An outbreak of enterotoxigenic Escherichia coli (ETEC) infection in Norway, 2012: a reminder to consider uncommon pathogens in outbreaks involving imported products.

We investigated an outbreak of gastroenteritis following a Christmas buffet served on 4-9 December 2012 to ~1300 hotel guests. More than 300 people were reported ill in initial interviews with hotel guests. To identify possible sources of infection we conducted a cohort investigation through which we identified 214 probable cases. Illness was associated with consumption of scrambled eggs (odds ratio 9·07, 95% confidence interval 5·20-15·84). Imported chives added fresh to the scrambled eggs were the suspected source of the outbreak but were unavailable for testing. Enterotoxigenic Escherichia coli (ETEC) infection was eventually confirmed in 40 hotel guests. This outbreak reinforces that ETEC should be considered in non-endemic countries when the clinical picture is consistent and common gastrointestinal pathogens are not found. Following this outbreak, the Norwegian Food Safety Authority recommended that imported fresh herbs should be heat-treated before use in commercial kitchens.

Serum long chain n-3 fatty acids (EPA and DHA) in the pregnant mother are independent of risk of type 1 diabetes in the offspring.

BACKGROUND: This article aims to study whether higher proportions of the long chain n-3 fatty acids eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) in the phospholipid fraction of serum samples in pregnancy were associated with a lower risk of childhood onset type 1 diabetes in the offspring. METHODS: In a prospective cohort of nearly 30 000 pregnant women who gave birth in Norway during 1992-1994, we analysed serum samples from 89 women whose child developed type 1 diabetes and was included in the nationwide Norwegian Childhood Diabetes Registry and 125 randomly selected women whose child did not develop type 1 diabetes before 15 years of age. Specific fatty acids were expressed as the proportion of total fatty acids (g/100 g) in the phospholipid fraction in serum analysed using solid phase extraction and gas chromatography with flame ionization detection. RESULTS: There was no significant association between EPA or DHA in maternal serum and risk of type 1 diabetes in the offspring. Odds ratio (OR) for upper versus lower quartile of EPA was 0.75 [95% confidence interval (CI) 0.34-1.65], test for trend p = 0.4, and for DHA OR = 0.71 (95% CI 0.33-1.53), test for trend p = 0.6. No significant association was found for the sum of n-3 fatty acids, or for n-6/n-3 ratio in the mother with risk of type 1 diabetes in the offspring. CONCLUSIONS: Our data did not support the hypothesis that higher proportions of maternal EPA or DHA during pregnancy are associated with a lower risk of type 1 diabetes in the offspring.

Maternal human parvovirus B19 infection and the risk of fetal death and low birthweight: a case-control study within 35 940 pregnant women.

OBJECTIVES: To assess the association between maternal parvovirus B19 infection and fetal death, birthweight and length of gestation. DESIGN: Case-control study. SETTING: Population based. POPULATION: Cases were all 281 women with fetal death within a cohort of 35 940 pregnant woxmen in Norway. The control group consisted of a random sample of 957 women with a live born child. METHOD: Information on pregnancy outcome was obtained from the Medical Birth Registry of Norway. First trimester serum samples were tested for antibodies against parvovirus B19 (IgM and IgG). In seronegative women, further serum was analysed to detect seroconversion during pregnancy. MAIN OUTCOME MEASURES: Fetal death, length of gestation and birthweight. RESULTS: Two of 281 (0.7%) of the women who experienced fetal death and nine of 957 (0.9%) of the controls had presence of IgM antibodies, crude odds ratio 0.8; 95% CI (0.2-3.5). In initially, seronegative women, 3.1% (2/65) with fetal death and 2.6% (8/307) with a live birth seroconverted, crude odds ratio 1.2; 95% CI (0.2-5.7). Presence of maternal parvovirus-specific IgG or IgM antibodies in the first trimester, or seroconversion during pregnancy were not associated with lower birthweight or reduced length of gestation in live born children, but was associated with low birthweight in stillborn offspring. CONCLUSION: Maternal parvovirus B19 infection was not associated with fetal death in our study. Very few cases of fetal death may be attributed to maternal parvovirus B19 infection.

Diagnosis of congenital Toxoplasma gondii infection by polymerase chain reaction (PCR) on amniotic fluid samples. The Norwegian experience.

