Implications of a change in case definition and screening of asylum seekers for hepatitis B surveillance in Germany in 2015 and 2016.

Since 2015, the number of hepatitis B virus (HBV) cases increased substantially in Germany. In 2015, a more sensitive HBV case definition was introduced. This coincided with an asylum seeker influx with differing screening strategies. Information on the asylum seeker status has been collected since 09/2015. We investigated this increase to interpret HBV notification data in Germany. We compared HBV surveillance data from 2010-2013 (baseline) with 2015-2016, excluding 2014 due to beginning of asylum seeker influx. We estimated the excess above the mean case number (baseline) using Poisson regression and compared asylum seeker cases and the excess of cases with the unknown asylum seeker status. HBV cases increased from 1855 (mean baseline) to 3873 (2015) and 3466 (2016) with 1903 asylum seeker cases and 1099 excess-cases with the unknown asylum seeker status in 2015-2016. Cases only fulfilling the changed case definition increased from 60% (1119) in baseline to 81% (P < 0.01) in 2015-2016; 69% of asylum seeker cases and 61% of excess-cases were males <40 years compared to 27% (baseline) (P < 0.01). Changed case definition increased the number of cases in official statistics substantially. Demographic and geographical distributions suggest that screening of asylum seekers increased the case numbers even to a higher extent than surveillance data indicates.

Are men who have sex with men in Europe protected from hepatitis B?

Hepatitis B vaccination is recommended for men who have sex with men (MSM) in many countries, but information on vaccine coverage is scarce. We studied hepatitis B vaccination programmes and coverage among MSM in Europe to guide prevention. From a large (N = 174 209) pan-European MSM survey (EMIS-2010), we used data on self-reported hepatitis B vaccination, age, education, settlement size and disclosure of the same-sex sexual orientation ('outness'). We excluded participants with a history of hepatitis B. In multilevel (participants, countries) logistic regression models, we calculated adjusted odds ratios (aOR) with 95% confidence intervals (95% CI). We analysed data of 163 987 MSM in 38 European countries: 38.3% were 'out' to all or almost all, 56.4% reported vaccination against hepatitis B and 65.5% lived in countries with free recommended hepatitis B vaccination for MSM. In the final model the odds for being vaccinated increased with outness ('out to all or almost all': aOR 1.76, 95% CI 1.70-1.83 vs. 'out to no one') and with living in countries, where hepatitis B vaccination was recommended and free-of-charge for MSM (aOR 2.21, 95% CI 1.47-3.32 vs. 'no or unclear recommendation'). To increase hepatitis B vaccination coverage among MSM, implementation of MSM-specific recommendations and improvement of the societal climate for MSM is needed.

Evaluation of the German surveillance system for hepatitis B regarding timeliness, data quality, and simplicity, from 2005 to 2014.

OBJECTIVES: Germany has a mandatory surveillance system for acute hepatitis B (AHB) with the Protection against Infection Act as the legal basis in place since 2001. An amendment was introduced in 2013. We aimed at evaluating the surveillance systems' performance regarding timeliness, data quality, and simplicity from 2005 to 2014 and at assessing the effect of the amendment on timeliness of AHB surveillance. STUDY DESIGN: This study is a trend analysis of surveillance data. METHODS: Aspects of simplicity versus complexity of the surveillance system were assessed by describing data flow, levels of reporting, and data management procedures. Data quality, in terms of data completeness, was evaluated by quantitative indicators, and timeliness was measured in days between different levels of the surveillance system, notification delay, and reporting delay. Trends over time in data quality were analyzed by logistic regression, while negative binomial regression was used to test for trend over time regarding mean notification and reporting delay. RESULTS: Between January 2005 and December 2014, a total of 22,549 AHB infections were reported at the national level. The data flow of the German AHB surveillance system showed structural characteristics of a complex system. Over the 10-year period, completeness of reporting sex, age, probable route of transmission, and hepatitis B virus (HBV) vaccination were 99%, 100%, 25%, and 73%, respectively. However, data quality decreased over the evaluation period. Although notification delay improved over time (incident rate ratio [IRR] = 0.95, 95% confidence interval [CI] = 0.95-0.96; P < 0.05), reporting delay improved only since the amendment (IRR = 0.76, 95% CI = 0.70-0.82; P < 0.05). In total, mean notification and reporting delay were 3.0 days and 14.3 days, respectively. CONCLUSIONS: The German AHB surveillance system is operating in a timely manner. Although timeliness improved over the evaluation period and the amendment to the Protection against Infection Act succeeded in reducing reporting time, data quality in terms of completeness of information decreased considerably. As improved data completeness is required to adequately design prevention activities, reasons for this decrease should further be explored.

