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.

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.

Molecular epidemiology of calicivirus infections in Norway.

The national reference laboratory for calicivirus diagnostics monitors the epidemiology of calicivirus infections in Norway. During winter 1998-1999, 406 fecal samples were received from patients with suspected calicivirus infection. Of these, 76 (19%) were calicivirus positive by a nested reverse transcription-polymerase chain reaction. A number of alternative PCR designs were employed to disclose false negatives, but none were found. One half of the PCR positive samples were sequenced in order to investigate whether various cases represented the same outbreak, and to what extent a single or multiple subtypes were responsible for the morbidity during this season. The sequence data revealed that the majority of cases represented a genotype related to the Lordsdale strain, whereas the remaining cases seemed more sporadic. Most often, samples from particular outbreaks were highly homogeneous. However, in a few cases, samples connected with the same outbreak proved to contain epidemiologically independent strains.

[Encephalitis after acute Epstein-Barr virus infection]. / Encefalitt etter akutt Epstein-Barr-virusinfeksjon.

BACKGROUND: Epstein-Barr virus (EBV) infection is known to cause severe neurological complications such as encephalitis. MATERIAL AND METHODS: We present the history of two men, aged 17 and 22, who developed encephalitis after acute primary EBV infection. One of them survived with cerebral complications, the other died. RESULTS: One of them had the classic presentation of infectious mononucleosis and EBV-specific findings in the cerebrospinal fluid. The other had neither signs of infectious mononucleosis nor specific findings in the cerebrospinal fluid such as EBV-PCR. Nevertheless, the clinical features of encephalitis were very similar. They were characterized by memory problems, personality changes, reduced consciousness, brainstem disorders and epileptic seizures. CT and MRI findings indicated involvement of basal ganglia and limbic structures. None of them responded to acyclovir. INTERPRETATION: We conclude that EBV infection can lead to severe cerebral complications without general symptoms of infectious mononucleosis and specific serologic findings in the cerebrospinal fluid.

No sequence variation in part of the hexon and the fibre genes of adenovirus 8 isolated from patients with conjunctivitis or epidemic keratoconjunctivitis (EKC) in Norway during 1989 to 1996.

BACKGROUND/AIMS: Several local epidemics of keratoconjunctivitis/conjunctivitis caused by adenovirus type 8 (Ad8) occurred in Norway from August 1995 to May 1996. A smaller epidemic occurred in 1992. The Ad8 hexon forms the surface of the virion and contains the hypervariable regions loop I(1) and loop I(2). The fibre mediates the primary contact with cells. Sequence variation in hexon and fibre genes might play an important role in the pathogenicity of adenoviruses. The aim of this study was to investigate the genetic variability at the hexon and fibre genes in 26 strains of Ad8 isolated from 1989 to 1996. METHODS: The genetic variability of 26 strains of Ad8 isolated from 1989 to 1996 was studied by sequencing part of the hexon and fibre genes. The Ad8 sequences were compared with each other and with two Ad8 strains from the EMBL database. In addition, 14 of the 26 isolates were subjected to restriction endonuclease analysis. RESULTS: No significant sequence variation was seen during the six year period. CONCLUSION: The Ad8 strains causing epidemics of keratoconjunctivitis/conjunctivitis in Norway are genetically stable.

Evaluation of 12 commercial tests for detection of Epstein-Barr virus-specific and heterophile antibodies.

