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Background This study applies an umbrella review approach to summarise the global evidence on the risk of severe COVID-19 outcomes in patients with pre-existing health conditions. Methods Systematic reviews (SRs) were identified in PubMed, Embase/Medline and seven pre-print servers until December 11, 2020. Due to the absence of age-adjusted risk effects stratified by geographical regions, a re-analysis of the evidence was conducted. Primary studies were extracted from SRs and evaluated for inclusion in the re-analysis. Studies were included if they reported risk estimates (odds ratio (OR), hazard ratio (HR), relative risk (RR)) for hospitalisation, intensive care unit admission, intubation or death. Estimated associations were extracted from the primary studies for reported pre-existing conditions. Meta-analyses were performed stratified for each outcome by regions of the World Health Organization. The evidence certainty was assessed using GRADE. Registration number CRD42020215846. Results In total, 160 primary studies from 120 SRs contributed 464 estimates for 42 pre-existing conditions. Most studies were conducted in North America, European, and Western Pacific regions. Evidence from Africa, South/Latin America, and the Eastern Mediterranean region was scarce. No evidence was available from the South-East Asia region. Diabetes (HR range 1.2–2.0 (CI range 1.1–2.8)), obesity (OR range 1.5–1.75 (CI range 1.1–2.3)), heart failure (HR range 1.3–3.3 (CI range 0.9–8.2)), COPD (HR range 1.12–2.2 (CI range 1.1–3.2)) and dementia (HR range 1.4–7.7 (CI range 1.2–39.6)) were associated with fatal COVID-19 in different regions, although the estimates varied. Evidence from Europe and North America showed that liver cirrhosis (OR range 3.2–5.9 (CI range 0.9–27.7)) and active cancer (OR range 1.6–4.7 (CI range 0.5–14.9)) were also associated with increased risk of death. Association between HIV and undesirable COVID-19 outcomes showed regional heterogeneity, with an increased risk of death in Africa (HR 1.7 (CI 1.3–2.2)). GRADE certainty was moderate to high for most associations. Conclusion Risk of undesirable COVID-19 health outcomes is consistently increased in certain patient subgroups across geographical regions, showing high variability in others. The results can be used to inform COVID-19 vaccine prioritisation or other intervention strategies.

Objectives To describe the characteristics of a large hepatitis A virus (HAV) outbreak among men who have sex with men (MSM) in Berlin and to assess the impact of measures implemented. Methods Cases of laboratory-confirmed, symptomatic HAV infection notified in Berlin, Germany between August 2016 and February 2018 were analysed using routine and enhanced surveillance data including genotyping results. Several studies involving different groups of participants were conducted to further investigate the outbreak, including surveys on knowledge and practices of HAV vaccination among physicians and vaccination coverage and determinants of vaccination status among MSM. The measures implemented were categorized by target group in a Gantt chart. To assess their impact, health insurance data on HAV vaccination uptake were analysed, comparing Berlin and other federal states. Results During the outbreak period, a total of 222 cases were reported (of which 91 were sequence-confirmed), with a peak in case numbers in January 2017. Physicians were aware of the existing vaccination recommendations, but vaccination coverage among 756 MSM was low, with 32.7% being completely vaccinated and 17.3% being incompletely vaccinated before 2017. HAV vaccination before 2017 was associated with being born in Germany (odds ratio 2.36) and HIV-positive (odds ratio 1.80). HAV monovalent vaccination uptake increased by 164% from 2016 to 2017 among males in Berlin, compared to 7% in other federal states. Conclusions Multiple measures targeting the MSM community, physicians, and public health to increase HAV vaccination uptake were successfully implemented. To prevent future HAV outbreaks, we recommend monitoring vaccination coverage among MSM, promoting awareness of existing recommendations among physicians, and ensuring access for foreign-born and young MSM.

The Delta variant (Phylogenetic Assignment of Named Global Outbreak (Pango) lineage designation B.1.617.2) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in October 2020 and has spread to more than 180 countries globally [1]. Concerns were raised about how well the currently available vaccines protect against this variant. Since January 2021, the Robert Koch Institute (RKI), in collaboration with the National Immunisation Technical Advisory Groups (NITAGs) network coordinated by the European Centre for Disease Prevention and Control (ECDC) is performing a living systematic review on the efficacy, effectiveness and safety of coronavirus disease (COVID-19) vaccines authorised in the European Union (EU) (PROSPERO registration: CRD42020208935) [2]. Here we present results on the effectiveness and the duration of protection provided by the EU-licensed COVID-19 vaccines in respect to the Delta variant.

Background The WHO European Region targets the elimination of measles, rubella, and the congenital rubella syndrome and welcomes mumps elimination via the joint MMR vaccine. In a push towards this elimination goal, Germany introduced a recommendation on MMR vaccination for adults in 2010 to prevent increasing numbers of measles cases among adults and to strengthen herd immunity. Methods The prevalence of anti-measles, -mumps, and -rubella IgG antibodies was analysed in 7,115 participants between the ages of 18 and 79 years in the German Health Interview and Examination Survey. Risk factors of seronegativity of adults born 1970 or later were determined. Findings The seroprevalence of anti-measles IgG antibodies was more than 97% in adults born before 1965 and less than 90% in adults born afterwards. Prevalence and GMTs declined with later years of birth. Seronegativity was associated with two-sided migration background and region of residence in East Germany. For anti-mumps IgG antibodies, the seroprevalence was less than 90% in almost all age groups. Prevalence and GMTs declined with later years of birth. Seronegativity was not associated with any socio-demographic factor. Anti-rubella IgG seropositivity was found in more than 90% of adults born before 1985. GMTs declined in younger age groups. Seronegativity was associated with birth between 1980 and 1993 and male gender. High socio-economic status lowered the odds of being seronegative. Interpretation These data reinforce the implementation of the vaccination recommendation for adults and provide the basis for further evaluation of this measure. Funding The Federal Ministry of Health, Germany.

Die Standige Impfkommission empfiehlt Erwachsenen Masern- und Pertussisimpfungen. Eine Masernimpfung sollen seit 2010 alle nach 1970 Geborenen mit weniger als zwei Impfungen in der Kindheit erhalten, einen azellularen Pertussisimpfstoff (ap) seit 2009 alle Erwachsenen mit der nachsten, alle 10 Jahre empfohlenen Tetanus(T)-Diphtherie(d)-Impfung als Tdap-Kombinationsimpfung. Ein Ziel der Arbeit ist die Bestimmung der jahrlichen Inanspruchnahme der Masernimpfung (Impfinzidenz) und ihres Anteils in padiatrischen und gynakologischen Praxen als fachgebietsfremde Leistungen (2009–2016). Zudem sollen die 10-Jahres-ap-Impfquote sowie verpasste Impfchancen als der Anteil ausschlieslich Td- an allen Td- und Tdap-Geimpften (2007–2016) berechnet werden. In der KV-Impfsurveillance des Robert Koch-Instituts und der Kassenarztlichen Vereinigungen (KVen) wurden in bundesweiten vertragsarztlichen Abrechnungsdaten Personen mit den relevanten Impfungen erfasst und auf die Versichertenzahlen bezogen. Die Masernimpfinzidenz lag 2009 bei 0,4 % und stieg mit 2013 auf jahrlich ≥1,0 %. Sie war in den westlichen Bundeslandern hoher als in den ostlichen und bei Frauen hoher als bei Mannern. 6,8 % aller Impfungen wurden in padiatrischen Praxen gegeben. Manner erhielten 2,6 % ihrer Impfungen in gynakologischen Praxen. Die ap-Impfquote betrug 32,4 %. Der Anteil ausschlieslich Td-Geimpfter sank von 84 % (2007) auf 24 % (ab 2013). Die KV-Impfsurveillance zeigt eine seit den Impfempfehlungen gestiegene Inanspruchnahme von Masern- und Pertussisimpfungen mit regionalen und geschlechtsspezifischen Unterschieden und liefert damit wichtige Daten zur Evaluation. Analysen zum fachgebietsubergreifenden Impfen und zu verpassten Impfchancen bieten einen Einblick in das Steigerungspotenzial von Impfquoten.

