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Fetal pathology in intrauterine death due to parvovirus B19 infection.

OBJECTIVES: To study the pathological features of fetuses dying because of parvovirus B19 infection, with particular reference to the presence of hydrops; to assess the usefulness of immunochemistry as a screening method for the detection of parvovirus infection at post-mortem examination. DESIGN: Review of clinical, sonographic, serological and pathological data; immunohistochemical staining of post-mortem tissue. SAMPLE: Cases of intrauterine fetal death occurring during the 18-month period January 1993 to June 1994 inclusive, referred for post-mortem examination to the Pathology Department, Royal Victoria Infirmary, Newcastle upon Tyne. RESULTS: Eleven cases of fetal death due to parvovirus infection were identified. Seven fetuses were less than 18-week size. Three fetuses showed conspicuous hydropic change. One of the 11 cases was detected for the first time by retrospective immunochemical screening. Of cases originating from the Newcastle district, parvovirus infection was responsible for about 10% of all non-malformed fetal deaths occurring between 10 and 24 weeks of gestation referred for pathological examination. CONCLUSIONS: During the period of study, parvovirus infection was a relatively common cause of mid-trimester fetal death. Many fetuses dying because of this infection are not noticeably hydropic, and the possibility of parvovirus infection should be considered in any case of intrauterine fetal death. Immunochemistry can be used to confirm the histopathological diagnosis, and may be of particular help where there is advanced autolysis; immunohistochemical screening may detect occasional cases not initially identified by examination of routinely stained tissue sections.

Autopsy↗

Human parvovirus B19 infection associated with hydrops fetalis.

Human parvovirus B19 infection has been associated with fetal anaemia, hydrops and in some cases fetal demise. We report our experience with nonimmune hydrops fetalis due to human parvovirus B19 infection in 17 pregnancies which were identified sonographically over a period of 10 years. The only baby who survived received repeated intrauterine transfusions and was normal neurodevelopmentally at 2 years follow-up. Two other fetuses who also received intrauterine transfusion did not survive. All pregnancies complicated with nonimmune hydrops should be investigated by fetal blood sampling looking for the evidence of parvovirus infection. Intrauterine transfusion should be reserved for hydropic fetuses with a low haematocrit. A greater understanding of the natural history of human parvovirus infection is needed prior to deciding the optimum mode of therapy.

Adult↗

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↗

Human parvovirus B19 in pregnancy.

Human parvovirus is an often unrecognized but potentially deadly infection when contracted by childbearing women who are seronegative. Although maternal symptoms and sequelae are mild, the exposed fetus quickly can develop nonimmune hydrops fetalis and die. Health care providers can prepare for appropriate maternal and fetal management by reviewing the history, disease process, and transmission mode of parvovirus.

Erythema Infectiosum↗

Thrombocytopenia induced by human parvovirus B19 infections.

Human parvovirus B19 (B19) has a remarkable tissue-tropism for erythroid elements--from erythroid precursors (BFU-E, CFU-E) to erythroblasts. B19 is thought to be incapable of propagating in cells other than erythroid progenitors. Leukocytopenia and thrombocytopenia sometimes occur in addition to erythrocytopenia in patients with B19 infection. We retrospectively investigated the possible cause of thrombocytopenia by B19 infection in 23 patients with thrombocytopenia admitted to our hospital in the past 5 years. Two patients were found to be infected by B19. Mild thrombocytopenia in both cases was thought to be an early event in B19 infection.

Child↗

Parvovirus B19 infection and Diamond-Blackfan anaemia.

It is the purpose of the study to report the frequency of parvovirus in children with a diagnosis of Diamond-Blackfan anaemia and to discuss the possible aetiological role of parvovirus in Diamond-Blackfan anaemia. We found parvovirus DNA in 3 of 11 bone marrow smears. Giant pronormoblasts showed low sensitivity (33%) and poor specificity (75%). The presence of giant pronormoblasts was associated with a very high myeloid:erythroid ratio, and may not be specific for parvovirus infection, but a feature of severely suppressed erythropoiesis. The three parvovirus-positive patients were the only children who experienced a remission, and who are free of medication. The seven surviving parvovirus-negative patients are all currently on steroid treatment.

Bone Marrow↗

[Studies on the relationship between anaphylactoid purpura and human parvovirus B19].

Human parvovirus B19 (B19) has been shown to be the cause of erthema infectiousum (EI). Recently the various clinical manifestations with B19 infection are coming to light. The relationship between B19 and anaphylactoid purpura (Schölein-Henoch purpura: SHP) was investigated in a retrospective study. There were sixteen patients (male 9, female 7, average age 6.0 +/- 1.7) who were diagnosed as SHP. Serum specimens were used in the present study. Specific IgM and IgG were assayed by enzyme immunoassay, B19 DNA was assayed by polymerase chain reaction (PCR). Five of the sixteen patients were positive for B19 DNA assayed by PCR, three were positive for B19 IgM in the acute phase. Kidney involvement appeared in one case with B19 infection and in two cases without infection. Abdominal involvement appeared in one case with infection and in three cases without. In this study, five of the sixteen patients had evidence of recent B19 infection by the existence of antibodies and PCR method. In conclusion, it is necessary to investigate the B19 infection with or without EI in the cases of SHP.

Child↗

[Human parvovirus B19-induced aplastic crisis in a case with spherocytosis].

