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Hepatitis E virus (HEV) is a major cause of acute viral hepatitis in many parts of the world but only a few cases have been diagnosed in Norway. To investigate the HEV exposure rate in a presumed low-risk area, we have conducted a population-based study of anti-HEV IgG seroprevalence in Northern Norway. A total of 1800 serum samples from 900 women and 900 men, age 40-79 years, were randomly selected from the 21,083 participants in the 7th Tromsø Study, representing the 32,591 inhabitants of the Tromsø municipality that were ≥ 40 years. All samples were analyzed by ELISA-1 (recomWell HEV IgG). Samples testing positive or borderline, as well as a 1.5-fold excess of negative samples, were retested by ELISA-2 (DiaPro HEV IgG). If still borderline or a result discordant from ELISA-1, the sample was retested by ELISA-3 (Wantai HEV IgG) and strip-immunoassay (recomLine HEV IgG). Anti-HEV IgG was detected in 205 individuals (11.4%), yielding an estimated seroprevalence of 10.4% in the age-matched population of Tromsø. Using logistic regression analysis followed by multivariable backward elimination analysis, increasing age (OR 1.036 per year; p < 0.001) and higher education (OR 2.167; p < 0.001) were found as potential risk factors, whereas travel abroad or eating of red meat were not. Our results indicate that HEV-infection is common in Northern Norway and suggest that HEV testing should be included in the evaluation of elevated liver enzymes.

From 6 September 2015-May 2016, a large mumps outbreak occurred among vaccinated students in Norway. A case was defined as a person presenting with a clinical mumps infection, notified between 1 September 2015 and 30 June 2016. Confirmed cases had positive laboratory confirmation and probable cases had an epidemiological link; PCR-positive specimens were genotyped. A total of 232 cases were notified (230 confirmed) with median age of 23 years (range 4-81) and 61% were male. Of 68 (30%) confirmed cases that were genotyped, 66 were genotype G and associated with the outbreak. Cases that had received two doses of the measles-mumps-rubella (MMR) vaccine had reduced risk of hospitalisation (adjusted relative risk (aRR): 0.14; 95%CI: 0.03-0.57), mumps-related orchitis (aRR: 0.21; 95% CI: 0.08-0.55) and severe outcome (aRR: 0.25; 95% CI: 0.10-0.62) compared with those unvaccinated. A third dose of the vaccine was offered to approximately 1,300 fully vaccinated close contacts and subsequently reported cases decreased. This large outbreak, occurring among predominately vaccinated students, suggests the current genotype A vaccine offers suboptimal protection against mumps genotype G. We recommend maintaining high vaccination coverage and offering the vaccine to all unvaccinated individuals.

In Norway, no published data on seroprevalence of hepatitis E virus (HEV) in humans and swine exists. Serum samples from blood donors, veterinarians, swine farm workers and swine were analysed by ELISA to estimate the seroprevalence of HEV in Norway and to investigate the association between direct contact with swine and HEV seroprevalence in humans. The seroprevalence of HEV IgG antibodies was 30% (24/79) in farm workers, 13% (21/163) in veterinarians, 14% (162/1200) in blood donors and 90% (137/153) in swine. Our results show a high seroprevalence of HEV in humans and swine in Norway. HEV seroprevalence in farm workers and blood donors increased with age, and veterinarians working with swine were twice as likely to be HEV seropositive compared to other veterinarians. High HEV seroprevalence in farm workers and veterinarians working with swine support previous reports suggesting swine as a reservoir for HEV infections in humans in Europe.

EoE in children presents with four main symptoms. Most common symptoms exhibited by our clinic population are dysphagia (D) and abdominal pain (AP). Despite similar treatments, we found in an earlier study that the outcomes between these two groups were different. Therefore, we investigated if there exist any histological differences between these groups that could further our knowledge of EoE. Aim . To compare esophageal histology in detail, apart from the eosinophil count, between EoE-D and EoE-AP. Method . Biopsies of patients with EoE-D and EoE-AP were reevaluated for 10 additional histological criteria, in addition to the eosinophil count. Results . Both groups had 67 patients; peak mean eosinophil was 33.9 and 31.55 for EoE-D and EoE-AP ( p < 0.05). Eosinophilic microabscesses, superficial layering of eosinophils, and epithelial desquamation were twice as common and significant in EoE-D group than EoE-AP. Eosinophil distribution around rete pegs was also significantly higher in EoE-D group. The remaining criteria were numerically higher in EoE-D, but not significant, with the exception of rete peg elongation. Conclusion . EoE-D patients have significantly higher eosinophils compared to EoE-AP, and the level of inflammation as seen from eosinophil microabscesses, superficial layering, desquamation, and the distribution around rete pegs is significantly higher.

