Epidemiological and serological investigation of a waterborne Campylobacter jejuni outbreak in a Danish town.

Following an unusually heavy rainfall in June 2009, a community-wide outbreak of Campylobacter gastroenteritis occurred in a small Danish town. The outbreak investigation consisted of (1) a cohort study using an e-questionnaire of disease determinants, (2) microbiological study of stool samples, (3) serological study of blood samples from cases and asymptomatic members of case households, and (4) environmental analyses of the water distribution system. The questionnaire study identified 163 cases (respondent attack rate 16%). Results showed a significant dose-response relationship between consumption of tap water and risk of gastroenteritis. Campylobacter jejuni belonging to two related flaA types were isolated from stool samples. Serum antibody levels against Campylobacter were significantly higher in cases than in asymptomatic persons. Water samples were positive for coliform bacteria, and the likely mode of contamination was found to be surface water leaking into the drinking-water system. This geographically constrained outbreak presented an ideal opportunity to study the serological response in persons involved in a Campylobacter outbreak. The serology indicated that asymptomatic persons from the same household may have been exposed, during the outbreak period, to Campylobacter at doses that did not elicit symptoms or alternatively had been exposed to Campylobacter at a time prior to the outbreak, resulting in residual immunity and thus absence of clinical signs.

A case-control study of risk factors for rotavirus infections in adults, Denmark, 2005-2009.

Rotavirus (RV) infections affect young children, but can also occur in adults. We sought to identify risk factors for RV infections in adults aged ⩾18 years in Denmark, and to describe illness and genotyping characteristics. From March 2005 to February 2009, we recruited consecutive cases of laboratory-confirmed RV infection and compared them with healthy controls matched by age, gender and municipality of residence. We collected information on illness characteristics and exposures using postal questionnaires. We calculated univariable and multivariable matched odds ratios (mOR) with conditional logistic regression. The study comprised 65 cases and 246 controls. Illness exceeded 10 days in 31% of cases; 22% were hospitalized. Cases were more likely than controls to suffer serious underlying health conditions [mOR 5·6, 95% confidence interval (CI) 1·7-18], and to report having had close contact with persons with gastrointestinal symptoms (mOR 9·4, 95% CI 3·6-24), in particular young children aged 18 years. Close contact with young children or adults with gastrointestinal symptoms is the main risk factor for RV infection in adults in Denmark. RV vaccination assessments should consider that RV vaccination in children may indirectly reduce the burden of disease in adults.

Impact of 10- and 13-valent pneumococcal conjugate vaccines on incidence of invasive pneumococcal disease in children aged under 16 years in Germany, 2009 to 2012.

We assessed the impact of 10-valent and 13-valent pneumococcal vaccines (PCV10 and PCV13), which were introduced in Germany in 2009, on the incidence of meningitis and non-meningitis invasive pneumococcal disease (IPD) in children aged under 16 years in a population previously vaccinated with a seven-valent vaccine (PCV7). Surveillance of IPD (isolation of Streptococcus pneumonia from a normally sterile body site) is based on data from two independent reporting sources: hospitals and laboratories. IPD incidence was estimated by capture-recapture analysis. Incidence rate ratios (IRRs) were calculated for 2009 and 2012, thus comparing pre- and post-PCV10 and PCV13 data. IPD incidence caused by serotypes included in PCV13 decreased in all age and diagnosis groups. A rise in non-vaccine serotype incidence was seen only in children aged under two years. The overall impact varied by age group and infection site: for meningitis IPD in children aged under 2, 2-4 and 5-15 years, incidence changed by 3% (95% CI: -31 to 52), -60% (95% CI: -81 to -17) and -9% (95% CI: -46 to 53), respectively. A more pronounced incidence reduction was observed for non-meningitis IPD: -30% (95% CI: -46 to -7), -39% (95% CI: -54 to -20) and -83% (95% CI: -89 to -73) in children aged under 2, 2-4 and 5-15 years, respectively. A higher tropism of the additional serotypes for non-meningitis IPD may be a potential explanation. The heterogeneous findings emphasise the need for rigorous surveillance

Measles outbreak spreading from the community to an anthroposophic school, Berlin, 2011.

Between April and July 2011 there was an outbreak of measles virus, genotype D4, in Berlin, Germany. We identified 73 case-patients from the community and among students of an anthroposophic school, who participated in a 4-day school trip, as well as their family and friends. Overall, 27% were aged ≥ 20 years, 57% were female and 15% were hospitalized. Of 39 community case-patients, 38% were aged ≥ 20 years, 67% were female and 63% required hospitalization. Unvaccinated students returning from the school trip were excluded from school, limiting transmission. Within the group of 55 school-trip participants, including 20 measles case-patients, a measles vaccine effectiveness of 97.1% (95% confidence interval 83.4-100) for two doses was estimated using exact Poisson regression. Our findings support school exclusions and the recommendation of one-dose catch-up vaccination for everyone born after 1970 with incomplete or unknown vaccination status, in addition to the two-dose routine childhood immunization recommendation.

