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Human parvovirus B19 infection in healthcare workers.

This paper reports the occurrence of human parvovirus B19 infection in seven healthcare workers in an acute hospital. The clinical presentation mimicked that of rubella and the diagnosis was made by the detection of human parvovirus B19 IgM antibody in blood samples taken from the affected members of staff. The paper discusses the importance of accurate diagnosis of B19 infection because this virus has been implicated in causing or exacerbating a variety of medical conditions. B19 infection may be serious for people with chronic haemolytic anaemias, those who are immunocompromised or those who are pregnant. B19 infection in pregnancy may be a cause of hydrops fetalis, particularly if the infection occurs during the second trimester. This is in contrast to the risk of intra-uterine rubella infection which is maximal in the first few weeks of pregnancy and which affects fetal development. The paper highlights the need for guidelines for occupational health practitioners on the management of parvovirus B19 infection and the need to make healthcare workers aware of the importance of this infection.

Adult↗

Dermatomyositis associated with the presence of parvovirus B19 DNA in muscle.

We report a case of dermatomyositis associated with molecular evidence of parvovirus B19 DNA in two muscle biopsies collected 5 months apart. IgG- but not IgM-specific antibodies were detected in serum. None of four serum samples was positive for parvovirus B19 DNA. The two biopsies contained B19 VP1 sequences and the second one was also positive for NS1. This is the first report of viral parvovirus B19 DNA in muscle of a patient with dermatomyositis. Latent muscle infection may contribute to the clinical picture.

DNA, Viral↗

Fifth (human parvovirus) and sixth (herpesvirus 6) diseases.

Fifth (erythema infectiosum) and sixth (roseola infantum) diseases are common rash illnesses of childhood that have long been recognized in clinical medicine. The discovery of the viruses that cause these illnesses has revealed relationships with other syndromes. Primary infection with the agent of erythema infectiosum, human parvovirus B19, is associated with transient aplastic crisis in hemolytic anemia, arthropathy in adults, chronic anemia in immunocompromised patients, and nonimmune fetal hydrops in pregnant women. The only documented illness associated with primary infection with human herpesvirus 6 is roseola or exanthema subitum in young children. However, reactivated infections in adults and immunocompromised patients may be associated with serious illness such as encephalitis/encephalopathy, and bone marrow suppression leading to transplant failure or graft-versus-host disease. Diagnostic studies for both viruses have been limited, although reliable serologic tests for human parvovirus B19 have recently become available. Diagnosis of human herpesvirus 6 remains problematic, because current tests cannot differentiate primary from reactivated disease. This is more of an issue for the putative relationship of these viruses to more chronic conditions, such as rheumatologic disease for human parvovirus B19 and multiple sclerosis for human herpesvirus 6. The relationship between the viruses and these conditions remains controversial, and better diagnostic tests and further information on viral pathogenesis for both viruses are required in order to make a reliable judgment in this regard.

Adolescent↗

Parvovirus-associated arthritis.

Human parvovirus B19 is the cause of several distinct clinical syndromes. The most common is erythema infectiosum (fifth disease), a febrile exanthem occurring primarily in children. Recent studies have shown that parvovirus B19 can cause acute arthritis and occasionally a chronic arthropathy, both in children and adults. Parvovirus B19 DNA has been detected in studies in the synovial tissue of patients with rheumatoid arthritis, but other studies have varied in their findings. Recent studies also indicate a possible connective tissue disease-like syndrome with parvoviral infections. The common features of this syndrome are malar eruption, arthralgias, arthritis, and laboratory abnormalities including antinuclear antibody and rheumatoid factor positivity. However, the data indicate it is unlikely that B19 infection causes rheumatoid arthritis or systemic lupus erythematosus. Continued studies of the pathogenesis of acute and chronic parvoviral B19 infections and arthropathy may provide insights into virus-host interactions and mechanisms of joint disease and connective tissue disease.

Adult↗

Human herpesvirus-6 and parvovirus B19 infections in children.

It was proved in the 1980s that human herpesvirus-6 and human parvovirus B19 cause diseases in humans. Human herpesvirus-6, a newly recognized herpesvirus, is a causative agent of exanthem subitum. The virus produces broad clinical features; complications, including fatal outcome, are frequently activated in immunosuppressed conditions such as organ transplantation. Parvovirus B19, a small-DNA virus, infects erythroid progenitor cells. Systemic infection with parvovirus B19 is responsible for several clinical entities, such as erythema infectiosum, arthropathy, aplastic crisis, fetal death, and other disease conditions, including those in immunosuppressed hosts. Reliable diagnostic technologies and carefully designed clinical, immunologic, and virologic studies will fully delineate the clinical significance of both viral infections.

Child↗

Acute parvovirus B19 infection mimicking congenital dyserythropoietic anemia.