A 43-year-old female with spherocytosis was admitted to the hospital because of fever, headache, and rapidly progressive anemia. On admission, she had severe anemia (Hb 3.9 g/dl) with marked decrease in reticulocytes (0.3%). Some premature leukocytes, such as promyerocyte, were observed in the peripheral blood. Bone marrow smear revealed normocellular marrow with normal presence of erythroid cells. Anti-human parvovirus B19 IgM and IgG antibody was positive in the serum on admission. The DNA of the virus was also detected in the peripheral blood by PCR assay. Thus, this case was diagnosed as acute aplastic crisis caused by human parvovirus B19 infection. Blood transfusion was performed on day 1 and day 2. The symptoms gradually disappeared and increase in reticulocyte (11.5%) was observed on day 5. Premature leukocytes in the peripheral blood disappeared on day 2. She recovered from anemia and was discharged on day 7.

Adult↗

Antibody response to human parvovirus B19 in patients with primary infection by immunoblot assay with recombinant proteins.

Human parvovirus B19 recombinant VP1 and VP2 capsid proteins were produced by a procaryotic pGEX expression plasmid to evaluate the humoral response by immunoblot assay in 14 patients with primary infection. The same concentrations of VP1 and VP2 recombinant proteins were used. This demonstrates that VP1 immunoglobulin M detection and/or VP1 immunoglobulin G seroconversion is a reliable marker of primary infections. Consequently, detection of antibodies to B19 VP1 might be helpful for identifying patients at risk for chronic B19 infection or patients who are susceptible to viral reinfection.

Adolescent↗

Chemiluminescence dot blot hybridization assay for detection of B19 parvovirus DNA in human sera.

A chemiluminescence dot blot hybridization assay was used for the detection of B19 parvovirus DNA in human sera by using digoxigenin-labeled probes. The probes were revealed immunoenzymatically by use of anti-digoxigenin Fab fragments conjugated with alkaline phosphatase. The chemiluminescence signal was obtained by reacting the labeled probe-target complex with an enzyme-triggerable dioxetane substrate. The emitted photons were detected with instant photographic films. In the search for B19 parvovirus DNA, 2,808 serum samples were analyzed.

DNA Probes↗

Detection of parvovirus B19 in donated blood: a model system for screening by polymerase chain reaction.

A highly sensitive and rapid method for routinely screening large numbers of donated blood units for parvovirus B19 by the polymerase chain reaction (PCR) was developed. Over a 3-month trial period in Edinburgh, B19 DNA was detected in 6 of 20,000 consecutive units of blood (0.03%), in concentrations ranging from 2.4 x 10(4) to 5 x 10(10) copies of viral DNA per ml. Seroconversion for B19-specific immunoglobulin M and immunoglobulin G and disappearance of circulating B19 DNA occurred in the interval between donation and recall in four of the five implicated donors who could be recalled. B19 DNA was detected in 18 of 27 separate batches of non-heat-treated factor VIII and IX concentrate manufactured from donated plasma unscreened for B19 DNA. Dry-heat treatment at 80 degrees C for 72 h reduced but did not always eliminate detectable B19 from factor VIII concentrates, consistent with recent observations that current methods for virus inactivation during blood product manufacture are insufficient to entirely eliminate B19 infectivity. The methods developed in this study for PCR screening could be applied routinely to prevent transfusion of B19 in blood and blood products and could play an important role in the prevention of iatrogenic transmission of infection. PCR screening could also be used for detection and exclusion of a range of other transmission-associated viruses for which current serological detection methods are only partially effective.

Base Sequence↗

Characterization of a nested polymerase chain reaction assay for detection of parvovirus B19.

The characterization and application of a nested polymerase chain reaction (PCR) assay for the detection of human parvovirus B19 DNA is described. The assay was evaluated with 149 diagnostic serum samples (collected up to 150 days after the onset of symptoms) previously tested by dot blot hybridization for B19 DNA and by class-specific capture radioimmunoassays for the detection of B19 immunoglobulin M (IgM) and IgG. B19 DNA was detectable by the PCR in 70% of the sera. There was a statistically significant association between the detection of B19 DNA by PCR and high B19 IgM values (P < 0.005), low B19 IgG values (P < 0.05), and a short interval between onset of symptoms and serum collection (P < 0.005). Serial serum samples, throat swabs, and peripheral blood mononuclear cells collected from 10 individuals during an outbreak of parvovirus B19 were also tested by the nested PCR. B19 DNA was detectable in the throat swabs at the time of the clinical illness and in the peripheral blood mononuclear cell fraction up to the end point of the study 6 months after infection. The location of the B19 DNA could not be determined in cytocentrifuge preparations of peripheral blood mononuclear cells with nonisotopic in situ hybridization and immunolabelling.

Antibodies, Viral↗

Application to immunoglobulin M capture hemadherence assays of hemagglutination of monkey erythrocytes by native and recombinant human parvovirus B19 antigens.

Human parvovirus B19 recently was shown to agglutinate baboon and human erythrocytes. We have now demonstrated that both recombinant and native B19 antigens agglutinate rhesus, cynomolgus, and Saimiri monkey erythrocytes. Using cynomolgus erythrocytes and the recombinant antigen, we developed an immunoglobulin M (IgM) antibody capture hemadherence test (MACHAT) for the detection of specific B19 IgM antibodies in human sera. The results obtained with MACHAT were compared with those obtained with an IgM capture enzyme immunoassay (MACEIA) employing the native antigen routinely used in our laboratory. For 229 patient serum samples, we found 96% agreement between the results of the two assays. There was some evidence that MACHAT was slightly more sensitive than MACEIA. Our results add to the range of erythrocytes that can be agglutinated by B19 virus and show that native as well as recombinant antigens may be used in MACHAT.

Animals↗