Multinational collaboration in solving a European Salmonella Braenderup outbreak linked to imported melons, 2021.

A genomic cluster of Salmonella Braenderup ST22, a serovar of Salmonella enterica subsp. enterica which causes symptoms of gastrointestinal illness, was notified by Danish authorities to the European Centre for Disease Prevention and Control (ECDC) on 3 May 2021. By 6 July 2021, S. Braenderup outbreak cases (n = 348) had been reported from 12 countries in the European Union/European Economic Area (EU/EEA) and the United Kingdom (UK), including 68 hospitalised cases. With support from affected EU/EEA countries, and in partnership with the European Food Safety Authority (EFSA), ECDC established an international outbreak investigation team to rapidly identify the source and prevent outbreak spread. Consumption information was shared with affected countries through a standard line list, revealing that 124 of 197 cases (63%) reported having eaten (any) melons within 7 days prior to disease onset. The speed and completeness of the investigation, which identified the outbreak vehicle as galia melons imported from Honduras in June 2021, was a direct result of extensive collaboration and information sharing between countries' national food safety and public health authorities. This article describes the outbreak and the benefits, successes, and challenges of multi-country collaboration for consideration in future large foodborne outbreaks across Europe.

Tumor-associated human dendritic cell subsets: Phenotype, functional orientation, and clinical relevance.

DCs play a pivotal role in orchestrating innate and adaptive antitumor immunity. Activated DCs can produce large amounts of various proinflammatory cytokines, initiate T-cell responses, and exhibit direct cytotoxicity against tumor cells. They also efficiently enhance the antitumoral properties of NK cells and T lymphocytes. Based on these capabilities, immunogenic DCs promote tumor elimination and are associated with improved survival of patients. Furthermore, they can essentially contribute to the clinical efficacy of immunotherapeutic strategies for cancer patients. However, depending on their intrinsic properties and the tumor microenvironment, DCs can be rendered dysfunctional and mediate tolerance by producing immunosuppressive cytokines and activating Treg cells. Such tolerogenic DCs can foster tumor progression and are linked to poor prognosis of patients. Here, we focus on recent studies exploring the phenotype, functional orientation, and clinical relevance of tumor-infiltrating conventional DC1, conventional DC2, plasmacytoid DCs, and monocyte-derived DCs in translational and clinical settings. In addition, recent findings demonstrating the influence of DCs on the efficacy of immunotherapeutic strategies are summarized.

Imported spring onions related to the first recorded outbreak of enteroinvasive Escherichia coli in Denmark, November to December 2021.

Between November and December 2021, the first ever recorded outbreak of enteroinvasive Escherichia coli in Denmark occurred at national scale. We describe the investigation of this outbreak, which was initially recognised in early December 2021. A total of 88 cases (58 female; 30 male) with a median age of 52 years (range: 0-91) were detected by PCR-based diagnostic methods. Case ascertainment was complicated by current culture-free diagnostic procedures, with only 34 cases confirmed by culture, serotyping and whole genome sequencing. Isolates from cases grouped into two serotypes (O136:H7 and O96:H19), which was supported by whole-genome-sequence-phylogeny, also yielding two clusters. Interviews of 42 cases and traceback investigation pointed towards consumption of ready-to-eat salads as the outbreak cause. While the ready-to-eat salads comprised different vegetables, imported spring onions were the only common ingredient and thus the likely source. Environmental investigations failed to recover outbreak strains. This report highlights the value of fast typing (here O-typing) to confirm cases in an outbreak situation. Timely communication and data sharing are also important, and were facilitated by the national collaboration between relevant laboratories, the public health institute and the veterinary and food administration. High hygiene standards for imported fresh vegetables intended for ready-to-eat products are essential.

Incubation Period, Spore Shedding Duration, and Symptoms of Enterocytozoon bieneusi Genotype C Infection in a Foodborne Outbreak in Denmark, 2020.

