Effect of rotavirus vaccine implementation on the prevalence of coinfections with enteric viruses in Norway.

Acute gastroenteritis (AGE) is a common illness in both adults and children worldwide and is caused by several microorganisms including viruses, bacteria, and parasites. Rotavirus (RV), which is the main cause of AGE, can occur as a mixed infection with other viruses. The aim of this study is to assess the molecular epidemiology of viral enteric viruses and assess RV coinfections with other enteric viruses and their influence on disease severity before and after RV vaccine introduction in children under 5 years of age. A total of 600 samples collected from children hospitalized for AGE in five large hospitals in Norway, and were analyzed for viral gastroenteritis agents by enzyme immunoassay and quantitative real-time polymerase chain reaction (qRT-PCR). Positive results confirmed either by Sanger sequencing or genotyped by multiplex semi-nested RT-PCR. In total, 243 of the 300 (81%) samples, collected from the prevaccine cohort, were positive for at least one of the four viruses tested in this study. RV was most frequently identified in 82.6% of the samples. In the postvaccine cohort, 114 of the 300 (38%) samples were positive for at least one of the viruses tested. RV found in 36.5% of the samples. Coinfections found less frequently in the postvaccine cohort. Among circulating enteric viruses in Norway, RV is the most important cause of viral gastrointestinal infection. As expected, there were fewer RV positive and fewer coinfections after RV vaccine implementation. The results provide valuable data that can aid in further evaluation of the vaccine impact.

Parvovirus B19 DNAemia in pregnant women in relation to perinatal death: A nested case-control study within a large population-based pregnancy cohort.

INTRODUCTION: Parvovirus B19 (B19V) is the infectious cause of exanthema infectiosum. In Europe around 40% of pregnant women are susceptible to infection. Having small children at home is the main risk factor for contracting an infection during pregnancy. The association between B19V-infection and perinatal death is not yet settled. The aims of the study were to estimate the association between maternal parvovirus B19 infection in pregnancy and perinatal death, and to assess the significance of a positive B19V PCR in pregnancy. MATERIAL AND METHODS: The study population consists of women included in the Norwegian Mother and Child Cohort Study, a prospective population-based pregnancy cohort of nearly 100 000 women. Blood samples were obtained during weeks 17-18 in pregnancy (M1), at birth, and in umbilical cord blood. Within participants in the pregnancy cohort, 138 cases of perinatal death and 1350 controls with live-born children were included in a nested case-control study. Samples were analyzed with B19V serology and B19V PCR according to a predefined test algorithm. For cases, medical records and laboratory results from hospitals were combined with the results of B19V serology and PCR. The reported causes of perinatal death were categorized using the classification system: Causes Of Death and Associated Conditions (CODAC). RESULTS: The B19V seroconversion rates were 9.8% for cases and 6.8% for control mothers. The odds ratio for maternal B19V infection in cases compared with controls was 1.28 (95% CI 0.35-4.70), adjusted for age, parity, body mass index and tobacco use. B19V-PCR-positive samples were detected at weeks 17-18 of gestation in both cases and controls. The proportion of positive samples was similar in cases and controls, 24% and 28.2%, respectively. Mothers with PCR-positive M1 samples transmitted B19V vertically in 9.1% of cases and in 11.9% of the controls. Of all perinatal deaths, 53% were attributed to placental pathology or unknown causes. CONCLUSIONS: B19V PCR positivity was high and similar in both cases and controls. In our study B19V DNAemia was not seen to be associated with fatal outcome of pregnancy. The clinical significance of B19V DNA detection during pregnancy is uncertain. Caution is needed when diagnosing a B19V infection based only on B19V DNAemia.

Modified vaccinia virus Ankara encoding influenza virus hemagglutinin induces heterosubtypic immunity in macaques.

