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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.

Objective: We describe epidemiological trends of human brucellosis in Germany over a 13 year period based on national surveillance data. Methods: We analyzed demographic, clinical, laboratory and exposure information of symptomatic laboratory-confirmed brucellosis cases notified 2006–18. Using official population data, we calculated incidences and risk ratios (RR). Results: From 2006 to 2018, 408 brucellosis cases were notified in Germany (mean annual incidence: 0.38/1,000,000 population), of which 75% were travel-associated. Yearly notifications peaked in 2014 (n = 47) and remained elevated compared to 2006–2013 (mean: n = 25). Asylum seekers (AS) arriving in Germany accounted for 9/44 (2015) and 15/36 (2016) cases, respectively. RR AS/non-AS 2015–2016: 28, 95% CI: 17–45. Unpasteurized milk products were most frequently notified as source of infection. Imported food and occupational exposure played a role in autochthonous cases. Conclusions: The incidence of human brucellosis has markedly increased in recent years. Most of the observed rise in notifications can be explained by infections in AS. Exposure still predominantly occurs abroad. Risk factors for autochthonous infections need to be investigated further, though imported dairy products seem to play a role. Physicians should consider brucellosis as differential diagnosis in AS and people with travel to endemic regions with compatible symptoms. Keywords: Brucellosis, Surveillance, Zoonosis, Human, Germany, Foodborne diseases, Asylum seekers

Highlights • Experts suggest primary objectives for national HEV surveillance in EU/EEA countries. • to monitor the incidence of acute HEV cases. • to monitor chronic HEV infections. • to describe the epidemiology of acute and chronic HEV infections. • Suggested secondary objectives for national HEV surveillance in EU/EEA countries: • to monitor HEV phylotypes/subtypes. • to identify potential clusters/outbreaks. • to collect information on possible routes of transmission. • Overall, the majority of EU/EEA countries collect the suggested data and meet the outlined requirements to confirm an acute case., Background Hepatitis E virus (HEV) infection is not notifiable at EU/EEA level, therefore surveillance relies on national policies only. Between 2005 and 2015, more than 20,000 cases were reported in EU/EEA countries. HEV testing is established in 26 countries and 19 countries sequence HEV viruses. Objective and study design WHO's European Action plan for viral hepatitis recommends harmonised surveillance objectives and case definitions. ECDC's HEV expert group developed minimal and optimal criteria for national hepatitis E surveillance to support EU/EEA countries in enhancing their capacity and to harmonise methods. Results The experts agreed that the primary objectives of national surveillance for HEV infections should focus on the basic epidemiology of the disease: to monitor the incidence of acute cases and chronic infections. The secondary objectives should be to describe viral phylotypes or subtypes and to identify potential clusters/outbreaks and possible routes of transmission. Seventeen of 20 countries with existing surveillance systems collect the minimal data set required to describe the epidemiology of acute cases. Eleven countries test for chronic infections. Twelve countries collect data to identify potential clusters/outbreaks and information on possible routes of transmission. Discussion Overall, the majority of EU/EEA countries collect the suggested data and meet the outlined requirements to confirm an acute case.

Hepatitis E virus (HEV) infection is a major public health concern in low-income countries, yet incidence and prevalence estimates are often lacking. Serum (n = 653) and faecal (n = 150) samples were collected from apparently healthy individuals using convenience sampling technique in six communities (Ore, Oke-Osun, Osogbo, Ede, Esa-Odo, and Iperindo) from Osun State, Nigeria. Serum samples were analysed for total anti-HEV IgG/IgM and anti-HEV IgM using commercially available HEV ELISA kits. Total anti-HEV positive serum and all stool samples were analysed for HEV RNA by RT-PCR. Overall, 15.0% (n = 98/653) and 3.8% (n = 25/653) of the serum samples were positive for anti-HEV total and IgM antibodies, respectively. Total anti-HEV and IgM in Ore, Oke-Osun, Osogbo, Ede, Esa-Odo, and Iperindo was 21.0% (n = 13/62) and 3.2% (n = 2/62), 19.4% (n = 20/103) and 6.8% (n = 7/103), 11.4% (n = 12/105) and 2.9% (n = 3/105), 8.0% (n = 16/199) and 1.5% (n = 3/199), 22.0% (n = 22/100) and 10.0% (n = 10/100), and 17.9% (n = 15/84) and 0.0% (n = 0/84), respectively. All samples (stool and serum) were HEV RNA negative. Anti-HEV seroprevalence was associated with rural location, increasing age, alcohol consumption, and rearing of animals. This study demonstrated a high anti-HEV seroprevalence in Osun State, indicating the need to implement surveillance and asses the hepatitis E burden in Nigeria.

