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.

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.

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.

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.

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.

[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.

Late presentation for HIV diagnosis and care in Germany.

OBJECTIVES: Antiretroviral therapy reduces mortality and morbidity in HIV-infected individuals most markedly when initiated early, before advanced immunodeficiency has developed. Late presentation for diagnosis and care remains a significant challenge. To guide public health interventions effectively it is crucial to describe the factors associated with late presentation. METHODS: Case surveillance data for all individuals newly diagnosed with HIV infection in Germany in the years 2001-2010 and data for the years 1999-2010 from the German Clinical Surveillance of HIV Disease (ClinSurv) cohort study, a large multicentre observational study, were analysed. Factors associated with late presentation (CD4 count < 350 cells/µL or clinical AIDS) were assessed using descriptive statistics and multivariable logistic regression methods. RESULTS: Among 22 925 eligible patients in the national surveillance database, 49.5% were late presenters for HIV diagnosis. Among 6897 treatment-naïve patients in the ClinSurv cohort, 58.1% were late presenters for care. Late presenters for care were older (median 42 vs. 39 years for early presenters), more often heterosexuals from low-prevalence countries (18.1% vs. 15.5%, respectively) and more often migrants (18.2% vs. 9.7%, respectively; all P < 0.005). The probability of late presentation was >65% throughout the observation period in migrants. The probability of late presentation for care clearly decreased in men who have sex with men (MSM) from 60% in 1999 to 45% in 2010. CONCLUSIONS: In Germany, the numbers of late presenters for HIV diagnosis and care remain high. The probability of late presentation for HIV diagnosis seems to be particularly high for migrants. These results argue in favour of targeted test promotion rather than opt-out screening. Late presentation for care seems to be an additional problem after HIV diagnosis.

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.

Clinical outcome of HIV-infected patients with discordant virological and immunological response to antiretroviral therapy.

BACKGROUND: A subgroup of human immunodeficiency virus type 1 (HIV-1)-infected patients with severe immunodeficiency show persistently low CD4+ cell counts despite sustained viral suppression. It is unclear whether this immuno-virological discordance translates into an increased risk for clinical events. METHODS: Data analysis from a large multicenter cohort incorporating 14,433 HIV-1-infected patients in Germany. Treatment-naive patients beginning antiretroviral therapy (ART) with CD4+ cell counts <200 cells/µL who achieved complete and sustained viral suppression <50 copies/mL (n = 1318) were stratified according to the duration of immuno-virological discordance (failure to achieve a CD4+ cell count ≥200 cells/µL). Groups were compared by descriptive and Poisson statistics. The time-varying discordance status was analyzed in a multivariable Cox model. RESULTS: During a total of 5038 person years of follow-up, 42 new AIDS events occurred. The incidence rate of new AIDS events was highest in the initial 6 months of complete viral suppression (immuno-virological discordance group, 55.06; 95% confidence interval [CI], 30.82-90.82; and immune responder group, 24.54; 95% CI, 10.59-48.35) and decreased significantly by 65% per year in patients with immuno-virological discordance (incidence risk ratio, 0.35; 95% CI, 0.14-0.92; P = .03). Immuno-virological discordance and prior AIDS diagnosis were independently associated with new AIDS events (hazard ratio, 3.10; 95% CI, 1.09-8.82; P = .03). CONCLUSION: Compared with immune responders, patients with immuno-virological discordance seem to remain at increased risk for AIDS. Absolute risk is greatly reduced after the first 6 months of complete viral suppression.

Bcl-2 proteins: regulators of apoptosis or of mitochondrial homeostasis?