European all-cause excess and influenza-attributable mortality in the 2017/18 season: should the burden of influenza B be reconsidered?

OBJECTIVES: Weekly monitoring of European all-cause excess mortality, the EuroMOMO network, observed high excess mortality during the influenza B/Yamagata dominated 2017/18 winter season, especially among elderly. We describe all-cause excess and influenza-attributable mortality during the season 2017/18 in Europe. METHODS: Based on weekly reporting of mortality from 24 European countries or sub-national regions, representing 60% of the European population excluding the Russian and Turkish parts of Europe, we estimated age stratified all-cause excess morality using the EuroMOMO model. In addition, age stratified all-cause influenza-attributable mortality was estimated using the FluMOMO algorithm, incorporating influenza activity based on clinical and virological surveillance data, and adjusting for extreme temperatures. RESULTS: Excess mortality was mainly attributable to influenza activity from December 2017 to April 2018, but also due to exceptionally low temperatures in February-March 2018. The pattern and extent of mortality excess was similar to the previous A(H3N2) dominated seasons, 2014/15 and 2016/17. The 2017/18 overall all-cause influenza-attributable mortality was estimated to be 25.4 (95%CI 25.0-25.8) per 100,000 population; 118.2 (116.4-119.9) for persons aged 65. Extending to the European population this translates into over-all 152,000 deaths. CONCLUSIONS: The high mortality among elderly was unexpected in an influenza B dominated season, which commonly are considered to cause mild illness, mainly among children. Even though A(H3N2) also circulated in the 2017/18 season and may have contributed to the excess mortality among the elderly, the common perception of influenza B only having a modest impact on excess mortality in the older population may need to be reconsidered.

Monitoring the HIV continuum of care in key populations across Europe and Central Asia.

OBJECTIVES: The aim of the study was to measure and compare national continuum of HIV care estimates in Europe and Central Asia in three key subpopulations: men who have sex with men (MSM), people who inject drugs (PWID) and migrants. METHODS: Responses to a 2016 European Centre for Disease Prevention and Control (ECDC) survey of 55 European and Central Asian countries were used to describe continuums of HIV care for the subpopulations. Data were analysed using three frameworks: Joint United Nations Programme on HIV/AIDS (UNAIDS) 90-90-90 targets; breakpoint analysis identifying reductions between adjacent continuum stages; quadrant analysis categorizing countries using 90% cut-offs for continuum stages. RESULTS: Overall, 29 of 48 countries reported national data for all HIV continuum stages (numbers living with HIV, diagnosed, receiving treatment and virally suppressed). Six countries reported all stages for MSM, seven for PWID and two for migrants. Thirty-one countries did not report data for MSM (34 for PWID and 41 for migrants). In countries that provided key-population data, overall, 63%, 40% and 41% of MSM, PWID and migrants living with HIV were virally suppressed, respectively (compared with 68%, 65% and 68% nationally, for countries reporting key-population data). Variation was observed between countries, with higher outcomes in subpopulations in Western Europe compared with Eastern Europe and Central Asia. CONCLUSIONS: Few reporting countries can produce the continuum of HIV care for the three key populations. Where data are available, differences exist in outcomes between the general and key populations. While MSM broadly mirror national outcomes (in the West), PWID and migrants experience poorer treatment and viral suppression. Countries must develop continuum measures for key populations to identify and address inequalities.

PO-18 - Fibronectin EDA/EDB is expressed in adherent SCLC NCI-H69 cells and in pleural effusions of lung cancer patients: possible implication for drug resistance.