A steep rise in Hepatitis E diagnoses is currently being observed in Germany and other European countries. The objective of this study was (i) to assess whether this trend mirrors an increase in infection pressure or is caused by increased attention and testing and (ii) estimate individual and population-based Hepatitis E Virus (HEV) seroconversion and seroreversion rates for Germany. We measured anti-HEV IgG prevalence in 10 407 adults participating in two linked, population-representative serosurveys (total n = 12 971) conducted in 1998 and 2010. In this period, we found a moderate but statistically significant decline of overall anti-HEV IgG prevalence from 18.6% to 15.3%. At both time points, seroprevalence increased with age and peaked in persons born between 1935 and 1959 suggesting a past period of increased infection pressure. Paired samples of individuals participating in 1998 and 2010 (n = 2564) revealed respective seroconversion and seroreversion rates of 6.2% and 22.6% among seronegative and seropositive individuals during 12 years, or 5.2 and 2.9 per 1000 inhabitants per year. This corresponds to a total of 417 242 [95%CI: 344 363-495 971] new seroconversions per year in the German population. While anti-HEV seroprevalence has decreased in the last decade, infection pressure and seroincidence remains high in Germany. Continuously rising numbers of Hepatitis E diagnoses in Europe are likely due to an increased awareness of clinicians and indicate that still there is a gap between incident and diagnosed cases. Studies on the true burden of the disease, specific risk factors and sources of autochthonous infections as well as targeted prevention measures are urgently needed.

Hepatitis A is a vaccine-preventable disease with a global distribution. It predominantly occurs in regions with inadequate living conditions, but also affects populations in industrialised countries. Children are frequently involved in the transmission of hepatitis A virus (HAV) and thus play a central role in the epidemiology of hepatitis A. Here, we investigated HAV infections, immunisations, and associated demographic determinants in a nationwide, population-based, cross-sectional survey conducted in Germany from 2003–2006. Out of 17,640 children and adolescents, complete data sets (HAV serology, demographic information and vaccination card) were available for 12,249 (69%), all aged 3–17 years. We found protective antibody levels (>=20 IU/L) in 1,755 (14%) individuals, 1,395 (11%) were vaccinated against hepatitis A, 360 (3%) individuals were HAV seropositive without prior hepatitis A vaccination, thus indicating a previous HAV infection. Antibody prevalence (attributable to vaccination or infection) increased significantly with age. Multivariate logistic regression revealed that predominantly children and adolescents with migration background–even if they were born in Germany–are affected by HAV infections. Our results provide a rationale to emphasise existing vaccination recommendations and, moreover, to consider additional groups with a higher risk of infection for targeted vaccination, especially children with a migration background.

Background Hepatitis E virus (HEV) is endemic in EU/EEA countries, but the understanding of the burden of the infection in humans is inconsistent as the disease is not under EU surveillance but subject to national policies. Study Countries were asked to nominate experts and to complete a standardised questionnaire about the epidemiological situation and surveillance of HEV in their respective EU/EEA country. This study reviewed surveillance systems for human cases of HEV in EU/EEA countries and nominated experts assessed the epidemiology in particular examining the recent increase in the number of autochthonous cases. Results Surveillance systems and case definitions across EU/EEA countries were shown to be highly variable and testing algorithms were unreliable. Large increases of autochthonous cases were reported from Western EU/EEA countries with lower case numbers seen in Northern and Southern European countries. Lack of clinical awareness and variability in testing strategies might account for the observed differences in hepatitis E incidence across EU/EEA countries. Infections were predominantly caused by HEV genotype 3, the most prevalent virus type in the animal reservoirs. Conclusion Discussions from the expert group supported joint working across countries to better monitor the epidemiology and possible changes in risk of virus acquisition at a European level. There was agreement to share surveillance strategies and algorithms but also importantly the collation of HEV data from human and animal populations. These data collected at a European level would serve the ‘One Health’ approach to better informing on human exposure to HEV.

