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The New England Journal of Medicine | 2011

Epidemic Profile of Shiga-Toxin–Producing Escherichia coli O104:H4 Outbreak in Germany

Christina Frank; Dirk Werber; Jakob P. Cramer; Mona Askar; Mirko Faber; Helen Bernard; Angelika Fruth; Rita Prager; Anke Spode; Maria Wadl; Alexander Zoufaly; Sabine Jordan; Markus J. Kemper; Per Follin; Luise Müller; Lisa A. King; Bettina Rosner; Udo Buchholz; Klaus Stark; Gérard Krause

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.


Eurosurveillance | 2015

Large and prolonged food-borne multistate hepatitis A outbreak in Europe associated with consumption of frozen berries, 2013 to 2014.

Ettore Severi; Verhoef L; Thornton L; B Guzman-Herrador; Mirko Faber; Lena Sundqvist; Rimhanen-Finne R; Roque-Afonso Am; Siew-Lin Ngui; Allerberger F; Baumann-Popczyk A; Luise Müller; Parmakova K; Alfonsi; Lara Tavoschi; Vennema H; Fitzgerald M; Myrmel M; M. Gertler; Josefine Lundberg Ederth; Kontio M; Vanbockstael C; Sema Mandal; Sadkowska-Todys M; Maria Elena Tosti; Schimmer B; Kathrine Stene-Johansen; Jürgen J. Wenzel; Jones G; Koye Balogun

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.


Epidemiology and Infection | 2012

Burden of acute gastrointestinal illness in Denmark 2009: a population-based telephone survey.

Luise Müller; Helle Korsgaard; Steen Ethelberg

A cross-sectional telephone survey was conducted in Denmark throughout 2009 to determine the incidence of acute gastrointestinal illness (AGI). Using the Danish population register, a random population sample stratified by gender and age groups was selected and mobile or landline phone numbers found. Representative numbers of interviews were performed by gender, age group and month. A recently proposed international case definition of AGI, including cases with diarrhoea and/or vomiting in a 4-week recall period, was used. A total of 1853 individuals were included and 206 (11·1%) fulfilled the case definition; 78% reported diarrhoea. This corresponds to an overall standardized incidence rate of 1·4 (95% CI 1·2-1·6) episodes of AGI per person-year. The incidence rate was generally higher in the younger age groups; only being 2·3, 1·9 and 0·80 per person-year in the 0-9, 10-39 and ≥40 years age groups, respectively. The incidence rate estimates were considerably higher when calculated from shorter recall periods.


Clinical Microbiology and Infection | 2011

Outbreak of listeriosis caused by infected beef meat from a meals-on-wheels delivery in Denmark 2009.

Birgitte Smith; Jonas T. Larsson; M Lisby; Luise Müller; S.B. Madsen; Jørgen Engberg; Jette Marie Bangsborg; Steen Ethelberg; Michael Kemp

An outbreak of listeriosis in Denmark occurred in May 2009. Multilocus variable number of tandem repeats analysis typing, later confirmed by pulsed-field gel electrophoresis typing, showed that isolates from eight patients had identical patterns and were distinguishable from Listeria monocytogenes isolates from other Danish patients. Seven out of eight patients had received a meal with beef from the same meals-on-wheels delivery catering company 3 weeks prior to onset of disease. Two patients died of their infection. Large-scale delivery of precooked meals to a vulnerable population represents a threat if proper measures against listeriosis are not taken.


Foodborne Pathogens and Disease | 2011

Molecular Characterization of Salmonella Typhimurium Highly Successful Outbreak Strains

Randi Føns Petersen; Eva Litrup; Jonas T. Larsson; Mia Torpdahl; Gitte Sørensen; Luise Müller; Eva Møller Nielsen

Three large clusters of Salmonella Typhimurium infections in Denmark in 2008 and 2009 were defined by multilocus variable number of tandem repeat analysis (MLVA). One of these proved to be the hereto largest Danish cluster of salmonellosis with 1446 cases. Two smaller clusters with a total of 197 and 89 cases, respectively, were seen concurrently. These clusters shared epidemiological characteristics such as age distribution, geography, and time. To investigate the possible genetic relationship between the cluster strains, these were further characterized by phage typing, pulsed-field gel electrophoresis, and Optical Mapping. Although the MLVA method proved robust and well-performing in detecting and defining clusters, the employment of a second typing method detected an additional fourth cluster among the isolates. The cluster strains were stable throughout the almost 2-year period, even though we detected changes in three of five MLVA loci in a small fraction of isolates. These changes were mainly due to the gain or loss of single repeats. Optical Mapping of the large cluster strain indicated no increased content of virulence genes; however, Optical Mapping did reveal a large insert, a probable prophage, in the main cluster. This probable prophage may give the cluster strain a competitive advantage. The molecular methods employed suggested that the four clusters represented four distinct strains, although they seemed to be epidemiologically linked and shared genotypic characteristics.


Epidemiology and Infection | 2015

Separate norovirus outbreaks linked to one source of imported frozen raspberries by molecular analysis, Denmark, 2010-2011.

