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Age specific antibody prevalence to parvovirus B19: how many women are infected in pregnancy?

Infection with parvovirus B19 is an important cause of late fetal mortality in the second trimester, and many infections in pregnancy remain undiagnosed. A serological survey stratified by age has been used to estimate the incidence of maternal infection with parvovirus B19 in pregnancy. Serum remaining from specimens submitted for diagnosis from 6864 people of all ages to seven public health laboratories in England was tested for antibody to parvovirus B19. The antibody prevalence rose with age to 45% at 10 years and 60% to 70% in adults. The age specific force of infection was highest in children aged less than 10 years and lowest in adults. Maternal infection with parvovirus B19 is estimated to occur in approximately one pregnancy in 400. It has been estimated that fetal death occurs in 9% of these cases, which suggests that parvovirus B19 may cause more than 150 fetal deaths in England and Wales each year. Testing for evidence of recent infection with parvovirus B19 should be considered for unexplained cases of fetal hydrops in the second trimester, especially in years of parvovirus B19 epidemics.

Adolescent↗

Parvovirus B19 infections in patients with chronic anemia.

BACKGROUND AND OBJECTIVE: Parvovirus B19 has a marked tropism for erythroid progenitor cells and this may lead to chronic anemia in predisposed individuals. It was the purpose of the present study to investigate prospectively the frequency of parvovirus B19 infections in patients with a diagnosis of chronic anemia. METHODS AND RESULTS: Evidence of parvovirus B19 infection was found in 13/43 (30%) patients by demonstrating viral DNA and/or specific IgM antibodies through the use of PCR and ELISA techniques. Parvovirus B19 infection was established in 4 of 7 patients with hemolytic anemia, in 2 of 3 patients with pure red cell aplasia, in 2 of 9 patients with myelodysplastic syndrome, and in 2 of 10 patients with aplastic anemia. In 8 of the 13 positive patients only parvovirus B19 DNA could be detected, while 4 patients tested positive for both parvovirus B19 DNA and specific IgM. In the remaining positive patient only specific IgM could be detected. CONCLUSIONS: Since no predictive paraclinical or clinical features were observed we recommend that all cases of chronic anemia be tested for the presence of parvovirus B19 infection. Due to the discrepancies between DNA and IgM results, the diagnostic procedures should include a search for specific DNA by PCR methods if specific IgM has been found to be negative.

Adult↗

In situ hybridization for the detection of human parvovirus B19 nucleic acid sequences in paraffin-embedded specimens.

Parvovirus infection of pregnant women leading to a transplacentar infection of the fetus may result in hydrops fetalis, and ultimately in intrauterine death of the fetus. In situ hybridization with a biotinylated as well as with a 35S-labeled probe for human parvovirus B19 was performed on formalin-fixed paraffin-embedded (FFPE) tissue from a fetus suffering from non-immunologic hydrops fetalis. Histology was suggestive of viral infection probably with human parvovirus. Parvovirus DNA could be detected and precisely localized mainly in the nuclei of erythroid precursors cells within fetal blood vessels of all organs examined. There was no detection of B19 nucleic acid in parenchymal cells of the placenta or the fetal organs, nor within maternal blood cells. These findings are in agreement with the well-known properties of animal parvoviruses to replicate exclusively in proliferating cells. Taking into consideration the problems in diagnosing human parvovirus infection by light microscopy, we conclude that in situ hybridization with an appropriate non-radioactive probe is a valuable, rapid and safe complementary detection method for the diagnosis and study of human parvovirus infections. The 35S-labeled probe is more sensitive than the biotinylated probe, but has the disadvantages of lower resolution of the signal, longer duration of the assay, the hazard of radioactivity and the shorter shelf-life of the probe.

Adult↗

Antineoplastic activity of parvoviruses.