Ten microbiological departments in Norway have participated in a multicenter evaluation of the following commercial tests for detection of Epstein-Barr virus (EBV)-specific and heterophile antibodies: CAPTIA Select viral capsid antigen (VCA)-M/G/EBNA (Centocor Inc.), Enzygnost anti-EBV/immunoglobulin M (IgM) and IgG (Dade Behring), Vironostika EBV VCA IgM/IgG/EBNA enzyme-linked immunosorbent assay (ELISA) (Organon Teknika), SEROFLUOR immunofluorescence assay and EBV Combi-Test (Institute Virion Ltd.), anti-EBV recombinant IgM- and IgG-early antigen/EBNA IgG ELISA (Biotest Diagnostics), EBV IgM/IgG/EBNA ELISA (Gull Laboratories), Paul-Bunnell-Davidsohn test (Sanofi Diagnostics Pasteur), Monosticon Dri-Dot (Organon Teknika), Avitex-IM (Omega Diagnostics Ltd.), Alexon Serascan infectious mononucleosis test (Alexon Biomedical Inc. ), Clearview IM (Unipath Ltd.), and Cards+/-OS Mono (Pacific Biotech, Inc.). The test panel included sera from patients with primary EBV infection, immunocompromised patients with recent cytomegalovirus infection, healthy persons (blood donors), and EBV-seronegative persons. Among the tests for EBV-specific antibodies the sensitivity was good, with only small differences between the different assays. However, there was a greater variation in specificity, which varied between 100% (Enzygnost) and 86% (Biotest). Tests for detection of heterophile antibodies based on purified or selected antigen (Avitex, Alexon, Clearview IM, and Cards+/-OS Mono) were more sensitive than the Paul-Bunnell-Davidsohn and Monosticon tests.

African tick-bite fever imported into Norway: presentation of 8 cases.

We report on 8 Norwegian travellers to Southern Africa with African tick-bite fever (ATBF), a recently described spotted fever group rickettsiosis. All patients had acute flu-like symptoms and developed I or multiple inoculation eschars. The patients were treated with either doxycycline or ciprofloxacin, and all recovered. The diagnosis of ATBF was confirmed by the detection of specific IgM antibodies to Rickettsia africae by microimmunofluoroscence in convalescent-phase serum samples.

Herpes simplex virus type 2 DNA detected in cerebrospinal fluid of 9 patients with Mollaret's meningitis.

We present clinical and virological data on 9 patients, 7 women and 2 men aged 31-56 years, with recurrent aseptic meningitis (Mollaret's meningitis). Polymerase chain reaction detected Herpes simplex virus type 2 DNA in cerebrospinal fluid samples from all patients collected during their latest attacks of meningitis. Six patients had no history of genital herpes. Only 1 patient was offered prophylactic antiviral treatment during the study period (45 months).

[Spotted fever imported into Norway in 1997]. / Flekkfeber importert til Norge i 1997.

Tick-borne rickettsioses are important zoonoses in many tropical and subtropical areas. There has recently been an increase in the number of reported cases among tourists returning to Scandinavia. In this article we present all five serologically confirmed cases of tick-borne rickettsioses imported into Norway in 1997. The patients were Norwegian tourists who had visited South Africa (three cases), Zimbabwe, and Italy. Four cases had typical eschar and three had maculopapular exanthema. The patients were treated with either doxycycline or ciprofloxacin. No complications were reported. The diagnosis of tick-borne rickettsiosis was confirmed by the detection of specific IgM antibodies to Rickettsia conorii using micro-immunofluorescence in serum samples.

Specific detection of Coxsackie viruses A by the polymerase chain reaction.

BACKGROUND: Most of the Coxsackie virus A strains are difficult to identify using traditional diagnostic methods such as virus isolation followed by neutralization with type-specific antisera. For the laboratory diagnoses of infections with Coxsackie viruses A, inoculation into newborn mice has traditional been the method of choice. However, such investigations are complicated and time-consuming. OBJECTIVES: To develop a reverse transcriptase (RT) and polymerase chain reaction (PCR) assay for specific detection of Coxsackie viruses A. STUDY DESIGN: A total of 43 clinical specimens containing Coxsackie viruses A, B or echoviruses were investigated retrospectively. Nineteen samples were Coxsackie virus A positive, whereas 24 samples were positive for Coxsackie viruses B or echoviruses. Thirteen non-typable specimens from eight patients were also included, since they were characterized as enterovirus-like by electron microscopy. RESULTS: All the specimens containing Coxsackie virus A were positive with the Coxsackie virus A PCR assay. In addition, five out of eight samples characterized as enterovirus-like by electron microscopy were PCR positive. The PCR assay did not amplify Coxsackie viruses B or echoviruses identified in our laboratory. CONCLUSION: The RT-PCR protocol established here should provide a useful alternative to the complicated and time-consuming diagnostic method based on live animals.

