Identification of a novel simian parvovirus in cynomolgus monkeys with severe anemia. A paradigm of human B19 parvovirus infection.

Although human B19 parvovirus infection has been clearly associated with a number of distinct syndromes (including severe anemia, abortion, and arthritis), detailed knowledge of its pathogenesis has been hindered by the lack of a suitable animal model. We have identified a novel simian parvovirus in cynomolgus monkeys with severe anemia. Sequencing of a 723-bp fragment of cloned viral DNA extracted from serum revealed that the simian parvovirus has 65% homology at the DNA level with the human B19 parvovirus but little homology with other known parvoviruses. Light microscopic examination of bone marrow from infected animals showed intranuclear inclusion bodies, and ultrastructural studies showed viral arrays characteristic of parvoviruses. Another striking feature was the presence of marked dyserythropoiesis in cells of the erythroid lineage, raising the possibility that B19 parvovirus infection may underlie related dyserythropoietic syndromes in human beings. Affected animals had concurrent infection with the immunosuppressive type D simian retrovirus, analogous to HIV patients who develop severe anemia because of infection with B19 parvovirus. The remarkable similarities between the simian and B19 parvoviruses suggest that experimentally infected cynomolgus monkeys may serve as a useful animal model of human B19 infection.     

Increased seroprevalence of parvovirus B 19 IgG in complex regional pain syndrome is not associated with antiendothelial autoimmunity.

The etiology of complex regional pain syndrome (CRPS) is unclear yet. Recently autoantibodies and antecedent viral infections have been discussed to be involved in the pathogenesis of CRPS. We investigated sera from 39 CRPS patients and healthy controls for parvovirus B19 IgG and the occurrence of antiendothelial autoantibodies (AECA). CRPS patients showed a higher seroprevalence of parvovirus B19 IgG than controls (p < 0.01). All CRPS 2 patients were positive. 10.2% of the CRPS patients and 10.0% of the controls had AECA (n.s.) and AECA were not associated with parvovirus B19 seropositivity. Our findings suggest the involvement of parvovirus B19, but not autoantibody-mediated endothelial cell damage, in the pathogenesis of CRPS.     

Clinical illness due to parvovirus B19 infection after infusion of solvent/detergent-treated pooled plasma

BACKGROUND: Lipid-enveloped viruses such as HIV, HBV, and HCV can be inactivated by treatment with solvents and detergents. HAV and human parvovirus B19 lack lipid envelopes and are not inactivated. Solvent/detergent-treated pooled plasma (S/D plasma) contains neutralizing antibodies, but it is not known whether the parvovirus B19 antibody content is sufficient to prevent transmission of the disease. A patient is described who developed a clinical illness due to parvovirus B19 infection after the infusion of S/D plasma. CASE REPORT: A 36-year-old woman with myasthenia gravis underwent five plasma exchange procedures from January 15 to January 25, 1999, using albumin, except for 5 units of SD plasma given because of a low fibrinogen level. Four of the 5 units were implicated in a recall after high levels of parvovirus B19 DNA were found in several lots. Two weeks after the infusion, the patient developed fatigue, a rash, and severe polyarthralgias. Parvovirus B19 IgG and IgM antibody titers were consistent with an acute infection. CONCLUSION: Clinically apparent parvovirus B19 infection can follow the use of S/D plasma that contains high levels of parvovirus B19 DNA.     

Clinical manifestations and outcomes of parvovirus B19 infection during pregnancy in Japan

Parvovirus B19 is a small DNA virus. Infection with parvovirus B19 during pregnancy may cause serious complications in the fetus, including hydrops fetalis and fetal death. The purpose of the present study is to clarify the clinical manifestations and outcomes of parvovirus B19 infection during pregnancy. This prospective study enrolled 478 women with suspected B19 infections during pregnancy between 1999 and 2004. One hundred cases (21%) of B19 infection were detected in 478 pregnant women who had been exposed to B19. Serological infection was confirmed by measurement of B19-specific IgM and IgG in sera. Forty-nine cases reported maternal clinical symptoms and 51 cases were asymptomatic. Facial rash was the most common symptom, with 51% (25/49) of the symptomatic patients complaining of either a facial, body or limb rash. The most common infectious source was children living in the home. Overall, the incidence of adverse fetal effects (including hydrops fetalis and fetal death) related to intrauterine B19 infection was 7% (7/100), and all seven cases were exposed to B19 infection before 20 weeks of gestation. Although half of the cases with parvovirus B19 infections during pregnancy were asymptomatic, patients with adverse fetal effects tended to be symptomatic including rash and fever. These clinical data may supply useful information to produce clinical guidelines for managing B19 infection during pregnancy.     