Infection with human parvovirus B19 is known to cause transient erythroid aplasia in children with hemolytic anemia but has also been associated with bone marrow necrosis and morphologic changes suggesting myelodysplasia. The authors describe a previously healthy child who presented with severe hypoplastic anemia. Initial bone marrow aspiration revealed erythroid hyperplasia, dyserythropoiesis, and multinucleated erythroid cells with nuclear budding and bridging, consistent with the diagnosis of congenital dyserythropoietic anemia. Serologic testing documented acute parvovirus infection, and on recovery the correct diagnosis of unsuspected congenital spherocytosis was established. This case expands the spectrum of hematologic disease associated with acute parvovirus infection.

Acute Disease↗

Clinical presentation of parvovirus B19 infection in children with aplastic crisis.

The records of 22 children with parvovirus B19-induced aplastic crisis were reviewed. The group consisted of 16 children with sickle cell hemoglobinopathies and 6 with hereditary spherocytosis. Children presented to the hospital 0.5 to 8 days (mean, 2.4 days) after the onset of symptoms. The children with sickle-cell disease presented earlier (mean, 1.4 days) than did children with hereditary spherocytosis (mean, 5 days; P = 0.02. Fever was the most common symptom, occurring in 73% of children. Rash did not occur in either group. Reticulocyte counts began to rise 1 week after onset of illness associated with a rise in parvovirus B19-specific IgG antibody. These data suggest that parvovirus B19 infection in children with sickle-cell hemoglobinopathies and heredity spherocytosis differs from infection in normal children.

Adolescent↗

Acute respiratory distress syndrome in a child with human parvovirus B19 infection.

A 6-year-old girl developed shock and multiple organ dysfunction including acute respiratory distress syndrome in association with parvovirus B19 infection. The diagnosis was based on positive antibodies and the detection of parvovirus 19 DNA in serum, bronchial secretions and skin biopsy. It seems likely, but it was not proved, that the parvovirus infection caused acute respiratory distress syndrome.

Antibodies, Viral↗

Autoimmune-like pulmonary disease in association with parvovirus B19: a clinical, morphologic, and molecular study of 12 cases.

Parvovirus B19, the agent responsible for fifth disease, has been emerging as a significant pathogenetic factor in various acute vasculitic syndromes such as Wegener's granulomatosis, Henoch-Schönlein purpura, and Kawasaki disease. It has also been implicated in more chronic vasculopathic syndromes, specifically in the context of scleroderma and dermatomyositis. The basis of this association is likely multifactorial; implicated mechanisms include the virus's affinity for endothelium, resulting in a state of neoantigenicity through varied mechanisms as well as the induction of tumor necrosis factor alpha, a factor involved in the propagation of ANCA-positive vasculitic syndromes. The authors present a series of 12 patients with interstitial lung disease including idiopathic pulmonary fibrosis, scleroderma-associated pulmonary fibrosis, lymphocytic interstitial pneumonitis, and septal capillaritis. In all cases there was evidence of chronic parvovirus B19 infection based on serologic assessment and the isolation of B19 DNA on lung samples in all patients. Furthermore, in two cases there was in situ localization of B19 RNA and tumor necrosis factor alpha to endothelium and stromal cells. On pathologic examination, there were varying degrees of both septal fibrosis and inflammation along with evidence of septal capillary injury. In those cases categorized as representing either scleroderma or idiopathic pulmonary fibrosis, the immunofluorescent studies showed evidence of anti-endothelial cell antibody formation. The ANCA-associated syndromes were, as expected, negative by fluorescent analysis. Significantly elevated factor VIII levels, a standard serologic index of endothelial cell injury, were seen in four of the six patients tested. The antiphospholipid profile revealed antiphospholipids in 7 of the 11 patients tested. This report highlights a possible causal role for parvovirus B19 in the pathogenesis of select pulmonary disorders.

Adult↗

Infection of apheresis cells by parvovirus B19.

Parvovirus B19 is the only member of the Parvoviridae family known to cause disease in humans. Owing to the high level of cell tropism the virus can only replicate in proliferating and differentiating erythroid precursor cells, which are present in human bone marrow and foetal liver. As human bone marrow is very difficult to obtain, an alternative in vitro system for the propagation of B19 virus has been developed, based on the application of mobilized haemapoietic progenitor (apheresis) cells. These cells are routinely harvested from cancer patients after treatment with recombinant human granulocyte/macrophage colony-stimulating factor. Replication of parvovirus B19 in vitro is possible in these cells after stimulation with erythropoietin. Therefore, this system is an easily, accessible alternative to the use of human bone marrow in parvovirus B19 infection assays.

Blood Component Removal↗

Construction and initial characterization of an infectious plasmid clone of a newly identified hamster parvovirus.

