 15 yrs, having lung, heart, kidney or liver disease, and being pregnant were independently associated with a fatal outcome. CONCLUSIONS: Countries in Eastern Europe have been able to collect data through routine monitoring of severe influenza and results on risk factors for a severe outcome in influenza-positive SARI cases have identified several risk groups. This is especially relevant in the light of an overall low vaccination uptake and antiviral use in Eastern Europe, since information on risk factors will help in targeting and prioritising vulnerable populations.

Seasonal and inter-seasonal RSV activity in the European Region during the COVID-19 pandemic from autumn 2020 to summer 2022.

Background: The emergence of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in early 2020 and subsequent implementation of public health and social measures (PHSM) disrupted the epidemiology of respiratory viruses. This work describes the epidemiology of respiratory syncytial virus (RSV) observed during two winter seasons (weeks 40-20) and inter-seasonal periods (weeks 21-39) during the pandemic between October 2020 and September 2022. Methods: Using data submitted to The European Surveillance System (TESSy) by countries or territories in the World Health Organization (WHO) European Region between weeks 40/2020 and 39/2022, we aggregated country-specific weekly RSV counts of sentinel, non-sentinel and Severe Acute Respiratory Infection (SARI) surveillance specimens and calculated percentage positivity. Results for both 2020/21 and 2021/22 seasons and inter-seasons were compared with pre-pandemic 2016/17 to 2019/20 seasons and inter-seasons. Results: Although more specimens were tested than in pre-COVID-19 pandemic seasons, very few RSV detections were reported during the 2020/21 season in all surveillance systems. During the 2021 inter-season, a gradual increase in detections was observed in all systems. In 2021/22, all systems saw early peaks of RSV infection, and during the 2022 inter-seasonal period, patterns of detections were closer to those seen before the COVID-19 pandemic. Conclusion: RSV surveillance continued throughout the COVID-19 pandemic, with an initial reduction in transmission, followed by very high and out-of-season RSV circulation (summer 2021) and then an early start of the 2021/22 season. As of the 2022/23 season, RSV circulation had not yet normalised.

Pertussis seroprevalence among adults of reproductive age (20-39 years) in fourteen European countries.

The reported incidence of pertussis in European countries varies considerably. We aimed to study specific Bordetella pertussis seroprevalence in Europe by measuring serum IgG antibody levels to pertussis toxin (anti-PT IgG). Fourteen national laboratories participated in this study including Belgium, Denmark, Finland, Greece, Hungary, Italy, Lithuania, Malta, Norway, Poland, Portugal, Romania, Spain, and Sweden. Each country collected approximately 250 samples (N = 7903) from the age groups 20-29 years (N = 3976) and 30-39 years (N = 3927) during 2010-2013. Samples were anonymous residual sera from diagnostic laboratories and were analyzed at the national laboratories by a Swedish reference method, a commercial ELISA kit, or were sent to Sweden for analysis. The median anti-PT IgG concentrations ranged from 4 to 13.6 IU/mL. The proportion of samples with anti-PT IgG ≥100 IU/mL, indicating a recent infection ranged from 0.2% (Hungary) to 5.7% (Portugal). The highest proportion of sera with anti-PT IgG levels between 50 and <100 IU/mL, indicating an infection within the last few years, was found in Portugal (12.3%) and Italy (13.9%). This study shows that the circulation of B. pertussis is quite extensive in adults, aged 20-39 years, despite well-established vaccination programs in Europe.

Circulation of pertussis and poor protection against diphtheria among middle-aged adults in 18 European countries.

Reported incidence of pertussis in the European Union (EU) and the European Economic Area (EEA) varies and may not reflect the real situation, while vaccine-induced protection against diphtheria and tetanus seems sufficient. We aimed to determine the seroprevalence of DTP antibodies in EU/EEA countries within the age groups of 40-49 and 50-59 years. Eighteen countries collected around 500 samples between 2015 and 2018 (N = 10,302) which were analysed for IgG-DTP specific antibodies. The proportion of sera with pertussis toxin antibody levels ≥100 IU/mL, indicative of recent exposure to pertussis was comparable for 13/18 countries, ranging between 2.7-5.8%. For diphtheria the proportion of sera lacking the protective level (<0.1 IU/mL) varied between 22.8-82.0%. For tetanus the protection was sufficient. Here, we report that the seroprevalence of pertussis in these age groups indicates circulation of B. pertussis across EU/EEA while the lack of vaccine-induced seroprotection against diphtheria is of concern and deserves further attention.