The family of Parvoviridae is composed of small, nuclear-replicating viruses that are without envelope and contain an essentially single-stranded, linear DNA genome. Certain parvoviruses proved to have the remarkable capacity to prevent the formation of spontaneous as well as virtually- and chemically-induced tumors in laboratory animals. Established tumor cells serve as targets for the antineoplastic activity of parvoviruses, since the growth of preformed cancer cells transplanted in recipient animals can also be inhibited by these viruses. Furthermore, epidemiological studies in humans have revealed a correlation between serological evidence of parvoviral infection and a lower incidence of certain cancers. The parvoviral life-cycle appears to depend on cellular factors that are expressed as a function of proliferation and differentiation. This subordination may account for the oncotropism of parvoviruses in vivo and for the specificity of their interactions with (pre-)neoplastic cells under appropriate culture conditions. Thus, certain parvoviruses were found to preferentially lyse initiated or stably transformed cells in vitro, as a possible result of the stimulation of the production and/or activity of cytotoxic viral proteins. Parvoviruses can also have a cytostatic effect and cause the reversion of transformation traits, parallel to the down-modulation of the expression of defined genes, in particular oncogenes. Such direct disturbance of neoplastic cells or their precursors may participate in the oncosuppressive activity of parvoviruses, although indirect viral effects mediated by host defense mechanisms also deserve to be considered. Altogether, these properties suggest the possible use of parvoviruses as probes to investigate the process of malignant transformation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

An erythema infectiosum-like illness caused by human parvovirus infection.

In the spring of 1980, an epidemic of an illness that resembled erythema infectiosum occurred in Manitoba, Canada. We initiated prospective epidemiologic, clinical, and microbiologic studies of this illness among elementary-school children and their families. Initial microbiologic studies failed to identify the cause of the exanthem. After a similar illness associated with serologic evidence of human parvovirus infection occurred in London, stored specimens of 12 patients with exanthem were investigated for parvovirus infection. Eleven patients had parvovirus-specific IgM antibody, as did two family contacts and a teacher with nonexanthematous illnesses, and two asymptomatic family members. None of 28 children with measles or rubella had serologic evidence of recent parvovirus infection. Human parvovirus was detected by DNA hybridization and immune electron microscopy in the serum of one patient who later had a rash and in one unaffected family contact. Parvovirus DNA was also detected in the pharyngeal specimen of the teacher who was ill but did not have a rash. We conclude that human parvovirus infection can be asymptomatic or cause a variety of clinical manifestations, including nonexanthematous illness and an illness resembling erythema infectiosum.

Adult↗

Hematologic and hematopoietic consequences of B19 parvovirus infection.

In hybridization experiments, B19 shows some reactivity with autonomous rodent parvoviruses but none with adenoassociated virus sequences; its termini are more closely related to adenoassociated virus than to autonomous parvoviruses. B19 shares with all parvoviruses regions of conserved homology in the left side of the genome. The absence of an internal promoter and its unusual pattern of transcription sets B19 apart from both dependent and autonomous parvoviruses. Although clearly an autonomous parvovirus, in its extraordinary fastidious behavior B19 resembles a dependent parvovirus, capable of replication only in the special nuclear milieu of terminally differentiating erythroid cells. Adaptations at the molecular level may have been necessary for B19 parvovirus to acquire its high degree of specificity and low level of pathogenicity and thus succeed in human populations.

Adult↗

Rodent parvovirus infections.

Parvoviruses are among the most common infectious agents of laboratory rodents and major impediments to rodent-based research. The original prototypic rodent parvoviruses-minute virus of mice, rat virus, and H-1 virus-have recently been joined by biologically and antigenically distinct parvoviruses in mice, rats, and hamsters. Recognition of the increased diversity of rodent parvoviruses presents new challenges for determining the impact of parvovirus infection on research and for detecting, preventing, and eliminating infection. This review summarizes current knowledge about rodent parvoviruses and parvovirus infections, highlighting recent research on newly isolated virus strains.

Animals↗

Cloning and sequencing of the simian parvovirus genome.

We recently reported the identification of a novel simian parvovirus in cynomolgus monkeys with severe anemia. We now describe the cloning and sequencing of 4986 nucleotides of the viral DNA. Like the human parvovirus B19, simian parvovirus encapsidates both positive and negative single-stranded DNA. The positive strand contains two large open reading frames, with the left open reading frame encoding the nonstructural protein(s) and the right reading frame encoding the two capsid proteins. Simian parvovirus has little homology with the autonomous parvoviruses or the dependovirus AAV-2 but 50% overall homology with parvovirus B19 DNA. At the amino acid level there was 70% homology with B19 capsid proteins and 50% homology with B19 nonstructural protein. Based on this genetic similarity and with the known tropism of the virus for cynomolgus erythroid precursors, we suggest that this new virus should be classified as a new member of the Erythrovirus genus of the Parvoviridae.

