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Because parvovirus B19 infection during pregnancy has been associated with increased risk of fetal loss in small or selected study populations, the authors evaluated the risk in a population-based study. A nested case-control study was conducted by using a population-based screening for syphilis in 3 regions in Denmark from 1992 to 1994. Cases of women with fetal loss were identified in the National Patient Register (n = 2,918), and control women with live-born children were identified in the Medical Birth Register (n = 8,429) by matching on age and sampling week. First-trimester serum samples were tested for parvovirus B19 immunoglobulin M positivity. Parvovirus B19 immunoglobulin M positivity was associated with a 71% increased risk of fetal loss (odds ratio = 1.71, 95% confidence interval: 1.02, 2.86). Adjustment for number of children or stratifying for gestational age at loss did not change the risk estimate. Assuming causality, only 0.1% of fetal losses were attributable to parvovirus B19 positivity, a proportion which could increase to approximately 1% during epidemic periods. In conclusion, acute parvovirus B19 infection during the first trimester of pregnancy was associated with an increased risk of fetal loss. However, the impact on the overall burden of fetal losses appeared small even during epidemics.

Background: Human cytomegalovirus (CMV) is the most common congenital infection in developed countries and is a known cause of intrauterine fetal death. We examined CMV infection in stillbirths and the relationship with histopathological findings at autopsy., Methods: We collected liver, kidney, and placenta specimens from 130 stillbirths. CMV DNA and protein were detected using polymerase chain reaction and immunohistochemistry, along with routine autopsy of stillborn infants., Results: Overall, CMV DNA was detected in 15% of singleton, >20-week stillborn infants. CMV DNA was detected in kidney (9%), liver (11%), and placenta (5%) specimens, with 75% of infections confirmed by immunohistochemistry. Fetal thrombotic vasculopathy was the only histopathological abnormality associated with CMV infection (in 60% CMV-infected vs 28% uninfected stillbirths P = .010)., Conclusions: Stillbirth has multiple etiologies. However, the detection of CMV DNA in 15% of fetal tissues or placentae suggests a strong association between CMV infection in pregnancy and stillbirth. Molecular testing during postmortem investigation has an important role to determine the contribution of CMV infection.

Bovine viral diarrhea virus (BVDV) infection in goats can result in severe reproductive losses, with abortion rates reaching 80%. Infection with BVDV in aborted goat fetuses and stillborn kids can result in placentitis, encephalitis, myocarditis, and thymic depletion. This study investigates the distribution of viral antigen within the organ systems of aborted goat fetuses, stillborn kids, and nonviable kids infected with BVDV at various stages of gestation using immunohistochemistry (IHC). Virus antigen was detected within the placenta (8/13), thymus (4/9), heart (4/11), and brain (4/15) of affected goats. Uncommonly, BVDV antigen was detected within the skin (1/14), liver (1/13), kidney (1/12), lung (1/11), and trachea (1/3). BVDV antigen was not detected within the spleen (0/9), nasal turbinate (0/2), or thyroid (0/3). The results of this study indicate that placenta, heart, thymus, and brain are the most reliable tissues for BVDV antigen detection using IHC in aborted goat fetuses.

Objective: To augment the understanding of parvovirus B19 infection in pregnancy with respect to maternal characteristics and their corresponding fetal outcomes., Study Design: Retrospective case-series of all women referred to Magee-Women_s Hospital with serologically-documented parvovirus B19 infection during pregnancy from 1998-2001., Results: All 25 cases that are available for analysis occurred from January through June. The frequency of cases varied substantially from year to year, with 14 cases in 1998, 0 cases in 1999 and 2000, and 11 cases in 2001. In contrast to previous reports, the minority of women [4/25(16%)] experienced symptoms attributable to parvovirus B-19 infection although 3 of 25 (12%) fetuses developed hydrops fetalis and 4/25 (16%) suffered an intrauterine of fetal death., Conclusions: These findings suggest that parvovirus B19 infection in pregnancy follows seasonal and annual trend variation, may produce a lower frequency of maternal symptoms and a higher fetal loss rate than previously reported. Synopsis. Maternal parvovirus B19 infection follows seasonal and annual variation is often asymptomatic and may have higher fetal loss rates than previously reported. Continued surveillance is warranted.

Objectives: The human cytomegalovirus (CMV) is universally distributed among human populations as one of the most common cause of congenital infection with an incidence of about 0.15-2.0% in developed countries. However, controversial data concerning intrauterine fetal death caused by CMV infection exist., Method: A case report., Results: In this case report we present a stillbirth in the 18th week of pregnancy, caused by a maternal serological and fetal histological congenital CMV infection., Conclusion: Every attending physician and obstetrician should be aware of the possibility of a primary or even recurrent congenital CMV infection that could be a reason for sudden unknown congenital fetal death.

