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Human parvovirus B19, varicella zoster virus, and human herpes virus 6 in temporal artery biopsy specimens of patients with giant cell arteritis: analysis with quantitative real time polymerase chain reaction.

OBJECTIVE: To evaluate the role of parvovirus B19 (B19), varicella zoster virus (VZV), and human herpes virus 6 (HHV-6) in the aetiopathology of giant cell arteritis (GCA). METHODS: Temporal artery biopsy specimens from 57 patients with GCA and 56 controls were investigated. DNA was obtained by biopsy, and quantitative real time polymerase chain reaction assay performed to establish the prevalence and viral load of B19, VZV, and HHV-6. Amplification of the human beta-globin gene was used as internal positive control. RESULTS: (a) B19 was detected in 31/57 (54%) patients (median viral load 45.2 (25th-75th centiles 0-180.2) copies/microg DNA) v 21/56 (38%) controls (median viral load 0 (0-66.7) copies/microg of DNA; p = 0.07 for DNA prevalence, p = 0.007 for viral load. Among 31 B19 positive samples, 21 (68%) patients with biopsy proven GCA had >10(2) B19 copies/microg of DNA v 5/21 (24%) controls; p = 0.001. (b) No significant difference was found for VZV (p = 0.94 for DNA prevalence; p = 0.76 for viral load) and HHV-6 (p = 0.89 for DNA prevalence; p = 0.64 for viral load) in the GCA group compared with controls. CONCLUSION: B19 may have a role in the aetiopathology of GCA, particularly in those patients with high viral load; no evidence was found for VZV and HHV-6.

Aged↗

Low frequency of recent parvovirus infection in a population-based cohort of patients with early inflammatory polyarthritis.

OBJECTIVE: To determine the contribution of human parvovirus B19 infection in explaining the incidence of early inflammatory polyarthritis (IP) in a population. SETTING: The Norfolk Arthritis Register (NOAR) is a community-based programme aiming to ascertain all new cases of IP arising in a population that lead to attendance at primary care. SUBJECTS: 147 newly ascertained subjects with IP with a disease duration of less than 16 weeks. METHODS: Full clinical appraisal of all subjects who were followed up for three years. B19 IgM assayed with a third generation antibody capture enzyme immunoassay. RESULTS: Only four (2.7%) patients had evidence of recent B19 infection, only one of whom did not satisfy criteria for rheumatoid arthritis (RA). CONCLUSION: B19 infection does not explain more than a small proportion of either RA or undifferentiated IP cases occurring in the population.

Adolescent↗

Parvovirus B19 infection, hepatitis C virus infection, and mixed cryoglobulinaemia.

BACKGROUND: Infection with human parvovirus B19 (B19) has been reported in a few patients with various vasculitis syndromes. Mixed cryoglobulinaemia (MC), a model of small vessel size vasculitis, may result from numerous infectious diseases, particularly hepatitis C virus (HCV) infection. AIM: To assess the prevalence of seric B19 infection markers in a large series of patients with MC, with or without HCV infection. PATIENTS AND METHODS: Sixty-four patients were studied: essential MC (EMC, n = 19), MC associated with non-infectious diseases (non-essential MC, n = 9), and patients with HCV infection with (HCV-MC, n = 18) or without MC (HCV-no-MC, n = 18). Patients were considered to have MC if two successive determinations of their serum cryoglobulin concentration were above 0.05 g/l. Serum samples were analysed for specific IgG and IgM antibodies to B19 by enzyme immunoassay. B19 DNA detection was performed by polymerase chain reaction using a set of primers located in the VP1 gene, separately in serum and in cryoprecipitates to investigate a possible capture of B19 DNA in cryoprecipitate. The study also looked for a possible enrichment for of IgG antibodies to B19 in MC. RESULTS: The presence of specific IgG antibodies to B19 was found in 68% EMC, 56% non-essential MC, 78% HCV-MC, and 78% HCV-no-MC. No patient of either group had specific IgM antibodies to B19, or B19 DNA in serum or in cryoprecipitate. Overall, IgG antibodies to B19 were found in 46 of 64 (72%) serum samples, a prevalence quite similar to the prevalence in general adult population (> 60%). A specific enrichment of IgG antibodies to B19 in the MC was not found. CONCLUSION: These results suggest that B19 infection is neither an aetiological factor of EMC, nor a cofactor that may lead to MC production in patients with chronic HCV infection.

Antibodies, Viral↗

Parvovirus B19 detected in Rosai-Dorfman disease in nodal and extranodal manifestations.