In Deutschland gibt die Ständige Impfkommission (STIKO) Empfehlungen zur Durchführung von Schutzimpfungen und zur Durchführung anderer Maßnahmen der spezifischen Prophylaxe übertragbarer Krankheiten. Die Umsetzung dieser Empfehlungen wird durch Mythen und Mutmaßungen bis hin zu Verschwörungstheorien in der öffentlichen Diskussion zu Impfungen gefährdet. Evidenz und Transparenz der Empfehlungen können die Diskussion versachlichen. Im November 2011 wurde eine neue STIKO-Standardvorgehensweise (Standard Operating Procedure [SOP]) für die Entwicklung evidenzbasierter Impfempfehlungen verabschiedet. Anhand der Vorgaben der SOP werden seit 2011 nicht nur neue Impfempfehlungen erarbeitet, sondern auch bereits bestehende Empfehlungen aktualisiert bzw. erweitert. Der Artikel gibt einen Überblick über die Methodik der SOP, beschreibt bisherige Erfahrungen in ihrer Anwendung und gibt einen Ausblick auf künftige Herausforderungen.

Passive immunisation with immunoglobulins as post-exposure prophylaxis after contact with measles is recommended by the German Standing Committee on Vaccination (STIKO) particularly for unprotected individuals at high risk of complications for whom active immunization is contraindicated, such as infants

In March 2021 several cases of cerebral venous sinus thrombosis (CVST) accompanied by thrombocytopenia were reported that occurred within two weeks after immunization with a viral vector-based COVID-19 vaccine. This study aimed to assess the background incidence of CVST and CVST with concurrent thrombocytopenia in adults using anonymized claims data from 2015-2019 in Germany. The average annual CVST incidence was 1.9 per 100,000 individuals (95%-CI 1.4-2.3). It was higher in women aged 18 to 59 years as compared to same-aged men. In contrast to the currently reported immunization-related cases, CVST was rarely associated with concurrent thrombocytopenia or death.

Background: This umbrella review summarises the global evidence on the risk of severe COVID-19 outcomes in patients with pre-existing health conditions. Methods: Systematic reviews (SRs) were identified in PubMed, Embase/Medline, and seven pre-print servers until December 11, 2020. Risk estimates (odds ratio (OR), hazard ratio (HR), relative risk (RR)) for hospitalisation, intensive care unit admission, intubation, and death were extracted from primary studies. Meta-analyses were performed stratified by regions of the World Health Organisation. The evidence certainty was assessed using GRADE. Registration number CRD42020215846. Findings: 160 primary studies from 120 SRs contributed 464 estimates for 42 pre-existing conditions. Most studies were conducted in North America, European, and Western Pacific regions. Evidence from Africa, South/Latin America, and Eastern Mediterranean region was scarce. No evidence was available from South-East Asia region. Diabetes (HR 1∙2-2∙0 (1∙1-2∙8)), obesity (OR 1∙5-1∙75 (1∙1-2∙3)), heart failure (HR 1∙3-3∙3(0∙9-8∙2)), COPD (HR 1∙12-2∙2 (1∙1-3∙2)), and dementia (HR 1∙4-7.7 (1∙2-39∙6)) were associated with fatal COVID-19 in different regions, although the estimates varied. Evidence from Europe and North America showed that liver cirrhosis (OR 3∙2-5∙9 (0∙9-27∙7)) and active cancer (OR 1∙6-4∙7 (0∙5-14∙9)) were also associated with increased risk of death. Association between HIV and severe COVID-19 showed regional heterogeneity, with an increased risk of death in Africa (HR 1∙7 (1∙3-2∙2)). GRADE certainty was moderate to high for most associations. Interpretation: Risk of severe COVID-19 is consistently increased in certain patient subgroups across geographical regions, showing high variability in others. The results can be used to inform COVID-19 vaccine prioritisation or other intervention strategies. Funding Statement: Project ImVaCov – German Federal Ministry of Health Declaration of Interests: Authors declare no conflicts of interest.

Evidence on COVID-19 vaccine efficacy/effectiveness (VE) in preventing asymptomatic SARS-CoV-2 infections is needed to guide public health recommendations for vaccinated people. We report interim results of a living systematic review. We identified a total of 30 studies that investigated VE against symptomatic and/or asymptomatic infection. In fully vaccinated individuals, VE against symptomatic and asymptomatic infections was 80–90% in nearly all studies. Fully vaccinated persons are less likely to become infected and contribute to transmission.

Background Universal mass vaccination (UMV) against rotavirus has been implemented in many but not all European countries. This study investigated the impact of UMV on rotavirus incidence trends by comparing European countries with UMV: Belgium, England/Wales and Germany versus countries without UMV: Denmark and the Netherlands. Methods For this observational retrospective cohort study, time series data (2001–2016) on rotavirus detections, meteorological factors and population demographics were collected. For each country, several meteorological and population factors were investigated as possible predictors of rotavirus incidence. The final set of predictors were incorporated in negative binomial models accounting for seasonality and serial autocorrelation, and time-varying incidence rate ratios (IRR) were calculated for each age group and country separately. The overall vaccination impact two years after vaccine implementation was estimated by pooling the results using a random effects meta-analyses. Independent t-tests were used to compare annual epidemics in the pre-vaccination and post-vaccination era to explore any changes in the timing of rotavirus epidemics. Results The population size and several meteorological factors were predictors for the rotavirus epidemiology. Overall, we estimated a 42% (95%-CI 23;56%) reduction in rotavirus incidence attributable to UMV. Strongest reductions were observed for age-groups 0-, 1- and 2-years (IRR 0.47, 0.48 and 0.63, respectively). No herd effect induced by UMV in neighbouring countries was observed. In all UMV countries, the start and/or stop and corresponding peak of the rotavirus season was delayed by 4–7 weeks. Conclusions The introduction of rotavirus UMV resulted in an overall reduction of 42% in rotavirus incidence in Western European countries two years after vaccine introduction and caused a change in seasonal pattern. No herd effect induced by UMV neighbouring countries was observed for Denmark and the Netherlands.