The construction and characterization of a full-length infectious plasmid clone of the newly identified hamster parvovirus (HaPV) are described. Following transfection of hamster BHK cells with the infectious clone, pHaPV, the specific intracellular DNA replicative forms, RNA transcripts and viral proteins that were expected for this rodent parvovirus were generated. Infected cells were lysed and progeny virus was produced, demonstrating that pHaPV could generate a productive virus infection. The complete sequences of both hairpin termini, which had not been previously determined, were obtained. Preliminary host-range studies, which compared virus production and macromolecular synthesis in various cell lines following either HaPV infection or pHaPV transfection, demonstrated an early block of infection of HaPV in both monkey COS-1 and murine A9 cells. The availability of an HaPV infectious clone will facilitate its genetic analysis and allow the elucidation of the determinants important in host range, tissue tropism and pathogenicity of this newly identified rodent parvovirus.

Animals↗

Genetic variability of porcine parvovirus isolates revealed by analysis of partial sequences of the structural coding gene VP2.

The 3'-terminal 853 nt (and the putative 283 aa) sequence of the VP2-encoding gene from 29 field strains of porcine parvovirus (PPV) were determined and compared both to each other and with other published sequences. Sequences were examined using maximum-parsimony and statistical analyses for nucleotide diversity and sequence variability. Among the nucleotide sequences of the PPV field strains, 26 polymorphic sites were encountered; 22 polymorphic sites were detected in the putative amino acid sequence. Mapping polymorphic sites of protein data onto the three-dimensional (3D) structure of PPV VP2 revealed that almost all substitutions were located on the external surface of the viral capsid. Mapping amino acid substitutions to the alignment between PPV VP2 sequences and the 3D structure of canine parvovirus (CPV) capsid, many PPV substitutions were observed to map to regions of recognized antigenicity and/or to contain phenotypically important residues for CPV and other parvoviruses. In spite of the high sequence similarity, genetic analysis has shown the existence of at least two virus lineages among the samples. In conclusion, these results highlight the need for close surveillance on PPV genetic drift, with an assessment of its potential ability to modify the antigenic make-up of the virus.

Amino Acid Sequence↗

Pathogenesis of aleutian mink disease parvovirus and similarities to b19 infection.

Aleutian mink disease parvovirus (ADV) is an unusual member of the autonomous parvoviruses in both its replication and pathogenesis. Infection of newborn mink kits results in an acute disease typified by virus replication in type II pneumocytes in the lung. This replication is permissive and cytopathic, characterized by the production of high levels of viral replicative intermediates and infectious progeny. However, infection of adult Aleutian mink leads to a chronic form of the disease termed Aleutian disease (AD). In this case, virus replication occurs predominantly in lymph node macrophages and is restricted, with viral DNA replication, RNA transcription, protein expression and production of infectious progeny occurring at low levels. B19 is the only autonomous parvovirus known to infect humans. The primary site of virus replication in both children and adults is in erythrocyte precursors in the blood and bone marrow, although viral genomes have been detected in various other tissues. B19 infection often causes a self-limiting disease although persistent infection of B19 can occur in both immuno-compromised and -competent people. Perhaps the most striking similarity between infection with ADV or with B19 is the important role the humoral immune response to infection has in pathogenesis. It can be both protective and pathogenic. Due to of the central role of antibody in the disease caused by either virus, understanding the specific roles of antibody production in protection, antibody-mediated enhancement of infection, the establishment of persistent infection and immune-mediated pathology will provide insight into the pathogenesis of these infections. A second similarity between the two viruses is the ability to establish persistent infection. Persistence of ADV is associated with restricted replication. Although many cellular factors may contribute to restricted virus replication, the interactions between the major non-structural protein, NS1, and the cells are likely to be critical. Parallels exist between the expression and post-translational modification of ADV and B19 NS1 proteins that may contribute to restriction of virus replication. Thus, a study of the regulation of NS1 expression and its interactions with cell signalling pathways may lead to increased understanding of the restricted replication of these two viruses, and perhaps of persistent infection.

Aleutian Mink Disease↗

A slide latex agglutination test for the rapid detection of antibodies in serum against porcine parvovirus.

A slide latex agglutination test (LAT) was developed and evaluated to detect serum antibodies against porcine parvovirus. Porcine parvovirus antigen was obtained by 10% PEG-6000 and 0.5 mol/l sodium chloride precipitation, and inactivated by 0.1% methanal. Two per cent suspensions of latex particles (0.5-0.8 microm) were coated by adding an equal volume of porcine parvovirus antigen at 0.34 microg/ml. Repeatability of latex agglutination test was evaluated with a panel of 100 sera using the same and different antigen lots. A good agreement between LAT and haemagglutination inhibit assay was observed. Because of convenience and speed of performance, this method would be used widely in clinic examination.

Animals↗

Human parvovirus B19 infection in patients with chronic hepatitis B or hepatitis C infection.