Determinants of Fatal Outcome in Patients Admitted to Intensive Care Units With Influenza, European Union 2009-2017.

BACKGROUND: Morbidity, severity, and mortality associated with annual influenza epidemics are of public health concern. We analyzed surveillance data on hospitalized laboratory-confirmed influenza cases admitted to intensive care units to identify common determinants for fatal outcome and inform and target public health prevention strategies, including risk communication. METHODS: We performed a descriptive analysis and used Poisson regression models with robust variance to estimate the association of age, sex, virus (sub)type, and underlying medical condition with fatal outcome using European Union data from 2009 to 2017. RESULTS: Of 13 368 cases included in the basic dataset, 2806 (21%) were fatal. Age ≥40 years and infection with influenza A virus were associated with fatal outcome. Of 5886 cases with known underlying medical conditions and virus A subtype included in a more detailed analysis, 1349 (23%) were fatal. Influenza virus A(H1N1)pdm09 or A(H3N2) infection, age ≥60 years, cancer, human immunodeficiency virus infection and/or other immune deficiency, and heart, kidney, and liver disease were associated with fatal outcome; the risk of death was lower for patients with chronic lung disease and for pregnant women. CONCLUSIONS: This study re-emphasises the importance of preventing influenza in the elderly and tailoring strategies to risk groups with underlying medical conditions.

A seroprevalence study for hepatitis B virus markers of infection in pregnant women in Romania: results and opportunities for prevention.

BACKGROUND AND AIMS: The Action Plan for viral hepatites in the WHO European Region aims to eliminate them as a public health threat by the end of 2030. The hepatitis B virus (HBV) perinatal transmission is a problem of major concern. The aim of our study was to estimate the prevalence of HBV markers in pregnant women in Romania, as scientific evidence for recommending public health interventions. METHODS: The serum samples were prospectively collected in randomly selected maternities, from pregnant women admitted for birth beginning with July 1st, 2016. Signed informed consent was requested and the confidentiality of personal data was assured. The laboratory investigations were performed in two regional public health laboratories. RESULTS: The prevalence of HBsAg was 5.1%. Among HBsAg positives, the HBeAg was present in 7.4% and the anti-HBeAb were detected in 55.6% of the pregnant women. CONCLUSION: The results of the study were comparable to those in 2013 for the women of the same age group, which proves the need for established public health interventions leading to reducing, and halting HBV transmission in the population. .

Estimating burden of influenza-associated influenza-like illness and severe acute respiratory infection at public healthcare facilities in Romania during the 2011/12-2015/16 influenza seasons.

BACKGROUND: Influenza is responsible for substantial morbidity and mortality, but there is limited information on reliable disease burden estimates, especially from middle-income countries in the WHO European Region. OBJECTIVES: To estimate the incidence of medically attended influenza-associated influenza-like illness (ILI) and hospitalizations due to severe acute respiratory infection (SARI) presenting to public healthcare facilities in Romania. PATIENTS/METHODS: Sentinel influenza surveillance data for ILI and SARI from 2011/12-2015/16, including virological data, were used to estimate influenza-associated ILI and SARI incidence/100 000 and their 95% confidence intervals (95% CI). RESULTS: The overall annual incidence of ILI and influenza-associated ILI per 100 000 persons in Romania varied between 68 (95% CI: 61-76) and 318 (95% CI: 298-338) and between 23 (95% CI: 19-29) and 189 (95% CI: 149-240), respectively. The highest ILI and influenza incidence was among children aged 0-4 years. We estimated that SARI incidence per 100 000 persons was 6 (95% CI: 5-7) to 9 (95% CI: 8-10), of which 2 (95% CI: 1-2) to 3 (95% CI: 2-4) were due to influenza. Up to 0.3% of the Romanian population were annually reported with ILI, and 0.01% was hospitalized with SARI, of which as much as one-third could be explained by influenza. CONCLUSIONS: This evaluation was the first study estimating influenza burden in Romania. We found that during each influenza season, a substantial number of persons in Romania suffer from influenza-related ILI or are hospitalized due to influenza-associated SARI.