BackgroundHaemophilus influenzae (Hi) serotype b (Hib) vaccination was introduced in Germany in 1990. This study presents a comprehensive overview on the burden of invasive Hi infections for 2001–2016, including serotype distribution and ampicillin resistance.MethodsNationwide data from statutory disease surveillance (2001–2016) were linked with laboratory surveillance data (2009–2016). Besides descriptive epidemiology, statistical analyses included multiple imputation to estimate secular trends.ResultsIn 2001–2016, 4044 invasive Hi infections were reported. The mean incidence was 3.0 per million inhabitants, higher in males (3.2 vs 2.9 in females) and in the age groups ConclusionsThis is one of the most comprehensive Hi data analyses since the introduction of Hib vaccines. NTHi and Hif cause an increasing disease burden among elderly patients and infants. Ampicillin resistance in NTHi must be considered in the treatment of invasive Hi infections.

BACKGROUND Routine rotavirus (RV)-vaccination is recommended in Germany since August 2013. Five years later, we evaluated the recommendation by examining vaccine uptake and the impact on RV-gastroenteritis (RVGE) burden in all age groups and on intussusceptions in infants. METHODS We estimated RV-vaccine uptake in the 2014-2018 birth cohorts using statutory health insurance prescription data. For impact assessment, we analyzed RVGE-surveillance data of the German infectious diseases notification system. We compared age-specific RVGE-incidences of different severity between pre-vaccination (2005/06-2007/08) and routine vaccination period (2013/14-2017/18) calculating incidence rate ratios (IRR) using Poisson regression. To determine the effect on intussusception, we used hospital discharge data (2006-2017) and compared incidences between pre-vaccination and routine vaccination period using Poisson regression. RESULTS Vaccination coverage increased from 59% (2014) to 80% (2018). Incidences of RVGE-outpatient cases, RVGE-hospitalization and nosocomial RVGE among

A live attenuated vaccine (Zostavax (R)) against herpes zoster (HZ) and posther-petic neuralgia (PHN) was licensed for persons 50 years of age and older in 2006 and became available in Germany in September 2013. Based on the conclusion, that an effective and sustainable reduction of the HZ disease burden cannot be achieved with this vaccine, the STIKO decided against issuing a recommendation for routine HZ vaccination at this time. This decision is based on a systematic review of available data on the efficacy, duration of protection, and safety of the vaccine, and is supported by the results of health economic modelling. Both, the risk of developing HZ and the severity of the illness increase markedly with age. The efficacy of the vaccine, however, decreases with advancing age, from 70% for persons in their 50s to 41% for persons in their 70s to less than 20% for persons 80 years of age and older. The duration of vaccine related protection is limited to only a few years. The modelling results show only a slight, age-dependent reduction in the total number of HZ cases through vaccination with the live attenuated vaccine. The reduction ranged from 2.6% for persons vaccinated at the age of 50 to 0.6% for those vaccinated at the age of 80, based on assumed vaccine coverage of 35.5%. In addition to the vaccine's poor efficacy and duration of protection, HZ vaccination does not offer any added value in terms of herd immunity, since HZ is a disease of an endogenously reactivated pathogen with low transmission potential. Finally, the live attenuated vaccine is often contraindicated in persons who are at greatest risk of HZ and its complications. Thus, in the overall appraisal, the epidemiological benefit-risk assessment of the HZ vaccination did not lead to a recommendation for routine vaccination with the live attenuated vaccine. An individual benefit-risk assessment may, however, lead to a different decision in individual patients.

Listeriosis has been a mandatorily notifiable disease in Germany since January 2001. Clinical cases with isolation of Listeria monocytogenes from sterile specimens or neonates are reported to the Robert Koch-Institut. Listeriosis incidence significantly increased from 0.26 per 100 000 inhabitants (217 cases) in 2001 to 0.62 per 100 000 (519 cases) in 2005.

In December 2013 Bexsero® became available in Germany for vaccination against serogroup B meningococci (MenB). In August 2015 the German Standing Committee on Vaccination (STIKO) endorsed a recommendation for use of this vaccine in persons at increased risk of invasive meningococcal disease (IMD). This background paper summarizes the evidence underlying the recommendation. Bexsero® is based on surface protein antigens expressed by about 80% of circulating serogroup B meningococci in Germany. The paper reviews available data on immunogenicity and safety of Bexsero® in healthy children and adolescents; data in persons with underlying illness and on the effectiveness in preventing clinical outcomes are thus far unavailable.STIKO recommends MenB vaccination for the following persons based on an individual risk assessment: (1) Persons with congenital or acquired immune deficiency or suppression. Among these, persons with terminal complement defects and properdin deficiency, including those under eculizumab therapy, are at highest risk with reported invasive meningococcal disease (IMD) incidences up 10,000-fold higher than in the general population. Persons with asplenia were estimated to have a ~ 20-30-fold increased risk of IMD, while the risk in individuals with other immune defects such as HIV infection or hypogammaglobulinaemia was estimated at no more than 5-10-fold higher than the background risk. (2) Laboratory staff with a risk of exposure to N. meningitidis aerosols, for whom an up to 271-fold increased risk for IMD has been reported. (3) Unvaccinated household (-like) contacts of a MenB IMD index case, who have a roughly 100-200-fold increased IMD risk in the year after the contact despite chemoprophylaxis. Because the risk is highest in the first 3 months and full protective immunity requires more than one dose (particularly in infants and toddlers), MenB vaccine should be administered as soon as possible following identification of the serogroup of the index case.

Rotavirus (RV) infection is the primary cause of severe gastroenteritis in children aged5 years in Germany and worldwide. In 2013 the German Standing Committee on Vaccination (STIKO) developed a national recommendation for routine RV-immunization of infants. To support informed decision-making we predicted the epidemiological impact of routine RV-vaccination in Germany using statistical modelling.We developed a population-based model for the dynamic transmission of RV-infection in a vaccination setting. Using data from the communicable disease reporting system and survey records on the vaccination coverage from the eastern federal states, where the vaccine was widely used before recommended at national level, we first estimated RV vaccine effectiveness (VE) within a Bayesian framework utilizing adaptive Markov Chain Monte Carlo inference. The calibrated model was then used to compute the predictive distribution of RV-incidence after achieving high vaccination coverage with the introduction of routine vaccination.Our model estimated that RV-vaccination provides high protection against symptomatic RV-infection (VE=96%; 95% credibility interval (CI): 91-99%) that remains at its maximum level for three years (95% CI: 1.43-5.80 years) and is fully waned after twelve years. At population level, routine vaccination at 90% coverage is predicted to reduce symptomatic RV-incidence among children aged5 years by 84% (95% prediction interval (PI): 71-90%) including a 2.5% decrease due to herd protection. Ten years after vaccine introduction an increase in RV incidences of 12% (95% PI: -16 to 85%) among persons aged 5-59 years and 14% (95% PI: -6 to 109%) within the age-group60 years was predicted.Routine infant RV-vaccination is predicted to considerably reduce RV-incidence in Germany among children5 years. Our work generated estimates of RV VE in the field and predicted the population-level impact, while adequately addressing the role of model and prediction uncertainty when making statements about the future.