In May 2014, a cluster of Yersinia enterocolitica (YE) O9 infections was reported from a military base in northern Norway. Concurrently, an increase in YE infections in civilians was observed in the Norwegian Surveillance System for Communicable Diseases. We investigated to ascertain the extent of the outbreak and identify the source in order to implement control measures. A case was defined as a person with laboratory-confirmed YE O9 infection with the outbreak multilocus variable-number tandem repeat analysis (MLVA)-profile (5-6-9-8-9-9). We conducted a case-control study in the military setting and calculated odds ratios (OR) using logistic regression. Traceback investigations were conducted to identify common suppliers and products in commercial kitchens frequented by cases. By 28 May, we identified 133 cases, of which 117 were linked to four military bases and 16 were civilians from geographically dispersed counties. Among foods consumed by cases, multivariable analysis pointed to mixed salad as a potential source of illness (OR 10.26; 95% confidence interval (CI): 0.85-123.57). The four military bases and cafeterias visited by 14/16 civilian cases received iceberg lettuce or radicchio rosso from the same supplier. Secondary transmission cannot be eliminated as a source of infection in the military camps. The most likely source of the outbreak was salad mix containing imported radicchio rosso, due to its long shelf life. This outbreak is a reminder that fresh produce should not be discounted as a vehicle in prolonged outbreaks and that improvements are still required in the production and processing of fresh salad products., Competing Interests: Conflicts of Interest: None declared., (This article is copyright of The Authors, 2016.)

We investigated a nationwide outbreak of Salmonella Coeln in Norway, including 26 cases identified between 20 October 2013 and 4 January 2014. We performed a matched case-control study, environmental investigation and detailed traceback of food purchases to identify the source of the outbreak. In the case-control study, cases were found to be more likely than controls to have consumed a ready-to-eat salad mix (matched odds ratio 20, 95% confidence interval 2·7-∞). By traceback of purchases one brand of ready-to-eat salad was indicated, but all environmental samples were negative for Salmonella. This outbreak underlines that pre-washed and bagged salads carry a risk of infection despite thorough cleaning procedures by the importer. To further reduce the risk of infection by consumption of ready-to-eat salads product quality should be ensured by importers. Outbreaks linked to salads reinforce the importance of implementation of appropriate food safety management systems, including good practices in lettuce production.

In March 2014, after an increase of notifications of domestically acquired hepatitis A virus infections, an outbreak investigation was launched in Norway. Sequenced-based typing results showed that these cases were associated with a strain that was identical to one causing an ongoing multinational outbreak in Europe linked to frozen mixed berries. Thirty-three confirmed cases with the outbreak strain were notified in Norway from November 2013 to June 2014. Epidemiological evidence and trace-back investigations linked the outbreak to the consumption of a berry mix cake. Identification of the hepatitis A virus outbreak strain in berries from one of the implicated cakes confirmed the cake to be the source. Subsequently, a cluster in Germany linked to the cake was also identified.

Background: Approximately 90% of new tuberculosis (TB) cases notified in Norway are asylum seekers and other immigrants from high-incidence countries. Asylum seekers are screened upon arrival at the National Immigration Centre. Other immigrants receive a letter from the Municipal Health Services requesting that they present for screening in their municipality of residence. In order to identify potential areas where the TB control programme could be better adapted for these groups, we studied the largest cluster of TB cases ("cluster X") notified in Norway until 2011., Methods: Cases were defined as TB notifications reported to MSIS between January 1997 and December 2011 with identical IS6110 RFLP assigned to cluster X. We described the cases in cluster X by using data from the Norwegian Surveillance System for Communicable Diseases (MSIS). Missing or incomplete information in MSIS was obtained from the National Reception Centre, Oslo University Hospital and Municipal Health services., Results: Of a total of 44 individuals meeting the case definition, 36 originated from Somalia and eight from other high-incidence countries. Twenty nine were asylum seekers and 15 were other immigrants. Upon arrival, 18/44 had been diagnosed with latent TB infection (LTBI), 9/44 tested negative for LTBI and 4/44 had been diagnosed with active TB. Results of TB-screening upon arrival were not available for the remaining 13/44 (one asylum seeker and 12 other immigrants). Five of the 12 other immigrants had still not been screened for TB after staying one year or longer in Norway., Conclusions: Most cases in cluster X with available results of TB-screening were already infected at arrival, indicating that their disease could be due to endogenous reactivation, rather than recent transmission after arrival to Norway. TB-status upon arrival was unknown for many of the other immigrants due to lack of initial screening. The reasons why conduction of the initial screening among other immigrants is failing should be explored and methods to simplify the TB screening at arrival should be implemented.