As part of a screening project for detection of Toxoplasma gondii infection among pregnant women in Norway, nested polymerase chain reaction (PCR) aimed at the detection of T. gondii in amniotic fluid samples was included in the diagnostic routine. The results were compared with the routine criteria for congenital infection: i) T. gondii detected in amniotic fluid or cord blood by mouse inoculation, ii) specific IgM or IgA in serum collected after birth, and/or iii) specific IgG persisting beyond one year of age. The PCR was based on the B1 gene with an internal control gene amplified together with the B1 gene. One hundred and two amniotic fluid samples collected during pregnancy and/or at delivery from 67 pregnant women with serological evidence of primary T. gondii infection were available for examination by both B1-PCR and mouse inoculation. Six samples were positive and 86 samples were negative by both methods (90% concordance). One sample was mouse inoculation positive and B1-PCR negative while nine samples were B1-PCR positive and mouse inoculation negative, of which five were associated with four infants without proven infection. 59%, and 41% of samples associated with infected infants were positive by B1-PCR and mouse inoculation, respectively. The difference was mainly due to a lower detection rate by mouse inoculation after antiparasitic treatment. The specificity of B1-PCR was 94%. Even though B1-PCR performed on amniotic fluid samples did not detect all infected infants, it represented a valuable tool in addition to conventional methods in the diagnosis of congenital T. gondii infection.

Humoral immunity to viral and bacterial antigens in lymphoma patients 4-10 years after high-dose therapy with ABMT. Serological responses to revaccinations according to EBMT guidelines.

The aim of this study was to investigate the late effects of ABMT on the immune system with regard to protective humoral immunity against common antigens and responses to recall antigens (vaccines). The vaccines were given according to EBMT guidelines from 1995. The protocol included 35 patients with malignant lymphoma in CR 4-10 years after ABMT, and 35 controls. The results show that prior to ABMT the proportion of patients with protective immunity against poliomyelitis, tetanus and diphtheria was similar to that of controls. At study entry 4-10 years after ABMT, the proportion of patients with protective immunity against poliomyelitis and diphtheria was reduced, while all patients maintained protection against tetanus. A significant decrease in geometric mean antibody concentrations or titres was observed against all three antigens during this period. Serum levels of antibodies against different pneumococcal serotypes were lower in the patients than in the controls prior to vaccination. The responses to pneumococcal vaccination, which is considered to be a T cell-independent vaccine, were studied. Unlike controls, a minority of patients achieved protective levels of antibodies after a single vaccination. Despite persistent levels of protective antibodies in many patients post ABMT, secondary booster responses after one vaccination with T cell-dependent vaccines (tetanus, diphtheria and polio) were absent. In conclusion, this study shows that post ABMT, a full re-vaccination program was necessary to mount responses comparable to those observed after a single vaccination in controls.

Detection of diphtheria antitoxin by four different methods.

OBJECTIVE: To investigate the reliability of the different methods used in Norway and Russia for detection of diphtheria antitoxin. METHODS: One hundred and twenty-two sera were selected among Russian serum samples previously collected for seroepidemiologic studies of diphtheria antitoxin. The sera were selected to cover the total antitoxin range and were analyzed by four different antidiphtheria toxin assays: an in vitro toxin neutralization test using Vero cells (in vitro NT), an in vivo neutralization test using rabbit skin inoculation (in vivo NT), an indirect enzyme immunoassay (EIA) and a passive hemagglutination assay (PHA). The results were expressed according to the international standard as: not protected (<0.01 IU/mL), relatively protected (0.01-0.1 IU/mL) or protected (≥0.1 IU/mL). The sensitivity, specificity and inter-rater agreement (K or Kw) of each method were related to the in vitro NT selected as the reference method. RESULTS: The in vivo NT test corresponded very well with the in vitro NT in its ability to differentiate between protection/relative protection and no protection (sensitivity 97%, specificity 87% and K=0.84). The EIA test showed a high sensitivity (96%), but since many sera were categorized as protected rather than not protected, the specificity (30%) and inter-rater agreement (K=0.29) were low. The PHA test had a very high specificity (100%) but a low sensitivity (86%). CONCLUSIONS: The agreement between the two neutralization tests was high. If none of the neutralization assays is routinely available, the PHA test can be used to predict the need for vaccination on an individual basis but should not be used for seroepidemiologic studies, since the protection rate for diphtheria would be falsely too low, due to the lower sensitivity. The indirect EIA test used in this study should not be used routinely.