Erratum zu: Bundesgesundheitsbl 2018 https://doi.org/10.1007/s00103-018-2761-8 Die Originalveroffentlichung dieses Artikels enthielt einen Fehler in der Autorenliste, in der der beitragende Autor Herr Professor Johannes G. Liese fehlte. Die Autorenliste wurde nun …

Mumps outbreaks in populations with high 2-dose vaccination coverage and among young adults are increasingly reported. However, data on the duration of vaccine-induced protection conferred by mumps vaccines are scarce. As part of a supra-regional outbreak in Germany 2010/11, we conducted two retrospective cohort studies in a primary school and among adult ice hockey teams to determine mumps vaccine effectiveness (VE). Via questionnaires we collected information on demography, clinical manifestations, and reviewed vaccination cards. We estimated VE as 1-RR, RR being the rate ratio of disease among two-times or one-time mumps-vaccinated compared with unvaccinated persons. The response rate was 92.6% (100/108—children cohort) and 91.7% (44/48—adult cohort). Fourteen cases were identified in the children and 6 in the adult cohort. In the children cohort (mean age: 9 y), 2-dose VE was 91.9% (95% CI 81.0–96.5%). In the adult cohort (mean age: 26 y), no cases occurred among the 13 2-times vaccinated, while 1-dose VE was 50.0% (95% CI –9.4–87.1%). Average time since last vaccination showed no significant difference for cases and non-cases, but cases were younger at age of last mumps vaccination (children cohort: 2 vs. 3 y, P = 0.04; adult cohort: 1 vs. 4 y, P = 0.03). We did not observe signs of waning immunity in the children cohort. Due to the small sample size VE in the adult cohort should be interpreted with caution. Given the estimated VE, very high 2-dose vaccination coverage is required to prevent future outbreaks. Intervention efforts to increase coverage must especially target young adults who received

Mumps ist eine akute virale Infektionskrankheit, die durch eine ein- bzw. beidseitige schmerzhafte Parotisschwellung gekennzeichnet ist. Seit 1976 empfiehlt die Standige Impfkommission (STIKO) in der Bundesrepublik die Mumpsimpfung als Standardimpfung im Kindesalter. In den ostlichen Bundeslandern wurde die Impfung nach der Wiedervereinigung eingefuhrt. In Deutschland hat es wahrend der letzten Jahrzehnte kein einheitliches Surveillancesystem zur Uberwachung der Mumpsepidemiologie gegeben. Fur die ehemalige DDR und die ostlichen Bundeslander konnen Mumpserkrankungen auf der Basis von Daten aus verschiedenen Uberwachungssystemen fur den Zeitraum von 1968 bis 2012 abgebildet werden. Demnach ist die Mumpsinzidenz von jahrlich > 200 Erkrankungen/100.000 Einwohner in der Vorimpfara auf mittlerweile weniger als 95 % gesteigert und bestehende Impflucken unter Erwachsenen geschlossen werden konnen.

Two rotavirus (RV) vaccines were introduced to the European market in 2006. To support the decision-making process of the German Standing Committee on Vaccination ("Standige Impfkommission", STIKO) regarding adoption of routine RV vaccination into the national vaccination schedule in Germany relevant scientific background was reviewed. According to STIKO’s Standard Operating Procedures for the development of evidence-based vaccination recommendations, a set of key questions was addressed and systematic reviews were performed with a focus on the efficacy, effectiveness, impact and safety of RV vaccines. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was applied to assess the quality of available evidence. Data from 5 randomized controlled trials demonstrated a high efficacy of RV vaccines in preventing severe RV-associated gastroenteritis (91%) and hospitalization (92%) in settings comparable to Germany. Post-marketing observational studies confirmed these findings. In several countries, impact studies suggest that age groups not eligible for vaccination might also benefit from herd effects and demonstrated a decrease in the number of nosocomial RV infections after RV vaccine introduction. The vaccines were considered safe, except for a slightly increased risk of intussusception shortly after the first dose, corresponding to 1-2 additional cases per 100,000 infants vaccinated (relative risk =1.21, 95% confidence interval [CI] 0.68-2.14). RV case-fatality is extremely low in Germany. However, RV incidence among children aged

In the German federal state Mecklenburg-Western Pomerania, routine rotavirus (RV) vaccination in infants has been recommended since 2009. The effectiveness of RV vaccination was investigated after an unexpectedly high number of RV infections in fully vaccinated children occurred.Intensified RV surveillance was performed in Mecklenburg-Western Pomerania between 2010 and 2011. The screening method was applied to assess vaccine effectiveness (VE) in children up to 24 months after vaccination. To identify risk factors for breakthrough infections, a case-control study and genotyping were conducted in vaccinated and unvaccinated RV-infected children.VE for the prevention of RV infection requiring medical attention or hospitalization was 68% (95% confidence interval [CI]: 61-71) and 80% (95% CI: 77-83), respectively. VE for preventing hospitalization but not medical attention remained stable over 2 years. Vaccinated were less often hospitalized (23%) than unvaccinated RV-infected children (61%; P0.001). Breastfeeding (odds ratio, 3.99; 95% CI: 1.92-8.27) and attending daycare (odds ratio, 3.42; 95% CI: 1.64-7.12) were independently associated with breakthrough infections. Genotype G1P[8] was detected more frequently in RotaTeq-vaccinated (44% versus 11%; P0.03) and G2P[4] in Rotarix-vaccinated children (42% versus 6%; P0.02).RV vaccination protects young children effectively from RV disease and can reduce disease severity. Breastfeeding might impair VE, but further research is needed to identify the critical time window for this interference and to develop appropriate recommendations.

Background: In 2013, the German Standing Committee on Vaccination (Standige Impfkommission, STIKO) recommended rotavirus (RV) vaccination for all infants while stating that this mildly increased the risk of intussusception, a potentially life-threatening event. Since this recommendation was issued, multiple observational studies on this topic designed as self-controlled case series (SCCS) have been published. The SCCS design is particularly suitable for the study of rare adverse effects of medications. Methods: We systematically searched the literature for SCCS studies on the risk of intussusception after RV vaccination. Relative risks (RR) corresponding to different doses of vaccine were summarized in a meta-analysis, and attributable risks (AR) were calculated. Results: Of the 16 initially identified studies, 10 with a predominantly low risk of bias were considered in the analysis. The RR for intussusception was 5.71 (95% confidence interval [4.50;7.25]) 1-7 days after the first dose, 1.69 [1.33;2.14] after the second, and 1.14 [0.75;1.74] after the third. The AR for children of the age at which RV vaccination is recommended was 1.7 [1.1;2.7] additional intussusceptions per 100 000 vaccinated children after the first dose and 0.25 [0.16;0.40] after the second. If >3-month-old infants are vaccinated, the AR is higher: 5.6 [4.3;7.2] per 100 000 after the first dose and 0.81 [0.63;1.06] per 100 000 after the second. Conclusion: RV vaccination is associated with a markedly elevated RR and a mildly elevated AR for intussusception 1-7 days after the first dose. Physicians should begin the series of vaccinations at age 6-12 weeks, as recommended by the STIKO, because the risk of intussusception is higher afterward. Current health insurance company claim data indicate that 11.2% of infants are still receiving the first dose of the vaccine at ages above 3 months. The parents of vaccinated children should be informed about the possible signs of intussusception (colicky pain, bilious vomiting, and red "currant jelly" stool).