The 14-3-3ζ gene, on 8q22, is often amplified in breast cancer and encodes a survival factor that interacts with and stabilizes many key signaling proteins. We examined the relationship between the expression of 14-3-3ζ, estrogen receptor α (ERα), and other parameters ( tumor size, grade, nodal status, progesterone receptor, HER2, EGFR, and p53) in matched primary and recurrence tumor tissue and how these factors impact time to recurrence, properties of the recurred tumors, and site of metastasis. In this cohort of over 100 patients, median time to recurrence was 3 years (range 1-17 years). Our analyses of primary tumor microarray cores revealed that 14-3-3ζ status was significantly correlated with tumor grade, size, and ERα. Women with 14-3-3ζ-positive and ERα-negative tumors had the earliest time to recurrence (median 1 yr, p < 0.001, hazard ratio 2.89), while median time to recurrence was 7 years for 14-3-3ζ-negative and ER-positive tumors. Of recurred tumors, 70-75 % were positive for 14-3-3ζ, up from the 45 % positivity of primary tumors. High expression of 14-3-3ζ also correlated with site of recurrence and showed a propensity for distant metastases to lung and chest wall. Multifactor correlation regression analysis revealed 14-3-3ζ to be a non-redundant, independent variable that adds clinical strength in predicting risk for early recurrence in ER-positive and -negative breast cancers, providing information beyond that of all other clinical pathological features examined. Thus, high expression of 14-3-3ζ in the primary tumor was significantly associated with earlier time to recurrence and with distant metastasis. Furthermore, even when the primary breast cancers were negative-low for 14-3-3ζ, the majority acquired increased expression in the recurrence. The findings underscore the detrimental role played by 14-3-3ζ in tumor aggressiveness and suggest that reducing its expression or interfering with its actions might substantially improve the clinical outcome for breast cancer patients.

Background: The aims of the study were to determine the molecular characteristics of a collection of Legionella pneumophila isolates from 45 cases with Legionnaires' disease and from 96 environmental samples, received by the national reference laboratory in Norway between 2001 and 2008, to use these characteristics to identify links between cases and suspected sources of infection, and to compare the isolate characteristics with those in other European countries., Methods: The isolates were characterized by 7-gene locus sequence-based typing and dot-blotting with monoclonal antibodies to various serogroups and subgroups., Results: The clinical isolates represented 12.6% of the 357 cases notified in Norway between 2001 and 2008, during which 3 outbreaks of L. pneumophila serogroup 1 occurred. Outbreak cases constituted 62.2% of the cases, followed by travel-associated (24.4%) and sporadic cases (11.1%). Forty-two (93.3%) of the clinical and 69 (71.9%) of the environmental isolates were serogroup 1, and 39 (86.7%) and 50 (52.1%) isolates, respectively, carried the monoclonal antibody (Mab) 3/1 virulence-associated epitope. The clinical isolates belonged to 17 sequence types and the environmental isolates to 19 sequence types. neuA was not detected in 23 environmental isolates., Conclusions: Matching characteristics of sequence types and monoclonal subgroups for case and environmental isolates were obtained for all 3 outbreaks and for 2 of 5 cases of sporadic disease. Sampling during the outbreaks accounted for the higher proportion of serogroup 1 and Mab 3/1-positive environmental isolates in comparison with other European strain collections.

Background: During the 2009-2010 pandemic in Norway, 12 513 laboratory-confirmed cases of pandemic influenza A(H1N1)pdm09, were reported to the Norwegian Surveillance System for Communicable Diseases (MSIS). 2.2 million persons (45% of the population) were vaccinated with an AS03-adjuvanted monovalent vaccine during the pandemic. Most of them were registered in the Norwegian Immunisation Registry (SYSVAK). Based on these registries, we aimed at estimating the vaccine effectiveness (VE) and describing vaccine failures during the pandemic in Norway, in order to evaluate the role of the vaccine as a preventive measure during the pandemic., Methods: We conducted a population-based retrospective cohort study, linking MSIS and SYSVAK with pandemic influenza vaccination as exposure and laboratory-confirmed pandemic influenza as outcome. We measured VE by week and defined two thresholds for immunity; eight and 15 days after vaccination., Results: The weekly VE ranged from 77% to 96% when considering 15 days or more after vaccination as the threshold of immunity and from 73% to 94% when considering eight days or more. Overall, 157 individuals contracted pandemic influenza eight or more days after vaccination (8.4/100,000 vaccinated), of these 58 had onset 15 days or more after vaccination (3.0/100,000 vaccinated). Most of the vaccine failures occurred during the first weeks of the vaccination campaign. More than 30% of the vaccine failures were found in people below 10 years of age., Conclusions: Having available health registries with data regarding cases of specific disease and vaccination makes it feasible to estimate VE in a simple and rapid way. VE was high regardless the immunity threshold chosen. We encourage public health authorities in other countries to set up such registries. It is also important to consider including information on underlying diseases in registries already existing, in order to make it feasible to conduct more complete VE estimations.