BACKGROUND: Microsporidia are rarely reported to cause outbreaks of diarrhea. We describe a foodborne outbreak of microsporidiosis from a workplace canteen in November 2020 in Denmark. METHODS: A probable case was defined as any person using the canteen between 4 November and 13 December 2020, reporting at least one gastrointestinal symptom, whereas a confirmed case also had an Enterocytozoon bieneusi positive stool sample. A web-based questionnaire was used to collect clinical, epidemiological, and food exposure data. We performed a retrospective cohort study and tested stool samples from affected individuals for bacterial, viral, and parasitic pathogens, including E. bieneusi. RESULTS: Altogether, 195 individuals completed the questionnaire. We identified 52 cases (65% male; median age 45 years [range 25-65]). Diarrhea (90%), fatigue (83%), and abdominal pain (79%) were the most commonly reported symptoms. Eight cases were laboratory-confirmed and had E. bieneusi genotype C. The incubation period was between 5 and 12 days, and polymerase chain reaction (PCR)-detectable spore shedding occurred up to 43 days after symptom onset. Disease was associated with consuming food from the workplace canteen on 4 November 2020 (relative risk [RR[, 2.8 [95% confidence interval [CI]: 1.4 - 5.4]) and lunchboxes containing open sandwiches (RR, 3.2 [95% CI: 1.4 - 7.2]) served that day. CONCLUSIONS: This is the second documented foodborne outbreak of E. bieneusi genotype C-associated diarrhea worldwide. Epidemiological findings advocated an open sandwiches lunchbox from 4 November 2020, as a likely source. E. bieneusi may be an under-reported cause of outbreaks of diarrhea, and testing for it might be useful in foodborne outbreak investigations.

Systematic assessment of monogenic etiology in adult-onset kidney stone formers undergoing urological intervention-evidence for genetic pretest probability.

Kidney stone disease (KSD) is a prevalent condition associated with high morbidity, frequent recurrence, and progression to chronic kidney disease (CKD). The etiology is multifactorial, depending on environmental and genetic factors. Although monogenic KSD is frequent in children, unbiased prevalence data of heritable forms in adults is scarce. Within 2 years of recruitment, all patients hospitalized for urological kidney stone intervention at our center were consecutively enrolled for targeted next generation sequencing (tNGS). Additionally, clinical and metabolic assessments were performed for genotype-phenotype analyses. The cohort comprised 155 (66%) males and 81 (34%) females, with a mean age at first stone of 47 years (4-86). The diagnostic yield of tNGS was 6.8% (16/236), with cystinuria (SLC3A1, SLC7A9), distal renal tubular acidosis (SLC4A1), and renal phosphate wasting (SLC34A1, SLC9A3R1) as underlying hereditary disorders. While metabolic syndrome traits were associated with late-onset KSD, hereditary KSD was associated with increased disease severity in terms of early-onset, frequent recurrence, mildly impaired kidney function, and common bilateral affection. By employing systematic genetic analysis to a less biased cohort of common adult kidney stone formers, we demonstrate its diagnostic value for establishing the underlying disorder in a distinct proportion. Factors determining pretest probability include age at first stone (<40 years), frequent recurrence, mild CKD, and bilateral KSD.

Effects of lifestyle interventions on epigenetic signatures of liver fat: Central randomized controlled trial.

BACKGROUND AND AIMS: In the CENTRAL trial context, we found diverse liver fat dynamics in response to different dietary interventions. Epigenetic mechanisms may contribute to the intraindividual variation. Moreover, genetic factors are involved in developing nonalcoholic fatty-liver disease (NAFLD), a disease reflected by an increase in intrahepatic fat (IHF). In this exploratory analysis, we primarily aimed to examine the effect of lifestyle interventions on DNA-methylation of NAFLD related genes associated with IHF. METHODS: For 120 participants from the CENTRAL trial, an 18-month regimen of either low-fat (LF) or Mediterranean-low carbohydrate (MED/LC) diets, with or without physical activity (PA+/PA-), was instructed. Magnetic resonance imaging was used to measure IHF%, which was analysed for association with CpG specific DNA-methylation levels of 41 selected candidate genes. Single-nucleotide polymorphisms known to be associated with NAFLD within the studied genes were genotyped by TaqMan assays. RESULTS: At baseline, participants (92% men; body mass index = 30.2 kg/m2 ) had mean IHF of 10.7% (59% NAFLD). Baseline-IHF% was inversely correlated with DNA-methylation at individual CpGs within AC074286.1, CRACR2A, A2MP1, FARP1 (P < .05 for all multivariate models). FARP1 rs9584805 showed association with IHF, with the prevalence of NAFLD and baseline methylation level of the CpG site (cg00071727) associated with IHF%. Following 18-month lifestyle intervention, differential DNA-methylation patterns were observed between diets at cg14335324 annotated to A2MP1 (P = .04, LF vs. MED/LC), and differential DNA-methylation between PA groups within AC074286.1, CRACR2A, and FARP1 CpGs (P < .05 for all, PA-vs. PA+). CONCLUSIONS: This study suggests epigenetic markers for IHF and potential epigenetic remodeling after long-term lifestyle interventions.

Societal activities associated with SARS-CoV-2 infection: a case-control study in Denmark, November 2020.

