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.

Case Report: Pure Red Cell Aplasia Caused by Refractory Parvovirus B19 Infection After Pancreas Transplantation Alone.

A multidisciplinary team of doctors is in charge or is involved in the follow-up of patients who undergo solid organ transplantation (SOT). Immunosuppressive drugs are required after SOT, some potential unwanted side effects can be difficult to detect, and physicians must be aware of potential pitfalls. We report a case of a recipient with brittle type 1 diabetes who experienced severe and refractory anemia after pancreas transplantation alone (PTA). Despite a broad diagnostic approach for anemia, the diagnosis was delayed. The patient had normocytic normochromic anemia with severe reticulocytopenia and marked reduction or absence of erythroid precursors in the bone marrow, compatible with pure red cell aplasia (PRCA). Analyses of serological parvovirus B19 anti-IgM and anti-IgG antibodies, including PCR, were initially inconclusive/negative. The diagnosis of parvovirus B19 infection was confirmed after bone marrow biopsy with immunohistochemical staining for parvovirus B19. A retrospective analysis revealed an early post-transplant primary parvovirus B19 infection. The patient was successfully treated with intravenous immunoglobulin (IVIg) therapy. There is a risk of diagnostic delay for the less common types of anemia following SOT. Parvovirus B19 infection-associated PRCA is curable in SOT recipients and should be actively considered in patients with persistent anemia and low reticulocytes.

Rapid SARS-CoV-2 variant monitoring using PCR confirmed by whole genome sequencing in a high-volume diagnostic laboratory.

OBJECTIVES: The emerging SARS-CoV-2 variants of concern (VoC), B.1.1.7, B.1.351 and P.1, with increased transmission and/or immune evasion, emphasise the need for broad and rapid variant monitoring. Our high-volume laboratory introduced a PCR variant assay (Variant PCR) in January 2021 based on the protocol by Vogels et al. STUDY DESIGN: To assess whether Variant PCR could be used for rapid B.1.1.7, B.1.351 and P.1 screening, all positive SARS-CoV-2 airway samples were prospectively tested in parallel using both the Variant PCR and whole genome sequencing (WGS). RESULTS: In total 1,642 SARS-CoV-2 positive samples from individual patients were tested within a time span of 4 weeks. For all samples with valid results from both Variant PCR and WGS, no VoC was missed by Variant PCR (totalling 399 VoC detected). Conversely, all of the samples identified as "other lineages" (i.e., "non-VoC lineages") by the Variant PCR, were confirmed by WGS. CONCLUSIONS: The Variant PCR based on the protocol by Vogels et al., is an effective method for rapid screening for VoC, applicable for most diagnostic laboratories within a pandemic setting. WGS is still required to confirm the identity of certain variants and for continuous surveillance of emerging VoC.

Diagnostic performance of a SARS-CoV-2 rapid antigen test in a large, Norwegian cohort.

BACKGROUND: Rapid antigen tests (RATs) may be included in national strategies for handling the SARS-CoV-2 pandemic, as they provide test results rapidly, are easily performed outside laboratories, and enable immediate contract tracing. However, before implementation further clinical evaluation of test sensitivity is warranted. OBJECTIVES: To examine the performance of Abbott's Panbio™ COVID-19 Ag Rapid Test Device for SARS-CoV-2 testing in a low to medium prevalence setting in Norway. STUDY DESIGN: A prospective study comparing the results of the Panbio RAT with PCR in 4857 parallel samples collected at a SARS-CoV-2 test station in Oslo, and from COVID-19 outbreaks in six Norwegian municipalities. RESULTS: A total of 4857 cases were included in the study; 3991 and 866 cases from the test station and the outbreak municipalities, respectively. The prevalence at the test station in Oslo was 6.3 %, and the overall sensitivity of the RAT was 74 %. Increased sensitivity was observed in patients who experienced symptoms (79 %) and when considering samples with viral loads above estimated level of infectivity (84 %), while it was lower in asymptomatic persons (55 %). In the outbreak municipalities, the overall prevalence was 6.9 %, and the total sensitivity of the RAT was 70 %. CONCLUSIONS: Our results indicate that the test correctly identified most infectious individuals. Nevertheless, the sensitivity is considerably lower than for PCR, and it is important that the limitations of the test are kept in mind in the follow-up of tested individuals.

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.

Immunity to varicella zoster virus among pregnant women in the Norwegian Mother and Child Cohort Study.

INTRODUCTION: Infection with varicella zoster virus (VZV) in pregnancy may lead to serious outcomes both for the mother and the newborn. Targeted screening and vaccination of non-immune women during reproductive age could prevent varicella infection in pregnancy. Currently, no universal varicella screening of pregnant women is implemented in Norway, but serological testing in pregnancy is recommended in particular situations. We examined seroprevalence of VZV in a national pregnancy cohort in order to help assess a need for VZV screening of women during reproductive age. METHODS: We determined the susceptibility to VZV and the reliability of self-reported history of VZV infection in the Norwegian obstetric population by using a random sample of 1,184 pregnant women from the Norwegian Mother and Child Cohort study (MoBa). The MoBa study included approximately 95,200 pregnant women in Norway between 1998 and 2009. Blood samples taken at gestational week 17-18 were analysed using a commercial enzyme immunoassay for specific IgG antibodies to Varicella-Zoster virus. Second sample taken at birth was tested if the first sample result was negative or equivocal. RESULTS: Of the 1,184 pregnant women, 98.6% (n = 1,167) were seropositive, 0.83% (n = 10) remained seronegative, and four women (0.34%) seroconverted during their pregnancy. No significant associations were found between serological status and women's age at birth, gestational age, women's country of birth and year of child's birth. One woman reported prior history of varicella, whereas 143 (12.1%) women reported a household exposure to childhood diseases with fever and rash, of which 25 reported exposure to varicella, of which all were seropositive. CONCLUSIONS: The findings support antenatal screening recommendations in Norway advising testing for VZV in pregnant women with unknown immunity to VZV. Further studies are however needed to better identify target groups for screening and vaccination.

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.

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.

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.

[Diagnosis of chronic hepatitis B infection]. / Diagnostikk av kronisk hepatitt B-infeksjon.

BACKGROUND: Infection with the hepatitis B virus can lead to chronic liver inflammation with the risk of developing cirrhosis and cancer of the liver. Increased knowledge and improved treatment of chronic hepatitis B infection in recent years mean that virological tests are increasingly used to ascertain the course of illness, status and response to treatment by the individual patient. The purpose is therefore to provide an updated overview of available diagnostics. METHOD: The article builds on a selection of original and review articles identified through a search in Medline, as well as experience of microbiological diagnostics from the national reference laboratory for the hepatitis virus in Norway. RESULTS: Detection of virus proteins and antibodies to these, as well as virus quantification and characterisation, form an important part of the assessment of hepatitis B infection, including confirmation of the chronic phase of the illness. INTERPRETATION: Proper diagnosis is based on a broad selection of different serological and virological markers. Genotype and certain mutations may affect the course of illness and the response to treatment. To prevent further transmission and offer effective treatment, it is important to identify chronic carriers, but also persons who have previously been infected with hepatitis B virus with risk of reactivation.