Campylobacter seroconversion rates in selected countries in the European Union.

As a major foodborne pathogen, Campylobacter is frequently isolated from food sources of animal origin. In contrast, human Campylobacter illness is relatively rare, but has a considerable health burden due to acute enteric illness as well as severe sequelae. To study silent transmission, serum antibodies can be used as biomarkers to estimate seroconversion rates, as a proxy for infection pressure. This novel approach to serology shows that infections are much more common than disease, possibly because most infections remain asymptomatic. This study used antibody titres measured in serum samples collected from healthy subjects selected randomly in the general population from several countries in the European Union (EU). Estimates of seroconversion rates to Campylobacter were calculated for seven countries: Romania, Poland, Italy, France, Finland, Denmark and The Netherlands. Results indicate high infection pressures in all these countries, slightly increasing in Eastern EU countries. Of these countries, the differences in rates of notified illnesses are much greater, with low numbers in France and Poland, possibly indicating lower probability of detection due to differences in the notification systems, but in the latter case it cannot be excluded that more frequent exposure confers better protection due to acquired immunity.

Background paper to the recommendation for the preferential use of live-attenuated influenza vaccine in children aged 2-6 years in Germany.

The German Standing Committee on Vaccination (STIKO) recommends seasonal influenza vaccination for children and adolescents with chronic medical conditions that put them at risk for severe influenza illness. In addition to trivalent inactivated influenza vaccines (TIV), a trivalent live-attenuated influenza vaccine (LAIV) was licensed for children and adolescents aged 2-17 years in the European Union in 2011. Employing the methodology of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group, we examined the evidence for efficacy and safety of LAIV relative to TIV to guide STIKO's decision on whether LAIV should be preferentially recommended for at-risk children. In our meta-analysis of data from two randomized trials directly comparing LAIV and TIV in children aged ≤ 6 years, the protective efficacy of LAIV against laboratory-confirmed influenza was 53 % [95 % confidence interval (CI): 45-61 %] higher than that of TIV. A similar study in individuals aged 6-17 years showed a 32 % (95 % CI: 3-52 %) higher efficacy of LAIV. The quality of the evidence for a superior protective efficacy of LAIV against all relevant clinical outcomes was rated 'moderate' for children aged 2-6 years and 'low' for the age group 7-17 years. Regarding safety outcomes, the available data suggest no significant differences between LAIV and TIV. Based on these results, STIKO recommends that LAIV should be used preferentially for influenza vaccination of at-risk children aged 2-6 years. In children and adolescents aged 7-17 years, either LAIV or TIV may be used without specific preference. Possible contraindications and the vaccinee's and his/her guardians' preferences should be taken into account.

Background paper to the revised recommendation for hepatitis B vaccination of persons at particular risk and for hepatitis B postexposure prophylaxis in Germany.

The German Standing Committee on Vaccination (Ständige Impfkommission, STIKO) recommends vaccinating risk groups against hepatitis B and gives advice for postexposure prophylaxis. STIKO has recently revised this recommendation, focusing on: (i) classification of risk groups, (ii) duration of protection after primary immunization, and (iii) anti-HBs threshold that defines successful hepatitis B vaccination. Orientating literature reviews were performed for the first objective. Examples of population subgroups at increased risk were identified and classified into three indication groups. Systematic reviews on the duration of vaccine-induced protection identified one randomized controlled trial (RCT) and nine cohort studies. When applying the grading of recommendation, assessment, development, and evaluation (GRADE) methodology, evidence from RCTs was considered of very low quality regarding the question of whether hepatitis B can be prevented for 15 years after successful primary vaccination (anti-HBs ≥ 10 IU/l) with a vaccine efficacy of 96 % against chronic hepatitis, 89 % against HBsAg positivity, and 73 % against isolated anti-HBc positivity. However, seven cohort studies showed that no cases of clinical hepatitis B or HBsAg positivity occurred during a maximum follow-up period of 10 years in settings comparable to the situation in Germany when anti-HBs ≥ 10 IU/l was used to indicate vaccination success. Less than 1 % of vaccinated study participants had isolated anti-HBc positivity. GRADE assessment of two cohort studies revealed that evidence of very low quality exists that the use of anti-HBs ≥ 100 IU/l to measure vaccination success leads to a lower frequency of anti-HBc positivity during follow-up than the use of anti-HBs ≥ 10 IU/l. The recommendation was revised according to this evidence.