Identification of societal activities associated with SARS-CoV-2 infection may provide an evidence base for implementing preventive measures. Here, we investigated potential determinants for infection in Denmark in a situation where society was only partially open. We conducted a national matched case-control study. Cases were recent RT-PCR test-positives, while controls, individually matched on age, sex and residence, had not previously tested positive for SARS-CoV-2. Questions concerned person contact and community exposures. Telephone interviews were performed over a 7-day period in December 2020. We included 300 cases and 317 controls and determined odds ratios (ORs) and 95% confidence intervals (95% CI) by conditional logistical regression with adjustment for household size and country of origin. Contact (OR 4.9, 95% CI 2.4-10) and close contact (OR 13, 95% CI 6.7-25) with a person with a known SARS-CoV-2 infection were main determinants. Contact most often took place in the household or work place. Community determinants included events with singing (OR 2.1, 95% CI 1.1-4.1), attending fitness centres (OR 1.8, 95% CI 1.1-2.8) and consumption of alcohol in a bar (OR 10, 95% CI 1.5-65). Other community exposures appeared not to be associated with infection, these included shopping at supermarkets, travel by public transport, dining at restaurants and private social events with few participants. Overall, the restrictions in place at the time of the study appeared to be sufficient to reduce transmission of disease in the public space, which instead largely took place following direct exposures to people with known SARS-CoV-2 infections.

Whole genome sequencing data used for surveillance of Campylobacter infections: detection of a large continuous outbreak, Denmark, 2019.

BackgroundCampylobacter is one of the most frequent causes of bacterial gastroenteritis. Campylobacter outbreaks are rarely reported, which could be a reflection of a surveillance without routine molecular typing. We have previously shown that numerous small outbreak-like clusters can be detected when whole genome sequencing (WGS) data of clinical Campylobacter isolates was applied.AimTyping-based surveillance of Campylobacter infections was initiated in 2019 to enable detection of large clusters of clinical isolates and to match them to concurrent retail chicken isolates in order to react on ongoing outbreaks.MethodsWe performed WGS continuously on isolates from cases (n = 701) and chicken meat (n = 164) throughout 2019. Core genome multilocus sequence typing was used to detect clusters of clinical isolates and match them to isolates from chicken meat.ResultsSeventy-two clusters were detected, 58 small clusters (2-4 cases) and 14 large clusters (5-91 cases). One third of the clinical isolates matched isolates from chicken meat. One large cluster persisted throughout the whole year and represented 12% of all studied Campylobacter cases. This cluster type was detected in several chicken samples and was traced back to one slaughterhouse, where interventions were implemented to control the outbreak.ConclusionOur WGS-based surveillance has contributed to an improved understanding of the dynamics of the occurrence of Campylobacter strains in chicken meat and the correlation to clusters of human cases.

Epidemiological characterisation of the first 785 SARS-CoV-2 Omicron variant cases in Denmark, December 2021.

By 9 December 2021, 785 SARS-CoV-2 Omicron variant cases have been identified in Denmark. Most cases were fully (76%) or booster-vaccinated (7.1%); 34 (4.3%) had a previous SARS-CoV-2 infection. The majority of cases with available information reported symptoms (509/666; 76%) and most were infected in Denmark (588/644; 91%). One in five cases cannot be linked to previous cases, indicating widespread community transmission. Nine cases have been hospitalised, one required intensive care and no deaths have been registered.

Veterinary Students Have a Higher Risk of Contracting Cryptosporidiosis when Calves with High Fecal Cryptosporidium Loads Are Used for Fetotomy Exercises.