Free PMC Article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6205254/ Between 1 June 2016 and 31 May 2017, 17 European Union (EU) and European Economic Area countries reported 4,096 cases associated with a multi-country hepatitis A (HA) outbreak. Molecular analysis identified three co-circulating hepatitis A virus (HAV) strains of genotype IA: VRD_521_2016, V16-25801 and RIVM-HAV16-090. We categorised cases as confirmed, probable or possible, according to the EU outbreak case definitions. Confirmed cases were infected with one of the three outbreak strains. We investigated case characteristics and strain-specific risk factors for transmission. A total of 1,400 (34%) cases were confirmed; VRD_521_2016 and RIVM-HAV16-090 accounted for 92% of these. Among confirmed cases with available epidemiological data, 92% (361/393) were unvaccinated, 43% (83/195) travelled to Spain during the incubation period and 84% (565/676) identified as men who have sex with men (MSM). Results depict an HA outbreak of multiple HAV strains, within a cross-European population, that was particularly driven by transmission between non-immune MSM engaging in high-risk sexual behaviour. The most effective preventive measure to curb this outbreak is HAV vaccination of MSM, supplemented by primary prevention campaigns that target the MSM population and promote protective sexual behaviour. info:eu-repo/semantics/publishedVersion

Background Travel to countries with high or intermediate hepatitis A virus (HAV) endemicity is a risk factor for infection in residents of countries with low HAV endemicity. Aim: The objective of this study was to estimate the risk for hepatitis A among European travellers using surveillance and travel denominator data. Methods: We retrieved hepatitis A surveillance data from 13 European Union (EU)/ European Economic Area (EEA) countries with comprehensive surveillance systems and travel denominator data from the Statistical Office of the European Union. A travel-associated case of hepatitis A was defined as any case reported as imported. Results: From 2009 to 2015, the 13 countries reported 18,839 confirmed cases of hepatitis A, of which 5,233 (27.8%) were travel-associated. Of these, 39.8% were among children younger than 15 years. The overall risk associated with travel abroad decreased over the period at an annual rate of 3.7% (95% confidence interval (CI): 0.7–2.7) from 0.70 cases per million nights in 2009 to 0.51 in 2015. The highest risk was observed in travellers to Africa (2.11 cases per million nights). Cases more likely to be reported as travel-associated were male and of younger age (Conclusion: Travel is still a major risk factor for HAV infection in the EU/EEA, although the risk of infection may have slightly decreased in recent years. Children younger than 15 years accounted for a large proportion of cases and should be prioritised for vaccination.

Background Notified cases of hepatitis E have increased 40-fold in the past 10 years in Germany. Food safety is a major concern as hepatitis E virus (HEV) RNA has been detected in ready-to-eat retail-level food products. The objective of this case–control study was to assess risk factors for autochthonous symptomatic hepatitis E and explore reasons for delays in diagnosis. Methods: Demographic, clinical and exposure data from notified hepatitis E cases and individually matched population controls were collected in semi-standardised telephone interviews. Conditional logistic regression analysis was used to calculate matched odds ratios (mOR) and population attributable fractions (PAF). Results: In total, 270 cases and 1,159 controls were included (mean age 53 years, 61% men in both groups). Associated with disease were: consumption of undercooked pork liver, pork, wild boar meat, frankfurters, liver sausage and raw vegetables; contact with waste water (occupational) and various host factors (mORs between 1.9 and 34.1, p value Conclusions: Our study suggests that there are indeed sex-specific differences in disease development and lends important epidemiological evidence to specific ready-to-eat pork products as a major source for autochthonous hepatitis E. A review of existing consumer recommendations and production methods may be indicated.

From January to June 2018, two ongoing hepatitis A outbreaks affected travellers returning from Morocco and cases in Europe without travel history, resulting in 163 patients in eight European countries. Most interviewed travel-related cases were unaware of the hepatitis A risk in Morocco. Molecular analysis revealed two distinct hepatitis A virus (HAV) strains (subgenotype IA DK2018_231; subgenotype IB V18-16428). Vaccination recommendations should be emphasised to increase awareness among non-immune travellers to Morocco and HAV-endemic countries. First, we thank the European Centre for Disease Prevention and Control (ECDC)’s Food- and Waterborne Diseases and Zoonoses team, particularly Ettore Severi and Johanna Takkinen for their support of this joint investigation. We also thank Lelia Thornton, HSE - Health Protection Surveillance Centre, Dublin, Ireland for sharing information on the Irish hepatitis A patient. Moreover, we greatly acknowledge the work of local and state health departments for their support of epidemiological investigations and molecular surveillance. Sí

