Self limiting lupus-like symptoms in patients with parvovirus B19 infection.
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AIMS: To compare the use of biotinylated and digoxigenin labelled probes for diagnosis of human fetal parvovirus B19 infection in formalin fixed, paraffin wax embedded tissues; and to assess the cellular distribution of the virus in positive cases. METHODS: Sections of lung tissue from 23 cases of anatomically normal non-immune fetal hydrops presenting between 1984 and 1989, and from 13 control cases of hydrops due to chromosomal abnormality were probed for B19 DNA by in situ hybridisation using both biotinylated and digoxigenin labelled probes. The distribution of the virus was then investigated in all cases of fetal B19 infection confirmed in this laboratory to date (n = 11) by combining in situ hybridisation for viral DNA (using the digoxigenin system) with immunohistological labelling for a range of cellular antigens. RESULTS: Five unequivocal cases of B19 infection were identified among the 23 fetuses with unexplained hydrops using both probe labels. When combined with data from previous studies of the period 1974-1983, the results indicate that B19 infection was responsible for 27% of cases of anatomically normal non-immune hydrops and 8% of all cases, of non-immune hydrops presenting to this hospital over 15 years. False positive signal was seen in an additional three cases, using biotinylated probes. Digoxigenin labelled probes gave greater specificity and permitted detailed investigation of tissues high in endogenous biotin. Though most cells containing B19 DNA colabelled as erythroid precursors, viral DNA was frequently detected within mononuclear-phagocytic cells. In three cases viral signal was also found within occasional myocardial cells labelled by antibody to desmin. CONCLUSIONS: A relatively high proportion of cases of anatomically normal, non-immune hydrops are caused by B19 infection. Digoxigenin is a more reliable probe label than biotin for in situ hybridisation in archival fetal tissues. Double labelling for cellular antigens and viral nucleic acid is a powerful technique for investigating virus-host cell interactions, and provides evidence that cell types other than those of erythroid lineage may have a role in human fetal parvovirus infection.
AIMS--To compare the sensitivity, specificity, and practicality of recombinant proteins in serological tests for the detection of human parvovirus B19 IgG and IgM. METHODS--Indirect enzyme linked immunosorbent assays using B19 structural proteins expressed in Escherichia coli were developed for the detection of B19 specific IgG and IgM (rELISA-G and rELISA-M). Cells infected with baculovirus expressing B19 structural proteins were also used in an indirect immunofluorescence assay for IgG and IgM antibodies (IFA-G and IFA-M). Antibody capture radioimmunoassays for IgG and IgM (GACRIA and MACRIA) were used as comparative assays. RESULTS--Twenty nine pools of intravenous immunoglobulin were clearly positive for B19 IgG by rELISA-G and contained low IgG titres by GACRIA. From 113 samples tested by all methods, sensitivities of 92% (77/84) and 97% (68/70) were obtained for ELISA and immunofluorescence, respectively, when compared with GACRIA. One hundred and sixteen samples from patients presenting with rash or arthralgia were compared by MACRIA, rELISA-M, and IFA-M. Sensitivities of both recombinant tests were more than 95%. Despite pretreatment to remove IgG or rheumatoid factor, false positive results were a problem in the rELISA-M but were not seen with the IFA-M. CONCLUSIONS--The limited supply of native antigen has severely restricted the wide application of serology for parvovirus B19. The use of recombinant antigens permitted the introduction of local screening tests which had many advantages, including quicker results and relief of the burden on the Reference Laboratory. The use of rELISA-M for sensitivity and IFA-M for specificity and confirmation proved a useful and practical combination for diagnosis of recent infection with B19, and rELISA-G allowed the immune response to be determined in selected populations.
Of 65 serum samples submitted for diagnostic purposes which proved to be anti-complementary by complement fixation test, 49 were parvovirus B19 IgM positive. Forty four of the 49 serum samples were from patients with arthropathy. Acute parvovirus B19 infection should be suspected when a patient has symptoms of disease of the joints and the serum is anticomplementary.
OBJECTIVE: To review the clinical and pathological features of parvovirus B19 meningoencephalitis and its sequelae in 12 previously published cases, and to perform additional tests to determine the pathogenesis of the disease. METHODS: Cases were reviewed and available serum and cerebrospinal fluid (CSF) tested for antiganglioside antibodies and a range of cytokines. In situ hybridisation for parvovirus B19 DNA was performed on postmortem brain tissue in two cases. HLA-DRB1 typing was undertaken on genomic DNA extracted from peripheral blood leucocytes. RESULTS: Cerebellar involvement was suggested either clinically or pathologically in four cases. In the two cases with postmortem histology, there was marked atrophy of the molecular and granular layers of the cerebellum with focal loss of Purkinje cells. Brain scanning by MRI or CT was done in six cases during the acute phase. Three were abnormal with evidence of demyelination. Three had markedly enlarged ventricles, in two of which there was high signal intensity from the white matter on both T1 and T2 weighted images. The three cases with abnormal brain scans had long term neurological sequelae (mental retardation, personality change, altered affect). In situ hybridisation on available postmortem brain tissue was negative in the two cases tested. All cases in which HLA-DR alleles were determined carried at least one of the following alleles: HLA-DRB1*01, *04, *07, *09, *15, *16. Available serum and CSF was tested for antiganglioside antibodies (all negative) and for a panel of cytokines, which had a similar profile in both serum (n = 5) and CSF (n = 1) during the acute phase. Cytokines that were consistently detectable were IL-6 (mean 726.20 pg/ml), TNFalpha (50.64 pg/ml), IFNgamma (39.64 pg/ml), GM-CSF (216.12 pg/ml), and MCP-1 (154.43 pg/ml); IL-1beta, IL-5, and IL-13 were undetectable. CONCLUSIONS: HLA-DR associations, an increased cytokine response, and benefit from immunomodulatory treatment (in one case) support a role for the immune response in the pathogenesis of parvovirus B19 meningoencephalitis.