Luise Müller; Anna Charlotte Schultz; Jannik Fonager; Tenna Jensen; M Lisby; K. Hindsdal; L. Krusell; A. Eshøj; L. T. Møller; Lone Jannok Porsbo; Blenda Böttiger; K. Kuhn; Jørgen Engberg; Steen Ethelberg

Norovirus outbreaks occur frequently in Denmark and it can be difficult to establish whether apparently independent outbreaks have the same origin. Here we report on six outbreaks linked to frozen raspberries, investigated separately over a period of 3 months. Norovirus from stools were sequence-typed; including extended sequencing of 1138 bp encompassing the hypervariable P2 region of the capsid gene. Norovirus was detected in 27 stool samples. Genotyping showed genotype GI.Pb_GI.6 (polymerase/capsid) with 100% identical sequences. Samples from five outbreaks were furthermore identical over the variable capsid P2 region. In one outbreak at a hospital canteen, frozen raspberries was associated with illness by cohort investigation (relative risk 6·1, 95% confidence interval 3·2-11). Bags of raspberries suspected to be the source were positive for genogroup I and II noroviruses, one typable virus was genotype GI.6 (capsid). These molecular investigations showed that the apparently independent outbreaks were the result of one contamination event of frozen raspberries. The contaminated raspberries originated from a single producer in Serbia and were originally not considered to belong to the same batch. The outbreaks led to consultations and mutual visits between producers, investigators and authorities. Further, Danish legislation was changed to make heat-treatment of frozen raspberries compulsory in professional catering establishments.


American Journal of Epidemiology | 2013

Associations of Age and Sex With the Clinical Outcome and Incubation Period of Shiga toxin–producing Escherichia coli O104:H4 Infections, 2011

Dirk Werber; Lisa A. King; Luise Müller; Per Follin; Udo Buchholz; Helen Bernard; Bettina Rosner; Steen Ethelberg; Henriette de Valk; Michael Höhle

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.


Eurosurveillance | 2017

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

Laure Fonteneau; Nathalie Jourdan-Da Silva; Laëtitia Fabre; Philip M. Ashton; Mia Torpdahl; Luise Müller; Brahim Bouchrif; Abdellah El Boulani; Eleni Valkanou; Wesley Mattheus; I. H. M. Friesema; Silvia Leon; Carmen Varela Martínez; Joël Mossong; Ettore Severi; Kathie Grant; François-Xavier Weill; C M Gossner; Sophie Bertrand; Tim Dallman; Simon Le Hello

Between 2014 and 2015, the European Centre for Disease Prevention and Control was informed of an increase in numbers of Salmonellaenterica 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.


Scandinavian Journal of Infectious Diseases | 2012

Salmonella Typhimurium outbreak associated with smoked pork tenderloin in Denmark, January to March 2011

Oktawia P. Wójcik; Charlotte Kjelsø; Katrin Gaardbo Kuhn; Luise Müller; Tenna Jensen; Marianne Kirstine Kjeldsen; Steen Ethelberg

Abstract Background: An outbreak of salmonellosis (Salmonella Typhimurium, phage type DT120) occurred from 26 January to 15 March 2011, in Denmark, with 22 laboratory confirmed cases. Hypothesis-generating patient interviews gave rise to the suspicion that smoked pork tenderloin was the source of infection. The primary objective of this study was to identify the source of the outbreak in order to initiate appropriate control measures. Methods: A matched (1:2) case–control study was conducted. A case was defined as a person residing in Denmark whose stool sample tested positive for S. Typhimurium, with a particular multilocus variable-number tandem repeat profile, from January to March 2011. Controls were matched to cases on age, gender, and municipality of residence. Results: Of 21 interviewed cases, 19 (91%) indicated that they typically ate smoked pork tenderloin more than once a week, compared with 13 (33%) of 39 interviewed controls (matched odds ratio 19.6, 95% confidence interval 2.6–153). Eighteen (86%) cases indicated that they might have consumed smoked pork tenderloin the week before becoming ill, compared with 1 (4%) control who had eaten the product a week before the interview. Two cases provided the brand name of the product and the supermarket where it was purchased. Conclusions: The results show a strong statistically significant association between the consumption of smoked pork tenderloin and S. Typhimurium infection. The European Rapid Alert System for Food and Feed was used to notify these findings to the competent authorities in the country of origin of the product. Subsequently, the smoked pork tenderloin of the brand in question, dating from 1 January to 1 May 2011, was recalled from consumers.


Epidemiology and Infection | 2013

Personal protective equipment, hygiene behaviours and occupational risk of illness after July 2011 flood in Copenhagen, Denmark

Oktawia P. Wójcik; J. Holt; A. Kjerulf; Luise Müller; Steen Ethelberg; Kåre Mølbak

Incidence of various diseases can increase following a flood. We aimed to identify professionals in Copenhagen who became ill after contact with 2 July 2011 floodwater/sediment and determine risks and protective factors associated with illness. We conducted a cohort study of employees engaged in post-flood management activities. Participants completed a questionnaire collecting information about demographics, floodwater/sediment exposure, compliance with standard precautions, and symptoms of illness. Overall, 257 professionals participated, with 56 (22%) cases. Risk of illness was associated with not washing hands after floodwater/sediment contact [relative risk (RR) 2∙45], exposure to floodwater at work and home (RR 2∙35), smoking (RR 1∙92), direct contact with floodwater (RR 1∙86), and eating/drinking when in contact with floodwater (RR 1∙77). Professionals need to follow standard precautions when in contact with floodwater/sediment, especially proper hand hygiene after personal protective equipment use and before eating/drinking and smoking.

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