From September 2015 to March 2016, hepatitis A notifications in Germany increased by 45% to 699 cases compared to 482 cases in the same period of the previous year. Children aged five to nine years were predominantly affected (22% of all cases in this period). We hypothesized that this increase could be explained by the marked influx of asylum seekers in this time period. We analysed national surveillance data and estimated the number of imported and autochthonous hepatitis A cases in asylum seekers. We also investigated molecular signatures of hepatitis A viruses sampled from asylum seekers to identify chains of transmission. We found that 40% (278 cases) of all 699 hepatitis A cases notified between September 2015 and March 2016 in Germany concerned asylum seekers. Most infections were acquired abroad, but at least 24% accounted for autochthonous infections. Among asylum seekers, children aged five to nine years were overrepresented with 97 of 278 (35%) notified cases. The analysed hepatitis A virus sequences were primarily subgenotype IB strains and clustered with previously isolated samples from the Middle East, Turkey, Pakistan and East Africa. Except one transmission from an asymptomatic child to a nursery nurse working in a mass accommodation, we are not aware of infection chains involving asylum seekers and German residents. We conclude that asylum-seeking children and adolescents are susceptible to hepatitis A virus infections, particularly children aged five to nine years. Measures to prevent secondary infections in asylum seekers such as extended hygiene measures and post-exposure prophylaxis seem advisable.

We report an ongoing, protracted and geographically dispersed outbreak of haemolytic uraemic syndrome (HUS) and gastroenteritis in Germany, involving 30 cases since December 2016. The outbreak was caused by the sorbitol-fermenting immotile variant of Shiga toxin-producing (STEC) Escherichia coli O157. Molecular typing revealed close relatedness between isolates from 14 cases. One HUS patient died. Results of a case–control study suggest packaged minced meat as the most likely food vehicle. Food safety investigations are ongoing.

After the emergence of unusual clusters of microcephaly among babies born in the fall of 2015 in Brazil—and, retrospectively, in French Polynesia—WHO declared a Public Health Emergency of International Concern in January 2016 (http://www.who.int/mediacentre/news/statements/2016/1st-emergency-committee-zika/en/). Based on the spatial and temporal correlation of these clusters with outbreaks of Zika virus infections a few months before, a causal link is suspected. Whether the observed link between infection and microcephaly is indeed causal needs careful assessment—not the least because we might fall into the trap of ecological fallacy, inferring a causal association on the individual level from an association on the aggregate or population level. Here, we organize the currently available data into Austin Bradford Hill's aspects of evidence for the consideration of causality (Hill, 1965). Although it is no longer considered a litmus test in itself, Hill's recipe for careful and multifaceted contemplation of the available evidence is still a rigorous method for separating what is known from what is not known. For each aspect, we first consider individual‐level evidence, but supplement it with likely more readily observable effects on the population level. Studies to characterize the strength of this association in terms of odds ratios from case–control studies or (preferable) relative risks from cohort studies are already underway. These should be able to answer how much more likely a mother infected with Zika virus any time during pregnancy, or in a specific time window, will be giving birth to a child with microcephaly compared to mothers who were not infected. On the ecological level, a strong increase in microcephaly cases is not by itself evidence for a strong causal association because there might be confounding or biases. Nevertheless, if there were a strong causal association, we would expect to see a large increase in cases of microcephaly in a population with …

Background We describe an outbreak of gastroenteritis and the hemolytic–uremic syndrome caused by Shiga-toxin–producing Escherichia coli in Germany in May, June, and July, 2011. The consumption of sprouts was identified as the most likely vehicle of infection. Methods We analyzed data from reports in Germany of Shiga-toxin–producing E. coli gastro enteritis and the hemolytic–uremic syndrome and clinical information on patients presenting to Hamburg University Medical Center (HUMC). An outbreak case was defined as a reported case of the hemolytic–uremic syndrome or of gastroenteritis in a patient infected by Shiga-toxin–producing E. coli, serogroup O104 or serogroup unknown, with an onset of disease during the period from May 1 through July 4, 2011, in Germany. Results A total of 3816 cases (including 54 deaths) were reported in Germany, 845 of which (22%) involved the hemolytic–uremic syndrome. The outbreak was centered in northern Germany and peaked around May 21 to 22. Most of the patients in whom the hemolytic–uremic syndrome developed were adults (88%; median age, 42 years), and women were overrepresented (68%). The estimated median incubation period was 8 days, with a median of 5 days from the onset of diarrhea to the development of the hemolytic–uremic syndrome. Among 59 patients prospectively followed at HUMC, the hemolytic–uremic syndrome developed in 12 (20%), with no significant differences according to sex or reported initial symptoms and signs. The outbreak strain was typed as an enteroaggregative Shiga-toxin–producing E. coli O104:H4, producing extended-spectrum beta-lactamase. Conclusions In this outbreak, caused by an unusual E. coli strain, cases of the hemolytic–uremic syndrome occurred predominantly in adults, with a preponderance of cases occur ring in women. The hemolytic–uremic syndrome developed in more than 20% of the identified cases.