Sinus histiocytosis with massive lymphadenopathy (SHML), also designated as Rosai-Dorfman disease (RDD), is a rare benign reactive lymphoproliferative disorder. It is defined by a characteristic histopathology with sinus histiocytosis and haemophagocytosis known as emperipolesis. In histiocytes S100 is strongly expressed, whereas CD1a staining typically is negative. The disease mainly manifests at a single lymph node; however, multilocular and extranodal affection can occur. Causative infectious agents, and virus infections in particular, have repeatedly been suspected, although until now the origin of the disease has been unclear. Four cases of RDD (two nodal sites and two extranodal upper respiratory tract sites) were analysed for parvovirus B19 (B19) infection by immunohistochemistry to detect B19 capsid proteins VP1/VP2. In all the four cases, huge numbers of B19-positive cells were partly detected. The positive cells were identified either as lymphocytes or, in one extranodal case, also as respiratory epithelial cells. This is the first report of B19 infection in RDD tissue, indicating that B19 may be associated with the pathogenesis of SHML.

Adult↗

Anaemia in lung transplant patient caused by parvovirus B19.

The case history is presented of a lung transplant patient who developed prolonged parvovirus B19 infection with severe transfusion dependent anaemia. The patient was treated with intravenous immunoglobulin after which the haemoglobin rose, together with a reticulocytosis. The patient then remained transfusion free and the virus cleared more than three months after the initial immunoglobulin treatment. The clinical and social implications for this group of patients are discussed.

Anemia↗

Evaluation of a dot ELISA kit for measuring immunoglobulin M antibodies to canine parvovirus and distemper virus.

A dot ELISA for the detection of immunoglobulin M (IgM) antibodies to canine distemper virus (CDC) and canine parvovirus (CPV) was assessed. The titres of IgM antibodies to CDV and CPV in 100 dogs were measured by the Immunocomb ELISA kit and compared with the results derived from the immunofluorescence assay (IFA). There was a strong correlation between the results of the dot ELISA technique and the IFA (P < 0.001). The dot ELISA kit was also used to assess the changes in the levels of immunoglobulin G (IgG) and IgM antibodies to CPV and CDV in 10 puppies vaccinated with a polyvalent vaccine. High levels of IgM antibodies to CPV were first detected seven days after they were vaccinated, and after nine days all the pups had high titres of IgG antibodies to CPV. High levels of IgM antibodies to CDV were detected after nine days and the highest average titres were recorded after 12 days. IgG antibodies to CDV were present from nine days after vaccination.

Animals↗

Serum antibody titres to canine parvovirus, adenovirus and distemper virus in dogs in the UK which had not been vaccinated for at least three years.

Antibody titres to canine distemper (CDV), canine parvovirus (CPV) and canine adenovirus (CAV) were measured in 144 adult dogs that had not been vaccinated for between three and 15 years. Protective antibodies to CPV were present in 95 per cent of the population, to CDV in 71.5 per cent and to CAV in 82 per cent. The prevalence of protective titres did not decrease with increasing time interval from the last vaccination for any of the three diseases studied. Booster vaccination increased the dogs CAV titres. For comparative purposes, 199 puppies were sampled at the time of their first and second vaccination. In the case of CPV and CAV a significantly higher proportion of the adult dogs were protected than of the puppies immediately after they were vaccinated. Natural CPV boosting was strongly suspected because the dogs had significantly higher titres three years after their primary vaccination than two weeks after it and three unvaccinated dogs had acquired protective antibody levels uneventfully. There was no evidence of natural exposure to CDV.

Adenoviridae Infections↗

Serological responses of adult dogs to revaccination against distemper, parvovirus and rabies.

Serum antibody titres to canine distemper virus (CDV), canine parvovirus (CPV) and rabies were measured in dogs that had not been revaccinated annually and compared with the titres in a control group of regularly vaccinated animals; 83 per cent (171 of 207) of the dogs vaccinated against CDV one or more years earlier had serum neutralising antibody titres equal to or greater than 16; 64 per cent (136 of 213) of the dogs vaccinated against CPV one or more years earlier had haemagglutination inhibiting titres equal to or greater than 80; and 59 per cent (46 of 78) of the dogs vaccinated against rabies two or more years earlier had serum neutralising antibody titres equal to or greater than 0.5 iu/ml. Three weeks after a single booster vaccination the dogs' antibody titres against CDV had increased above the threshold level in 94 per cent of the dogs, against CPV in 68 per cent, and against rabies in 100 per cent.

Animals↗

Comparative trial of the canine parvovirus, canine distemper virus and canine adenovirus type 2 fractions of two commercially available modified live vaccines.