Background: The International Health Regulations (IHR (2005)) require countries to notify WHO of any event which may constitute a public health emergency of international concern. This notification relies on reports of events occurring at the local level reaching the national public health authorities. By June 2012 WHO member states are expected to have implemented the capacity to "detect events involving disease or death above expected levels for the particular time and place" on the local level and report essential information to the appropriate level of public health authority. Our objective was to develop tools to assist European countries improve the reporting of unusual events of public health significance from frontline healthcare workers to public health authorities., Methods: We investigated obstacles and incentives to event reporting through a systematic literature review and expert consultations with national public health officials from various European countries. Multi-day expert meetings and qualitative interviews were used to gather experiences and examples of public health event reporting. Feedback on specific components of the toolkit was collected from healthcare workers and public health officials throughout the design process., Results: Evidence from 79 scientific publications, two multi-day expert meetings and seven qualitative interviews stressed the need to clarify concepts and expectations around event reporting in European countries between the frontline and public health authorities. An analytical framework based on three priority areas for improved event reporting (professional engagement, communication and infrastructure) was developed and guided the development of the various tools. We developed a toolkit adaptable to country-specific needs that includes a guidance document for IHR National Focal Points and nine tool templates targeted at clinicians and laboratory staff: five awareness campaign tools, three education and training tools, and an implementation plan. The toolkit emphasizes what to report, the reporting process and the need for follow-up, supported by real examples., Conclusion: This toolkit addresses the importance of mutual exchange of information between frontline healthcare workers and public health authorities. It may potentially increase frontline healthcare workers' awareness of their role in the detection of events of public health concern, improve communication channels and contribute to creating an enabling environment for event reporting. However, the effectiveness of the toolkit will depend on the national body responsible for dissemination and training.

The estrogen receptor (ER) is a major prognostic and therapeutic marker that is expressed in nearly 75% of breast tumors. We have previously shown that the presence of inflammatory mediators can alter the genomic function of the estrogen receptor (ER) in a gene specific manner. In particular, 17β-estradiol (E2) works in combination with the pro-inflammatory cytokines to enhance the expression of a number of pro-survival factors, including the Inhibitor of Apoptosis (IAP) family member, cIAP2. Here we confirm that mRNA and protein levels for cIAP2, but not the related family members cIAP1 and XIAP, are highly up-regulated in MCF-7 breast cancer cells by E2 and cytokines. Similar regulation of cIAP2 is evident in other ER positive but not ER negative cell lines. In agreement with its role as a pro-survival factor, cIAP2 is highly expressed in a subset of invasive breast carcinomas but not in normal breast tissue or ductal carcinoma in situ. Antagonizing IAPs with mimetics of SMAC, which is a known endogenous IAP antagonist, or knockdown of IAPs by siRNA led to greater cell death by TNFα and prevented E2 from promoting cell survival. In addition, a SMAC mimetic reversed TNFα resistance in ER positive breast cancer cells that express high levels of endogenous IAPs. In summary, our findings indicate a new mechanism by which E2 allows breast cancer cells to evade cell death and suggest that an antagonist of IAPs may be a potential therapeutic option for a subset of ER positive breast tumors.

During the 2007-08 influenza season, high levels of oseltamivir resistance were detected among influenza A(H1N1) viruses ina number of European countries. We used surveillance data to describe influenza A(H1N1) cases for whom antiviral resistance testing was performed. We pooled data from national studies to identify possible risk factors for infection with a resistant virus and to ascertain whether such infections led to influenza illness of different severity. Information on demographic and clinical variables was obtained from patients or their physicians. Odds ratios for infection with an oseltamivir resistant virus and relative risks for developing certain clinical outcomes were computed and adjusted through multivariable analysis. Overall, 727 (24.3%) of 2,992 tested influenza A(H1N1) viruses from 22 of 30 European countries were oseltamivir-resistant. Levels of resistance ranged from 1% in Italy to 67% in Norway. Five countries provided detailed case-based data on 373 oseltamivir resistant and 796 susceptible cases. By multivariable analysis, none of the analysed factors was significantly associated with an increased risk of infection with anoseltamivir-resistant virus. Similarly, infection with an oseltamivir-resistant virus was not significantly associated with a different risk of pneumonia, hospitalisation or any clinical complication. The large-scale emergence of oseltamivir-resistant viruses in Europe calls for a review of guidelines for influenza treatment.