[Cytomegalovirus infection in neonates. Diagnosis and therapeutic experiences]. / Cytomegalovirusinfeksjon hos nyfødte. Erfaringer med diagnostikk og behandling.

Approximately 0.5-1% of all newborns are born infected with cytomegalovirus (CMV), but of these only one out of ten show symptoms at birth, most often with hepatosplenomegaly, thrombocytopenia, and/or brain affection. Of the remaining nine, one may later develop sequelae with hearing loss and/or mental retardation. CMV infection may also be acquired perinatally or in the newborn period, and may cause pneumonia and/or sepsis, possibly also gastrointestinal symptoms like blood in the stool, and poor weight-gain. We have diagnosed CMV infection in ten neonates and infants, and describe these patients in terms of symptoms, diagnosis and treatment. Ganciclovir is being tested in clinical trials as a treatment for congenital CMV infection, and was given to two of our patients with apparently good results.

[Q-fever imported into Norway]. / Q-feber importert til Norge.

Q fever is an important zoonosis that occurs throughout the world. In contrast to most other European countries, there has been no evidence of endemic Q fever in Norway up to now. The disease is caused by Coxiella burnetii, a rickettsia-like bacterium. Humans are infected mainly by inhalation of contaminated aerosols from cattle, sheep and goats. Clinical manifestations are protean, ranging from asymptomatic infection to life-threatening endocarditis. In this article we present the first four cases of serological proven acute Q fever imported into Norway. The patients were Norwegian tourists who had visited Bhutan, the Canary Islands, and Morocco. Two patients had fever with maculopapular exanthema, one had pneumonia, and one had biopsy-proven granulomatous hepatitis. Three were treated with tetracyclines. All four patients recovered well.

[Dengue fever imported to Norway. Serologically confirmed cases 1991-96]. / Denguefeber importert til Norge. Serologisk verifiserte tilfeller 1991-96.

With up to 100 million cases annually, dengue fever is today's most important arboviral disease. Dengue fever is endemic in many parts of South-East Asia, the Indian subcontinent, Oceania and the Americas. The disease mainly affects the local population, but occasionally also visitors from non-endemic areas. In this article we present epidemiological and clinical data on all 26 cases with serological confirmed dengue fever diagnosed in Norway in 1991-1996. 21 patients (81%) were infected in Asia. Typical exanthema, leucopenia, and thrombocytopenia were seen in 71%, 79% and 84% of the cases, respectively. A 37-year-old Indian-born woman developed dengue haemorrhagic fever grade 1 after a visit to New Delhi, while the remaining 25 patients had classical dengue fever. Postinfectious complications were common, and four weeks after the acute illness, hair loss, mental depression and asthenia were reported by 45%, 50% and 100% of the cases, respectively.

[Outbreak of food-borne gastroenteritis caused by a Norwalk-like virus. Evaluation of methods for confirmation of the etiology in suspected viral gastroenteritis]. / Utbrudd av naeringsmiddelbåren gastroenteritt forårsaket av Norwalk-liknende virus. Vurdering av metoder for påvisning av etiologi ved mistenkt virusgastroenteritt.

Acute gastroenteritis is a common disease and can be food-borne. We describe an outbreak of acute gastroenteritis, probably caused by Norwalk-like virus, which struck 250 people in the course of one week in a small Norwegian community. The source of the infection was probably an infected food handler in a bakery who contaminated cream cakes with the virus. The sensitivity of electronmicroscopy and analyses of IgG antibodies in serum to detect the etiologic agent was very low. The sensitivity to Norwalk Virus Polymerase Chain Reaction was much higher, and this was a considerable diagnostic benefit during the epidemic. Close cooperation between the local health authorities, the food control authorities, the bakery and the public was necessary to diagnose the etiology, source and spread of this food-borne infection.

[Virological diagnostics in acute encephalitis. Experience with nucleic acid detection and ratio examination during the period 1991-94]. / Virologisk diagnostikk ved akutt encefalitt. Erfaringer med nukleinsyrepåvisning og ratioundersøkelse i perioden 1991-94.