Introduction: On May 3, 2009, a first case of influenza A/H1N1 infection occurred in the federal state of Saxony-Anhalt, Germany. In order to stop the possible spread of the virus and to study the epidemiological and clinical characteristics of the infection, an investigation was launched by the local health authorities and the RKI. Methods: Standardised questionnaires were used to assess demographic and clinical data. Specimens were collected from case patients and close contacts and were analysed for influenza A/H1N1 using real-time PCR. Results: The index patient showed fever and coughing 3.5 days after returning from a holiday in Mexico. The local health authorities were informed on May 3, and measures were rapidly implemented. These measures included a trace-back of possible contact persons, isolation of the case and close contacts, prophylactic treatment with Oseltamivir. Virological investigations showed that the case shedded viral genome up until the last day of antiviral therapy. Viral genome was also detected in the spouse and the son of the patient. Both showed no symptoms under a prophylactic treatment with antiviral medication. No viral genome was detected in three other family members, and in six other contact persons outside of the family. Discussion: The spread of the virus was contained due to the fast response of the local health authorities. Two secondary cases occurred in the family. These cases remained asymptomatic, possibly due to antiviral prophylaxis. Epidemiological and virological results suggest that the influenza A/H1N1 virus has a longer incubation period and that viral shedding may probably be prolonged when compared with seasonal influenza.

Background In Germany, 17 % of the general human population have antibodies to hepatitis E virus (HEV) (recomLine HEV-IgG/IgM immunoassay [Mikrogen GmbH]). Wild boars represent an animal reservoir for HEV genotype 3, which is the common genotype in Germany. We estimated the seroprevalence among hunters with contact to wild boars to identify factors that may be associated with past or present HEV infection. Methods In 2013, the local veterinarian authority in a district in Central Germany attended meetings of hunters who provided blood specimens and completed a questionnaire collecting information on age, sex, hunting-related activities and consumption of wild boar meat. Specimens of wild boars were taken during drive hunts in this district during the season 2012/2013. All specimens were tested for HEV RNA and anti-HEV IgM and IgG antibodies. Log-binomial regression was used to estimate prevalence ratios (PR) for the hunters. Results Of 126 hunters (median age 55; 94 % male) 21 % tested positive for anti-HEV IgG antibodies (95 % confidence interval [CI] 13–28 %) (recomWell HEV IgG assay [Mikrogen GmbH]). Anti-HEV prevalence was highest in the age group of the 70–79-year-olds (67 %; 95 % CI 39–95 %). Wild boars showed an average anti-HEV prevalence of 41 %. HEV RNA was detected in 4/22 (18 %) liver specimens and in 1/22 (4.5 %) muscle specimens. Most wild boars were tested positive for HEV RNA (3/10; 30 %) and HEV-specific antibodies (7/15; 47 %) in the southwestern part of the district. Hunters preferring this hunting ground had a lower anti-HEV prevalence when gloves were frequently used during disembowelling of wild boars compared to hunters using gloves never or infrequently (age-adjusted PR 0.12; 95 % CI 0.02–0.86). Conclusions Hunters may benefit from wearing gloves when in contact with blood or body fluids of HEV animal reservoirs. Anti-HEV prevalence among the hunters of this study did not significantly differ from that of the general population suggesting that other factors play a major role in the epidemiology of HEV in Germany. Electronic supplementary material The online version of this article (doi:10.1186/s12879-015-1199-y) contains supplementary material, which is available to authorized users.

In May 2013, Italy declared a national outbreak of hepatitis A, which also affected several foreign tourists who had recently visited the country. Molecular investigations identified some cases as infected with an identical strain of hepatitis A virus subgenotype IA. After additional European Union/European Economic Area (EU/EEA) countries reported locally acquired and travel-related cases associated with the same outbreak, an international outbreak investigation team was convened, a European outbreak case definition was issued and harmonisation of the national epidemiological and microbiological investigations was encouraged. From January 2013 to August 2014, 1,589 hepatitis A cases were reported associated with the multistate outbreak; 1,102 (70%) of the cases were hospitalised for a median time of six days; two related deaths were reported. Epidemiological and microbiological investigations implicated mixed frozen berries as the vehicle of infection of the outbreak. In order to control the spread of the outbreak, suspected or contaminated food batches were recalled, the public was recommended to heat-treat berries, and post-exposure prophylaxis of contacts was performed. The outbreak highlighted how large food-borne hepatitis A outbreaks may affect the increasingly susceptible EU/EEA general population and how, with the growing international food trade, frozen berries are a potential high-risk food.