INTRODUCTION: Small cell lung cancer (SCLC) is an extremely aggressive tumour which metastasizes early. Even if chemotherapy can achieve an initial regression, relapses due to chemo-resistance are almost inevitable. Sethi et al (Nat Med. 1999;5:662-668) reported that matrix proteins are essentially involved in the development of drug resistance. SCLC cells in suspension culture secrete negligible amounts of matrix proteins AIM: For a more detailed study of the SCLC ability to produce matrix proteins we applied a recently introduced cell culture model of adherence selected SCLC (Salge et al. J Cancer Res Clin Oncol. 2001;127(2):139-411) and analysed pleural effusions form lung cancer patients. MATERIALS AND METHODS: Adherent cells were selected from the SCLC cell line NCI-H69 after exposure to cellular stress. Pleural effusion were obtained from lung cancer patients (SCLC and NSCLC) and from pleural effusions (PE) with congestive heart failure Protein expression was analysed by western blotting (WB) and flow cytometry using specific antibodies against the fibronectin extra domain A (FnEDA) and B (FnEDB) (Sirius, Italy), and for integrins alpha 1-5 and beta 1-3. Drug resistance was assessed with the metabolic stain MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium-bromid). RESULTS: SCLC suspension cells expressed negligible amounts of fibronectin. In contrast, adherent H69 cells, which showed a significantly reduced chemo-sensitivity against carboplatin and doxorubicin, strongly expressed FnEDA and to a lesser extent FnEDB. Furthermore, in adherent cells expression of various integrins was up-regulated, in particular integrins alpha5/beta3, representing potential binding sites for FnEDA/FnEDB. Analysis of pleural effusions clearly showed the presence of FnEDA/ FnEDB in those of lung cancer patients, whereas in benign pleural effusion almost no FnEDA/ FnEDB was found. CONCLUSIONS: Our data reveal the presence of Fn, and its splice variants FnEDA/EDB in particular, in adherent SCLC cells as well as in malignant PE. We assume that the splice variants FnEDA/ FnEDB are linked to cancer progression and chemo-resistance in this tumour type.

The impact of meeting locations for men having sex with men on the risk for bacterial sexually transmitted infections: analyses from a cross-sectional online survey.

OBJECTIVES: Opportunities for men having sex with men (MSM) to meet each other have very much improved by new communication technologies. Meeting venue-based characteristics can impact how many partners are met and how much sexual risk is taken. We analysed the association between physical and virtual venues and the risk for bacterial sexually transmitted infections (bSTIs) among participants in an MSM online survey. METHODS: Data were collected during 2013/2014 with a survey targeting MSM living in Germany. The impact of the meeting place with the last non-steady anal sex partner on diagnosis with a bSTI in the previous year was analysed using bivariate and multivariate regression analysis, taking into account self-reported HIV status, serostatus communication, condom use, partner number, age and city size. RESULTS: The study sample consisted of 8878 respondents (7799 not diagnosed with HIV; 1079 diagnosed with HIV). Meeting partners online was most common (62% HIV-/51% HIV+), followed by sex venues (11% HIV-/25% HIV+); other venues were each reported by 2-6% of the respondents. Venue-dependent proportions reporting bSTIs in the recent year were 2-4 folds higher among men diagnosed with HIV. In multivariate analysis, HIV status was the strongest predictor for bSTIs (OR=5.0; 95% CI 2.8 to 8.7). Compared with meeting partners online, sex (OR 1.6; 95% CI 1.0 to 2.5) and social venues (OR 1.9; 95% CI 1.4 to 2.6) were associated with increased bSTI risk for men not diagnosed with HIV, but the risk when meeting partners by smartphone apps was only of borderline significance (OR 1.5; 95% CI 0.9 to 2.3). For men diagnosed with HIV, bSTI risk increased for sex venues (OR 1.5; 95% CI 1.1 to 2.1), and was lower for non-gay/other venues (OR 0.2; 95% CI 0.1 to 0.5). CONCLUSIONS: Venues are connected to social-behavioural facets of corresponding sexual encounters, and may be important arenas for differential HIV and STI education, treatment and prevention.