Programmed cell death (apoptosis) is used by multicellular organisms during development and to maintain homeostasis within mature tissues. One of the first genes shown to regulate apoptosis was bcl-2. Subsequently, a number of Bcl-2-related proteins have been identified. Despite overwhelming evidence that Bcl-2 proteins are evolutionarily conserved regulators of apoptosis, their precise biochemical function remains controversial. Three biochemical properties of Bcl-2 proteins have been identified: their ability to localize constitutively and/or inducibly to the outer mitochondrial, outer nuclear and endoplasmic reticular membranes, their ability to form heterodimers with proteins bearing an amphipathic helical BH3 domain, and their ability to form ion-conducting channels in synthetic membranes. The discovery that mitochondria can play a key part in the induction of apoptosis has focused attention on the role that Bcl-2 proteins may have in regulating either mitochondrial physiology or mitochondria-dependent caspase activation. Here we attempt to synthesize our current understanding of the part played by mitochondria in apoptosis with a consideration of how Bcl-2 proteins might control cell death through an ability to regulate mitochondrial physiology.

Monitoring bacterial contamination of blood components in Germany: effect of contamination reduction measures.

BACKGROUND AND OBJECTIVES: National guidelines for monitoring bacterial contamination of blood components were introduced in Germany in 1997. Between 1998 and 2002, numerous measures were implemented to prevent bacterial contamination. This study investigates their impact on contamination rates. MATERIALS AND METHODS: Culture-based testing for bacterial detection on a random sample of blood components is part of routine quality control in German blood establishments. Using standardized questionnaires, data from the production periods 1998, 2001 and 2005/2006 were collected and analysed. RESULTS: The bacterial contamination rate of RBCs was reduced from 0·157% in 1998 to 0·029% in 2005/2006 (P<0·001). While the contamination rate of apheresis PCs remained nearly unchanged over the years, it dramatically decreased for pooled PCs by 70% to a contamination rate of 0·158% (P=0·001) within the last observation period, similar to that of apheresis PCs. The contamination rate of plasma decreased from 0·100% in 1998 to 0·019% in 2005/2006 (P=0·002). CONCLUSIONS: Precautionary measures significantly reduced bacterial contamination rates of blood components. Long-term monitoring with standardized methods is appropriate to evaluate the cumulative effect of contamination-preventing measures.

Enhanced surveillance during a large outbreak of bloody diarrhoea and haemolytic uraemic syndrome caused by Shiga toxin/verotoxin-producing Escherichia coli in Germany, May to June 2011.

Germany has a well established broad statutory surveillance system for infectious diseases. In the context of the current outbreak of bloody diarrhoea and haemolytic uraemic syndrome caused by Shiga toxin/ verotoxin-producing Escherichia coli in Germany it became clear that the provisions of the routine surveillance system were not sufficient for an adequate response. This article describes the timeline and concepts of the enhanced surveillance implemented during this public health emergency.

[Potential of hematopoietic stem cells as the basis for generation of advanced therapy medicinal products]. / Potenzial hämatopoetischer Stammzellen als Ausgangsmaterial für Arzneimittel für neuartige Therapien.

Individualized, (stem) cell-based therapies of congenital and acquired illnesses are among the most exciting medical challenges of the twenty-first century. Before the full potential of such therapies can be achieved, many basic scientific and biotechnological questions remain to be answered. What is the ideal source for the generation of such cellular drugs is one of those issues. In many respects, hematopoietic stem cells fulfill the requirements for stem cells as starting material for novel cellular therapeutics, including the simple access to large amounts of stem cells, the availability of good phenotypic markers for their prospective isolation, and an extensive body of knowledge about the in vitro manipulation of these cells. This manuscript discusses the general and specific usability of hematopoietic stem cells as starting material for novel cellular therapeutics and presents some examples of hematological and nonhematological therapeutic approaches which are based on hematopoietic stem cells.

Inventory management.