BACKGROUND Food safety authorities discovered that wild boar meat products contaminated with Trichinella spiralis had entered the food chain in Germany in March 2013. Public health authorities issued guidelines for health professionals including post-exposure prophylaxis (PEP) using mebendazole and advised the public to seek medical advice if exposed. Our objective was to identify factors associated with the development of trichinellosis and to evaluate post exposure prophylaxis. METHODS Persons who reported to local public health departments as exposed were interviewed concerning exposure, symptoms, and medication. Serum samples were tested by an in-house Trichinella-specific enzyme-linked innunosorbent assay. Cases were defined as persons presenting with myalgia and/or periorbital edema and Trichinella-specific immunoglobulin M and immunoglobulin G antibodies after exposure to implicated products. RESULTS Of 101 persons interviewed, 71 were exposed and serologically tested. Antibodies were detected in 21/71 (30%) and 14/71 (20%) met the case definition. Attack rates were positively correlated to the amount of implicated product consumed. Among n = 37 persons who received anthelmintics as PEP, 6 persons developed trichinellosis. These cases exclusively occurred among persons starting PEP 6 days or later post-exposure. Exposure to implicated products and delaying PEP were also significantly associated with developing trichinellosis (P < .01) in a multivariable analysis. CONCLUSIONS Concerted efforts by food safety and public health authorities lead to timely outbreak control and facilitated the provision of early PEP. PEP appears to be effective in preventing trichinellosis when given early, preferably within 6 days. We therefore recommend initiating PEP without delay in similar settings and encourage public health professionals to fast-track this intervention.

Background and objective Cytochrome P450 (CYP) 1A2 activity is induced by cigarette smoking. Thus smoking cessation in patients while they are undergoing therapy with a CYP1A2 substrate such as theophylline or clozapine increases its concentrations and may cause adverse effects. Our objective was to determine the time course of CYP1A2 activity changes after smoking cessation in heavy smokers as the basis for dosing adaptation schemes. Methods The study was conducted in 8 men and 4 women (all white) who smoked 20 cigarettes or more per day. Sudden smoking cessation was carried out after a 14-day run-in period. Subjects were phenotyped for CYP1A2 activity at 6, 4, and 1 day before smoking cessation and at 0, 1, 2, 3, 6, 8, 10, and 13 days thereafter by use of the paraxanthine-to-caffeine ratio in plasma 6 hours after a 148-mg caffeine test dose. A monoexponential decay of CYP1A2 activity to a residual value was fitted to the data by nonlinear regression analysis. Results On cessation of smoking, initial caffeine clearance (estimated geometric means and 95% confidence intervals) decreased significantly (P < .01), by 36.1% (30.9%-42.2%), from 2.47 mL · min−1 · kg−1 body weight (2.03–3.00 mL · min−1 · kg−1 body weight) to a new steady state of 1.53 mL · min−1 · kg−1 body weight (1.24–1.89 mL · min−1 · kg−1 body weight). The apparent half-life of CYP1A2 activity decrease was 38.6 hours (27.4–54.4 hours). Conclusion Doses of CYP1A2 substrates with a narrow therapeutic range should be decreased immediately on cessation of heavy smoking. As a rule of thumb, a stepwise daily dose reduction of approximately 10% until the fourth day after smoking cessation is proposed, which should be accompanied by therapeutic drug monitoring. Clinical Pharmacology & Therapeutics (2004) 76, 178–184; doi: 10.1016/j.clpt.2004.04.003

Humanpathogene, vektorubertragene Infektionserreger spielen fur Deutschland eine bedeutende Rolle. Die endemischen, zoonotischen Infektionserreger sind entweder bundesweit verbreitet (Borrelia burgdorferi sensu latu) oder kommen in bestimmten geografischen Regionen vor (FSME-Viren, Hantaviren). Sie verursachen eine erhebliche Krankheitslast. Ihre Pravention und Kontrolle beruhen im Wesentlichen auf Aufklarung und personlichen Schutzmasnahmen (FSME-Impfung, Schutz vor Vektoren). Eine gute Surveillance, erganzt um gezielte epidemiologische Studien, ist Voraussetzung zur Bewertung der raumlich-zeitlichen Infektionsrisiken und der Wirksamkeit von Praventionsmasnahmen. Neben den endemischen Erregern mussen die importierten, durch Vektoren – zumeist Mucken – ubertragenen Erreger im Rahmen der Surveillance-Aktivitaten ebenfalls systematisch und intensiv beobachtet werden, zum einen, um das Risiko fur Reisende aus Deutschland einschatzen zu konnen, zum anderen, um das Risiko einer moglichen autochthonen Ubertragung adaquat bewerten zu konnen. Hierbei sind weitere Faktoren zu berucksichtigen (Etablierung von invasiven Muckenarten in Deutschland, zunehmende Erwarmung). Unter diesen Erregern sind vor allem das West-Nil-Virus, das Denguevirus, das Chikungunyavirus und der Malariaerreger (Plasmodien) zu nennen. Im vorliegenden Beitrag geben wir einen Uberblick uber die epidemiologische Situation bei ausgewahlten, fur Deutschland besonders relevanten, durch Vektor-ubertragene Erreger ausgelosten Infektionskrankheiten.