In 2006, in The Netherlands, an outbreak of Salmonella Typhimurium phage type 561 (STM DT7, corresponding to the rare DT7 in the international typing scheme) was detected, accumulating to over 200 cases. By telephone interviews, data were collected from all laboratory-confirmed cases. In addition, in August 2006, a case-control study was performed in a subset of cases. Environmental and microbiological investigation was performed on a suspected dairy farm. In the case-control study (51 cases, 105 matched controls), hard cheese purchased from a farm, specifically farm X, and from a market stall were found to be associated with infection. The dairy production room of farm X tested STM DT7-positive in August. However, it was only in November, after earlier unsuccessful attempts, that a low-level contamination was confirmed in the hard farmhouse cheese, triggering control measures. A timely and adequate response was hampered during this outbreak for several reasons. Measures for improvement in handling future similar incidents are discussed.

Background: A new A(H1N1) influenza virus was detected in April 2009. The virus is now causing a pandemic of influenza. The article presents an overview of symptoms, complications, vulnerable groups, diagnosis and treatment., Material and Methods: The overview is based on literature identified through a search in PubMed (using PubMed's own search strategy) and on official reports from WHO and the disease control centres of EU and the USA., Results: The new influenza A(H1N1) has so far mainly affected young people, only few people over 60 years. The clinical presentation is similar to that of ordinary influenza; but nausea, vomiting and diarrhoea seem to be more common. The reported risk of complications and case fatality are low, but hospitalisation, pneumonia and deaths have occurred, also in previously healthy young individuals. Antiviral treatment with oseltamivir or zanamivir is likely to be as effective as in ordinary influenza., Interpretation: Mild cases may be underrepresented in the published literature. It is important to keep up-to-date on international reports on the nature of the disease in order to best prepare clinicians to diagnose and treat patients when the epidemic hits Norway with full force.

Background: An unprecedented high proportion of oseltamivir resistant influenza A(H1N1) viruses emerged in the 2007-08 influenza season. In Norway, two thirds of all tested A(H1N1) viruses were resistant to the antiviral drug. In order to see if this emergence could be explained by a drug induced selection pressure, we analysed data on the sales of oseltamivir in Norway for the years 2002-07., Methods: We used data from two sources; the Norwegian Drug Wholesales Statistics Database and the Norwegian Prescription Database (NorPD), for the years 2002-2007. We calculated courses sold of oseltamivir (Tamiflu) per 1000 inhabitants per year., Results: Our data showed that, except for the years 2005 and 2006, sales of oseltamivir were low in Norway; courses sold per 1000 inhabitants varied between 0.17-1.64. The higher sales in 2005 and 2006 we believe were caused by private stockpiling in fear of a pandemic, and do not represent actual usage., Conclusion: A drug induced selection pressure was probably not the cause of the emergence of oseltamivir resistant influenza A(H1N1) viruses in 2007-08 in Norway.

Background: Gonorrhoea, a bacterial infection caused by Neisseria gonorrhoeae, has been increasing in several European countries, particularly among men who have sex with men (MSM) and teenagers. We describe the epidemiology of gonorrhoea in Norway in the recent 15 years in order to guide recommendations on the diagnosis, treatment and prevention of gonorrhoea. An evaluation of the Norwegian Surveillance System for Communicable Diseases (MSIS) in 1994, involving GPs and microbiological laboratories, suggested that the system has a high coverage, capturing over 90% of patients diagnosed with gonorrhoea., Methods: Using MSIS data on gonorrhoea cases we analysed specific trends by route of transmission, age, gender, anatomical sampling site, antimicrobial resistance and travel history from 1993-2007 and, to focus on more recent trends, from 2003-2007. MSM and heterosexual cases were defined by route of transmission., Results: From 1993 to 2007, 3601 gonorrhoea cases were reported. MSM cases increased from 10 in 1994 to 109 cases in 2004. From 2003-2007, the incidence of gonorrhoea was 5.4/100,000 person-years (95%CI: 4.9-6.0). Over these five years, MSM accounted for an average of 80 cases per year, of which 69% were infected by casual partners. In the same period, 98% of heterosexually infected had a positive swab from urethra only and only two (0.3%) from the pharynx. Only one woman (0.5%) was positive from the rectum. From 1993 - 2007, antimicrobial resistance results were reported for 3325 N. gonorrhoeae isolates (98% of cultured samples). The proportion resistant to quinolone has risen from 3% in 1995 to 47% in 2007, with 81% of the latter isolated from patients infected in Asia., Conclusion: The overall incidence of gonorrhoea in Norway remains low, but the increasing number of MSM cases calls for new, more effective approaches to prevention. Infections originating from abroad represent a constant risk of importing antimicrobial resistant N. gonorrhoeae. Due to the prevalence of quinolone resistant N. gonorrhoeae in Norway, third-generation cephalosporins should replace quinolones as the first choice in treatment guidelines. We advocate antimicrobial susceptibility testing for all cases and recommend taking samples for culture from all exposed anatomical sites.