Amino Acid Sequence↗

Sickle cell acute chest syndrome associated with parvovirus B19 infection: case series and review.

Acute Chest Syndrome (ACS) continues to be a major source of morbidity and mortality among patients with sickle cell disease. It is characterized by the presence of pleuritic chest pain, fever, raises on lung auscultation, and pulmonary infiltrates on chest x-ray [Castro et all: Blood 84:643-649]. The pathophysiology of this disorder remains poorly understood leading to the descriptive term "Acute Chest Syndrome" designated by Charache et al. [Arch Intern Med 139:67-69, 1979]. Typical bacterial pathogens are seldom isolated in adults, although they play a significant role in the pathogenesis of this entity in children. Until recently, the technology to accurately study viral infection as a precipitating cause of ACS has been unavailable. Parvovirus B19 is being increasingly recognized as an important human pathogen, and has been established as the cause of transient "aplastic crisis" in patients with sickle cell diseases [Saarien et al: Blood 67:-11411-11417, 1986; Young: Sem Hematol 25:159-172, 1988]. We present three patients with hemoglobin SC variant of sickle cell disease who developed ACS in association with acute parvovirus B19 infection, one of which died of respiratory failure. Parvovirus B19 infection was established by polymerase chain reaction for parvovirus B19 DNA, and the presence of parvovirus B19 specific IgM antibodies. These cases suggest that parvovirus B19 may be associated with more than self-limited illness in patients with sickle cell disease, and that this ubiquitous virus may merit further study as a precipitating cause of ACS.

Acute Disease↗

Parvovirus B19 infection in pregnancy: quantitative viral DNA analysis using a kinetic fluorescence detection system (TaqMan PCR).

Human parvovirus B19 infections are common in the general population, and infection during pregnancy may cause hydrops fetalis and fetal death. To initiate adequate treatment, accurate laboratory diagnosis is essential. The most sensitive tests are nested PCR systems, but these assays provide semiquantitative results at best. A parvovirus B19 DNA assay was developed based on the real time TaqMan PCR. This method was calibrated on the basis of serial plasmid dilutions and tested with an international parvovirus B19 standard. The assay was capable of quantifying parvovirus B19 DNA from one to about 5 x 10(7) genome equivalents per reaction (corresponding to 100 to 5 x 10(9) genome equivalents per ml serum). Samples from 51 pregnant women with suspected acute parvovirus B19 infection were tested, and positive PCR results were obtained in at least one of the materials investigated in 41 cases. The median viral DNA load in maternal blood samples was 1.3 x 10(4) copies/ml (range 7.2 x 10(2)-2.6 x 10(7)). Maternal virus DNA concentration was not associated with the presence of maternal symptoms and/or fetal complications. As the stage of infection was not known in the majority of cases, our data do not exclude an association between peak levels of parvovirus B19 DNA and the development of complications. Maternal sera and corresponding fetal material were available for concurrent testing from 15 DNA-positive cases: in most fetal samples, viral DNA concentrations were several orders of magnitude higher (up to 2.1 x 10(12) copies/ml) compared to the corresponding maternal blood samples.

Antibodies, Viral↗

Goose parvovirus--an autonomous member of the dependovirus genus?

Goose parvovirus is the etiological agent of Derzsy's disease, a fatal hepatitis of young geese. The virus infects geese and Muscovy ducks and can be propagated in the laboratory in primary embryonic goose fibroblasts. To date the virus has only been classified by morphological, biochemical, and culture characteristics as an autonomous parvovirus. We now report the cloning and partial sequencing of 3434 nucleotides of the viral genome. Three overlapping clones were obtained, encoding regions in the nonstructural and capsid coding region. The nucleotide sequence show little homology to other autonomous parvoviruses but 55% homology to the dependovirus AAV2. The homology to AAV2 was also confirmed at the amino acid level (nonstructural protein 55%, capsid coding region 51%). DNA cross hybridization studies indicate an even closer similarity of goose parvovirus to the yet unsequenced human dependoviruses AAV1 and AAV3 than to AAV2. These findings suggest that goose parvovirus may be genetically related to the dependovirus genus rather than to the other autonomous parvoviruses.

Amino Acid Sequence↗

Parvovirus variation for disease: a difference with RNA viruses?