In every single case of acute encephalitis it is important to confirm the clinical diagnosis by means of virological investigations. Previously, examination by brain biopsy was regarded as the gold standard for detecting the presence of virus or virus antigen in suspected cases of encephalitis caused by herpes simplex virus, but the extraction of the sample material requires experience, and is not without risk. In recent years, detection of herpes simplex DNA using the polymerase chain reaction is recommended as the method of choice during the acute state of the illness, followed by ratio determination, e.g. the relation between IgG antibodies in serum and cerebrospinal fluid during the reconvalescence period. Between 1991 and 1994, the clinical diagnosis of acute encephalitis was confirmed by laboratory investigations in 42 cases in our laboratory. Detection of viral DNA and subsequent ratio determination showed the encephalitis to have been caused by herpes simplex virus in 21 cases, and by varicella zoster virus in eight cases. Nucleic acid was detected in 21 cases, and 16 patients showed pathological ratio values. These results show that the polymerase chain reaction is a valuable diagnostic tool during the first two weeks of the illness, whereas ratio determination is a better way of investigating samples taken after this period.

Intratypic genome variability of echovirus type 30 in part of the VP4/VP2 coding region.

The genetic relationship of 33 echovirus type 30 (E30) isolates associated with three different outbreaks of meningitis in Norway and one outbreak in USA was assessed using direct sequencing of amplicons derived from a region covering part of the capsid proteins VP4 and VP2. The E30 sequences were compared to each other, and to other enteroviruses. Less sequence variation was observed between the isolates from a single outbreak (2-3%) than between groups of isolates from different outbreaks (4-9%). All observed nucleotide substitutions were amino acid silent. Homology between enteroviruses obtained from GenEMBL and the nucleotide consensus sequence generated from the E30 isolates varied between 44.8% (coxsackievirus A24) and 72.6% (coxsackievirus A9). Comparing the E30 sequences in this part of the genome with other enteroviruses, E30 clearly belongs to the coxsackie B-like virus group.

Evaluation of five commercial tests for detection of immunoglobulin M antibodies to human parvovirus B19.

The following commercial tests for detection of immunoglobulin M antibodies to human parvovirus B19 were evaluated: Ideia Parvovirus B19-IgM, MRL Diagnostics Human Parvovirus B19 IgM ELISA, Parvoscan-B19, and Biotrin Parvo B19 IgM EIA and IF. A total of 203 serum specimens from patients who probably have current B19 infections or have other viral infections and sera with rheumatoid factor were investigated. Between 75 and 79 of 102 serum samples from patients thought to have current B19 infections yielded positive results with the different tests. Ideia had the highest specificity (94.8%), while Parvoscan showed a specificity of only 70.1%. Our evaluation results show that Ideia, MRL, and Biotrin EIA and IF can be recommended for diagnostic purposes.

Restriction endonuclease analysis of adenovirus type 3 isolated in Norway from 1970 to 1991.

Forty-three strains of adenovirus type 3 isolated from patients in Norway between 1970 and 1991 were analyzed with four restriction endonucleases. Bg1 II was the most discriminative enzyme. Five genotypes were identified and one of these has not been described before (Ad3a12). During both the epidemics in this period, new genotypes were introduced into the population. The same genotypes were identified in Norway as have previously been found in the northern parts of Europe, America and the Soviet Union.

[Erythema infectiosum in pregnancy. A follow-up of children after 2 years]. / Erythema infectiosum i svangerskapet. Oppfølging av barna etter to år.

During an epidemic of erythema infectiosum in Norway 1984-86, infection with human parvovirus B19 was diagnosed in 22 pregnant women by detection of specific IgM antibodies. Information about the outcome of pregnancy was obtained in 19 cases. 17 women delivered live babies. In two cases, spontaneous abortion occurred in week 16 of the pregnancy. In 11 cases, cord blood and serum samples were obtained from the children at an age of between six and 15 months. No specific IgM antibodies were found in cord blood. Clinical information on 16 children at two years of age revealed normal growth and development in 15 cases. One child was hyperactive and showed delayed language development. B19 IgG antibodies were detected in three children with normal growth and development. According to our findings, there was no association between infection with human parvovirus B19 in pregnancy and congenital abnormalities.