Parvovirus B19 is a significant human pathogen that causes a wide spectrum of clinical complications ranging from mild, self-limiting erythema infectiosum in immunocompetent children to lethal cytopenias in immunocompromised patients and intrauterine foetal death in primary infected pregnant women. The infection may also be persistent and can mimic or trigger autoimmune inflammatory disorders. Another important clinical aspect to consider is the risk of infection through B19-contaminated blood products. Recent advances in diagnosis and pathogenesis, new insights in the cellular immune response and newly discovered genotypes of human parvoviruses form a platform for the development of modern therapeutic and prophylactic alternatives.

Objective: To determine whether cell-mediated immunity against porcine reproductive and respiratory syndrome (PRRS) virus is correlated with protection against reproductive failure in sows during clinical outbreaks of PRRS in commercial herds., Design: Outbreak investigation in 4 swine breeding herds., Animals: 97 sows., Procedures: On each farm, blood samples were collected from sows with clinical signs (abortion or increased fetal death; case sows) and from clinically normal sows (control sows). The intensity of the cell-mediated immune (CMI) response was determined by use of an interferon-gamma enzyme-linked immunospot (ELISPOT) assay. Multiple logistic regression analyses and t tests were used to compare ELISPOT assay values between case and control sows. Multiple linear regression was used to investigate associations between cell-mediated immunity and the magnitude of clinical signs., Results: In 2 farms, case sows had lower ELISPOT assay values than control sows. A negative association between the intensity of the CMI response and the number of pigs born dead per litter was detected on 1 farm. In 1 farm, no association was detected between the intensity of the CMI response and protection against reproductive failure., Conclusions and Clinical Relevance: Evidence that a strong CMI response was correlated with protection against clinical PRRS was detected in 3 of 4 farms. However, farms and sows within farms varied considerably in their immune responsiveness and in the degree to which they were protected clinically. Increasing cell-mediated immunity within infected herds has the potential to decrease clinical reproductive disease, but only if the sources of intra- and interfarm variation in the intensity of cell-mediated immunity to PRRS virus can be identified.

In order to examine an association between porcine circovirus type-2 (PCV2) infection and reproductive failure in pigs, sera (n = 171) from stillborn fetuses were collected from 3 different farms with prolonged histories of reproductive problems. These sera were tested for the presence of antibodies to PCV2 using an immunoperoxidase monolayer assay. Of the 171 sera tested, 28 had PCV2 antibody titers of > or = 1:16. When these 28 samples were tested by a polymerase chain reaction assay,13 were found to contain PCV2 viral DNA. Of these 13 samples containing both PCV2 antibodies and viral DNA, 9 yielded PCV2 on virus isolation. Amino acid sequences comprising open reading frame 2 of PCV2 from 2 of these isolates were compared to PCV2 isolates from cases of post-weaning multi-systemic wasting syndrome (PMWS). The amino acid sequences of the 2 isolates from stillborn pigs were shown to be nearly identical to each other, as well as to other PCV2 isolates associated with reproductive failure. When compared with PMWS isolates, the isolates from the stillborn fetuses showed differences of at least 2 amino acids. These results confirm previous findings that transplacental infection of PCV2 occurs in the field and that stillbirths in pigs may be associated with PCV2 infections. At present, the significance of minor differences in amino acid sequences is not known.

Adverse pregnancy outcome due to human parvovirus B19 (hereafter referred to as "parvovirus B19") has been characterized, in numerous reports, as an event that occurs during the first and second trimesters and is strongly associated with symptoms of fetal hydrops. Recent findings have indicated that parvovirus B19-associated intrauterine fetal death (IUFD) is also a problem in late gestation, although its clinical presentation is aberrant, lacking signs of fetal hydrops. We outlined the clinical presentation and assessed the frequency of parvovirus B19 infection in a retrospective analysis of 92 unselected cases of IUFD that occurred during or after gestational week 22. By polymerase chain reaction, parvovirus B19 DNA was detected in 13 (14%) of the 92 cases. Only 2 of the parvovirus B19 DNA-positive cases were hydropic, both representing early IUFDs. This finding indicates that parvovirus B19-associated IUFD in late gestation is a common finding and that hydropic presentation is rare. This knowledge may contribute to a reduction in the number of unexplained cases of IUFD.

We report a case of monozygotic twins whose mother was infected with measles at 19 weeks' gestation. One of the twins died in utero at 32 weeks' gestation. The placenta of the stillbirth showed massive fibrin deposition, and some residual trophoblasts contained many inclusion bodies positive for measles virus antigen. Fetal organs and cells other than a few splenic lymphocytes showed no evidence of measles virus infection. The placenta of the surviving infant showed focal intervillous fibrin deposits, and only a few syncytiotrophoblasts were positive for measles virus antigen. At present, 7 months after the delivery, the surviving infant has not developed any sign of measles virus infection. Postpartum course of the mother has been uneventful, although high titers of serum anti-measles virus IgM persisted for 6 months after delivery. This case is informative in the following respects: the villous trophoblasts had diagnostic inclusion bodies and ultrastructural evidence of measles virus infection, the degree of viral involvement within the monochorionic placenta was uneven, both of the twins were virtually free from measles virus infection despite the marked involvement of the placenta, and measles virus infection had persisted in the monochorionic placenta for approximately 13 weeks.