The results of vaccinating two groups of puppies with commercial vaccines, both of which claimed to provide adequate protection with a final vaccination at 10 weeks of age, were compared. Groups of 19 and 20 puppies with similar titres of maternally derived antibodies against canine parvovirus (cpv), canine distemper virus (cdv) and canine adenovirus type 2 (cav-2) at four weeks of age were vaccinated at six and 10 weeks of age and their responses to each vaccination were measured by comparing the titres against cpv, cdv and cav-2 in the serum samples taken immediately before the vaccination and four weeks later. After the vaccination at six weeks of age, all 19 of the puppies in group 1 had responded to cpv and cdv, and 14 had responded to cav-2; in group 2, 17 of the 20 had responded to cpv, 19 to cdv and 15 to cav-2. In both groups the puppies that did not respond to the first vaccination had responded serologically to cpv, cdv and cav-2 at 10 weeks of age.

Adenoviridae Infections↗

Human parvovirus B19 infection in multiple sclerosis.

The association of human parvovirus B19 (PVB19) infection with the development of several systemic autoimmune diseases has been confirmed in other studies. To determine if there is any association of PVB19 infection with multiple sclerosis (MS), we studied the prevalence of serum anti-PVB19 IgG and IgM by an enzyme-linked immunosorbent assay and PVB19-specific DNA in the cerebrospinal fluid (CSF) by the polymerase chain reaction method in a total of 46 patients during exacerbation or remission of MS. Anti-PVB19 IgG was detected in 65.8% of the patients' sera. The percentage was significantly higher than that in age-matched healthy control subjects (40%; p = 0.019), but was not higher in patients with other neurological diseases (50%; p = 0.16). There was no correlation between serum anti-PVB19 IgG status and antinuclear antibodies or oligoclonal IgG bands in CSF. Serum anti-PVB19 IgM and PVB19 DNA in CSF were consistently negative in the patients during exacerbation of MS. Although MS patients may be commonly infected with PVB19, our results suggest that there is no active PVB19 infection during exacerbation of MS.

Adolescent↗

Screening of blood donors for human parvovirus B19 and characterization of the results.

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.

Blood Donors↗

Efficiency of donor screening for human parvovirus B19 by the receptor-mediated hemagglutination assay method.

BACKGROUND AND OBJECTIVES: Mass screening for parvovirus B19 (B19) by receptor-mediated hemagglutination assay (RHA) may be inadequate to eliminate the virus from plasma pools. We characterized B19 carriers detected in blood donor screening by RHA to explain why some carriers were not detected by RHA. MATERIALS AND METHODS: Donor plasma was screened for B19 by RHA, B19 DNA by nested polymerase chain reaction (PCR) assay, and anti-B19 by enzyme immunoassay. RESULTS: B19 DNA-positive specimens (n = 73) screened from 456,665 donors were divided into group A (n = 41) with high DNA and high RHA titers, group B (n = 16) with low DNA and low RHA titers, and group C (n = 16) RHA-negative. Most (37/41) of the group A samples were without anti-B19, while most (15/16) of the group B samples were positive for anti-B19. Group C specimens were screened by PCR from 3, 042 random RHA-negative specimens. Analysis of samples from early infections revealed that the viremic period, corresponding to group A, lasted only 8-10 days after infection. The RHA reactivity fell rapidly with the appearance of anti-B19 and disappeared 28-30 days after infection, thus corresponding to group B. The RHA reactions of group B specimens were often unstable, probably because of the formation of immune complexes. The B19 DNA-positive, RHA-negative state lasted for several months, which corresponded to group C. CONCLUSION: Only group A specimens are reliably eliminated in donor screening by RHA. Therefore, although donors with high B19 DNA could be screened out by testing for B19 by the RHA, most B19 carriers, with low B19 DNA and RHA-negative, will not be eliminated.

Antibodies, Viral↗

Large-scale screening for human parvovirus B19 DNA by PCR: application to the quality control of plasma for fractionation.

BACKGROUND AND OBJECTIVES: Because human parvovirus B19 (B19) has been transmitted by various plasma-derived medicinal products, the 'Laboratoire français du Fractionnement et des Biotechnologies' (LFB) implemented PCR screening of plasma pool samples for B19 DNA as part of the quality control of plasma source material. MATERIALS AND METHODS: Plasma pool samples (average of 46.5 donations) were tested for B19 DNA by PCR and by immunological detection of PCR products. The viral DNA content was determined by means of a TaqMantrade mark-based, quantitative PCR. RESULTS: From plasma corresponding to 2-year collections in France, and representing 4.26 million donations from approximately 1.25 million voluntary unpaid donors, the average frequency of positive donations was 1/5,950 and reached 1/1,420 during an epidemic. Levels of B19 DNA in positive pools ranged from <10(2) to 10(11) copies/ml. CONCLUSION: A large-scale PCR plasma screening increased the safety of LFB's wide range of products with respect to B19, a virus particularly resistant to physicochemical inactivation procedures.

Consumer Product Safety↗

Renal involvement induced by human parvovirus B19 infection.