Bexsero, a new vaccine against serogroup B meningococcal disease (MenB), was licensed in Europe in January 2013. In Germany, Bexsero is recommended for persons at increased risk of invasive meningococcal disease, but not for universal childhood vaccination. To support decision making we adapted the independently developed model for England to the German setting to predict the potential health impact and cost-effectiveness of universal vaccination with Bexsero® against MenB disease. We used both cohort and transmission dynamic mathematical models, the latter allowing for herd effects, to consider the impact of vaccination on individuals aged 0-99 years. Vaccination strategies included infant and adolescent vaccination, alone or in combination, and with one-off catch-up programmes. German specific data were used where possible from routine surveillance data and the literature. We assessed the impact of vaccination through cases averted and quality adjusted life years (QALY) gained and calculated costs per QALY gained. Assuming 65% vaccine uptake and 82% strain coverage, infant vaccination was estimated to prevent 15% (34) of MenB cases over the lifetime of one birth cohort. Including herd effects from vaccination increased the cases averted by infant vaccination to 22%, with an estimated 8461 infants requiring vaccination to prevent one case. In the short term the greatest health benefit is achieved through routine infant vaccination with large-scale catch-up, which could reduce cases by 24.9% after 5 years and 27.9% after 10 years. In the long term (20+ years) policies including routine adolescent vaccination are most favourable if herd effects are assumed. Under base case assumptions with a vaccine list price of €96.96 the incremental cost-effectiveness ratio (ICER) was >€500,000 per QALY for all considered strategies. Given the current very low incidence of MenB disease in Germany, universal vaccination with Bexsero® would prevent only a small absolute number of cases, at a high overall cost.

Summary Importance Human serum bactericidal antibody levels (hSBA) are commonly used as an immune correlate of protection after vaccination against meningococcal disease. We performed a systematic review of how well this marker correlates with protection induced by outer membrane vesicle (OMV) vaccines against meningococcal B (MenB) disease. Objective To compare vaccine effectiveness (VE) of OMV vaccines against MenB predicted by hSBA (predicted protection) to VE from clinical studies (observed protection). Data sources Studies identified by searching Medline, Embase, Global Health, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews and Database of Abstracts of Reviews of Effects. Study selection Studies reporting hSBA after vaccination with OMV vaccines and subsequent efficacy/effectiveness in a MenB outbreak were included. Data extraction and synthesis Data extraction and risk of bias assessments were performed by two independent investigators. Main outcomes and measures Predicted VE and observed VE measured during MenB outbreaks. Results We included 19 studies (eleven randomized controlled trials, six cohort studies, two case-control studies). Four different OMV vaccines were applied during nine different outbreaks (six countries, 1987–2009). A comparison between predicted and observed VE was possible using results from studies performed during five outbreaks. Predicted VE differed from observed VE by 2–59%, with greater differences observed in younger age groups. In general, predicted VE tended to be lower than observed VE. Conclusion and relevance hSBA induced by OMV vaccines correlates moderately well with protection against MenB in older children and adults. The correlation was poor at very young ages, for which low VE was observed.

Meningococcal serogroup C (MenC) vaccination of men who have sex with men (MSM) was temporarily recommended to control an outbreak of invasive MenC disease among MSM in Berlin in 2012–2013. Vaccination was offered to HIV-infected MSM free of charge; others had to request reimbursement or pay out of pocket. We aimed to assess (i) awareness and acceptance of this recommendation through an online survey of MSM, (ii) implementation through a survey of primary care physicians and analysis of vaccine prescriptions, and (iii) impact through analysis of notified cases. Among online survey respondents, 60% were aware of the recommendation. Of these, 39% had obtained vaccination (70% of HIV-infected, 13% of HIV-negative/non-tested MSM). Awareness of recommendation and vaccination were positively associated with HIV infection, primary care physicians’ awareness of respondents’ sexual orientation, and exposure to multiple information sources. Most (26/30) physicians informed clients about the recommendation. Physicians considered concerns regarding reimbursement, vaccine safety and lack of perceived disease risk as primary barriers. After the recommendation, no further outbreak-related cases occurred. To reach and motivate target groups, communication of a new outbreak-related vaccination recommendation should address potential concerns through as many information channels as possible and direct reimbursement of costs should be enabled.

In Germany, routine RV-vaccination is not adopted into the national immunization schedule as of 2012. Because RV-vaccines were already on the market since 2006, in 2010 a moderate (58%) and low (22%) vaccine uptake was observed in the 5 eastern federal states (EFS) and the 11 western federal states (WFS), respectively. To assess the impact of RV-vaccination, we compared the incidence rates (IR) of RV-related hospitalizations before (2004‒2006) and in seasons after (2008/09–2010/11) RV-vaccine introduction in Germany by utilizing data from the national mandatory disease reporting system. In the EFS, the IR was significantly reduced in age-groups < 18 mo in 2008/09 and in age-groups < 24 mo in 2009/10–2010/11. In the WFS an IR-reduction was observed only in age-groups < 12 mo in 2008/09 and in age-groups < 18 mo in 2009/10–2010/11. Overall IR-reduction in age-groups < 24 mo comparing 2008–11 with 2004–06 was 36% and 25% in EFS and WFS, respectively. In addition, we computed IR-ratios (IRR) in the seasons after mid-2006 with negative binomial regression. The effect of vaccination was independent from the geographic region. Vaccination was associated with a significant reduction in RV-related hospitalizations in the age-groups 6–23 mo. Most prominently, vaccination of 50% of infants led to an estimated decrease in age group 6–11 mo by 42%. No significant reduction was observed in age-groups ≥ 24 mo. In conclusion, in the German setting with low to moderate vaccine uptake, RV-related hospitalization incidence decreased substantially depending on the achieved vaccination coverage, but only in the first two years of life.

SUMMARYIn industrialized countries, acute infectious enteric diseases are usually mild, but they can also cause death. They do so, however, at different ages. Using 2004–2008 German notification data, we computed and compared crude and premature mortality [three different measures of years of potential life lost (YPLL)] of illnesses caused by Campylobacter spp., Listeria monocytogenes, norovirus, rotavirus, non-typhoidal Salmonella spp., and Shiga toxin-producing E. coli (STEC). Among ∼1·5 million notified illnesses, those caused by norovirus were the most frequent. The highest annual mortality was registered for salmonellosis (0·55/1 000 000 population), but listeriosis accounted for the highest number of YPLL (n=4245). Disregarding death at advanced age (i.e. >70 years), STEC illness (n=757) and rotavirus gastroenteritis (n=648) ranked second and third, following listeriosis (n=2306). Routine surveillance captures only a fraction of all incident cases and deaths, under-ascertaining the true burden of disease. Weighting death by age permits a different view on the disease burden individual enteric pathogens cause and particularly underscores the public health importance of listeriosis prevention.

The aims of this study were to compare the prevalence of psychiatric disorders and "psychopathy" in homicidal and nonhomicidal sexual offenders and to investigate the specificity of previous studies on psychiatric morbidity of a sample of sexual murderers. Information from court reports of 166 homicidal and 56 nonhomicidal sex offenders was evaluated using standardized instruments (SCID-II, PCL-R) and classification systems (DSM-IV). Sexual murderers were diagnosed more often with a personality disorder (80.1% vs. 50%; p0.001), especially schizoid personality disorder (16.3% vs. 5.4%; p0.05), as well as with sexual sadism (36.7% vs. 8.9%; p0.001) and sexual dysfunctions (21.7% vs. 7.1%; p0.05). Additionally, they had more often used alcohol during the offense (63.2% vs. 41%; p0.05). The results indicate that sexual murderers have more and a greater variety of psychiatric disorders when compared to nonhomicidal sex offenders.