人类第6型疱疹病毒感染与特发性血小板减少性紫癜

探讨人类第６型疱疹病毒（ＨＨＶ－６）感染与特发性血小板减少性紫癜（ＩＴＰ）的关系。方法采用聚合栈 反应（ＰＣＲ）方法检测１０５例ＩＴＰ患者骨髓单个核细胞（ＢＭＭＮＣ）ＨＨＶ－６ＤＮＡ及部分患者微小病毒Ｂ１９、巨细胞病毒（ＨＣＭＶ）ＤＮＡ序列;用竞争性ＥＬＩＳＡ方法检测６６例ＩＴＰ患者血小板相关抗体（ＰＡＩｇ）,并采用间接免疫荧光法动态观察１９例ＩＴＰ患者抗ＨＨＶ－６血清抗体滴度变化。结果①ＩＴＰ患     

Cytokines in parvovirus b19 infection as an aid to understanding chronic fatigue syndrome

Human parvovirus B19 infection has been associated with various clinical manifestations of a rheumatic nature such as arthritis, fatigue, and chronic fatigue syndrome (CFS), which can persist for years after the acute phase. The authors have demonstrated recently that acute B19 infection is accompanied by raised circulating levels of IL-1β, IL-6, TNF-α, and IFN-γ and that raised circulating levels of TNF-α and IFN-γ persist and are accompanied by MCP-1 in those patients who develop CFS. A resolution of clinical symptoms and cytokine dysregulation after intravenous immunoglobulin (IVIG) therapy, which is the only specific treatment for parvovirus B19 infection, also has been reported. Although CFS may be caused by various microbial and other triggers, that triggered by B19 virus is clinically indistinguishable from idiopathic CFS and exhibits similar cytokine abnormalities and may represent an accessible model for the study of CFS.     

An assay for parvovirus B19 neutralizing antibodies based on human hepatocarcinoma cell lines

BACKGROUND: Although intravenous immune globulin (IVIG) is used widely for managing parvovirus B19 infections, IVIG products are not monitored routinely for the presence of parvovirus B19 neutralizing antibody. STUDY DESIGN AND METHODS: An assay has been developed to measure parvovirus B19 infectivity and neutralization activity based on two hepatocarcinoma cell lines (HepG2 and HuH7). The sources of parvovirus B19 were B19-DNA-containing plasma samples. Neosynthesized progeny in supernatants of infected cells were quantified by nested polymerase chain reaction. To validate the model, purified rabbit antibodies to different capsid protein sequences and IVIG preparations were tested. RESULTS: The number of parvovirus B19 infectious neovirions in supernatants of infected cells increased with infection time. Both rabbit antibodies and IVIG products inhibited parvovirus B19 infectivity when incubated overnight with virus. The efficacy of IVIG to neutralized parvovirus B19 was product-related. CONCLUSION: This assay for parvovirus B19 neutralization activity provides an improved and more specific method for selecting donors to produce IVIG with a high titer of parvovirus B19 neutralizing activity.     

Diagnosing human parvovirus B19 infection: guidelines for test selection.

Human parvovirus B19 is the cause of a common childhood disease that usually has a mild and self-limited course. Complete viral replication and subsequent cell lysis are limited to early erythroid precursor cells expressing the globoside receptor. Individuals with shortened red blood cell half-lives and immunocompromised or immunosuppressed patients, as well as pregnant women and developing fetuses, are at risk for severe anemia and/or persistent infection from human parvovirus B19. Selection of the diagnostic test(s) to use to detect parvovirus B19 is patient dependent. Serological testing is most appropriate in immunocompetent individuals, including children and pregnant women, who have symptoms consistent with parvovirus B19 infection or a history of recent exposure. Conversely, a molecular amplification assay should be chosen to detect parvovirus B19 DNA in individuals lacking an adequate antibody-mediated immune response. In summary, it is critical that clinicians are educated about the most appropriate diagnostic test to detect parvovirus B19 infection in their patients because selecting an inappropriate or inaccurate test for parvovirus B19 can lead to misinformation and/or misdiagnosis.     