In Norway in January 2008, unprecedented levels of oseltamivir resistance were found in 12 of 16 influenza viruses A (H1N1) tested. To investigate the epidemiologic and clinical characteristics of these viruses, we used sequence analysis to test all available subtype H1N1 viruses from the 2007-08 season for resistance. Questionnaires from physicians provided information on predisposing diseases, oseltamivir use, symptoms, and complications. Clinical data were obtained for 265 patients. In total, 183 (67.3%) of 272 viruses were oseltamivir resistant. Resistance was not associated with prior use of antiviral drugs. Symptoms and hospitalization rates did not differ for patients infected with a resistant or a susceptible virus. Oseltamivir-resistant influenza viruses A (H1N1) did not show diminished capability to spread in the absence of selective pressure. The ability of these viruses to sustain their fitness and spread among persons should be considered when shaping future strategies for treating and preventing seasonal and pandemic influenza.

Background: On 7 May 2007 the medical officer in Røros (population 5600) reported 15 patients with gastroenteritis. Three days later he estimated hundreds being ill. Untreated tap water from a groundwater source was suspected as the vehicle and chlorination was started 11 May. Campylobacter was isolated from patients' stool samples. We conducted an investigation to identify the source and describe the extent of the outbreak., Methods: We undertook a retrospective cohort study among a random sample of customers of Røros and neighbouring Holtålen waterworks. Holtålen, which has a different water source, was used as a control city. We conducted telephone interviews to gather data on illness from all household members. One randomly selected household member was asked about detailed exposure history. The regional hospital laboratory tested patients' stools for enteropathogens. Campylobacter isolates were typed by AFLP for genetic similarity at the Norwegian Institute of Public Health. Local authorities conducted the environmental investigation., Results: We identified 105 cases among 340 individuals from Røros and Holtålen (Attack Rate = 31%). Tap water consumption was the only exposure associated with illness. Among randomly selected household members from Røros, a dose-response relationship was observed in daily consumed glasses of tap water (chi2 for trend = 8.1, p = 0.004). Campylobacter with identical AFLP was isolated from 25 out of 26 submitted stool samples. No pathogens were detected in water samples. We identified several events that might have caused pressure fall and influx of contaminated water into the water distribution system. On two occasions, pressure fall was noticed and parts of the distribution system were outdated., Conclusion: The investigation confirmed a waterborne outbreak of campylobacteriosis in Røros. Although no single event was identified as the cause of contamination, this outbreak illustrates the vulnerability of water distribution systems. Good quality source water alone is not enough to ensure water safety. For a better risk management, more focus should be put on the distribution system security. Waterworks personnel should monitor the pressure regularly; reduce the leakage by upgrading the distribution network and use chlorination when conducting maintenance work.

The aim of the present study was to evaluate yield and effectiveness of a large-scale contact investigation around a supermarket employee with infectious tuberculosis. Supermarket customers were screened by tuberculin skin test (TST) and/or radiography, depending on individual characteristics. The number of recent infections was estimated based on historical reference data after correction for false-positive TST results. TST screening of 15,518 subjects yielded 12 cases of tuberculosis disease as a direct result of the investigation (1,293 screenings per case identified). Radiographical screening of 5,945 subjects yielded no cases. There were 359 (2.6%) positive TSTs; 117 (34%) were estimated to be due to recent exposure. The number of customers screened in order to find one case of recent infection was 114, varying from 43 for customers who visited the supermarket twice per week or more, to 4,148 for customers who visited less than once per month. In conclusion, although this patient probably transmitted Mycobacterium tuberculosis to at least 117 customers, the contact investigation was inefficient, as large numbers of customers had to be screened and the majority of identified tuberculosis infections were probably not related to the index case. The efficiency could have been improved by omitting radiographical screening and limiting tuberculin skin test screening to customers who reported frequent supermarket visits.