UNLABELLED: Current influenza virus vaccines primarily aim to induce neutralizing antibodies (NAbs). Modified vaccinia virus Ankara (MVA) is a safe and well-characterized vector for inducing both antibody and cellular immunity. We evaluated the immunogenicity and protective efficacy of MVA encoding influenza virus hemagglutinin (HA) and/or nucleoprotein (NP) in cynomolgus macaques. Animals were given 2 doses of MVA-based vaccines 4 weeks apart and were challenged with a 2009 pandemic H1N1 isolate (H1N1pdm) 8 weeks after the last vaccination. MVA-based vaccines encoding HA induced potent serum antibody responses against homologous H1 or H5 HAs but did not stimulate strong T cell responses prior to challenge. However, animals that received MVA encoding influenza virus HA and/or NP had high frequencies of virus-specific CD4(+) and CD8(+) T cell responses within the first 7 days of H1N1pdm infection, while animals vaccinated with MVA encoding irrelevant antigens did not. We detected little or no H1N1pdm replication in animals that received vaccines encoding H1 (homologous) HA, while a vaccine encoding NP from an H5N1 isolate afforded no protection. Surprisingly, H1N1pdm viral shedding was reduced in animals vaccinated with MVA encoding HA and NP from an H5N1 isolate. This reduced shedding was associated with cross-reactive antibodies capable of mediating antibody-dependent cellular cytotoxicity (ADCC) effector functions. Our results suggest that ADCC plays a role in cross-protective immunity against influenza. Vaccines optimized to stimulate cross-reactive antibodies with ADCC function may provide an important measure of protection against emerging influenza viruses when NAbs are ineffective. IMPORTANCE: Current influenza vaccines are designed to elicit neutralizing antibodies (NAbs). Vaccine-induced NAbs typically are effective but highly specific for particular virus strains. Consequently, current vaccines are poorly suited for preventing the spread of newly emerging pandemic viruses. Therefore, we evaluated a vaccine strategy designed to induce both antibody and T cell responses, which may provide more broadly cross-protective immunity against influenza. Here, we show in a translational primate model that vaccination with a modified vaccinia virus Ankara encoding hemagglutinin from a heterosubtypic H5N1 virus was associated with reduced shedding of a pandemic H1N1 virus challenge, while vaccination with MVA encoding nucleoprotein, an internal viral protein, was not. Unexpectedly, this reduced shedding was associated with nonneutralizing antibodies that bound H1 hemagglutinin and activated natural killer cells. Therefore, antibody-dependent cellular cytotoxicity (ADCC) may play a role in cross-protective immunity to influenza virus. Vaccines that stimulate ADCC antibodies may enhance protection against pandemic influenza virus.

Susceptibility to cytomegalovirus, parvovirus B19 and age-dependent differences in levels of rubella antibodies among pregnant women.

Infections caused by cytomegalovirus (CMV), parvovirus B19 (B19), and rubella can lead to serious complications in pregnant women. The aim of this study was to determine the susceptibility to CMV, B19, and rubella antibodies in pregnant women in Norway. Consecutive sera samples were collected from pregnant women in two different regions in Norway. Sera were collected from age groups; ≤19, 20-24, 25-29, 30-34, 35-39, and ≥40 years old. Of the 2,000 pregnant women tested, anti-CMV IgG was positive in 62.8% anti-parvovirus B19 IgG in 59.7% and anti-rubella IgG in 94.4%. CMV IgG susceptibility has decreased in pregnant women less than 30 years of age, from 60% in a study conducted in 1973-1974 to 37.2% in present study. There was a significant difference in CMV IgG seropositivity rate between the two regions (58.6% and 67.1%). Serum levels of rubella IgG was lowest in age group 25-29 years with a positivity rate of 91.0%. Women born before vaccination with two doses of MMR started, had both a higher positivity rate and significantly higher levels of rubella antibody titre, 96.1% and 82.2 IU/ml compared to those born after 92.9% and 41.7 IU/ml. Significantly lower anti-rubella IgG titre found in the youngest age groups highlights the need for continued antenatal screening. A considerable increase in anti-CMV-IgG seropositivity rate was observed and might be associated with higher rate of breastfeeding and a higher percentage attending day-care centres.

Detection of specific IgG antibodies in blood donors and tick-borne encephalitis virus in ticks within a non-endemic area in southeast Norway.