Relevance of a combined HIV antigen/antibody assay to detect early HIV infections in a low prevalence population: case reports.

The AxSYM HIV Ag/Ab Combo assay (Abbott) has proven to possess excellent sensitivity on seroconversion samples. Since its introduction in Sweden and Norway approximately one year ago, eight cases of acute HIV infections were found earlier compared to assays detecting only antibodies either to screen or to confirm an HIV infection. Data of the presented cases indicate that the early detection of primary HIV infection is of benefit to the individual patient and may reduce further spread of the disease. The impact of HIV combo assays on screening and diagnosis in a low prevalence population is discussed.

Sources of toxoplasma infection in pregnant women: European multicentre case-control study. European Research Network on Congenital Toxoplasmosis.

OBJECTIVE: To determine the odds ratio and population attributable fraction associated with food and environmental risk factors for acute toxoplasmosis in pregnancy. DESIGN: Case-control study. SETTING: Six large European cities. PARTICIPANTS: Pregnant women with acute infection (cases) detected by seroconversion or positive for anti-Toxoplasma gondii IgM were compared with pregnant women seronegative for toxoplasma (controls). MAIN OUTCOME MEASURES: Odds ratios for acute infection adjusted for confounding variables; the population attributable fraction for risk factors. RESULTS: Risk factors most strongly predictive of acute infection in pregnant women were eating undercooked lamb, beef, or game, contact with soil, and travel outside Europe and the United States and Canada. Contact with cats was not a risk factor. Between 30% and 63% of infections in different centres were attributed to consumption of undercooked or cured meat products and 6% to 17% to soil contact. CONCLUSIONS: Inadequately cooked or cured meat is the main risk factor for infection with toxoplasma in all centres. Preventive strategies should aim to reduce prevalence of infection in meat, improve labelling of meat according to farming and processing methods, and improve the quality and consistency of health information given to pregnant women.

Rapid identification of Escherichia coli from routine urine specimens based on macroscopic criteria.

In our laboratory, selected strains of Gram-negative rods from urine samples are identified as Escherichia coli on the basis of smell and morphology on lactose agar. To investigate the accuracy of this routine practice, 211 consecutive strains were tested in the urea-indole tube of the Three-tube method (3-TM), in the PGUA test detecting beta-glucuronidase activity and in the Simmons' citrate test, to select the strains that were non-E. coli. Additional 1022 strains were tested by the indole and urease tests of the 3-TM only. The identification of E. coli based on the macroscopic evaluation of colonies on lactose agar gave correct results for 99.1% of the strains. Citrobacter freundii was the most frequent cause of erroneous identification.

Antibodies against Chlamydia measured by an ELISA method.

An enzyme-linked immunosorbent assay (ELISA) for the detection of serum IgG and IgM antibodies against chlamydia group antigen is presented. 187 selected sera were tested both in the ELISA and in the complement-fixation test (CFT). Of 71 sera with negative results in the CFT, 19 (26.8%) were positive in the ELISA. Of 116 CFT positive sera, ten (8,6%) were ELISA negative. In 35 of 72 sera (48.6%) with CFT titre less than 40 chlamydial IgM was demonstrated, while 11 of 115 sera (9.5%) with CFT titre less than 40, were IgM positive. IgM may inhibit binding of IgG to the antigen by competition. The ELISA showed a greater discrimination between titre-values compared to the CFT. The results are presented as "estimated titers". This method is based on linear logarithmic dose-response curves. The method gives a continuous titre scale, is easily understood, is reproducible and may be used in seroepidemiology. One single serum dilution is required except for sera with high titre which have to be retested at a higher dilution.

[Toxoplasmosis and pregnancy]. / Toksoplasmose og graviditet.

The ongoing national project for prevention of congenital toxoplasmosis has created a need for general information on both toxoplasmosis in relation to pregnancy and on congenital toxoplasmosis. This paper presents an up-to-date survey of these facts. It briefly describes the clinical picture and what can happen to the foetus after primary maternal infection. Special emphasis is placed on diagnosis, and recommendations are made for the treatment of infected mothers and babies. Prevention of congenital toxoplasmosis is discussed from both an individual point of view and in a social perspective.