Diagnosis of parvovirus B19 infection in hematological patients with partial red cell aplasia of the bone marrow

AIM: To assess diagnosis of parvovirus B19 infection (PI) in patients with aplastic crises by combined use of polymerase chain reaction (PCR) and enzyme immunoassay (EIA) of specific IgM and IgG. MATERIAL AND METHODS: A total of 159 serum samples from 77 PI suspects were examined. The examination for virus DNA was conducted with modified "net" PCR in 108 samples, for specific IgM and IgG with EIA in 110 samples. RESULTS: The percentage of patients infected with parvovirus detected by PCR or EIA reached 60%. 21 of 77 patients with hemolytic anemias were infected with parvovirus B19, the virus persisting in 8 cases (40%). persistence of the virus was registered if viremia occurred in immunodeficiency due to the disease or immunosuppressive therapy. Immunity to parvovirus has not developed: IgM expression was the same as in patients without hemopoietic abnormalities, while IgG was not detected. The absence of specific immunity to parvovirus B19 occurred in patients treated with immunosuppressive drugs early after the end of viremia period in high IgM level and at the initial phase of IgG synthesis. IgM levels also remained unchanged; the level of IgG declined and was not identified furthermore. There were cases of reinfection. CONCLUSION: Combined use of PCR and EIA is optimal for diagnosis of parvovirus B19 infection in patients with hemolytic anemias. It was found that there are correlations between defects in specific immunity, persistence and immunodeficiency onset regarding viremia. Abnormal for the disease course levels of IgM and IgG indicate the persisting virus, the condition of specific immune response to parvovirus B19 and feasibility of reinfection. Reliable diagnosis of parvovirus infection is possible only in simultaneous use of PCR and EIA.     

Parvovirus B19 infection in pregnancy

Transplacental transmission of human parvovirus B19 (B19 virus) to the fetus is an important cause of intrauterine death, abortion, stillbirth, and nonimmune hydrops fetalis. Adverse outcome of pregnancy can occur after symptomatic and asymptomatic maternal infection. Only rare cases of congenital malformations and fetal disease in live-born infants have been associated with intrauterine B19 virus infection. Laboratory results obtained from paired maternal and fetal cord blood samples indicate that a reliable diagnosis of fetal B19 virus infection should be based on detection of parvovirus B19 DNA.     

Exposure of hematologic patients to parvovirus B19 as a contaminant of blood cell preparations and blood products

BACKGROUND: Patients with hematologic malignancies often require blood products, and parvovirus B19 is known to be transmitted by this route. Primary infection with parvovirus B19 shows a wide variety of disease manifestation. In immunocompromised patients, symptoms are severe and viral clearance is delayed or missing. STUDY DESIGN AND METHODS: A total of 2123 blood products given to all patients of a hematologic ward over a period of 6 months were retrospectively examined for the presence of parvovirus B19 DNA by an in-house real-time polymerase chain reaction (PCR; TaqMan). Patients who had received B19 DNA-positive blood products were further investigated serologically and by PCR for the presence of parvovirus B19 antibodies and DNA. RESULTS: Twenty-one (1%) of 2123 blood products tested positive for the presence of B19 DNA (2% of pooled products, 0.7% of single-donor products, and 17.6% of allogeneic peripheral blood progenitor cells), the median viral load was 700 genome equivalents per mL. During the study period, 114 patients were treated on the ward, and 14 (12%) of them received B19 DNA-positive blood components. None of them developed symptoms of an acute B19 infection, although one had a short low-level viremia. CONCLUSIONS: Although B19 DNA was detected in 1 percent of blood products given to hematologic patients, the exposure of 12 percent of patients did not result in symptomatic infections.     

Intrauterine management of fetal parvovirus B19 infection.

OBJECTIVES: The aim of our study was to determine the outcome of pregnancies after intrauterine management of fetal parvovirus B19 infection. DESIGN: Retrospective study. SUBJECTS: A total of 37 cases of maternofetal parvovirus B19 infection, 35 of which were associated with hydrops fetalis, were referred to our tertiary level center between 1989 and 1996. With regard to fetal hydrops, no apparent cause other than parvovirus B19 infection was found in any patient. METHODS: In all patients, cordocentesis was performed to assess the degree of fetal anemia. When anemia was present, cordocentesis was followed by intrauterine transfusion with packed red cells into the umbilical vein. Further management depended on the degree of fetal anemia and gestational age and included follow-up fetal blood sampling/transfusion as well as ultrasound examinations as deemed appropriate. RESULTS: Packed red cell transfusion was performed in 30 patients with significant fetal anemia (Z-score 1.6-7.8 below the mean for gestational age). The fetal hemoglobin values ranged from 2.1 to 9.6 g/dl. Serum levels of platelets in the transfusion group were 9-228 x 10(9)/l with Z-scores in the range of < 1 to 3.8 below the mean. During treatment and follow-up, there were five intrauterine deaths (13.5%), one neonatal death (2.7%) and 31 live births (83.8%). CONCLUSIONS: Fetal parvovirus infection can lead to marked anemia and hydrops formation. Cordocentesis allows precise assessment of fetal anemia which can then be corrected by intravenous transfusion. Under this regimen, the outcome proved favorable in the majority of fetuses, even those that were severely anemic.     