Hepatitis E ist eine seltene, seit 2001 in Deutschland meldepflichtige Erkrankung. Seither wurden jedes Jahr zwischen 11 und 62 importierte Hepatitis-E-Virus-(HEV) Infektionen ubermittelt. Von diesen waren mehr als die Halfte auf dem Indischen Subkontinent erworben worden. Wahrend die Zahl der gemeldeten importierten HEV-Infektionen in den letzten 10 Jahren weitestgehend konstant blieb, stieg die Zahl der gemeldeten autochthonen Infektionen von 11 im Jahr 2001 auf uber 160 im Jahr 2010 an. Typischerweise ist bei importierten HEV-Fallen eine Infektion mit dem HEV-Genotyp 1 und bei autochthonen HEV-Fallen eine Infektion mit dem Genotyp 3 als Ursache der akuten Hepatitis nachweisbar. Als mogliche Infektionsquelle fur autochthone Erkrankungen in Deutschland konnten vor Kurzem kontaminierte Fleischprodukte identifiziert werden, insbesondere Wildschwein-Produkte und Schweineleber. Bei reiseassoziierten Infektionen erfolgt die Ubertragung meist unter schlechten hygienischen Bedingungen, in der Regel uber kontaminiertes Trinkwasser. Klinisch zeigen sich keine wesentlichen Unterschiede zwischen den beiden HEV-Formen. Arzte sollten zur Abklarung einer akuten Hepatitis auch bei negativer Reiseanamnese eine HEV-Infektion differenzialdiagnostisch in Erwagung ziehen. Hepatitis E is a rare disease in Germany. Since it became a notifiable disease in 2001, every year between 11 and 62 imported hepatitis E virus (HEV) infections were reported to the national surveillance system. Of these, more than half were acquired on the Indian Subcontinent. In contrast to the number of notified imported HEV-cases, which remained stable over the past ten years, the number of reported autochthonous HEV-infections increased steadily from 11 in 2001 to more than 160 in 2010. Typically HEV genotype 1 is identified among imported HEV-cases and genotype 3 among autochthonous HEV-cases as the causative pathogen. In recent years contaminated meat products have been identified in Germany as a possible source of autochthonous infection, especially wild boar meat and pig liver. In contrast, travel-associated HEV-infections are usually acquired through contaminated water. Clinically there seem to be no major differences in the disease manifestations of both hepatitis E forms. Health care professionals should consider HEV-infection as a potential cause for acute hepatitis even in patients without travel history.

A commercial cheese (acid curd) made from pasteurized milk caused a large listeriosis outbreak in Germany from October 2006 through February 2007. The Listeria monocytogenes outbreak strain was identified in humans and in cheese samples from a patient's home and from the production plant. During the outbreak period, 189 patients were affected, which was 97% above the mean case number for the respective time period of the years 2002 to 2005. Of patients with available detailed information on cheese consumption (n=47), 70% reported to have consumed the incriminated cheese product. Recent European food safety alerts due to Listeria-contaminated cheeses more often concerned products made from pasteurized or heat-treated milk than from raw milk. The findings should be considered in prevention guidelines addressing vulnerable populations.

Summary Objectives To characterize the seroepidemiological features of Pneumocystis jirovecii infection in healthy Chilean children using overlapping fragments (A, B, C) of the P. jirovecii major surface glycoprotein (Msg). Methods Serum antibodies to MsgA, MsgB, and MsgC were measured every 2 months by enzyme-linked immunosorbent assay (ELISA) in 45 Chilean infants from about age 2 months to 2 years. Results Peak antibody levels (usually reached at age 6 months) and the force (or rate) of infection were somewhat greater for MsgC than for MsgA. Significant seasonal variation in antibody levels was only found with MsgA. Respiratory infections occurred in most children, but nasopharyngeal aspirates were of limited value in detecting the organism. In contrast, serological responses commonly occurred, and higher levels only to MsgC were significantly related to the number of infections. Conclusions Serological responses to recombinant Msg fragments provide new insights into the epidemiological and clinical features of P. jirovecii infection of early childhood. MsgA, the amino terminus fragment, is more sensitive in detecting seasonal influences on antibody levels, whereas MsgC is better able to detect changes in antibody levels in response to clinical infection.

Despite medical advances, Pneumocystis jirovecii remains a major cause of lethal pneumonia (Pneumocystis pneumonia [PCP]) in patients with HIV infection. A recent study of >500 episodes of PCP in patients with HIV infection at a single medical center revealed no statistically significant changes in the mortality rate over the past 2 decades [1]. The development of sensitive molecular techniques has permitted detection of P. jirovecii in the respiratory tract of different patient populations. The highest frequency of P. jirovecii colonization or subclinical infection occurs among patients with HIV infection; specific risk factors, such as low CD4+ cell counts and smoking, have been identified [2]. P. jirovecii colonization induces local and systemic inflammatory responses and has been associated with more-severe airway obstruction [3, 4]. Thus, the potential problems resulting from the interaction of P. jirovecii with its human host extend not only to immunocompromised patients but also to immunocompetent patients. Analysis of immune responses to P. jirovecii has long been hampered by the lack of suitable reagents [5–14]. The development of recombinant P. jirovecii antigens has begun to change this situation [15–20]. We selected the major surface glycoprotein (Msg) as our target antigen, because it is highly immunogenic, contains protective B and T cell epitopes, and plays a central role in the interaction of the organism with the host [21–25]. We developed 3 over-lapping recombinant fragments (MsgA, MsgB, and MsgC) that span the entire length of a single Msg isoform. Our studies have shown that MsgC, the carboxyl terminus, is the fragment that is most strongly recognized by serum antibodies of patients with HIV infection who have recovered from PCP [19, 20, 26]. To better delineate this antibody reactivity, we developed 3 variants of our original MsgC (termed MsgC1)—MsgC3, MsgC8, and MsgC9—which exhibited 70%–99% homology at the amino acid level [27]. So far, our studies have shown that these variants react with serum specimens independently, but they also seem to have unique epitopes. The Multicenter AIDS Cohort Study (MACS) is an ongoing, prospective cohort study of HIV infection in men who have sex with men that began in 1984 and involves 4 cities: Baltimore, Maryland; Chicago, Illinois; Pittsburgh, Pennsylvania; and Los Angeles, California. The careful patient follow-up and extensive database of the MACS have made it an invaluable resource for numerous studies of HIV infection and its complications. From 1992 through 2000, 106 patients from this cohort died and had lung tissue samples obtained at autopsy. Fifteen patients died from PCP. Ninety-one patients died from other causes, and of these, 42 (46%) were colonized with P. jirovecii, as determined by polymerase chain reaction (PCR) [28]. Multivariate analysis showed that cigarette smoking was associated with an increased risk for colonization, whereas residence in Los Angeles was associated with a decreased risk. These data raised intriguing questions about the relationship between the clinical and epidemiologic factors of P. jirovecii colonization, the occurrence of PCP, and serologic responses to Msg. In the present study, we have examined the serologic responses to the MsgC constructs over the last 5.5 years of life in these MACS patients according to their status at death (PCP, P. jirovecii colonization, or neither), the specific host and environmental factors for all patients associated with high antibody levels, and whether the first AIDS-defining illness was PCP.