Comparison of two syphilis antibody assays based on cardiolipin antigen.

Two different antisyphilis screening tests based on cardiolipin antigen, the VDRL test and an RPR test (Sysmic, Diagast), were compared. A total of 2155 sera were examined by both tests. Positive results were confirmed with TPHA and TPI tests. RPR Sysmic test was as sensitive and specific as the VDRL. However, the RPR Sysmic test was easier and quicker, especially when the number of sera tested was high.

Development of specific immunoglobulins G, M, and A following primary Toxoplasma gondii infection in pregnant women.

The development of specific antibodies following primary Toxoplasma gondii infection during pregnancy was assessed by six different antibody assays: dye test, Platelia Toxo-IgG, Toxo-Screen DA IgG, Platelia Toxo-IgM, Toxo-ISAGA IgM, and Platelia Toxo-IgA. A total of 126 sera from 27 pregnant women, for whom the time of acquisition of infection could be estimated fairly accurately, were included. All tests showed great individual variation in the peak amounts of antibodies detected. The times elapsed after infection until the peak was reached also varied greatly from individual to individual: the ranges were 2 to 21 weeks for the dye test, 4 to 36 weeks for Platelia Toxo-IgG, 4 to 30 weeks for Toxo-Screen DA IgG, 2 to 18 weeks for Platelia Toxo-IgM, 1 to 6 weeks for Toxo-ISAGA IgM, and 2 to 21 weeks for Platelia Toxo-IgA. In the early phase of the infection the dye test and the specific-IgM tests were the most sensitive. Toxo-Screen DA IgG was more sensitive than Platelia Toxo-IgG in the acute phase, while Platelia Toxo-IgA was clearly the least sensitive assay. Of the sera collected 21 to 52 weeks after infection, all were positive by the dye test, all except one (which was negative by Platelia Toxo-IgG) were positive by the specific-IgG tests, approximately 80% were positive by the IgM tests, and 45% were positive by the IgA test. Due to the great individual variation it seems impossible to estimate when the infection occurred based on results obtained from a single serum, and it may even be difficult to assess when a titer increase in paired sera is detectable unless the first sample is only marginally positive. As a diagnostic criterion a dye test titer of >/=300 IU/ml has a low sensitivity for recent primary infection.

[Lyme borreliosis]. / Lyme-borreliose.

In Norway, physicians and patients alike are becoming increasingly aware of Lyme borreliosis. This fact has created a need for information on different aspects of this disease. This paper reviews the historical background for Lyme borreliosis and the epidemiological situation in Norway, based on data collected by the national system for notification of infectious diseases (MSIS) in 1993. The role of the tick vector and the overall clinical picture is presented briefly. The authors discuss indications for and possibilities of different microbiological diagnostic methods, and finally list the recommendations for treatment and prophylaxis.

Improved diagnosis of primary Toxoplasma gondii infection in early pregnancy by determination of antitoxoplasma immunoglobulin G avidity.

The ability to discriminate between primary Toxoplasma gondii infection acquired in early pregnancy and infection that occurred prior to pregnancy was assessed by an enzyme immunoassay (EIA) to determine the avidity of toxoplasma-specific immunoglobulin G (IgG). The results were compared to those of the Platelia Toxo-IgM EIA and the dye test. The mean IgG avidity of 73 serum samples collected within 20 weeks after the estimated time of infection was 5.9%. Among 26 serum samples showing latent infection (toxoplasma-specific IgG positive and IgM negative) and 56 IgM-positive serum samples with a low dye test titer (<300 IU/ml), the mean avidities were 51.3 and 57.5%, respectively. A total of 72.8% of 92 IgM-positive serum samples with a high dye test titer (>300 IU/ml), suggesting a recent toxoplasma infection, had an IgG avidity of >20%, indicating that the infection started more than 20 weeks earlier. By introducing high IgG avidity as a criterion in the first half of pregnancy to exclude the possibility that toxoplasma infection was acquired during gestation, many women will avoid unnecessary examinations, treatment, and anxiety.