Ebola response missions: to go or not to go? Cross-sectional study on the motivation of European public health experts, December 2014.

We surveyed European infectious disease epidemiologists and microbiologists about their decisions to apply for Ebola response missions. Of 368 respondents, 49 (15%) had applied. Applicants did not differ from non-applicants in terms of age, sex or profession but had more training in field epidemiology and more international experience. Common concerns included lack of support from families and employers. Clearer terms of reference and support from employers could motivate application and support outbreak response in West Africa.

The growing number of hemophilia registries: Quantity vs. quality.

Registries for rare diseases provide a tool for obtaining an overview of the clinical situation and can be used to discover points of improvement and to monitor long-term safety. Registries could also become a powerful tool to provide supporting information for marketing authorization. There is an urgent need for a pan-European or global strategy that supports consistent data. Therefore, transparency in data collection, harmonization of the database structures, and the convergence of scientific approaches are required.

Estimating the residual risk for HIV, HCV and HBV in different types of platelet concentrates in Germany.

BACKGROUND AND OBJECTIVES: We estimated and compared the residual risks due to window-period donations for pooled and apheresis platelets in Germany using a modification of a previously described statistical model. This model directly utilizes the reported interdonation intervals before a positive donation and reflects in this aspect the look-back procedures used in haemovigilance. MATERIALS AND METHODS: Data from the German National Blood Donor Surveillance System for the years 2006-2012, including reports about donations from repeat donors with confirmed positive test results for HIV, HCV and HBV, were used to estimate the risk of undetected infectious units for both pooled and apheresis platelets. RESULTS: Demographics of whole-blood and apheresis donors differed in age, gender, catchment area and interdonation interval. These differences impact on the prevalence and incidence of transfusion relevant infections and consequently the residual risk. The estimates for the residual risks for pooled and apheresis platelets were comparable. For HIV, there was no significant difference, for HCV apheresis platelets had a lower residual risk, whereas pooled platelets had a lower risk for undetected HBV infections. CONCLUSION: These findings do not support calls for a shift to an apheresis platelets-only policy in Germany.

Sexual risk behaviour and donor deferral in Europe.

One of the most controversial policies in blood transfusion worldwide is the permanent deferral from donating blood of men with sexual contacts to other men (MSM). This policy was implemented for safety reasons as sex between men is known to be a high risk factor for acquiring severe infectious diseases transmissible by blood transfusion. Sexual contacts among heterosexual persons may hold similar risks but a clear-cut discrimination between different individual risks is impossible. Nevertheless, the current blood donor deferral periods defined by European Union (EU) legislation depend on a distinction of different grades of risk with respect to sexual behaviour. Under the aegis of the Steering Committee on Blood Transfusion (CD-P-TS) of the Council of Europe (CoE), an international working group evaluated epidemiological and behavioural data, modelling studies on residual risk and spread of infections, and studies on adherence to donor selection criteria. The aim was to distinguish sexual behaviour of different risk categories. It was concluded, that existing data confirm that MSM and commercial sex workers (CSW) are groups at high risk. Any further grading lacks a scientific data base. Modelling studies indicate that adherence to deferral policies is of major relevance suggesting that good donor adherence may outweigh the small negative effects on blood safety postulated for changing from permanent to temporary deferral periods for high risk sexual behaviours. The fact that a considerable percentage of donors are MSM - despite the permanent deferral policy - demonstrates the need to increase donor understanding and adherence.

A shared regulatory perspective on deferral from blood donation of men who have sex with men (MSM).

National Regulatory Authorities (NRAs) establish deferral criteria for donors with risk factors for transfusion transmissible infections (TTI). In most jurisdictions, epidemiological data show that men who have sex with men (MSM) have a significantly higher rate of TTI than the general population. Nevertheless, changes from an indefinite donor deferral for MSM have been considered in many countries in response to concerns over a perceived discrimination and questioning of the scientific need. Changes to MSM donor deferral criteria should be based on sound scientific evidence. Safety of transfusion recipients should be the first priority, and stakeholder input should be sought.