The Parvoviridae, a family of viruses with single-stranded DNA genomes widely spread from invertebrates to mammal and human hosts, display a remarkable evolutionary capacity uncommon in DNA genomes. Parvovirus populations show high genetic heterogeneity and large population sizes resembling the quasispecies found in RNA viruses. These viruses multiply in proliferating cells, causing acute, persistent or latent infections relying in the immunocompetence and developmental stage of the hosts. Some parvovirus populations in natural settings, such as carnivore autonomous parvoviruses or primate adeno associated virus, show a high degree of genetic heterogeneity. However, other parvoviruses such as the pathogenic B19 human erythrovirus or the porcine parvovirus, show little genetic variation, indicating different virus-host relationships. The Parvoviridae evolutionary potential in mammal infections has been modeled in the experimental system formed by the immunodeficient scid mouse infected by the minute virus of mice (MVM) under distinct immune and adaptive pressures. The sequence of viral genomes (close to 10(5) nucleotides) in emerging MVM pathogenic populations present in the organs of 26 mice showed consensus sequences not representing the complex distribution of viral clones and a high genetic heterogeneity (average mutation frequency 8.3 x 10(-4) substitutions/nt accumulated over 2-3 months). Specific amino acid changes, selected at a rate up to 1% in the capsid and in the NS2 nonstructural protein, endowed these viruses with new tropism and increased fitness. Further molecular analysis supported the notion that, in addition to immune pressures, the affinity of molecular interactions with cellular targets, as the Crml nuclear export receptor or the primary capsid receptor, as well as the adaptation to tissues enriched in proliferating cells, are major selective factors in the rapid parvovirus evolutionary dynamics.

Animals↗

Low prevalence of active parvovirus B19 infection in HIV-infected patients.

In a prospective study to determine the prevalence of parvovirus B19 in adult patients positive for the human immunodeficiency virus, a series of 55 consecutively presenting patients was tested for antibodies to parvovirus B19 and parvovirus B19 DNA. Specific IgG antibodies were detected in 96% of cases; specific IgM antibodies were present in 10%. Viral DNA was not detected in any of the sera analysed by polymerase chain reaction. Anemia could not be correlated with the presence of either IgG or IgM antibodies to parvovirus B19. Thus, no evidence of acute or chronic parvovirus B19 infection was found in the 55 patients. These findings suggest that active parvovirus B19 infection is uncommon in HIV-infected patients.

AIDS-Related Opportunistic Infections↗

Parvovirus B19 infection in HIV-1 infected patients with anemia.

Serum samples were analysed for IgM and IgG antibodies to parvovirus by ELISA and for parvovirus B19 DNA by polymerase chain reaction (PCR) in 69 HIV-1 infected Swedish patients with anemia and in 37 HIV-1 infected subjects without anemia. In 5/69 anemic patients, parvovirus B19 DNA was detected despite the lack of IgM antibody activity to the virus. The detection of parvovirus B19 DNA was significantly correlated to the degree of anemia in the anemic patients. In two patients who had a chronic anemia, a persistent parvovirus infection was detected by PCR, but not by serology, for 1 and 1.5 years, respectively. The results suggest that persistent parvovirus infection is a rare cause of anemia, but important to identify, since the infection is potentially treatable with intravenous immunoglobulin.

AIDS-Related Opportunistic Infections↗

Generalized petechial eruption induced by parvovirus B19 infection.

Parvovirus infection classically causes erythema infectiosum. During the past 2 decades, other unusual skin eruptions have been noted in association with parvovirus infection. Papular purpuric gloves and socks syndrome is one form of parvovirus infection described mostly in white, young adult patients. Recently, there have been reports of a few patients with acropetechial syndrome consisting of a papular purpuric gloves and socks syndrome-like presentation with additional involvement of the perioral and chin area, temporally associated with acute parvovirus B19 infection. We report a case of a 7-year-old boy with serologic evidence of acute parvovirus B19 infection who developed a generalized petechial eruption with lesions concentrated on his extremities and face. We also reviewed the literature and summarized the various cutaneous presentations of parvovirus infection.

Child↗

No detection of parvovirus B19 or herpesvirus DNA in giant cell arteritis.