Porcine circovirus type 2 was detected in several stillborn and nonviable neonatal piglets presenting with chronic passive congestion, cardiac hypertrophy, and severe diffuse myocarditis. The presence of the virus in the heart and other tissues of affected piglets was confirmed by polymerase chain reaction, immunohistochemistry, and virus isolation techniques. Other reproductive losses and associated infectious agents in the herd are discussed.

Virus isolation, reverse transcription-polymerase chain reaction (RT-PCR), immunohistochemistry, and in situ hybridization methods were compared for the detection of porcine reproductive and respiratory syndrome virus (PRRSV). Seven aborted fetuses and 6 stillborn piglets naturally infected with PRRSV were used in the study. Viral antigen and viral nucleic acid were detected in macrophages and dendritic cells in the spleen, tonsil, lymph nodes, and thymus; in macrophages of liver, heart, and lung; and in endothelial cells and myocytes of the heart. Viral antigen and viral nucleic acid were most consistently detected in the spleen. Of the 13 samples, 6 were positive for PRRSV by all 4 techniques. Four (31%) samples were positive for PRRSV by RT-PCR, in situ hybridization, and virus isolation. Two (15%) samples were positive for PRRSV by virus isolation, RT-PCR, and in situ hybridization. One (8%) was positive for PRRSV by virus isolation and RT-PCR. The RT-PCR identified the presence of PRRSV more frequently than the other methods. However, when only formalin-fixed tissues are submitted, immunohistochemistry and in situ hybridization would be useful methods for the detection of PRRSV antigen and nucleic acid.

Background: Transmission of hepatitis C virus from mother to child is well documented. The prevalence of antibodies against hepatitis C virus among pregnant women in Norway is however, not known. The aim of this study was to estimate the maternal prevalence of antibodies against hepatitis C virus and to study the association between presence of antibodies and fetal death., Material and Methods: From a study of 35,940 pregnant women, a random sample of 970 women and all women with fetal death after 16 weeks of gestation (n = 283), were tested for antibodies against hepatitis C virus., Results: 7 out of 970 women in the random sample (0.7%; 0.2-1.3%, 95% confidence interval) had antibodies against hepatitis C virus. The same prevalence (0.7%, 2 out of 283) was found among women with fetal death., Interpretation: The prevalence of antibodies against hepatitis C virus among Norwegian women was unexpectedly high. Further research is necessary to understand the causes and implications of this observation.

Porcine circovirus 2 (PCV2) is a recently identified agent that has been associated with postweaning multisystemic wasting syndrome (PMWS) in swine populations. In this report, the potential spectrum of disease associated with PCV2 is expanded by evidence of vertical transmission and associated reproductive failure. PCV2 was isolated from a litter of aborted piglets from a farm experiencing late-term abortions and stillbirths. Severe, diffuse myocarditis was present in 1 piglet associated with extensive immunohistochemical staining for PCV2 antigen. Variable amounts of PCV2 antigen were also present in liver, lung, and kidney of multiple fetuses. The presence of other agents that have been associated with fetal lesions and abortion in swine, including porcine parvovirus, porcine reproductive respiratory syndrome virus, encephalomyocarditis virus, and enterovirus, could not be established.

Objective: Mouse strains carrying endogenous ecotropic murine leukemia viruses (MuLV) are capable of expressing infective virus throughout life. Risk of transplacental transmission of MuLV raises concerns of embryo infection and induction of pathogenic effects, and postnatal MuLV infection may lead to tumorigenesis., Methods: Endogenous ecotropic MuLV-negative SWR/J embryos were implanted into Akv-infected viremic SWR/J mice, into spontaneously provirus-expressing AKR/J mice, and into noninfected SWR/J control mice; virus integration and virus expression were investigated at 14 days' gestation. Tumor development was monitored over 18 months., Results: Of 111 embryos, 20 (18%) recovered from Akv-infected SWR/J mice, which had developed normally, were infected. New proviruses were detected in 10 of 111 (9%) embryos from Akv-infected SWR/J mice, and in 2 of 60 (3%) embryos from AKR/J mice; none expressed viral protein. Of 127 embryos recovered from Akv-infected SWR/J mice, 16 (13%) were dead; 4 of 5 (80%) were infected and expressed viral protein. Of 71 embryos from AKR/J mice, 11 (15%) were dead, and 2 of 2 had virus integration; virus expression was not detected. Numbers of dead embryos recovered from experimentally infected, viremic SWR/J mice and from spontaneously endogenous MuLV-expressing AKR/J mice were significantly higher, compared with numbers from nonviremic SWR/J control mice, and embryo lethality was significantly associated with prenatal provirus expression. Postnatal inoculation of Akv induced lymphoblastic lymphomas in 15 of 24 (61%) SWR/J mice within mean +/- SD latency of 14 +/- 2.4 months. Only 3 of 39 (8%) control mice developed lymphomas (P < 0.005)., Conclusion: Embryos in MuLV-viremic dams are readily infected, and inappropriate prenatal expression of leukemogenic endogenous retroviruses may play a critical role in embryo lethality and decreased breeding performance in ecotropic provirus-positive mouse strains.