A Seroprevalence Study of Hepatitis B and C Virus Infections in a Hospitalized Population in Romania, an Opportunity for a Better National Prevention and Control Strategy.

BACKGROUND AND AIMS: The most recent prevalence data for hepatitis B virus (HBV) infection in Romania came from an ESEN 2 study (2002), and from a Romanian population-based study performed in 2008. Most of the previous studies were regional and performed in specific groups (blood donors, pregnant women, institutionalized people, etc) and had limited representativeness at the national level, both for HBV and hepatitis C virus (HCV) infection. The scarcity of prevalence data for HBV and HCV infection coming from the routine surveillance was also considered. The aim of our study was to obtain overall and age group specific estimates of the prevalence of HBV and HCV infections markers in Romania, in order to recommend evidence-based public health interventions. The main outcome was the proportion of persons with HBV, HCV and HBV+HCV infection markers, overall and by age group and gender. METHODS: Our seroprevalence study ensured national representativeness for the targeted hospitalized population. A prospective collection of serum samples in hospital laboratories was completed between September and November 2013, using a systematic sampling. The study respected the confidentiality of personal data. We calculated the sample size using EpiInfo7 and used Z test - Two-tailed probability for statistical significance. RESULTS: The overall prevalence data estimated in our study were HBc Ab 28%, HBs Ag 4.2%, HBs Ab regardless of titer 64.1%, HBs Ab in titer of at least 10 mUI/ml and negative HBc Ab 17.5%; HCV Ab 5.6%; HBc Ab and HCV Ab 2.8%, as markers of double infection. CONCLUSION: The overall prevalence data estimated in our study for HBs Ag (4.2%) and HCV Ab (5.6%) correspond to a medium endemicity based on the WHO criteria. The estimated prevalence of HBV and HCV infection markers in the study population should represent an opportunity for a better national prevention and control strategy.

Risk factors associated with fatal influenza, Romania, October 2009-May 2011.

BACKGROUND: Limited data are available from Central and Eastern Europe on risk factors for severe complications of influenza. Such data are essential to prioritize prevention and treatment resources and to adapt influenza vaccination recommendations. OBJECTIVES: To use sentinel surveillance data to identify risk factors for fatal outcomes among hospitalized patients with severe acute respiratory infections (SARI) and among hospitalized patients with laboratory-confirmed influenza. METHODS: Retrospective analysis of case-based surveillance data collected from sentinel hospitals in Romania during the 2009/2010 and 2010/2011 winter influenza seasons was performed to evaluate risk factors for fatal outcomes using multivariate logistic regression. RESULTS: During 2009/2010 and 2010/2011, sentinel hospitals reported 661 SARI patients of which 230 (35%) tested positive for influenza. In the multivariate analyses, infection with influenza A(H1N1)pdm09 was the strongest risk factor for death among hospitalized SARI patients (OR: 6·6; 95% CI: 3·3-13·1). Among patients positive for influenza A(H1N1)pdm09 virus infection (n = 148), being pregnant (OR: 7·1; 95% CI: 1·6-31·2), clinically obese (OR: 2·9;95% CI: 1·6-31·2), and having an immunocompromising condition (OR: 3·7;95% CI: 1·1-13·4) were significantly associated with fatal outcomes. CONCLUSION: These findings are consistent with several other investigations of risk factors associated with influenza A(H1N1)pdm09 virus infections. They also support the more recent 2012 recommendations by the WHO Strategic Advisory Group of Experts on Immunization (SAGE) that pregnant women are an important risk group for influenza vaccination. Ongoing sentinel surveillance can be useful tool to monitor risk factors for complications of influenza virus infections during each influenza season, and pandemics as well.