[Antibodies against Herpes simplex virus type 2 among pregnant women in Norway]. / Herpes simplex-virus type 2-antistoffer hos gravide i Norge.

The prevalence of antibodies against herpes simplex virus type 2 (anti-HSV-2) among pregnant women in Norway is not known. To study the prevalence of anti-HSV-2, a random sample of 961 women was drawn from a study population of 35,940 pregnant women in Norway during 1992-94. 27% (256/961) had anti-HSV-2. The prevalence increased with age. 17% of the 20-24-year-olds and 34% of the 35 year-old or older had anti-HSV-2. The presence of antibodies also varied geographically, from 18% in the south to 39% in the north of Norway. Among women with repeated anti-HSV-2 tests during pregnancy, 2.6% of the seronegative women seroconverted (16/623). HSV-2 infection is common among pregnant women in Norway. The public health implications of this infection need to be clarified.

Herpes simplex virus type-2 antibodies in pregnant women: the impact of the stage of pregnancy.

In this study the impact of pregnancy duration on the measured level of HSV-2 antibodies was assessed. The study population comprised 35,940 pregnant women in Norway, in 1992-4, followed during pregnancy. A random sample of 960 women was selected. A mean of 2.6 serum samples from each woman were analysed for HSV-2 specific IgG antibodies at different times in pregnancy. Crude and adjusted odds ratios were estimated in logistic regression models taking all observations per women into account. Twenty-seven percent of the pregnant women had antibodies against HSV-2 in the first trimester. The adjusted odds ratio of being HSV-2 antibody positive decreased during the pregnancy and was 0.5 (0.2-0.9, 95% confidence interval) in the 40th as compared to the 10th week of pregnancy. About 50% of initially HSV-2 positive women did not have detecable antibodies by the end of the pregnancy. This may be explained by haemodilution during pregnancy. Our findings have diagnostic implications and should encourage further studies.

Prenatal diagnosis of tracheal obstruction: possible association with maternal pertussis infection.

A fetus with the sonographic appearance of echogenic and enlarged lungs and dilated trachea and bronchi, indicating laryngotracheal obstruction, is reported. Additionally, the fetus had ascites and subcutaneous edema and the amniotic fluid volume was reduced. Doppler flow investigation of the systemic venous circulation revealed signs of heart failure, and color Doppler visualized possible increased pulmonary flow. Following termination of pregnancy, autopsy confirmed the sonographic observations and revealed a hypoplastic thymus. During the present pregnancy the mother suffered from sustained cough, and serological tests revealed acute pertussis infection. Polymerase chain reaction investigation for Bordetella pertussis in the amniotic fluid was negative. The possibilities of pertussis toxins as noxious factors and of an atypical presentation of DiGeorge anomaly are discussed.

Is preeclampsia an infectious disease?

BACKGROUND: Studies have suggested a strong paternal factor in the etiology of preeclampsia. If preeclampsia is caused by an infectious agent transmitted by the woman's partner, seronegative women who may experience primary infection in pregnancy should be at increased risk of preeclampsia as compared to previously infected women. The aim of this study was to assess the impact of being seronegative for some viruses transmitted by close contact on the risk of developing preeclampsia. METHODS: Nine hundred and seventy-eight women were randomly drawn from a basic study population of 35,940 pregnant women in Norway. A serum sample drawn at the first antenatal visit was analyzed for specific IgG antibodies against herpes simplex virus type-2, cytomegalovirus and Epstein-Barr virus. For comparison, antibody status against Toxoplasma gondii was also assessed. Information on preeclampsia in pregnancy was obtained through linkage to the Medical Birth Registry of Norway. RESULTS: Thirty-three (3%) women developed preeclampsia. The risk of developing preeclampsia seemed to be increased for women who were seronegative for the viruses studied. Seronegativity for Toxoplasma gondii did not show such a pattern. INTERPRETATION: Women who are seronegative for antibodies against viral agents transmitted through close contact seem more likely to develop preeclampsia. This finding indicates that women who are seronegative to such agents may acquire primary infection in pregnancy, and subsequently be at increased risk of preeclampsia. This hypothesis could represent a new approach to the causes of preeclampsia, and encourage search for yet unidentified microbes as a possible causal factor.