BACKGROUND: Tick-borne encephalitis (TBE) is an emerging tick-borne disease in Europe. In Norway, the first TBE case occurred in 1997, and since then 1-14 cases have been detected annually along the southern coast. No TBE cases have yet been notified from the eastern coastal area. This study was conducted to assess the need for diagnostic tests and vaccine recommendation for this part of Norway. METHODS: Four hundred and sixty-one blood donors living in the county of Østfold were enrolled. After informed consent was obtained, the participants submitted a blood sample and filled out a questionnaire regarding tick bites, outdoor activities, and Flavivirus vaccines and diseases. Ixodes ricinus ticks were collected from the immediate vicinity and were examined in pools of 10 for TBE virus. RESULTS: Eight human samples were TBE virus IgG-positive by ELISA and 5 of these samples were confirmed positive by neutralization test. Excluding the 2 samples from participants who had reported previous TBE vaccination, this shows a seroprevalence among blood donors of 0.65%. The existence of TBEV in the region was verified in nymphs of Ixodes ricinus by a prevalence of 0.14%. CONCLUSIONS: The seroprevalence of TBE virus IgG and the TBE virus detected in ticks, indicate that TBE cases could occasionally occur in the area. The results should be made available to health care personnel to raise awareness for preventative measures.

Characterization in vitro and in vivo of pandemic (H1N1) 2009 influenza viruses isolated from patients.

The first influenza pandemic of the 21st century was caused by novel H1N1 viruses that emerged in early 2009. Molecular evolutionary analyses of the 2009 pandemic influenza A H1N1 [A(H1N1)pdm09] virus revealed two major clusters, cluster I and cluster II. Although the pathogenicity of viruses belonging to cluster I, which became extinct by the end of 2009, has been examined in a nonhuman primate model, the pathogenic potential of viruses belonging to cluster II, which has spread more widely in the world, has not been studied in this animal model. Here, we characterized two Norwegian isolates belonging to cluster II, namely, A/Norway/3568/2009 (Norway3568) and A/Norway/3487-2/2009 (Norway3487), which caused distinct clinical symptoms, despite their genetic similarity. We observed more efficient replication in cultured cells and delayed virus clearance from ferret respiratory organs for Norway3487 virus, which was isolated from a severe case, compared with the efficiency of replication and time of clearance of Norway3568 virus, which was isolated from a mild case. Moreover, Norway3487 virus to some extent caused more severe lung damage in nonhuman primates than did Norway3568 virus. Our data suggest that the distinct replicative and pathogenic potentials of these two viruses may result from differences in their biological properties (e.g., the receptor-binding specificity of hemagglutinin and viral polymerase activity).

Avian-type receptor-binding ability can increase influenza virus pathogenicity in macaques.

The first influenza pandemic of the 21st century was caused by novel H1N1 viruses that emerged in early 2009. An Asp-to-Gly change at position 222 of the receptor-binding protein hemagglutinin (HA) correlates with more-severe infections in humans. The amino acid at position 222 of HA contributes to receptor-binding specificity with Asp (typically found in human influenza viruses) and Gly (typically found in avian and classic H1N1 swine influenza viruses), conferring binding to human- and avian-type receptors, respectively. Here, we asked whether binding to avian-type receptors enhances influenza virus pathogenicity. We tested two 2009 pandemic H1N1 viruses possessing HA-222G (isolated from severe cases) and two viruses that possessed HA-222D. In glycan arrays, viruses possessing HA-222D preferentially bound to human-type receptors, while those encoding HA-222G bound to both avian- and human-type receptors. This difference in receptor binding correlated with efficient infection of viruses possessing HA-222G, compared to those possessing HA-222D, in human lung tissue, including alveolar type II pneumocytes, which express avian-type receptors. In a nonhuman primate model, infection with one of the viruses possessing HA-222G caused lung damage more severe than did infection with a virus encoding HA-222D, although these pathological differences were not observed for the other virus pair with either HA-222G or HA-222D. These data demonstrate that the acquisition of avian-type receptor-binding specificity may result in more-efficient infection of human alveolar type II pneumocytes and thus more-severe lung damage. Collectively, these findings suggest a new mechanism by which influenza viruses may become more pathogenic in mammals, including humans.