Background: Human hepatitis E virus (HEV) infections are considered an emerging disease in industrialized countries. In the Netherlands, Hepatitis E virus (HEV) infections have been associated with travel to high-endemic countries. Non-travel related HEV of genotype 3 has been diagnosed occasionally since 2000. A high homology of HEV from humans and pigs suggests zoonotic transmission but direct molecular and epidemiological links have yet to be established. We conducted a descriptive case series to generate hypotheses about possible risk factors for non-travel related HEV infections and to map the genetic diversity of HEV., Methods: A case was defined as a person with HEV infection laboratory confirmed (positive HEV RT-PCR and/or HEV IgM) after 1 January 2004, without travel to a high-endemic country three months prior to onset of illness. For virus identification 148 bp of ORF2 was sequenced and compared with HEV from humans and pigs. We interviewed cases face to face using a structured questionnaire and collected information on clinical and medical history, food preferences, animal and water contact., Results: We interviewed 19 cases; 17 were male, median age 50 years (25-84 y), 12 lived in the North-East of the Netherlands and 11 had preexisting disease. Most common symptoms were dark urine (n = 16) and icterus (n = 15). Sixteen ate pork >/= once/week and six owned dogs. Two cases had received blood transfusions in the incubation period. Seventeen cases were viremic (genotype 3 HEV), two had identical HEV sequences but no identified relation. For one case, HEV with identical sequence was identified from serum and surface water nearby his home., Conclusion: The results show that the modes of transmission of genotype-3 HEV infections in the Netherlands remains to be resolved and that host susceptibility may play an important role in development of disease.

Previous publications have indicated that between 2002 and 2003 in the Netherlands, the antimicrobial resistance in gonococci increased. Repeat measurements in 2004 and 2005 suggest a further increase in resistance ofgonococci, to quinolones in particular, from 7% in 2002 to 26% in 2005. National surveillance of gonococcal antimicrobial resistance is important for public health. In 2006 a further survey will be implemented, in which resistance data and epidemiological information on the patients are combined and collected in a project called 'Gonococcal resistance to antimicrobials surveillance' (GRAS).

In 2004, an outbreak of hepatitis A occurred in European tourists returning from Egypt. The reported hepatitis A attack rates varied considerably between tourists from different European countries. To determine the reason for this divergence in attack rates, a survey was undertaken with the following objectives: (a) documentation of national hepatitis A prevention policies for people travelling to Egypt and (b) documentation of hepatitis A reporting practices in these countries. A questionnaire was compiled and distributed to 13 European countries. All eight of the countries that responded had produced guidelines for the prevention of travel-associated hepatitis A. Between 2001-2003, 40% (range 4-51) of hepatitis A cases reported annually were associated with travel abroad. This occurred despite the fact that all countries recommended active vaccination with hepatitis A vaccine for people travelling to Egypt for holidays. There was no standard case definition for reporting confirmed cases in the countries that reported hepatitis A cases. As it is likely that travel-associated infections will increase as more people take overseas holidays, innovative ways to increase the number of travellers who seek and adhere to appropriate medical advice prior to travel must be explored. In addition, we recommend the use of the European Commission case definition for notification of confirmed cases of hepatitis A.

Enterococcus faecalis harbors a virulence-associated surface protein encoded by the esp gene. This gene has been shown to be part of a 150-kb putative pathogenicity island. A gene similar to esp has recently been found in Enterococcus faecium isolates recovered from hospitalized patients. In the present study we analyzed the polymorphism in the esp gene of E. faecium, and we investigated the association of esp with neighboring chromosomal genes. The esp gene showed considerable sequence heterogeneity in the regions encoding the nonrepeat N- and C-terminal domains of the Esp protein as well as differences in the number of repeats. DNA sequencing of chromosomal regions flanking the esp gene of E. faecium revealed seven open reading frames, representing putative genes implicated in virulence, regulation of transcription, and antibiotic resistance. These flanking regions were invariably associated with the presence or absence of the esp gene in E. faecium, indicating that esp in E. faecium is part of a distinct genetic element. Because of the presence of virulence genes in this gene cluster, the lower G+C content relative to that of the genome, and the presence of esp in E. faecium isolates associated with nosocomial outbreaks and clinically documented infections, we conclude that this genetic element constitutes a putative pathogenicity island, the first one described in E. faecium. Except for the presence of esp and araC, this pathogenicity island is completely different from the esp-containing pathogenicity island previously disclosed in E. faecalis.