BACKGROUND AND AIM: Parvovirus B19 has been reported to be detected in the sera of patients with acute or chronic hepatitis. The prevalence and clinical significance of B19 DNA in serum samples from patients with chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection were investigated. METHODS: Serum samples from 54 patients with HBV infection, 51 with HCV infection and 53 normal controls were examined for anti-B19 antibodies and B19 DNA by enzyme-linked immunosorbent assay (ELISA), the nested polymerase chain reaction (PCR), Southern blotting and direct nucleotide sequencing, respectively. RESULTS: Anti-B19 IgM and IgG antibodies were detected in 19 (35.2%) and 46 (85.2%) of 54 serum samples from patients with HBV infection, and eight (15.7%) and 36 (70.6%) of 51 serum samples from patients with HCV infection. B19 DNA was detected in serum samples of 20 (37%) of 54 patients with HBV infection and 12 (23.5%) of 51 patients with HCV infection, but not in 53 serum samples from normal controls. The occurrence of liver dysfunction was not affected by B19 infection in patients with HBV and HCV infection (P > 0.05). All of the 20 serum samples with B19 DNA from patients with chronic HBV infection and all of the 12 serum samples with B19 DNA from patients with chronic HCV infection exhibited TW-3 subtype and TW-9 subtype, respectively. The variant subtypes of B19 were found to be distinctive in patients with HBV or HCV infection. CONCLUSIONS: These data revealed that human parvovirus B19 infection was frequently found in patients with chronic HBV or HCV infection. The variant genotypes were present in patients with different chronic hepatitis. The coinfection of B19 with HBV or HCV did not increase the frequency of liver dysfunction in patients with chronic hepatitis. Long-term longitudinal studies are required to determine the natural course of parvovirus B19 infection and whether its coinfection affects the natural history of chronic hepatitis B or hepatitis C.

Adolescent↗

Seroprevalence of varicella zoster virus, parvovirus B19 and Toxoplasma gondii in a Melbourne obstetric population: implications for management.

At an antenatal clinic at a Melbourne obstetric hospital, 308 women were questioned about a known past history of infection with varicella zoster virus (VZV), human parvovirus B19 and Toxoplasma gondii. Immunoglobulin G (IgG) concentrations were determined for the 3 infectious agents and a recalled history of infection was compared with the presence of specific antibody. Exactly 66% of women recalled being infected with chickenpox (VZV) and 94% showed serological evidence of past exposure. Although 64% of women had parvovirus specific IgG, only one gave a definite history of past parvovirus infection. None of the 23% of women with evidence of previous exposure to Toxoplasma gondii recalled a past infection. The proportion of antenatal women at risk in this study was used to estimate the potential burden of disease from congenital infections in Australia and to examine implications for management of pregnancies complicated by these 3 infections.

Adolescent↗

Hepatitis-associated aplastic anemia and acute parvovirus B19 infection: a report of two cases and a review of the literature.

Hepatitis-associated aplastic anemia is rare in general, but occurs in up to 28% of patients receiving liver transplantation for fulminant non-A, non-B hepatitis. Cases are commonly young men with mild hepatitis but severe aplastic anemia. Although cases have been reported in association with hepatitis A, B, and C, most appear to be due to a non-A-B-C virus. We report two cases of acute hepatitis subsequently complicated by marrow hypoplasia in patients with acute parvovirus B19 infection. Hepatic manifestations of parvovirus B19 infection range from liver chemistry abnormalities to fulminant hepatic failure and aplastic anemia. Our cases demonstrate a less severe form of hepatitis-associated aplastic anemia, and together with other data, suggest that parvovirus B19 is at least one cause of hepatitis-associated aplastic anemia, and may be a heretofore underrecognized hepatotrophic virus.

Acute Disease↗

[A girl with systemic onset juvenile rheumatoid arthritis suspected to be due to human parvovirus B19 infection].

We encountered a case of a girl where Human Parvovirus B19 infection was considered to have been concerned with the development of systemic type juvenile rheumatoid arthritis (JRA). While the affected child did not show any evident infectious erythema-like findings, changes in the serum antibody titer by the EIA method presented the pattern of first infection. During the clinical course the condition of the disease as JRA was serious and hemophagocytic syndrome developed concurrently. Furthermore, the resistance to the treatment was also noted. So the patient was treated with prednisolone combined with low dose weekly MTX therapy. The possibility of Human parvovirus B19 being concerned with the development of rheumatoid arthritis in one form or another has been suggested in recent years. In the disease type with systemic angititis as main pathophysiology, which is called systemic JRA we encountered this time, it is not clear how Human Parvovirus B19 was concerned with the development of this disease, but it appeared to hold a key position in studying pathophysiology of the development.

Anti-Inflammatory Agents↗