Maternal cytomegalovirus infection and delayed language development in children at 3 years of age-a nested case-control study in a large population-based pregnancy cohort.

INTRODUCTION: Maternal cytomegalovirus (CMV) infection in pregnancy may result in vertical transmission of CMV to the child. Long-term effects of congenital CMV infection include visual, cognitive as well as neurological impairment. The aim of this study was to estimate the odds ratios for CMV seropositivity and seroconversion in mothers, with and without delayed language development in 3 year old children, nested within a large cohort. MATERIAL AND METHODS: The Norwegian Mother, Father and Child Cohort Study (MoBa) is a prospective population-based pregnancy cohort that includes 95 200 mothers and 114 500 children. Blood samples were obtained from mothers during pregnancy weeks 17 or 18 in pregnancy and after birth. We included 300 women from MoBa with children suffering from delayed language development at three years of age, based on validated questionnaires. Within the cohort, 1350 randomly selected women were included as controls to perform a nested case-control study. The cases and controls were tested for CMV IgG antibodies by an enzyme-linked immunosorbent assay. RESULTS: Among mothers of cases, 63.2% were CMV-IgG positive in the sample at birth, as compared to 55.9% among controls; OR 1.36, (95% CI; 1.05 to 1.76). Also, among case mothers, 8/118 (6.8%) initially seronegative cases, seroconverted. Among initially seronegative controls, seroconversion occurred in 23/618 (3.7%) mothers. The OR for seroconversion in cases as compared to control mothers was 1.88 (CI; 0.82 to 4.31), thus not statistically significant different. CONCLUSION: This study shows a higher risk of delayed language development at three years of age in children born by mothers seropositive for CMV, compared to children born from seronegative mothers.

Sales of oseltamivir in Norway prior to the emergence of oseltamivir resistant influenza A(H1N1) viruses in 2007-08.

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.

Maternal and congenital cytomegalovirus infections in a population-based pregnancy cohort study.

CMV is the most common cause of congenital infection. During the past few decades, there has been a change in behaviour that possibly has affected the CMV infection rate of mother and child. We investigated 1350 randomly selected pregnant women from the Norwegian Mother and Child Cohort Study using an algorithm for detection of maternal and congenital CMV (cCMV) infection including both serology and nucleic acid amplification assay. The CMV IgG seroprevalence was 54% and 23 (3.7%) mothers seroconverted. Three (0.22%) children had a positive CMV PCR in the umbilical cord blood. The transmission rate was lower than reported in previous studies, probably due to lower sensitivity in plasma compared to saliva and urine. The prevalence of cCMV in the present study was compared with the number registered with the ICD-10 code P.35.1-congenital CMV infection in the Norwegian Patient Register. The number registered was lower than the number of estimated infections. Factors like lower level of education and parity were associated with higher CMV IgG seroprevalence, but no significant difference could be linked to age. In conclusion, in this cohort of pregnant women, a high CMV IgG seroconversion rate was found, while the vertical transmission rate was low.

Response to third rubella vaccine dose.

Limited data exist on the immunogenicity of a third dose of the measles, mumps, and rubella vaccine (MMR). In this study, our aim was to evaluate the long-term rubella immunogenicity afforded by two childhood MMR doses of the Norwegian vaccination program in a cohort of conscripts and to determine the effect of an additional dose of MMR vaccine, in order to inform vaccination policy. Blood samples from Norwegian conscripts (n = 495) taken both before and eight months after administration of a dose of MMR vaccine were tested using an enzyme immunoassay to measure anti-rubella IgG. Concentrations <5 IU/mL were regarded as negative, 5.0-9.9 IU/mL as equivocal, and ≥10 IU/mL as positive. Overall, the seropositivity before vaccination was 84.6%, and 99.0% of the conscripts had anti-rubella IgG concentrations ≥5 IU/mL. The seropositivity after vaccination was 94.5%, and 99.8% of the conscripts had antibody concentrations ≥5 IU/mL. The geometrical mean IgG concentrations increased from 21.4 IU/mL before vaccination to 28.9 IU/mL after. Four out of five conscripts, with seronegative concentrations before administrations of an additional MMR dose, had equivocal or seropositive results following vaccination. The cohort of young adults in Norway, which was eligible for two childhood MMR doses, was protected against rubella, and efforts should be made to maintain high vaccine coverage to ensure immunity in the future. A third dose of MMR administered in early adulthood led to an increase in the antibody concentration in our cohort and seroconversion for the majority of seronegative persons.