Suspected zoonotic transmission of rotavirus group A in Danish adults.

Group A rotaviruses infect humans and a variety of animals. In July 2006 a rare rotavirus strain with G8P[14] specificity was identified in the stool samples of two adult patients with diarrheoa, who lived in the same geographical area in Denmark. Nucleotide sequences of the VP7, VP4, VP6, and NSP4 genes of the identified strains were identical. Phylogenetic analyses showed that both Danish G8P[14] strains clustered with rotaviruses of animal, mainly, bovine and caprine, origin. The high genetic relatedness to animal rotaviruses and the atypical epidemiological features suggest that these human G8P[14] strains were acquired through direct zoonotic transmission events.

Estimation of incidences of infectious diseases based on antibody measurements.

Owing to under-ascertainment it is difficult if not impossible to determine the incidence of a given disease based on cases notified to routine public health surveillance. This is especially true for diseases that are often present in mild forms as for example diarrhoea caused by foodborne bacterial infections. This study presents a Bayesian approach for obtaining incidence estimates by use of measurements of serum antibodies against Salmonella from a cross-sectional study. By comparing these measurements with antibody measurements from a follow-up study of infected individuals it was possible to estimate the time since last infection for each individual in the cross-sectional study. These time estimates were then converted into incidence estimates. Information about the incidence of Salmonella infections in Denmark was obtained by using blood samples from 1780 persons. The estimated incidence was about 0.094 infections per person year. This number corresponds to 325 infections per culture-confirmed case captured in the Danish national surveillance system. We present a novel approach, termed as seroincidence, that has potentials to compare the sensitivity of public health surveillance between different populations, countries and over time.

Analysis of integrated virological and epidemiological reports of norovirus outbreaks collected within the Foodborne Viruses in Europe network from 1 July 2001 to 30 June 2006.

The Foodborne Viruses in Europe network has developed integrated epidemiological and virological outbreak reporting with aggregation and sharing of data through a joint database. We analyzed data from reported outbreaks of norovirus (NoV)-caused gastroenteritis from 13 European countries (July 2001 to July 2006) for trends in time and indications of different epidemiology of genotypes and variants. Of the 13 countries participating in this surveillance network, 11 were capable of collecting integrated epidemiological and virological surveillance data and 10 countries reported outbreaks throughout the entire period. Large differences in the numbers and rates of reported outbreaks per country were observed, reflecting the differences in the focus and coverage of national surveillance systems. GII.4 strains predominated throughout the 5-year surveillance period, but the proportion of outbreaks associated with GII.4 rose remarkably during years in which NoV activity was particularly high. Spring and summer peaks indicated the emergence of genetically distinct variants within GII.4 across Europe and were followed by increased NoV activity during the 2002-2003 and 2004-2005 winter seasons. GII.4 viruses predominated in health care settings and in person-to-person transmission. The consecutive emergence of new GII.4 variants is highly indicative of immune-driven selection. Their predominance in health care settings suggests properties that facilitate transmission in settings with a high concentration of people such as higher virus loads in excreta or a higher incidence of vomiting. Understanding the mechanisms driving the changes in epidemiology and clinical impact of these rapidly evolving RNA viruses is essential to design effective intervention and prevention measures.

Data quality of 5 years of central norovirus outbreak reporting in the European Network for food-borne viruses.

BACKGROUND: The food-borne viruses in Europe (FBVE) network database was established in 1999 to monitor trends in outbreaks of gastroenteritis due to noroviruses (NoVs), to identify major transmission routes of NoV infections within and between participating countries and to detect diffuse international food-borne outbreaks. METHODS: We reviewed the total of 9430 NoV outbreak reports from 13 countries with date of onset between 1 January 2002 and 1 January 2007 for representativeness, completeness and timeliness against these objectives. RESULTS: Rates of reporting ranged from a yearly average of 1.8 in 2003 to 11.6 in 2006. Completeness of reporting of an agreed minimum dataset improved over the years, both for epidemiological and virological data. For the 10 countries that provided integrated (epidemiological AND virological) reporting over the 5-year period, the completeness of the minimum dataset rose from 15% in 2003 to 48% in 2006. Two countries have not been able to combine both data types due to the structure of the national surveillance system (England and Wales and Germany). Timeliness of reporting (median days between the onset of an outbreak and the date of reporting to the FBVE database) differed greatly between countries, but gradually improved to 47 days in 2006. CONCLUSION: The outbreaks reported to the FBVE reflect the lack of standardization of surveillance systems across Europe, making direct comparison of data between countries difficult. However, trends in reported outbreaks per country, distribution of NoV genotypes, and detection of diffuse international outbreaks were used as background data in acute questions about NoV illness and the changing genotype distribution during the 5-year period, shown to be of added value. Integrated reporting is essential for these objectives, but could be limited to sentinel countries with surveillance systems that allow this integration. For successful intervention in case of diffuse international outbreaks, completeness and timeliness of reporting would need to be improved and expanded to countries that presently do not participate.