A male fetus of gestation day 187 was aborted from a Holstein-Friesian cow in an epizootic of the Aino virus (AINOV) in September 1995. Neutralizing antibody titers against AINOV were 1:128, 1:16 and 1:64 in the dam serum, fetal ascites and cerebrospinal fluid, respectively. A 10% brain suspension of the aborted fetus was prepared immediately after autopsy, rinsed three times and sonicated before centrifugation. The supernatant was then inoculated into HmLu-1 cell cultures. A cytopathic effect was noted on post-inoculation day 7. The isolated virus was identified as the AINOV based on the physicochemical properties and cross neutralization test. This is the first report on the isolation of AINOV from an aborted bovine fetus.

Aims: To compare the application of a non-radioactive in situ hybridisation (ISH) technique with an immunocytochemical technique for the detection of human parvovirus B19 in formalin fixed, paraffin wax embedded sections of macerated fetal tissue., Methods: Archived samples of liver, lung or kidney from 19 human fetuses were investigated for parvovirus B19 using a full length digoxigenin labelled DNA probe of 5.5 kb; bound probe was detected using an anti-digoxigenin (alkaline phosphatase) conjugate and visualised using NBT/BCIP. Immunocytochemical detection of parvovirus B19 was performed using a monoclonal mouse antiparvovirus B19 antiserum, with a streptavidin-biotin complex (horse radish peroxidase) method. Cases were selected to provide a range of diagnostic certainty and a range of degrees of macerative degeneration., Results: Parvovirus B19 was found in 15 of 19 cases using the B19 ISH technique compared with 8 of 19 cases using the immunocytochemical technique. The four negative cases were all controls known to be parvovirus B19 free. All ISH positive cases showed excellent staining with low background regardless of extent of maceration and tissue type. In comparison, sections stained by the immunocytochemical method showed considerable non-specific immunoreactivity in many cases, particularly with severe maceration. Kidney and lung tissues gave the cleanest results., Conclusions: ISH is more effective than the immunocytochemical technique for the detection of human parvovirus B19 in macerated fetal tissue. The lack of detectable background staining with the ISH technique led to easier interpretation suggesting that this technique should be the method of choice for the investigation of parvovirus B19 in macerated postmortem tissues.

The teratogenic potential of three bunyaviruses, two California serogroup bunyaviruses, LaCrosse virus and San Angelo virus, and a Bunyamwera serogroup member, Main Drain virus, in sheep was studied following in utero inoculation of ewes in early gestation. Although Main Drain virus appeared to be most teratogenic, all three viruses induced a range of lesions including arthrogryposis, hydrocephalus, fetal death, axial skeletal deviations, anasarca, and oligohydramnios. The teratogenic effects of these viruses are identical to those described in ovine infections by Cache Valley and Akabane viruses. Demonstration of a common bunyaviral tropism for fetal tissue infection that results in congenital brain and musculoskeletal malformations provides evidence that human in utero infection by bunyaviruses could result in similar malformations in human infants.

Infectious virus resembling type D simian retrovirus (SRV) was isolated from Ethiopian baboons (Papio cynocephalus) (SRV-Pc) housed at the University of Washington Regional Primate Research Center. When baboon peripheral blood mononuclear cells (PBMC) or tissues were cocultured with the H-9 human T-cell line or the Raji human B-cell line, large multinucleated syncytia positive for SRV-2 antigens were observed microscopically. Immunoblot analysis of purified SRV-Pc from cell culture supernatants demonstrated that the viral core and envelope proteins reacted with rabbit anti-SRV-2 serum. Fresh PBMC and cocultured cells were positive by polymerase chain reaction using two different sets of SRV-2 primers. Preliminary sequence analysis of two separate isolates from portions of the SRV-Pc p27 and gp20 regions revealed homology with SRV-1, SRV-2, and Mason-Pfizer monkey virus. The homologies in the p27 segment were 91-94% and the homologies in the gp20 segment were 72-75%.