High incidence of maternal parvovirus B19 infection in a large unselected population-based pregnancy cohort in Norway.

BACKGROUND: Around 40% of pregnant women in Norway are parvovirus B19 (B19V) seronegative and thus at risk for B19 V infection. Studies on samples from women with symptomatic disease or known exposure have shown that nucleic acid amplification assays combined with serology increase the sensitivity and improves the diagnostic procedure. OBJECTIVES: The aim was to investigate the seroprevalence of B19V infection, the occurrence of new infections and vertical transmission in a population-based pregnancy cohort, with special emphasis on the diagnostic methods. STUDY DESIGN: We randomly selected 1350 pregnant women from the Norwegian Mother and Child Cohort Study (MoBa), using an algorithm for the detection of B19V infection, including both serology and PCR. RESULTS: Maternal infection was confirmed in 50 subjects (3.7% of 1349 women), of which 35(70%) were viremic. Of the initially seronegative 33(6.8%) seroconverted. The estimated average annual seroconversion rate was 15.5%, with the highest estimated annual seroconversion rate of 31.6%. The rates of yearly seroconversion followed the pattern found in reports from Norwegian microbiology laboratories. Among all women, 31 (2.3%) had an inconclusive serological profile and 17 (54.8%) had detectable virus. Of the 16 women with virus detectable at gestational week 17-18, seven were still seronegative with absent seroconversion in the second sample taken at birth. All together 10 children were vertically infected. CONCLUSIONS: High incidence of viremic B19V infections and high estimated annual seroconversion rates were found. Lack of seroconversion despite longstanding viremia emphasizes the importance of including PCR when testing for B19V infection during pregnancy.

Circulation and diagnostics of Puumala virus in Norway: nephropatia epidemica incidence and rodent population dynamics.

Hantaviruses pose a public health concern worldwide causing haemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). Puumala virus (PUUV) is the most prevalent hantavirus in Central and Northern Europe, and causes a mild form of HFRS, also known as nephropathia epidemica (NE). In nature, the main host of PUUV is the bank vole (Myodes glareolus), and transmission to humans occurs through inhalation of aerosols from rodent excreta. Nephropathia epidemica is particularly prevalent in Nordic countries, however, few studies of PUUV have been performed in Norway. The aim of this study was to analyse the dynamics of PUUV in Norway and compare with bank vole population dynamics, and also to complement the current diagnostic methodology of NE in Norway. Our results showed a significant seasonal and geographical variation of NE, and a general parallel peak trend between bank vole population densities and human NE incidence. A real-time and a nested PCR were successfully established as an invaluable diagnostic tool, with detection and sequencing of PUUV in a human serum sample for the first time in Norway. Phylogenetic analysis showed clustering of the obtained human sample with previous Norwegian bank vole isolates.

[HIV/AIDS--from lethal syndrome to chronic disease]. / Fra dødelig syndrom til kronisk sykdom.

BACKGROUND: At its discovery in 1981, AIDS was a fatal syndrome that rapidly led to death. Combination treatment with at least three drugs has radically improved the prognosis. MATERIAL AND METHODS: The study includes all HIV-patients controlled at the Department of Infectious Diseases, Ullevål University Hospital from 1982 to 2005. Development of immune deficiency, morbidity and causes of death were registered prospectively. Possible connections between death and HIV-infection and treatment were evaluated. RESULTS: 1632 patients were followed at our department. 32 % of these patients have died. The number of patients who died annually during the 5 years from 1986 to 1990 was 47 % and this was reduced to 11 % in 2001 - 05. Many patients still die because they either present too late for treatment or have received insufficient treatment. 22 patients have died during the last 10 years irrespective of starting treatment with at least 3 antiretroviral drugs: 7 died from cancers, 6 from treatment failure, one from unknown cause and 8 from other causes. The 6 patients who died from treatment failure had very low CD4 counts and serious opportunistic infections that could not be treated effectively at the time of diagnosis. INTERPRETATION: Patients who start and adhere to treatment with 3 HIV-medications have a good prognosis, but they may still have an increased risk of non-AIDS defining cancers and cardiovascular disease. HIV/AIDS has become a chronic disease with a good prognosis.