Detecting non-typhoid Salmonella in humans by ELISAs: a literature review.

Non-typhoid salmonellosis is one of the most common causes of foodborne illness throughout the world. Serological methods for the diagnosis of Salmonella infections vary widely and the most commonly used test is limited by high running costs as well as low sensitivity and specificity. Fast and reliable immunoassays which detect subunit antigens for Salmonella enterica subsp. enterica serovar Typhi are commercially available but at present there is no international consensus on similar tests for non-typhoid salmonellosis. In contrast to the veterinary and food sectors, most immunoassays for non-typhoid human Salmonella diagnosis are developed in-house and used in-house for research or surveillance purposes, rather than for routine diagnostics. Considering the current burden of disease, the development of a validated and standardized, commercially available antibody assay for diagnosing non-typhoid human salmonellosis could be of great benefit for diagnostic and surveillance purposes throughout the world.

A foodborne outbreak of enterotoxigenic E. coli and Salmonella Anatum infection after a high-school dinner in Denmark, November 2006.

In industrialized countries enterotoxigenic Escherichia coli (ETEC) is mainly diagnosed as a cause of travellers' diarrhoea, but it is also known to cause foodborne outbreaks. We report an outbreak of acute gastroenteritis caused by ETEC serotypes O92:H- and O153:H2 as well as Salmonella Anatum, which affected around 200 students and teachers after a high-school dinner in Greater Copenhagen, Denmark, November 2006. A retrospective cohort study showed that consumption of pasta salad with pesto was associated with an increased risk of illness (attack rate 59.4%; risk ratio 2.6, 95% confidence interval 1.2-5.7). Imported fresh basil used for preparation of the pesto was the most likely source of contamination. Although ETEC is associated with travellers' diarrhoea in Denmark, this outbreak suggests that a proportion of sporadic ETEC infections might be caused by contaminated imported foodstuffs. To improve food safety further, it is important to target this poorly regulated and researched area.

Outbreak of group A streptococcal throat infection: don't forget to ask about food.

We report a large foodborne outbreak due to group A streptococci (GAS), which caused acute tonsillo-pharyngitis in 200-250 patrons of a company canteen in Copenhagen, Denmark, in June 2006. A retrospective cohort study of canteen users showed that consumption of cold pasta was associated with an increased risk of illness (attack rate 68%, risk ratio 4.1, P<0.0001). Indistinguishable GAS strains (emm89, T-type 3/13/B3264) were cultured from three cases and a cook, who had prepared the pasta. To our knowledge, pasta has previously only twice been incriminated as the source of a GAS outbreak. Only six foodborne GAS outbreaks have been reported in Europe since 1970, four of them in Sweden or Denmark. This geographical clustering suggests that foodborne GAS outbreaks are probably under-recognized elsewhere.

High mite-allergen exposure increases the risk of sensitization in atopic children and young adults.

Concentrations of major allergens of Dermatophagoides pteronyssinus (Dpt) and D. farinae (Df), Der p I and Der f I, were determined in 183 dust samples of mattresses of 133 atopic and 50 nonatopic children by a sandwich-type ELISA. Atopic children and young adults living in houses with high levels of Der p I and Der f I (greater than or equal to 2000 ng/gm of dust) were found to have significantly higher serum IgE levels to Dpt and Df (p less than 0.0001) compared to patients with low mite-allergen exposure. Washed leukocytes of 55 atopic children and 14 control subjects were investigated for in vitro histamine release to serial dilutions of Der p I; 86% of highly exposed (greater than or equal to 10,000 ng/gm) children demonstrated positive histamine release in response to Der p I compared to 17% in the group with very low exposure (less than 400 ng/gm). There was a positive correlation between basophil sensitivity (rs = 0.6; p less than 0.0001) and reactivity (rs = 0.54; p less than 0.0001) to Der p I and mite-allergen exposure. The relative risk for sensitization in the highly exposed group versus the group with very low exposure was sevenfold to 32-fold increased. We conclude that high concentrations of mite allergen (greater than or equal to 2000 ng/gm) increase the risk of specific sensitization in atopic children and young adults and thus may facilitate allergic airway disease.