Two cases of systemic vasculitis are described; one presenting with adult Henoch-Schonlein purpura secondary to a concomitant Chlamydia infection and the other with leucocytoclastic vasculitis and mesangioproliferative glomerulonephritis secondary to a recent parvovirus B19 infection. Association of chlamydial infection has not previously been described with Henoch-Schonlein purpura and this infection should, perhaps, be added to the list of aetiologies of this disease. Parvovirus B19 causing significant urinary sediment abnormalities associated with mesangioproliferative glomerulonephritis and leucocytoclastic vasculitis has also not been described previously.
Adults developing primary human parvovirus B19 (B19) infection may present with arthralgia, fever, and maculopapular rash. Recovery is linked to the development of specific neutralising antibodies. In immunosuppressed patients, including those with HIV infection, such humoral responses are impaired and severe chronic bone marrow suppression and arthritis may occur.
BACKGROUND AND OBJECTIVES: Human parvovirus B19 (B19 virus) can be transmitted through blood transfusion and plasma-derived products. In a previous report, we utilized the simple hemagglutination method based on the interaction between the B19 virus and P antigen on human erythrocytes in order to screen the blood donors. We called this method receptor-mediated hemagglutination (RHA) [Lancet 1995;346:1237-1238]. In this paper, we report on a large-scale screening of the B19 virus by RHA and discuss the results. MATERIALS AND METHODS: Donor sera from September 1995 to March 1997 and seroconversion panels were enrolled. Donor sera were examined by RHA for large-scale screening. The positive sera in the first screening were then further investigated by the RHA inhibition test, countercurrent immunoelectrophoresis (CIE), an enzyme-linked immunosorbent assay, and polymerase chain reaction (PCR). We also evaluated the infectivity and neutralizing activity of various kinds of sera by the erythroid colony forming unit (CFU-e) assay. To examine the detection limits of the B19 virus by RHA, B19-viremic sera were purified by sucrose gradient ultracentrifugation. RESULTS: Among 257,710 sera specimens, 293 sera (0.11%) gave a positive reaction in the first screening using RHA. Out of these 293 sera specimens, 31 were positive for PCR, of which 28 were also RHA inhibition-positive, and 25 of the 28 CIE-positive. In the CFU-e injury assay, all the RHA inhibition (+) sera showed a decrease in the number of erythroid colonies. The RHA inhibition (-) PCR (+) B19 antibody (+) sera did not affect the erythroid colony formation and protected CFU-e from injury by the B19 virus. By measuring the amount of purified B19 protein and its RHA titer, the detection limit of the B19 virus by RHA was calculated to the 0.37+/-0.03 ng/ml. CONCLUSION: These results suggest that the RHA(+) RHA inhibition (+) sera were infectious in vitro. The combination of RHA and the RHA inhibition test is considered to be useful for the large-scale screening of infectious B19 virus in blood donors with high specificity.
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We previously described an acute dermatosis characterized by pruritic erythematous and slightly papular lesions on the hands and feet in a 'gloves and socks' distribution associated with oral aphthoid lesions and fever (papular-purpuric 'gloves and socks' syndrome = PPGSS). We strongly suspected a viral origin, but serologic tests for a large panel of viruses remained negative. Subsequently, 2 cases of PPGSS with serologic evidence of a parvovirus B19 infection have been reported in the literature. Since then we observed 5 additional patients with a PPGSS. Parvovirus B19 infection could be confirmed in only 2 cases. Our findings suggest that the PPGSS can be another, yet undescribed manifestation of parvovirus infection. However, this cannot be shown in all the cases. As the papular acrodermatitis of childhood, this syndrome may be caused by various viral agents.
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We describe a case of primary infection by human parvovirus B19 in a 20-year-old woman; it manifested as erythemato-maculo-papular lesions, pharyngotonsillitis, lymphadenopathy, fever, arthralgia and myalgia, asthenia and anorexia. Laboratory tests revealed anaemia, leucopenia, thrombocytopaenia and a rise in some inflammatory indices. Elisa test was positive for anti-human parvovirus B19 IgM. Clinical symptoms spontaneously regressed in 2 weeks. Thirty days after hospital admission all the laboratory tests returned to normal values; furthermore, specific IgM and IgG were detectable.