Risk factors, incidence and persistence of symptoms from the eyes among professional computer users.

BACKGROUND: Symptoms from the eyes are common among computer users. Knowledge is scarce about these problems, however. OBJECTIVES: The aim was to study risk-factors, incidence and persistence of eye-symptoms among professionally active computer users. METHODS: This was a questionnaire based prospective study where 1283 males and females from different professions and companies answered a baseline questionnaire about individual factors and working conditions, e.g. duration of daily computer work, comfort of screen work, psychosocial factors. Subjects were at baseline and 10 follow-ups asked about the number of days with eye-symptoms during the preceding month. RESULTS: The incidence-rate of symptoms persisting minimum three days was 0.38/person-year. A multivariate Hazard-ratio model showed significant associations with extended continuous computer work, tasks with high demands on eye-hand coordination, low level of control, visual discomfort, female sex and nicotine use. Eye-symptoms at baseline was a strong risk factor for new symptoms. CONCLUSION: The incidence of eye-symptoms among professional computer users is high and related to both individual and work-related factors. The organization of computer work should secure frequent breaks from near-work at the computer screen. The severity of vision-related problems could in field studies be quantified by asking for the persistence of symptoms.

[New data from the German Haemophilia Registry]. / Neue Daten aus dem Deutschen Hämophilieregister.

UNLABELLED: The German Haemophilia Registry records online data from patients with haemophilia A, haemophilia B, von Willebrand`s disease and other coagulation factor deficiency disorders since 2009. Patient's pseudonymised data will only be enrolled in the German Haemophilia Registry if the patient signs an informed consent. Without the informed consent, only aggregated data according to §21 German Transfusion Law are reported. These data include the number of persons with congenital haemostasis disorders classified to type of disease and severity as well as patients' age, and the consumption of clotting factor according to each group. RESULTS: The highest number of patients with haemophilia was reported in 2010: 3375 patients with haemophilia A and 614 with haemophilia B respectively; the highest number of patients with von Willebrand's disease was 1473, reported in 2011. CONCLUSION: In comparison to data from registries in Austria and Switzerland it can be assumed that most of the patients with severe haemophilia are registered in the German Haemophilia Registry whereas patients with moderate and mild forms are still missing.

[Report on notifications pursuant to §21 German Transfusion Act for 2010 and 2011]. / Bericht zur Meldung nach § 21 TFG für die Jahre 2010 und 2011.

This report covers the blood supply situation in Germany over the past 12 years and provides detailed data on the years 2010 and 2011. Nearly 7.6 million donations, thereof 4.9 million whole blood donations, were reported in 2011 - the highest number since 1998. At the same time, 4.8 million red blood cell concentrates (RBC) were produced, the highest amount per year to date. While the RBC loss rate increased for both the manufacturers and the users, the RBC transfusion rate decreased for the first time since 2003. The number of platelet concentrates increased again to 0.57 million. About 60 % of this originated from apheresis donations. An amount of 3.4 million liters of plasma for fractionation was provided. Around 60 % was processed in Germany. The number of hematopoietic stem cell transplantations increased from 5,922 in 2009 to 7,093 in 2011. More than 99 % of the 16,364 transplants derived from peripheral blood and marrow; 43 % of the preparations were transplanted in Germany and 27 % were exported. Overall, the supply of blood products is considered to be good. However, because data are collected on an annual basis, seasonal shortages cannot be detected.

[Contributions of the Council of Europe's Blood Transfusion Steering Committee to the determination of rules for the selection of donors of blood and blood components and the study of sexual behaviors having an impact on blood safety]. / Contributions du comité directeur de transfusion sanguine du Conseil de l'Europe à la détermination des règles de sélection des donneurs de sang et de composants sanguins et à l'étude des conduites sexuelles ayant un impact sur la sécurité transfusionnelle.