An outbreak of cryptosporidiosis among veterinary students performing fetotomy exercises on euthanized calves took place in September 2018 in Denmark. A prospective cohort investigation was performed to identify risk factors and provide guidance for preventing outbreaks of cryptosporidiosis in this setting. Ninety-seven students attended the fetotomy exercises and completed a questionnaire about symptoms and potential risk behavior. Real-time PCR was used to detect Cryptosporidium spp. in stool samples from students and to quantify the fecal parasite load in the calves used for the exercises. gp60 subtyping was carried out for the Cryptosporidium-positive samples. Our case definition was based on participation in a fetotomy exercise, reported symptoms, and laboratory results. Eleven laboratory-confirmed or probable cases (11%) were identified in two outbreaks during the prospective study period, with attack rates of 4/10 (40%) and 7/9 (78%), respectively. The risk factors for cryptosporidiosis we identified were performing the exercise on a diarrheic calf, reporting visible fecal contamination on the personal protective equipment (PPE), and reporting problems with PPE during the exercise. Cryptosporidium parvum IIaA15G2R1 was detected in both cases and calves. A significantly higher proportion of the calves aged 7 days old and above were positive compared with younger calves. Furthermore, a high fecal Cryptosporidium load in a calf was associated with a higher probability of an outbreak among the students. Based on our results, using noninfected calves for the exercises, appropriate use of PPE, and thorough hand hygiene are recommended to reduce the risk of contracting cryptosporidiosis in connection with fetotomy exercises.IMPORTANCECryptosporidium spp. can cause severe diarrhea in infected individuals. Cryptosporidium parvum is zoonotic, and cattle are the main reservoir. In several countries, outbreaks of cryptosporidiosis have occurred in veterinary students after handling calves. We carried out a 1-year-long prospective study to investigate the occurrence of these recurrent cryptosporidiosis outbreaks in Denmark. Our investigation used a One Health approach and combined comprehensive epidemiological approaches and laboratory methods applied to both students and calves in the setting of the fetotomy exercises. Two outbreaks took place during the study period; additionally, we retrospectively identified two more suspected outbreaks prior to the study period. The results illustrated a high risk of contracting cryptosporidiosis among veterinary students in the setting of the fetotomy exercises, especially when using calves with high fecal Cryptosporidium loads. Our data can be used to inform future efforts to prevent transmission of Cryptosporidium parvum to students during fetotomy exercises.

Cross-border outbreak of Yersinia enterocolitica O3 associated with imported fresh spinach, Sweden and Denmark, March 2019.

In April 2019, a cross-border outbreak of Yersinia entercolitica O3 was identified in Sweden and Denmark and confirmed using whole genome sequencing. Close cross-border collaboration with representatives from human and food authorities helped direct resources and investigations. Combined epidemiological and trace-back investigations pointed to imported fresh spinach as the outbreak vehicle and highlight that other vehicles of Y. enterocolitica outbreaks than pork should be considered.

Travel-associated hepatitis A in Europe, 2009 to 2015.

BackgroundTravel 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 (< 25 years). 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.

Two concurrent outbreaks of hepatitis A highlight the risk of infection for non-immune travellers to Morocco, January to June 2018.

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.

Hepatitis A outbreak disproportionately affecting men who have sex with men (MSM) in the European Union and European Economic Area, June 2016 to May 2017.

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.

Cross-border outbreak of listeriosis caused by cold-smoked salmon, revealed by integrated surveillance and whole genome sequencing (WGS), Denmark and France, 2015 to 2017.

In August 2017, an outbreak of six listeriosis cases in Denmark was traced to cold-smoked salmon, using epidemiological investigations and whole-genome sequencing (WGS) analyses. Exchange of genome sequences allowed identification in France of a food isolate from a salmon-derived product and a human isolate from 2016 within the same cgMLST cluster as the Danish isolates (L2-SL8-ST8-CT771). The salmon product came from a third European Union country. WGS can rapidly link human cases and food isolates across Europe.

Multinational outbreak of travel-related Salmonella Chester infections in Europe, summers 2014 and 2015.

Between 2014 and 2015, the European Centre for Disease Prevention and Control was informed of an increase in numbers of Salmonella enterica serotype Chester cases with travel to Morocco occurring in six European countries. Epidemiological and microbiological investigations were conducted. In addition to gathering information on the characteristics of cases from the different countries in 2014, the epidemiological investigation comprised a matched case-case study involving French patients with salmonellosis who travelled to Morocco that year. A univariate conditional logistic regression was performed to quantify associations. The microbiological study included a whole genome sequencing (WGS) analysis of clinical and non-human isolates of S. Chester of varied place and year of isolation. A total of 162 cases, mostly from France, followed by Belgium, the Netherlands, Spain, Denmark and Sweden were reported, including 86 (53%) women. The median age per country ranged from 3 to 38 years. Cases of S. Chester were more likely to have eaten in a restaurant and visited the coast of Morocco. The results of WGS showed five multilocus sequence types (ST), with 96 of 153 isolates analysed clustering into a tight group that corresponded to a novel ST, ST1954. Of these 96 isolates, 46 (48%) were derived from food or patients returning from Morocco and carried two types of plasmids containing either qnrS1 or qnrB19 genes. This European-wide outbreak associated with travel to Morocco was likely a multi-source outbreak with several food vehicles contaminated by multidrug-resistant S. Chester strains.

Whole-genome Sequencing Used to Investigate a Nationwide Outbreak of Listeriosis Caused by Ready-to-eat Delicatessen Meat, Denmark, 2014.