Transfusion-transmitted human parvovirus B19 infection in a thalassemic patient

BACKGROUND: Human parvovirus (HPV) B19 infection has been shown to be transmissible by clotting factor concentrates, most often resulting in asymptomatic seroconversion. So far, no case of B19 transmission due to single-donor transfusion has been documented. CASE REPORT: A case of transfusion-transmitted HPV B19 infection in a 22-year-old female thalassemia major patient is described. She presented with an aplastic crisis; this was followed 1 week later by transitory heart failure and acute tricuspid incompetence. The echocardiogram revealed a grade III tricuspid regurgitation and a floating vegetation on the atrial face of the tricuspid lateral leaflet. The tricuspid regurgitation and vegetation spontaneously disappeared within 15 days. Blood cultures for bacteria were repeatedly negative. IgM anti-HPV B19 seroconversion was documented in the acute phase. B19 DNA was detected by polymerase chain reaction and remained detectable up to 4 months after diagnosis. High- titer IgM anti-HPV and B19 DNA were also found in serum samples collected at the time of donation from one of the donors of the blood transfused before the onset of clinical symptoms. CONCLUSION: This case documents the transmission of HPV B19 by the transfusion of 1 red cell unit and the occurrence of possible transient cardiac involvement in this infectious complication.     

1例刀砍伤合并人细小病毒B19感染的护理

目的 总结1例刀砍伤合并人细小病毒 B19 感染的护理经验,为此类患者护理提供参考。方法 1例患者的主要护理措施包括：争分夺秒急救处置,肺功能康复训练,改善血液系统三系减少相关症状,感染人细小病毒B19后的护理,提供心理康复等。结果 患者临床症状改善,经过精心的治疗与护理,患者病情好转并顺利出院,电话随访1个月,恢复良好。结论 刀砍伤后发生人细小病毒B19感染较为少见,疾病早期做好急救处置,严密观察病情变化,重点围绕预防人细小病毒B19感染,及时纠正血液三系进行性下降,改善肺部功能,做好心理护理,使患者身心尽快康复。     

Symptomatic parvovirus B19 infection caused by blood component transfusion

BACKGROUND: Although a risk of transfusion‐transmitted human parvovirus B19V (TT‐B19V) infection has been a concern, there have been very few reports of clinically relevant TT‐B19V caused by the transfusion of a B19V‐containing blood component. It has therefore been a matter of debate whether a universal B19V screening with an appropriate sensitivity is required. STUDY DESIGN AND METHODS: Through the Japanese Red Cross hemovigilance system, clinical reports on possible TT‐B19V were collected from 1999 to 2008, during which B19V donor screening (sensitivity, 10¹⁰ IU/mL) was conducted and repository blood samples from donors were available. RESULTS: Eight patients with TT‐B19V caused by component transfusion have been identified. Four patients developed sustained anemia and pure red blood cell (RBC) aplasia and one patient developed pancytopenia. The underlying diseases in these five patients were either hematologic malignancy or hemolytic diseases. The viral loads of the responsible components for these cases ranged from 10³ to 10⁸ IU/mL. Two patients who underwent surgical treatment without any hematologic disorder exhibited only moderate symptoms. The B19V DNA sequence identity between a patient and the linked blood donor was confirmed in five of the eight patients. All of the components responsible for the eight cases were positive for anti‐B19V immunoglobulin (Ig)M. CONCLUSION: Vulnerability to serious B19V‐related hematologic disorders depended on the patient's underlying disease state of an enhanced erythropoiesis, not on the viral load of the component transfused. To prevent clinically relevant TT‐B19V, a strategy is suggested in which patients at risk of acquiring RBC aplasia or pancytopenia are targeted.     

Immune response to B19 parvovirus and an antibody defect in persistent viral infection.