From 20 September through 5 October 2012, the largest recorded food-borne outbreak in Germany occurred. Norovirus was identified as the causative agent. We conducted four analytical epidemiological studies, two case–control studies and two surveys (in total 150 cases) in secondary schools in three different federal states. Overall, 390 institutions in five federal states reported nearly 11,000 cases of gastroenteritis. They were predominantly schools and childcare facilities and were supplied almost exclusively by one large catering company. The analytical epidemiological studies consistently identified dishes containing strawberries as the most likely vehicle, with estimated odds ratios ranging from 2.6 to 45.4. The dishes had been prepared in different regional kitchens of the catering company and were served in the schools two days before the peaks of the respective outbreaks. All affected institutions had received strawberries of one lot, imported frozen from China. The outbreak vehicle was identified within a week, which led to a timely recall and prevented more than half of the lot from reaching the consumer. This outbreak exemplifies the risk of large outbreaks in the era of global food trade. It underlines the importance of timely surveillance and epidemiological outbreak investigations for food safety.

Since November 2012, there has been an increase in reported cases of hepatitis A in tourists returning from Egypt in several European countries. As of 24 April, 80 HAV cases in travellers with symptom onset after 1 November 2012 visiting different areas in Egypt have been reported. Four cases from Norway, six cases from the Netherlands and five cases from England share an identical hepatitis A viral RNA sequence. This increase in cases suggests that vaccination recommendations for travellers to hepatitis A endemic countries should be reinforced.

We assessed hepatitis E virus (HEV) antibody seroprevalence in a sample of the adult population in Germany. Overall HEV IgG prevalence was 16.8% (95% CI 15.6%–17.9%) and increased with age, leveling off at >60 years of age. HEV is endemic in Germany, and the lifetime risk for exposure is high.

A large outbreak of the hemolytic-uremic syndrome caused by Shiga-toxin-producing Escherichia coli O104:H4 occurred in Germany in May 2011. The source of infection was undetermined.We conducted a matched case-control study and a recipe-based restaurant cohort study, along with environmental, trace-back, and trace-forward investigations, to determine the source of infection.The case-control study included 26 case subjects with the hemolytic-uremic syndrome and 81 control subjects. The outbreak of illness was associated with sprout consumption in univariable analysis (matched odds ratio, 5.8; 95% confidence interval [CI], 1.2 to 29) and with sprout and cucumber consumption in multivariable analysis. Among case subjects, 25% reported having eaten sprouts, and 88% reported having eaten cucumbers. The recipe-based study among 10 groups of visitors to restaurant K included 152 persons, among whom bloody diarrhea or diarrhea confirmed to be associated with Shiga-toxin-producing E. coli developed in 31 (20%). Visitors who were served sprouts were significantly more likely to become ill (relative risk, 14.2; 95% CI, 2.6 to ∞). Sprout consumption explained 100% of cases. Trace-back investigation of sprouts from the distributor that supplied restaurant K led to producer A. All 41 case clusters with known trading connections could be explained by producer A. The outbreak strain could not be identified on seeds from the implicated lot.Our investigations identified sprouts as the most likely outbreak vehicle, underlining the need to take into account food items that may be overlooked during subjects' recall of consumption.

Since early May 2011, an increased incidence of haemolytic uraemic syndrome (HUS) and bloody diarrhoea related to infections with Shiga toxin-producing Escherichia coli (STEC) has been observed in Germany, with most cases in the north of the country. Cases reported from other European countries had travelled to this area. First results of a case–control study conducted in Hamburg suggest an association between the occurrence of disease and the consumption of raw tomatoes, cucumber and leaf salad.