BACKGROUND: Listeriosis is a serious foodborne infection. Outbreaks of listeriosis occur rarely, but have often proved difficult to solve. In June 2014, we detected and investigated a listeriosis outbreak in Denmark using patient interviews and whole-genome sequencing (WGS). METHODS: We performed WGS on Listeria monocytogenes isolates from patients and available isolates from ready-to-eat foods and compared them using single-nucleotide polymorphism (SNP) analysis. Case patients had L. monocytogenes with ≤3 SNPs (the outbreak strain) isolated in September 2013-December 2014. Through interviews, we established case patients' food and clinical histories. Food production facilities were inspected and sampled, and we performed trace-back/trace-forward of food delivery chains. RESULTS: In total, 41 cases were identified; 17 deaths occurred (41%). An isolate from a delicatessen meat (spiced meat roll) from company A was identical to the outbreak strain. Half of the patients were infected while hospitalized/institutionalized; institutions were supplied food by company A. The outbreak strain was repeatedly isolated from further samples taken within this company and within companies in its distribution chain. Products from company A were traced and recalled from >6000 food establishments, after which the outbreak ended. CONCLUSIONS: Ready-to-eat spiced meat roll from a single production facility caused this outbreak. The product, served sliced and cold, is popular among the elderly; serving it at hospitals probably contributed to the high case-fatality rate. WGS used for patient isolates and isolates from food control inspections, coupled with routine epidemiological follow-up, was instrumental in swiftly locating the source of infections, preventing further illnesses and deaths.

Epidemic profile of Shiga-toxin-producing Escherichia coli O104:H4 outbreak in Germany.

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 gastroenteritis 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 occurring in women. The hemolytic-uremic syndrome developed in more than 20% of the identified cases.

Associations of age and sex with the clinical outcome and incubation period of Shiga toxin-producing Escherichia coli O104:H4 infections, 2011.

We pooled data on adults who reported diarrhea or developed life-threatening hemolytic uremic syndrome (HUS) in any of 6 closed cohorts from 4 countries (1 cohort each in Denmark, France, and Sweden and 3 in Germany) that were investigated during a large outbreak of Shiga toxin-producing Escherichia coli (STEC) O104:H4 infection in 2011. Logistic regression and Weibull regression for interval censored data were used to assess the relation of age and sex with clinical outcome and with incubation period. Information on the latter was used in a nonparametric back-projection context to estimate when adult cases reported in Germany were exposed to STEC O104:H4. Overall, data from 119 persons (median age, 49 years; 80 women) were analyzed. Bloody diarrhea and HUS were recorded as the most severe outcome for 44 and 26 individuals, respectively. Older age was significantly associated with bloody diarrhea but not with HUS. Woman had nonsignificantly higher odds for bloody diarrhea (odds ratio = 1.81) and developing HUS (odds ratio = 1.83) than did men. Older participants had a statistically significantly reduced incubation period. The shortest interval that included 75% of exposures in adults spanned only 12 days and preceded outbreak detection. In conclusion, the frequency of bloody diarrhea but not of HUS and the length of the incubation period depended on the age of individuals infected with STEC O104:H4. A large number of people were exposed to STEC O104:H4 for a short period of time.

Implication of DNA methylation during lifestyle mediated weight loss.

Over the past 50 years, the number of overweight/obese people increased significantly, making obesity a global public health challenge. Apart from rare monogenic forms, obesity is a multifactorial disease, most likely resulting from a concerted interaction of genetic, epigenetic and environmental factors. Although recent studies opened new avenues in elucidating the complex genetics behind obesity, the biological mechanisms contributing to individual's risk to become obese are not yet fully understood. Non-genetic factors such as eating behaviour or physical activity are strong contributing factors for the onset of obesity. These factors may interact with genetic predispositions most likely via epigenetic mechanisms. Epigenome-wide association studies or methylome-wide association studies are measuring DNA methylation at single CpGs across thousands of genes and capture associations to obesity phenotypes such as BMI. However, they only represent a snapshot in the complex biological network and cannot distinguish between causes and consequences. Intervention studies are therefore a suitable method to control for confounding factors and to avoid possible sources of bias. In particular, intervention studies documenting changes in obesity-associated epigenetic markers during lifestyle driven weight loss, make an important contribution to a better understanding of epigenetic reprogramming in obesity. To investigate the impact of lifestyle in obesity state specific DNA methylation, especially concerning the development of new strategies for prevention and individual therapy, we reviewed 19 most recent human intervention studies. In summary, this review highlights the huge potential of targeted interventions to alter disease-associated epigenetic patterns. However, there is an urgent need for further robust and larger studies to identify the specific DNA methylation biomarkers which influence obesity.