Vancomycin-resistant enterococci (VRE) have frequently been isolated from Norwegian poultry production following the prohibition of the glycopeptide growth promoter avoparcin since 1995. In the present study, a close genetic linkage between the vanA and erm(B) determinants in an Enterococcus hirae isolate of poultry origin is demonstrated, a result that indicates a mechanism for co-selection and maintenance of vancomycin resistance in absence of selective pressure from avoparcin. A total of 36 vanA-positive enterococci of poultry origin, also phenotypically resistant to erythromycin and/or tetracycline, were analyzed by PCR for identification of erm and tet resistance determinants. An E. hirae isolate harbored erm(B) and tet(K), and in this isolate vanA and erm(B) were located on a BamHI fragment of an approximately 50-kb plasmid. Approximately 3 kb of this fragment was amplified by PCR with vanA and erm(B) primers. Sequence analysis of the region between erm(B) and vanZ of Tn1546 showed a truncated IS1216V inserted downstream of the erm(B) stop codon, aligned with a conserved copy of the 3'-inverted terminal repeat of Tn1546. Mating experiments with the E. hirae isolate as donor and E. faecalis JH2-2 as recipient did not result in any transconjugants, indicating that the vanA/erm(B)-carrying plasmid was nonconjugative under the given experimental conditions.

The genetic relationship between 197 vancomycin-resistant Enterococcus faecium (VREF) isolates and 21 vancomycin-susceptible E. faecium isolates from Norwegian poultry was analyzed by amplified fragment length polymorphism (AFLP). The isolates were compared to 255 VREF isolates from various sources and countries. The Norwegian isolates constituted a relatively homogeneous population of E. faecium and clustered in a previously defined poultry AFLP genogroup.

Avoparcin was used as a growth promoting feed additive in Norwegian broiler and turkey production from 1986 until it was banned in 1995, when an association between vancomycin-resistant enterococci (VRE) and avoparcin use became apparent. A recent study regarding faecal samples documented a continuing high prevalence of VRE among Norwegian poultry 3 years after avoparcin was banned. In the present study, carcasses of broilers and turkeys from farms where avoparcin had previously been in use and carcasses of layer chickens from farms where avoparcin had never been used were examined for the presence of VRE. One carcass from each of 150 different farms was included. By a direct plating method, VRE were isolated from 30 of 100 samples of broilers and turkeys, but not from any samples of layer chickens. When an enrichment step was included, VRE were isolated from a total of 81 of the 100 samples of broilers and turkeys and from nine of the 50 samples of layer chickens. All VRE isolated were highly resistant to vancomycin (MIC > or = 256 microg/ml) and possessed the vanA gene. These results correspond to the prevalence of VRE recently documented in faecal samples from Norwegian poultry. The present study reveals a high prevalence of VRE in broiler and turkey carcasses. Consequently, consumers are exposed to VRE when handling raw poultry meat, although the public health significance of such exposure is unclear.

Five Norwegian broiler farms previously identified as housing broilers carrying vancomycin-resistant enterococci (VRE) were examined for the presence of VRE 4 years after avoparcin was banned. Environmental samples were obtained from empty, cleaned broiler houses. Faecal samples were collected weekly from the flock housed after the environmental sampling. The hatchery from where the chicks originated was also sampled. VRE were found to be present in the farm environment after depopulation and cleanup of the broiler houses. Within 3 weeks after introduction to the farm, all broiler flocks tested positive for VRE. VRE were not isolated from the hatchery.

Avoparcin was used as a feed additive in Norwegian broiler and turkey production from 1986 until 1995. It was banned due to the selection of VanA-type vancomycin-resistant enterococci (VRE) in animal husbandry and to reduce the potential for human exposure to VRE. The aim of the present study was to investigate the prevalence of VRE carriage in Norwegian poultry farmers and their poultry three years after avoparcin was banned. Corresponding faecal samples from poultry and humans on farms where avoparcin had previously been used (exposed farms, n = 73) and farms where avoparcin had never been used (unexposed farms, n = 74) were analysed for the presence of VRE. For each farm, one sample from the poultry house and one sample from the farmer were obtained. VRE were isolated from 72 of 73 (99%) and eight of 74 (11%) poultry samples from exposed and unexposed farms, respectively. VRE were isolated from 13 of 73 (18%) and one of 74 (1%) farmer samples from exposed and unexposed farms, respectively. All VRE isolates were highly resistant to vancomycin and possessed the vanA gene, as shown by PCR. The high prevalence of VRE is in accordance with previous Norwegian studies, and shows a remarkable stability of the VanA resistance determinant in an apparently non-selective environment.