Current efforts to prevent antimicrobial resistance include limiting antimicrobial use, providing education about appropriate use, and developing better point-of-care tests, but what do physicians actually think of rational prescribing and potential interventions? We tried to ascertain which factors can influence a physician's decision to start antimicrobial therapy on a patient, and their opinions on measures to promote rational prescribing.We conducted a nationwide, cross-sectional survey of 10,600 physicians from medical registries of all known board-certified physicians in Germany.Among respondents (n = 3,492; 33%; detailed non-response bias analysis included), 90% indicated that they decide to start antimicrobial therapy on a patient at least weekly, and 66% reported that they decide daily. We identified correlates for deciding to start antimicrobial therapy on a patient. Predictors were status as a hospital physician (odds ratio (OR) 1.29 (95% confidence interval (CI) 1.00-1.68)), male physician (OR 1.81 (95% CI 1.42-2.31)), being age 50-59 (OR 1.56 (95% CI 1.10-2.21)), and practising in states in the former East Germany (OR 1.60 (95% CI 1.15-2.21)). Each specialist was significantly less likely to decide to start a course of antimicrobial therapy than ENTs and urologists. Other predictors were agreeing to prescribe to be on the safe side (OR 1.34 (95% CI 1.03-1.76)), believing that the quality of prescribing practice improves after receiving continuing education from pharmaceutical companies (OR 1.43 (95% CI 1.11-1.84)), and having experience with failed therapy for resistant pathogens (OR 2.42 (95% CI 1.83-3.19)).Physicians in our sample decide to start antimicrobial therapy on a patient, and they value intervention to support prudent use, for example continuing education, practice guidelines and implementation of surveillance measures. Socio-behavioural factors, regional variation, gender, and age merit further research to promote rational antimicrobial prescribing and explore related influencing factors.

Physicians mention patients' expectations as a reason for prescribing antibiotics for common (viral) upper respiratory tract infections despite clinical evidence against their use and the physicians' better judgement. We aimed to assess the prevalence of such expectations and factors of influence (knowledge and attitudes) in Germany's general population. In November 2008, 1,778 persons registered with a large market research company were invited to complete an online questionnaire on expectations concerning prescription of antibiotics and on knowledge and attitudes regarding the effectiveness and use of antibiotics for upper respiratory tract infections. A total of 1,076 persons aged 15-78 years participated (response: 61%), of whom 91.8% reported using antibiotics 'only if absolutely necessary'. Prescription of antibiotics was expected by 113 (10.5%) of the 1,076 respondents for the common cold and by 997 (92.7%) for pneumonia. In a logistic regression analysis, predictors for expecting a prescription for antibiotics for the common cold included the following opinions: 'common cold or flu can effectively be treated with antibiotics' (prevalence: 37.6%; odds ratio (OR): 9.6; 95% confidence interval (CI): 3.8 to 24.3) and 'antibiotics should be taken when having a sore throat to prevent more serious illness' (prevalence 8.6%; OR: 7.6; 95% CI: 3.9 to 14.5). Among those expecting a prescription (n=113), 80 (71%) reported that they would trust their physician when he or she deems a prescription unnecessary; a further eight (7%) would be unsatisfied, but would accept the decision. Our results suggest that only a minority expects antibiotics for the treatment of cold symptoms. Physicians should be educated that their decisions not to prescribe antibiotics for the common cold, even when against patients' expectations, are apparently accepted by the majority.

Approximately 60% of hepatitis A virus infections in Germany occur in persons without a travel history to disease-endemic areas and for whom sources of infection are unknown. Recommendation of pretravel vaccination fails to prevent the remaining imported infections. Using enhanced surveillance in 2007–2008, we analyzed epidemiologic patterns of hepatitis A in Germany and appropriateness and adequacy of current immunization recommendations. Young patients with a migration background who had visited friends and family in their ancestral countries accounted for most imported cases. Phylogenetic analysis showed high diversity of sequence data and clustering of strains with similar regions of origin or patient migration backgrounds. Virologic fi ndings are compatible with those of low-incidence countries, where virtually all infections are directly or indirectly imported from other regions. Germans with a migration background are seen as a special risk group so far insuffi ciently reached by pretravel vaccination advice.

Since early May 2011, a large outbreak of haemolytic uraemic syndrome (HUS) and bloody diarrhoea related to infections with Shiga toxin-producing Escherichia coli (STEC) has been observed in Germany. The outbreak is focused in the north, but cases have been reported from all German states and other countries. Since our report last week, the number of HUS cases has increased to 470 and STEC serotype O104 has been confirmed in many cases.

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.