SUMMARYIn Baden-Wuerttemberg, a federal state in south-west Germany, a large outbreak of 1089 laboratory-confirmed human Puumala virus (PUUV) infections occurred in 2007. We conducted a survey to describe the disease burden and a case-control study to identify risk factors for acquiring PUUV. Case-patients were interviewed about clinical outcome and both case-patients and randomly recruited controls were interviewed about exposure. We calculated matched odds ratios (mOR) using a conditional logistic regression model. Multivariable analysis of 191 matched case-control pairs showed that case-patients were more likely than controls to have seen small rodents/their droppings (mOR 1·9, 95% CI 1·2–3·0), cleaned utility rooms (mOR 1·8, 95% CI 1·0–3·4) and visited forest shelters (mOR 3·9, 95% CI 1·1–14·3). Two thirds of case-patients required hospitalization. During PUUV epidemics rodent control measures and use of protective equipment should be considered in utility rooms and shelters.

Die Pravention und Kontrolle lebensmittelbedingter Zoonosen hat im nationalen und europaischen Kontext einen hohen Stellenwert. Um zielgerichtete Kontrollmasnahmen ergreifen zu konnen, werden umfangreiche Daten uber Zoonosen beim Menschen und zum Vorkommen von Zoonoseerregern in der Lebensmittelkette benotigt. Daher wurden gemeinschaftliche Rechtsvorschriften geschaffen, die die Erfassung und Zusammenfuhrung der notwendigen Daten auf nationaler und europaischer Ebene ermoglichen. Erforderliche Strukturen wurden etabliert und fortlaufend optimiert. Auserdem wurden Surveillance- und Schnellwarnsysteme verbessert bzw. eingerichtet, um lebensmittelbedingte Krankheitsausbruche zeitnah erkennen und untersuchen zu konnen. Weiterhin konnen Informationen uber nicht sichere Lebens- und Futtermittel schnell uber nationale Grenzen hinweg ausgetauscht werden. Eine effektive Pravention und Kontrolle erfordert klar definierte Zustandigkeiten der Gesundheits-, Veterinar- und Lebensmitteluberwachungsbehorden sowie deren enge Zusammenarbeit. Im vorliegenden Beitrag werden die vorhandenen Strukturen sowie die Zusammenarbeit der zustandigen Stellen unter Berucksichtigung der gultigen Rechtsvorschriften mit speziellem Fokus auf der europaischen Dimension dargestellt. Es ist zu erwarten, dass die Datenlage und die Kooperation auf nationaler und europaischer Ebene zukunftig weiter verbessert werden kann und dass sich die Inzidenz lebensmittelbedingter Zoonosen durch gezielte Kontrollmasnahmen, insbesondere in der Primarproduktion, nachhaltig reduzieren lasst.

We examined the effects of surfactant protein A (SP-A), a collectin, on the interaction of Pneumocystis murina with its host at the beginning, early to middle, and late stages of infection. Pneumocystis murina from SP-A wild-type (WT) mice inoculated intractracheally into WT mice (WT(S)-WT(R)) adhered well to alveolar macrophages, whereas organisms from SP-A knockout (KO) mice inoculated into KO mice (KO(S)-KO(R)) did not. Substitution of WT mice as the source of organisms (WT(S)-KO(R)) or recipient host macrophages (KO(S)-WT(R)) restored adherence to that found with WT(S)-WT(R) mice. In contrast, when immunosuppressed KO and WT mice were inoculated with P. murina from a homologous source (KO(S)-KO(R), WT(S)-WT(R)) or heterologous source (WT(S)-KO(R), KO(S)-WT(R)) and followed sequentially, WT(S)-KO(R) mice had the highest levels of infection at weeks 3 and 4; these mice also had the highest levels of the chemokine macrophage inflammatory protein-2 and neutrophils in lavage fluid at week 3. Surfactant protein-A administered to immunosuppressed KO(S)-KO(R) mice with Pneumocystis pneumonia for 8 wk as a therapeutic agent failed to lower the organism burden. We conclude that SP-A can correct the host immune defect in the beginning of P. murina infection, but not in the middle or late stages of the infection.

The changing epidemiology of vector-borne diseases represents a growing threat to human health. Contemporary surveillance systems have to adapt to these changes. We describe temporal trends and geographic origins of vector-borne diseases in Germany with regard to strengths of existing disease surveillance and to areas marked for improvement. We focused on hantavirus infection (endemic in Germany), chikungunya fever (recently emerging in Europe) and dengue fever (imported from tropical regions), representing important subgroups of vector-borne infections. Routine surveillance data on demographics, origin of infection and the date of reporting were analysed. From 2001 through 2007, 3,005 symptomatic hantavirus infections, and 85 cases of chikungunya fever were reported, similarly 1,048 cases of dengue fever in 2002 through 2007. The geographic origin of hantavirus infection was reported for 95.5% of all cases (dengue virus, 98.4%; chikungunya virus, 100%). Hantavirus infections were acquired in Germany in 97.6% of cases (n = 2800). In 2007, there was a marked increase of hantavirus cases, mainly in areas known to be endemic for hantavirus. In 2006, imported cases of chikungunya fever primarily returned from several islands of the Indian Ocean, while the majority of imported cases in 2007 came from India. The reported number of dengue fever cases have increased since 2004. Thailand contributed the largest proportion of cases (17-43% in individual years), followed by India, Brazil and Indonesia. Surveillance of notifiable vector-borne diseases in Germany is able to timely detect spatial and temporal changes of autochthonous an imported infections. Geographic and temporal data obtained by routine surveillance served as a basis for public health recommendations. In addition to surveillance of vector-borne infections in humans, nationwide monitoring programs and inventory techniques for emerging and reemerging vectors and for wildlife disease are warranted.

SUMMARYAn outbreak of haemolytic uraemic syndrome (HUS) among children caused by infection with sorbitol-fermenting enterohaemorrhagicEscherichia coliO157:H−(SF EHEC O157:H−) occurred in Germany in 2002. This pathogen has caused several outbreaks so far, yet its reservoir and routes of transmission remain unknown. SF EHEC O157:H−is easily missed as most laboratory protocols target the more common sorbitol non-fermenting strains. We performed active case-finding, extensive exploratory interviews and a case-control study. Clinical and environmental samples were screened for SF EHEC O157:H−and the isolates were subtyped by pulsed-field gel electrophoresis. We identified 38 case-patients in 11 federal states. Four case-patients died during the acute phase (case-fatality ratio 11%). The case-control study could not identify a single vehicle or source. Further studies are necessary to identify the pathogen's reservoir(s). Stool samples of patients with HUS should be tested with an adequate microbiological set-up to quickly identify SF EHEC O157:H−.