BACKGROUND: Compelling arguments exist for a role of infectious agent in giant cell arteritis (GCA). Parvovirus B19 and several herpesviruses have focussed the attention in recent years, but the few studies to date have yielded inconsistent results. OBJECTIVES: To study the relationship between the presence of parvovirus B19 DNA or major known herpesviruses and the histopathological features of GCA. STUDY DESIGN: Between January 1997 and March 2002, 147 consecutive temporal artery biopsies were performed in our center because of a clinical suspicion of GCA. Using polymerase chain reaction (PCR) procedures validated by the World Health Organization and employed routinely by our laboratory, we examined the paraffin-embedded specimens for DNA from parvovirus B19, herpes simplex viruses (HSV) 1 and 2, Epstein-Barr virus (EBV), varicella-zoster virus (VZV), human cytomegalovirus (HCMV), and human herpesvirus 6 (HHV-6). We investigated positive results further with immunohistochemistry studies. RESULTS: Fifty of the 147 temporal artery biopsies (34%) showed histological features of GCA. Three biopsies (2.5%) were initially PCR positive for parvovirus B19. None of the herpesvirus PCR assays were positive. Upon repeat testing by both PCR and immunohistochemistry, none of the three initially positive parvovirus B19 assays were confirmed. The results of both positive and negative control assays in these studies validated these findings. We confirmed the presence of amplifiable DNA in the temporal artery biopsy specimens using PCR primers for beta-globin and indoleamine 2,3-dioxygenase (IDO). CONCLUSIONS: The results of our study do not support a role in the etiopathogenesis of GCA for either parvovirus B19 or any of these six herpesviruses.

Aged↗

Management of parvovirus infection in pregnancy and outcomes of hydrops: a survey of members of the Society of Perinatal Obstetricians.

OBJECTIVE: Our purpose was to investigate the evaluation and management of parvovirus infection during pregnancy. STUDY DESIGN: Surveys were mailed to members of the Society of Perinatal Obstetricians residing in the United States and Canada in July 1997. They were asked about their evaluation and management of parvovirus infection, including whether they repeated and confirmed serologic studies, what their initial and follow-up evaluations included, whether they had had any cases of parvovirus-associated hydrops in the past 2 years, and if so, what were the management and outcomes of the hydropic fetuses. RESULTS: Surveys were mailed to 1623 members of the Society of Perinatal Obstetricians and 541 completed surveys were returned. Sixty-eight percent of the respondents repeated and confirmed serologic studies. Eighty-nine percent used ultrasonography in their initial management of pregnant patients with recent parvovirus infection, 7.5% used amniocentesis for polymerase chain reaction, and 2% used fetal blood sampling. The outcomes of the 539 cases of parvovirus-induced hydrops included spontaneous resolution in 34%, death without intrauterine transfusion in 30%, resolution after intrauterine transfusion in 29%, death after intrauterine transfusion in 6%, and pregnancy termination in 1%. Almost all cases of nonimmune hydrops reported occurred between 16 and 32 weeks. CONCLUSIONS: Approximately one third of the cases of parvovirus-induced nonimmune hydrops resolved spontaneously, whereas 83.5% of hydropic fetuses transfused survived.

Amniocentesis↗

[Varicella and parvovirus B19 immunity among pregnant women in Gijón, Spain].

BACKGROUND: We aimed at determining the inmunological status regarding varicella and parvovirus B19 in pregnant women in Gijón, Spain, and its correlation with several clinical and epidemiological parameters. PATIENTS AND METHOD: Blood samples taken during the first trimester of pregnancy in the area of Gijón were analysed to determine the immunological status with respect to varicella and parvovirus B19. The study included 2 groups: 99 non-European (all tested for both varicella and parvovirus) and 2,188 Europeans (406 were randomly selected for varicella test and 287 for parvovirus test). All patients underwent a clinical-epidemiological survey. RESULTS: With regard to varicella, while 89% of pregnant women aged 14 to 35 years displayed immunity, this percentage reached 100% in those older than 35 years. Sensitivity was 73.8%, specificity 74.4%, positive predictive value 96.6% and negative predictive value was 22.6%. As for parvovirus B19, immunity was observed in 59.9% of Europeans and 67.7% of non-Europeans, without significant differences in the analysed parameters. CONCLUSIONS: Susceptibility to infection by varicella among pregnant women younger than 36 years reaches 10% in Gijón. Clinical surveys are useful to avoid a pre-vaccination serological study in an already immune population. Just over one third of these pregnant women are susceptible to infection by parvovirus B19.

Adolescent↗