In November 2009, the Council of Europe's Blood Transfusion Steering Committee created a group of experts to explore the problem of behaviors having an impact on the management of donors of blood and blood components and on blood transfusion safety in Europe. This ad hoc group sought a harmonised interpretation of temporary exclusion (or temporary deferral), as opposed to permanent exclusion (or permanent deferral), in the context of the selection of donors of blood and blood components. It was also given the mandate to assess, on the basis of available data, the possibility of differentiating "at risk" behaviours from behaviours "at high risk" of contamination by serious infectious diseases transmitted by blood, blood components or derived therapeutic products. The primary objective of this work was to ensure the safety of blood, blood components and derived therapeutic products for future recipients by promoting a risk analysis-based approach, given that some countries envisaged amending their provisions for donor selection. However, a risk analysis can only be performed on groups, not individuals, which may give the impression of a discriminatory approach, so it needed to be justified in the context of transfusion safety. A collaborative project, which included an investigation phase, led to the drafting of a technical memorandum that summarised the data collected in ten Council of Europe member states on the selection criteria for blood donors and the epidemiology of infectious diseases (with a focus on human immunodeficiency virus) in the general population and among blood donors. The technical memorandum was published in 2011 on the European Directorate for the Quality of Medicines and Healthcare website dedicated to this project. A draft resolution of the Committee of Ministers of the Council of Europe was then developed by the Council of Europe's Blood Transfusion Steering Committee. This text was circulated among member and observer states of the Council of Europe for review and comments.

Incidence and risk factors for symptoms from the eyes among professional computer users.

Personal computers are used by a majority of the working population in their professions. Little is known about risk-factors for incident symptoms from the eyes among professional computer users. The aim was to study the incidence and risk-factors for symptoms from the eyes among professional computer users.This study is a part of a comprehensive prospective follow-up study of factors associated with the incidence of symptoms among professional computer users. 1531 computer users of different professions at 46 companies were invited, whereof 1283 answered a baseline questionnaire (498 men; 785 women) and 1246 at least one of 10 monthly follow-up questionnaires. The computer work-station and equipment were generally of a good standard. The majority used CRT displays.During the follow-up period 329 subjects reported eye symptoms. The overall incidence rate in the whole study group was 0.38 per person-year, 0.23 in the subgroup of subjects who were symptom free at baseline and 1.06 among subjects who reported eye symptoms at baseline. In the bivariate analyses significant associations were found with all explanatory variables, except BMI. The reduced multivariate model showed significant associations with extended computer work, visual discomfort (dose-response), eye symptoms at baseline (higher risk), sex (women=higher risk) and nicotine use.The incidence of eye problems among professional computer users is high and related to both individual and work-related factors.

Benefit of transfusion-related acute lung injury risk-minimization measures--German haemovigilance data (2006-2010).

OBJECTIVE: Based on the frequency of immune-mediated and non-immune-mediated transfusion-related acute lung injury (TRALI), the effect of risk-minimization measures was evaluated during a period of 5 years (2006-2010). Risk-minimization measures were implemented in 2008/2009, consisting of exclusion of female donors with a history of pregnancy or exclusion of female donors with human leucocyte antigen (HLA)/human neutrophil alloantigen (HNA) antibodies. METHODS: TRALI was confirmed according to the criteria of the International Haemovigilance Network. Based upon the results of donor testing of white-blood-cell antibodies (WBC-Ab) against HLA or HNAs, confirmed cases were classified as immune- or non-immune-mediated TRALI. Reporting rates were calculated on the basis of the annually transfused blood components, and pre- and post-implementation periods were compared. RESULTS: In total, 60 immune-mediated (75%) and 20 non-immune-mediated (25%) TRALI reactions were confirmed. A total of 68 (64 women and four men) donors were involved: seven red-blood-cell concentrates donors (13%), six platelet concentrate donors (10%), and 48 fresh frozen plasma (FFP) donors (77%). The reporting rate of immune-mediated TRALI caused by FFP decreased continuously; from 12·71 per million units in 2006/2007 to 6·81 per million units in 2008/2009 and no case in 2010. CONCLUSION: The comparison of the pre- and the post-implementation period demonstrated a significantly reduced risk of TRALI events comparing 2006/2007 with 2010 (P-value: <0·01). Furthermore, no case of TRALI-induced fatality occurred after the implementation of risk-minimization measures.