B19 parvovirus has been shown to persist in some immunocompromised patients, and treatment with specific antibodies can lead to decreased quantities of circulating virus and hematologic improvement. A defective immune response to B19 parvovirus in these patients was shown by comparison of results using a capture RIA and immunoblotting. In normal individuals, examination of paired sera showed that the dominant humoral immune response during early convalescence was to the virus major capsid protein (58 kD) and during late convalescence to the minor capsid species (83 kD). In patients with persistent parvovirus infection, variable titers against intact particles were detected by RIA, but the sera from these patients had minimal or no IgG to capsid proteins determined by Western analysis. Competition experiments suggested that this discrepancy was not explicable on the basis of immune complex formation alone and that these patients may have a qualitative abnormality in antibody binding to virus. In neutralization experiments, in which erythroid colony formation in vitro was used as an assay of parvovirus activity, sera from patients with poor reactivity on immunoblotting were also inadequate in inhibiting viral infectivity. A cellular response to purified B19 parvovirus could not be demonstrated using proliferation assays and PBMC from individuals with serologic evidence of exposure to virus. These results suggest that production of neutralizing antibody to capsid protein plays a major role in limiting parvovirus infection in man.     

Acute parvovirus B19 infection during anti-retroviral therapy

Human parvovirus B19 (B19) has been described as a causative agent of chronic anemia in human immunodeficiency virus type-1 (HIV-1)-infected patients. We report an HIV-1 infected patient who had been receiving anti-retroviral therapy who showed sudden pancytopenia. Primary B19 infection was confirmed by the detection of plasma viremia and seroconversion. Although clearance required a prolonged period of time, the patient eventually cleared the B19 viral DNA from the plasma. More than likely, highly active anti-retroviral therapy (HAART), including a protease inhibitor, played a role in clearing the virus. Received: April 7, 2000 / Accepted: March 6, 2001     

Pathogenesis of nonimmune hydrops fetalis caused by intrauterine B19 infection

Intrauterine human parvovirus B19 infection is related to non-immune hydrops fetalis and fetal death. First, we performed epidemiological studies to determine the critical period during which maternal infection led to hydrops fetalis. The studies showed that the hepatic period of hematopoietic activity was correlated with the critical period of maternal infection, which suggested that B19 might have affinity for erythroid lineage cells at the stage of hematopoiesis. We next established an in vitro infection experimental system of B19 using erythroid lineage cells derived from fetal liver cells. We demonstrated that the erythroid lineage cells proved to be appropriate targets for B19 virus and that B19 infection could induce apoptosis of infected cells. The massive destruction of erythroid lineage cells through apoptosis seems to cause severe anemia and to result in heart failure of the fetus. To analyze the cytotoxic mechanism in more detail, we established a stringent regulatory expression system of the NS1 protein encoded by the B19 genome and indicated that the apoptosis induced by B19 was directly caused by the NS1 protein. Experiments using mutations engineered in the ATP-binding domain of NS1 indicated that this domain played a critical role for the apoptosis induction. The present studies may contribute to a better understanding of the pathogenesis of hydrops fetalis associated with B19 infection during pregnancy.     

The association of VP1 unique region protein in acute parvovirus B19 infection and anti-phospholipid antibody production

BACKGROUND: Previous studies have postulated a connection between human parvovirus B19 (B19) infection and anti-phospholipid antibodies (aPL). Recently, the phospholipase domain of B19 has been linked to B19-VP1 unique region (VP1u). To elucidate the roles of VP1u in B19 infection and aPL production, the major reactivity of anti-B19-VP1u, anti-cardiolipin antibody (aCL), and anti-beta2-glycoprotein I (beta2GPI) antibody was evaluated. METHODS: Sera from 102 clinically suspected cases of B19 infection were analyzed by nested PCR and ELISA. Humoral responses of anti-B19-VP1u and anti-B19-VP1uD175A IgM/IgG antibodies, aCL and the anti-beta2GPI antibody were assessed by Western blot and ELISA. Absorption experiments were also performed to determine the binding specificity of immunoglobulins to B19-VP1u, CL and beta2GPI. RESULTS: Sera from patients with the diagnostic pattern DNA+/IgM+/IgG+ had a high frequency (57%) for recognition of CL and beta2GPI. Furthermore, adsorption experiments were performed by adding purified B19-VP1u, which partially suppressed the reactivity of anti-B19VP1u to CL and beta2GPI. CONCLUSIONS: Serum from patients with acute B19 infection has a high frequency in recognition of CL and beta2GPI, and the phospholipase domain observed in the B19-VP1u may have contributed to the production of aPL. These findings may provide a clue for understanding the roles of B19-VP1u in B19 infection and aPL production.     

Infection by human parvovirus B19: "gloves and socks" papular purpuric syndrome

Human parvovirus B19 is the cause of erythema infectiosum a benign and self-limited infection, but sometimes the virus causes an acute and self-limiting dermatosis. It consists of a edema and erythema of the hands and feet in a gloves and sock distribution and is associated with oral lesions and fever. We report a case of a "gloves and socks" infection by human parvovirus B19.