In an attempt to clarify the renal involvement induced by human parvovirus B19 (HPB19) infection, we investigated 6 adult patients with transient urinary abnormalities followed by erythema infectiosum. All patients had HPB19-specific IgM antibody and showed mild proteinuria of 0.2-1.2 g/day with or without microscopic hematuria. In 5 patients a decrease of complement was present, and in 2 the circulating immune complex levels were elevated. All patients showed mild or moderate endocapillary proliferation with leukocytic infiltrates in glomeruli and leukocytic infiltrates with edema around interlobular arteries and arterioles. Immunofluorescence microscopy revealed C3c deposits with immunoglobulins along the glomerular capillary walls and in the walls of small arteries and arterioles. Electron microscopic studies showed swelling of the endothelial cells and small electron-dense deposits in mesangium (in all 6 patients) and subendothelium (in 5 of 6 patients). However, HPB19 VP1 and VP2 capsid antigens were not demonstrated in the glomerulus or the vascular wall in any patient. These findings suggest that the renal lesions caused by an immune complex mediated phenomenon would be closely correlated with the HPB19 infection, although the precise mechanism is not entirely clear, and that in adults HPB19 should be thought of as a possible cause of acute postinfectious glomerulonephritis.

Adult↗

Two-year follow-up study after human parvovirus B19 infection.

BACKGROUND: Acute human parvovirus B19 (B19) infection induces systemic lupus erythematosus (SLE)-like symptoms. It has been controversial whether B19 infection causes SLE and rheumatoid arthritis (RA). OBJECTIVES: This study prospectively investigated whether symptoms of B19 infection persisted for more than 2 years and whether persistent symptoms contributed to the development of SLE and RA. METHODS: In this prospective study, clinical findings were examined and laboratory examinations were performed in 42 adult patients 1, 2, 6, 12 and 24 months after the first consultation. RESULTS: Most acute symptoms disappeared within 2 weeks. However, arthralgia continued for 2 months in 2 women, 6 months in 1 woman and more than 2 years in 1 woman with positive antinuclear antibody and hypocomplementemia. The clinical findings of the patient with persistent arthralgia did not fulfill the criteria for SLE and RA. CONCLUSION: The symptoms caused by B19 infection were transient in most cases but persisted in 1 case in our series.

Adolescent↗

Neutropenia due to parvovirus B19 infections in patients with paroxysmal nocturnal hemoglobinuria. Blood transfusion and natural infection cases.

Two patients with paroxysmal nocturnal hemoglobinuria (PNH) and parvovirus B19 (PVB19) infection are reported. One was infected by PVB19-contaminated blood transfusion, whereas the other had become infected naturally. Both patients completely recovered after transient pancytopenia, but showed severe and intermediate neutropenia (0.216 and 0.768 x 10(9)/l, respectively) at the nadirs of aplastic crises. In the literature, PNH cases also showed neutropenia (0 and 0.54 x 10(9)/l) at aplastic crises. When patients with PNH are infected by PVB19, they may show severe neutropenia and mild thrombocytopenia in addition to severe reticulocytopenia. Therefore, these patients might have to be treated with granulocyte colony-stimulating factor to be able to recover from severe neutropenia.

Aged↗

Retrospective study on the influence of human parvovirus B19 infection among children with malignant diseases.

Human parvovirus B19 (B19) is a known cause of erythema infectiosum (fifth disease) and aplastic crisis in patients with hemolytic anemias. When patients with malignant diseases are infected by B19 during chemotherapy, erythroid suppression of bone marrow sometimes occurs. We performed a retrospective investigation of B19 infection among 95 children with malignant diseases in our hospital during the past 14 years. By the method of dot blot hybridization, 9 of 95 patients were found to be positive for B19 DNA during chemotherapy. All 9 patients had reticulocytopenia at the time B19 DNA was detected in their serum samples. Neutropenia and thrombocytopenia were not found. Seven of them had only transient reticulocytopenia. Serum samples from 2 other patients were positive for B19 DNA for a longer time. They suffered from persistent anemia for about 2 and 13 month, respectively. The years when B19 DNA was detected from the 9 patients corresponded to the prevalence of erythema infectiosum in Japan.

Child↗

Nonimmune hydrops fetalis caused by intrauterine human parvovirus B19 infection: a case of spontaneous reversal in utero.

We report a case of spontaneous reversal in utero of hydrops fetalis caused by parvovirus B19 maternal-fetal infection. The route leading to fetal hydrops is not fully understood. Severe anemia with hypoxemia and viral fetal myocarditis have been incriminated. Then the main issue is fetal death or spontaneous abortion. Cases of spontaneous reversal of hydrops fetalis are unusual. Fetal regenerative anemia is a good prognostic factor and emphasizes the place of conservative management.

Adult↗