Background The food-borne viruses in Europe (FBVE) network database was established in 1999 to monitor trends in outbreaks of gastroenteritisdue to noroviruses (NoVs), to identify major transmission routes of NoV infections within and between participating countries and to detectdiffuse international food-borne outbreaks.Methods We reviewed the total of 9430 NoVoutbreak reports from 13 countries with date of onset between 1 January 2002 and 1 January2007 for representativeness, completeness and timeliness against these objectives.Results Rates of reporting ranged from a yearly average of 1.8 in 2003 to 11.6 in 2006. Completeness of reporting of an agreed minimumdataset improved over the years, both for epidemiological and virological data. For the 10 countries that provided integrated (epidemiological ANDvirological) reporting over the 5-year period, the completeness of the minimum dataset rose from 15% in 2003 to 48% in 2006. Two countrieshave not been able to combine both data types due to the structure of the national surveillance system (England and Wales and Germany).Timeliness of reporting (median days between the onset of an outbreak and the date of reporting to the FBVE database) differed greatly betweencountries, but gradually improved to 47 days in 2006.Conclusion The outbreaks reported to the FBVE reflect the lack of standardization of surveillance systems across Europe, making directcomparison of data between countries difficult. However, trends in reported outbreaks per country, distribution of NoV genotypes, and detectionof diffuse international outbreaks were used as background data in acute questions about NoV illness and the changing genotype distributionduring the 5-year period, shown to be of added value. Integrated reporting is essential for these objectives, but could be limited to sentinelcountries with surveillance systems that allow this integration. For successful intervention in case of diffuse international outbreaks, completenessand timeliness of reporting would need to be improved and expanded to countries that presently do not participate.Keywords Epidemiology, Food safety, Public health

The epidemiology of infectious foodborne diseases has changed. Outbreaks more frequently occur geographically dispersed or protractedly over longer periods of time, and they often appear as a scatter of seemingly sporadic cases. This hampers and delays the identification of their epidemiological link. The surveillance of infectious foodborne diseases has to be refined accordingly to be able to detect these diffuse outbreaks. The German Protection against Infection Act, enacted in 2001, offers the potential of increased sensitivity due to timely electronic reporting of individual cases and detailed data accompanying each report. In addition to a timely and comprehensive reporting system, subtyping of pathogens has become an invaluable tool in identifying epidemiologically linked cases, i.e. outbreaks. Still, the sensitivity of foodborne disease surveillance still hinges on the willingness of physicians to order stool testing for enteric pathogens (and to report suspected outbreaks to local health departments). Without the active participation of physicians, the chance of detecting outbreaks and successfully investigating them is markedly reduced. Consequently, the general preventive strategy would be jeopardised, namely to understand the (often new) mechanisms by which contamination and disease transmission occur well enough to interrupt them.

Noroviren verursachen einen Grosteil der weltweit auftretenden akuten viralen Gastroenteritiden. Sie verbreiten sich uber kontaminierte Lebensmittel und Wasser, als Schmierinfektion oder uber Aerosole, die beim Erbrechen entstehen. Aufgrund der hohen Viruskonzentration im Stuhl oder Erbrochenen, ihrer hohen Umweltstabilitat, der niedrigen infektiosen Dosis sowie dem Fehlen einer langerfristigen Immunitat fuhren Noroviruserkrankungen neben sporadischen Einzelerkrankungen uberwiegend in Gemeinschaftseinrichtungen wie Krankenhausern und Altenheimen zu Ausbruchen von beachtlichem Ausmas. Die Bewaltigung dieser Krankheitsgeschehen erfordert ein striktes Hygienemanagement. Kinder und alte Menschen sind von der Erkrankung, die durch plotzlich einsetzendes haufig schwallartiges Erbrechen gekennzeichnet ist, besonders betroffen. Kennzeichnend fur Noroviren ist die extreme Genomvariabilitat, durch die fortlaufend neue Virusvarianten mit einem unterschiedlich stark ausgepragten pathogenen Potenzial entstehen. Abhangig von der zirkulierenden Virusvariante differiert dadurch vor allem der Wintergipfel der saisonal verlaufenden Erkrankung deutlich. Fur die Diagnostik stehen neben dem elektronenmikroskopischen Nachweis insbesondere der virale RNA-Nachweis in der PCR bzw. des viralen Antigens im Antigen-Enzymimmunoassay (EIA) zur Verfugung. Die Genomsequenzierung liefert wertvolle Informationen zur Identifikation der Virusvariante und zur Aufklarung von Infektionsketten. Erst nach Umsetzung des Infektionsschutzgesetzes (IfSG) im Januar 2001 mit Einfuhrung der Meldepflicht von Norovirusinfektionen ist es moglich, einen detaillierten Uberblick zur bundesweiten Epidemiologie dieser Erkrankung in Deutschland zu erhalten.

A nationwide outbreak of Salmonella Agona caused by aniseed-containing herbal tea occurred from October 2002 through July 2003 among infants in Germany. Consumers should adhere strictly to brewing instructions, although in exceptional cases this precaution may not be protective, particularly when preparing tea for vulnerable age groups.

The development of Pneumocystis murina pneumonia and host response were characterized over time and at different levels of infection in corticosteroid immunosuppressed surfactant protein A (SP-A) knockout and wild-type (WT) mice. Infection increased over time in both strains of mice; however, significantly more cyst forms were detected in the knockout mice at intermediate and late stages of infection. In mice with heavy infections, TNF-alpha and IFN-gamma protein concentrations were significantly higher in pulmonary lavage fluid from knockout mice. There was a significant positive correlation between TNF-alpha and IFN-gamma concentrations and the level of infection in knockout mice, but not in WT mice. No significant differences were detected in IL-1 levels between the two strains of mice at any of the time points or at any level of infection. At heavier infection levels, significantly more MIP-2 protein was detected in the lungs of knockout mice, but a significant positive correlation between MIP-2 concentrations and the infection level was detected in both groups of mice. At the intermediate stage of infection, a significantly higher percentage of neutrophils was detected in the lungs of knockout mice than in WT mice. There was no difference in SP-D levels between WT and KO mice with identical levels of infection. These data support a protective role for SP-A in host defense against Pneumocystis and suggest that the effects of SP-A on the host response vary based on the intensity of the infection.

Human VAT-1 (hVAT-1) is a homologue of the synaptic vesicle membrane protein of Torpedo californica. Its coding gene is located near the BRCA1 locus and thus hVAT-1 may be linked to an inherited predisposition to breast and ovary cancer. However, the hVAT-1 protein expression pattern in normal epithelial tissues such as skin, mammary gland and ovary, as well as in tumours of the mammary gland and ovary, has not been studied.To address this issue, an immunohistological analysis of biopsies of normal epidermis and lesional epidermis of bullous pemphigoid and pemphigus vulgaris patients was undertaken.hVAT-1-expression was observed in basal keratinocytes of lesional epidermis of bullous pemphigoid patients but not in normal epidermis or in lesional epidermis of pemphigus vulgaris patients. Moreover, hVAT-1 expression in HaCaT cells was found to be calcium-dependent. Normal and malignant mammary and ovary epithelium were found to be hVAT-1-negative.Our results indicate that hVAT-1 exerts a specific function in keratinocyte physiology, in particular in calcium-regulated processes, with no evident deregulation in malignancies of the breast and ovary.