Seroprevalence of antibodies to tick-borne encephalitis virus and Anaplasma phagocytophilum in healthy adults from western Norway.

The aim of this study was to assess the seroprevalence of antibodies to tick-borne encephalitis virus (TBEV) and Anaplasma phagocytophilum in a healthy adult population from Sogn and Fjordane county in western Norway. Sera from 1, 213 blood donors were analysed for IgG-antibodies to TBEV, and a random subgroup of 301 donors for IgG to A. phagocytophilum. In the TBEV ELISA, five (0.4%) sera were positive. These were all interpreted as "false" positives, as four had received vaccines against flaviviruses, and the remaining was negative for neutralizing antibodies to TBEV. Antibodies to A. phagocytophilum were detected by indirect immunofluorescence in 49 (16.2%) subjects (titer range 80-1280). The results indicate that TBE currently is not endemic in this part of western Norway. However, there is serological evidence of the existence of human granulocytic anaplasmosis in the population.

High frequency of enterovirus D68 in children hospitalised with respiratory illness in Norway, autumn 2014.

OBJECTIVES: An unexpectedly high proportion of children were admitted for severe respiratory infections at the Oslo University Hospital, Ullevål, Norway, during September and October, 2014. In light of the ongoing outbreak of enterovirus-D68 (EV-D68) in North America a real-time RT-PCR for screening of enterovirus and enterovirus D68 was established. DESIGN: We developed a duplex real-time RT-PCR for rapid screening of enterovirus D68. The method target the 5' non-translated region (NTR) of the HEV genome at a location generally used for enterovirus detection. SAMPLE: Nasopharyngeal samples (n = 354), from children <15 years of age, received for respiratory virus analysis in OUH during September 1st and October 31nd, 2014, were tested for enterovirus and screened for enterovirus D68. MAIN OUTCOME MEASURES AND RESULTS: The duplex real-time RT-PCR method was an efficient tool for rapid screening for EV-D68 in respiratory specimens. Enterovirus was detected in 66 (22%) of 303 pediatric nasopharyngeal samples collected from children hospitalised with acute respiratory infection within the two-month period. Out of these, 33 (50%) were EV-D68. EV-D68 was associated with acute flaccid paralysis in one child. CONCLUSIONS: An unexpectedly high proportion of children admitted for severe respiratory infections at the Oslo University Hospital, Ullevål, Norway, were diagnosed with EV- D68 during September 1st and October 31nd, 2014. These results emphasise that greater vigilance is required throughout Europe as enteroviruses are cause of severe respiratory disease.

Toxoplasma prevalence among pregnant women in Norway: a cross-sectional study.

Infection by Toxoplasma gondii may lead to complications in the foetus if the mother suffers from primary infection during pregnancy. Previously infected women have produced toxoplasma-specific IgG antibodies. The most recent study on prevalence of toxoplasma IgG in the Norwegian pregnant population was conducted 20 years ago. The present study is part of a research programme initiated by the Norwegian Institute of Public Health. We aimed to update the knowledge regarding the prevalence of toxoplasma IgG among pregnant women in Norway. In this cross-sectional study, sera from 1922 pregnant women in Buskerud (992) and Sør-Trøndelag counties (930) in Norway were collected consecutively. The presence of toxoplasma IgG was identified by values ≥8 IU/mL using an ELISA test. The overall prevalence of toxoplasma IgG seropositivity was 9.3% (95% CI 8.1-10.7); Sør-Trøndelag 10.4% (95% CI 8.6-12.6) and Buskerud 8.3% (95% CI 6.7-10.2). There was no difference between the counties (p = 0.13), and the result did not differ from prevalences found in 1974 (12.1%) and 1994 (10.7%). We found a higher prevalence among women ≥40 years (OR 2.65, 95% CI 1.30-5.42). The prevalence of toxoplasma IgG among pregnant women in Norway is low and has been stable during the last decades.