A critical aspect of blood transfusion is the timely provision of high quality blood products. This task remains a significant challenge for many blood services and blood systems reflecting the difficulty of balancing the recruitment of sufficient donors, the optimal utilization of the donor's gift, the increasing safety related restrictions on blood donation, a growing menu of specialized blood products and an ever-growing imperative to increase the efficiency of blood product provision from a cost perspective. As our industry now faces questions about our standard practices including whether or not the age of blood has a negative impact on recipients, it is timely to take a look at our collective inventory management practices. This International Forum represents an effort to get a snap shot of inventory management practices around the world, and to understand the range of different products provided for patients. In addition to sharing current inventory management practices, this Forum is intended to foster an exchange of ideas around where we see our field moving with respect to various issues including specialty products, new technologies, and reducing recipient risk from blood transfusion products.

Low hepatitis B immunogenicity of a hexavalent vaccine widely used in Germany: results of the German Health Survey for Children and Adolescents, 2003-2006.

The success of childhood vaccination against hepatitis B relies on persistence of immunity into adolescence and adulthood. In 2000, two hexavalent vaccines with a hepatitis B component (Hexavac, Infanrix hexa) were introduced in Germany. Hexavac was withdrawn in 2005 amidst concerns about its long-term hepatitis B protection. We compared hepatitis B surface antibody (anti-HBs) levels in children fully vaccinated with Hexavac or Infanrix hexa (n=477) in a secondary data analysis of a large cross-sectional health survey in Germany. On average 2.4 years after vaccination, 25.3% of Hexavac vaccinees had anti-HBs levels <10 mIU/ml (95% CI 19.0-32.8) compared to 4.7% of Infanrix hexa vaccinees (95% CI 2.4-8.9). These findings suggest that short-term hepatitis B immunogenicity in Hexavac vaccinees may also be weaker. Further studies are warranted to assess whether Hexavac vaccinees should be re-vaccinated or receive a booster vaccination before these birth cohorts reach adolescence.

Household transmissibility and other characteristics of seasonal oseltamivir-resistant influenza A(H1N1) viruses, Germany, 2007-8.

During the influenza season 2007-8, the proportion of seasonal influenza A(H1N1) viruses resistant to the neuraminidase inhibitor oseltamivir increased worldwide. We conducted an investigation to compare patients infected with oseltamivir-resistant (ose-R) and oseltamivir- susceptible (ose-S) influenza A(H1N1) viruses regarding risk factors for resistance and the capability to transmit in the household setting. Within a cohort of 396 laboratory confirmed influenza patients from sentinel physicians we conducted a nested case-control study among patients infected with A(H1N1). Thirty patients in the cohort were infected with influenza B, none with influenza A(H3N2) and 366 with A(H1N1). Of the 366 A(H1N1) viruses 52 (14%) were ose-R. Demographic characteristics, oseltamivir exposure, travel history and outcome were not significantly different between ose-S and ose-R patients. Among 133 households in the nested case-control study, secondary household attack rates in households with ose-R cases and households with ose-S cases were similar (23 versus 26%; p-value=0.54). Ose-R household status and occurrence of secondary cases were associated with an odds ratio of 0.85 (95% confidence interval 0.38-1.88). We conclude that seasonal ose-R influenza A(H1N1) viruses have transmitted well in the household setting.

[Documentation of haemophilia treatment supported by the German Hemophilia Registry]. / Dokumentation in der Hämophilietherapie mit Unterstützung des Deutschen Hämophilieregisters.

The DHR (Deutsches Hämophilieregister, German Haemophilia Register) records patient data on haemophilia A, haemophilia B, von Willebrand disease, and other coagulation factor deficiency disorders. The DHR has been online since 2009. The participation in the DHR leads to additional administrative workload for the hospitals and physicians, but provides many advantages as well: A standard of documentation will be developed to give evidence for the hospitals. They may use their own data as well as with new possibilities for data processing at any time. Reports in accordance with Section21 TFG (Transfusionsgesetz, German Transfusion Act) are compiled automatically and transmitted to the Paul-Ehrlich-Institut. The DHR may support the searching for patients fulfilling the requirements for participation in a study.