Prevalence of tick-borne encephalitis virus in Ixodes ricinus ticks from three islands in north-western Norway.

Tick-borne encephalitis (TBE) is the most important viral tick-borne disease in Europe and can cause severe disease in humans. In Norway, human cases have been reported only from the southern coast. The aim of this study was to investigate the prevalence of tick-borne encephalitis virus (TBEV) in questing Ixodes ricinus ticks from the north-western part of Norway. A total of 4509 ticks were collected by flagging in May and June 2014. A subpopulation of 2220 nymphs and 162 adult ticks were analysed by real-time PCR and positive samples were confirmed by pyrosequencing. The estimated prevalence of TBEV was 3.08% among adult ticks from Sekken in Møre og Romsdal County and 0.41% among nymphs from both Hitra and Frøya in Sør-Trøndelag County. This study indicates that TBEV might be more widespread than the distribution of reported human cases suggests.

Tick-borne encephalitis virus and louping-ill virus may co-circulate in Southern Norway.

The European subtype of tick-borne encephalitis virus (TBEV-Eu) and louping-ill virus (LIV) are two closely related tick-borne flaviviruses. However, whereas the first is the cause of one of Europe's most important zoonoses, the latter most often only causes disease in sheep and grouse. TBEV-Eu is typically found in the forests of central and northeastern Europe, and LIV typically is found in sheep pastures in the British Isles. In the 1980s, however, LIV was isolated from sheep with encephalomyelitis in Norway. In the 1990s, the first cases of human TBEV were also detected in this country, but while Louping-ill in sheep is very rare, the number of human TBEV cases is increasing. No larger investigations of TBEV and/or LIV seroprevalence and distribution in Norway have been published. However, before such studies are initiated, it is pertinent to know if LIV and TBEV are potentially co-circulating. In the current study, we examined if antibodies against LIV and TBEV were found in wild cervids in one location (Farsund) in southern and one location (Molde) in northwestern Norway using a commercially available enzyme-linked immunosorbent assay for detection of anti-TBEV immunoglobulin G (IgG) and a hemagglutination inhibition test for anti-LIV IgG. Positive results were confirmed by serum neutralization tests. In Farsund, 22 of 54 cervids had antibodies against TBEV and 8 antibodies against LIV. In Molde, 1 of 64 cervids was confirmed positive for TBEV, whereas none were positive for LIV. This shows that TBEV and LIV may co-circulate in southern Norway and that virus(es) antigenetically very similar to TBEV may be found in northwestern Norway. The latter is intriguing, because the climatic conditions typical of TBEV locations should not be expected this far north.

HIV related and non-HIV related mortality before and after the introduction of highly active antiretroviral therapy (HAART) in Norway compared to the general population.

The objective of the study was to compare the mortality in HIV infected individuals to the general population, and to explore the relative contribution of HIV to mortality before and after the introduction of highly active antiretroviral therapy (HAART). All HIV patients attending Ullevål University Hospital, Oslo, Norway before (cohort 1) and after (cohort 2) the introduction of HAART were included. Causes of deaths were classified as HIV related or not. Mortality in the Norwegian general population was standardized according to the distribution of age and gender in our cohorts. Ratios between mortality in our cohorts and the standardized mortality were calculated. The risk ratio (RR) for 5-y mortality compared to the general population was 22.6 (95% confidence interval (CI), 19.5-26.4) in cohort 1 (n = 782), and 3.96 (95% CI 2.25-6.97) in cohort 2 (n = 398). The non-HIV related mortality RR was 4.42 (95% CI 3.18-6.13) in cohort1 and 0.89 (95% CI 0.29-2.76) in cohort 2. Higher age and low CD4 cell count were associated with increased mortality. Thus, in the HAART era the mortality in HIV patients was reduced by 80%. However, the mortality in the HAART era was still 4 times higher than in the general population.