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The prevalence of antibody to parvovirus B19 in hemophiliacs and in the general population.

The prevalence of antibodies to parvovirus B19 (B19) was measured in the sera of 566 hemophiliacs and 524 individuals of the general population by immunofluorescence assays, using antigen expressed by the baculovirus system. In the general population, anti-B19 IgG seroprevalence was found to continuously decline from 64 percent at birth to 0 percent in the age of 9-11 months and thereupon to increase to 61 percent in the age of 12 years. In younger adults and older people, IgG seroprevalence only slowly increased with age, reaching 77 percent in people aged 60 and above. In contrast, in hemophilic children treated exclusively with virally inactivated clotting factor concentrates, neither decrease nor increase of B19 IgG antibody was detectable and the overall seroprevalence was 92 percent. In the group of hemophiliacs older than 12 years and treated before 1984 with non-inactivated clotting factor concentrates, 98 percent showed antibody to B19. Anti-B19 IgM seroprevalence was significantly higher in hemophilic than in non-hemophilic individuals older than 12 years. Since it seems to be unlikely that the high seroprevalence in hemophiliacs is acquired by immunization with inactivated viral antigen, the results suggest that infection with B19 is transmitted by clotting factor concentrates, even if subjected to virucidal methods.

Adolescent↗

Comparison of seven commercial tests for the detection of parvovirus B19-specific IgM.

Several enzyme immunoassays (EIA) for the detection of parvovirus B19 IgM (anti-B19 IgM) are now commercially available. In this study, seven commercial EIAs (Biotrin, DAKO, Viramed, Viratech, R-Biopharm, Mast) were compared with an in-house EIA (MvP-EIA) using native viral B19 particles and the reference IgM radioimmunoassay (MACRIA). A total of 88 sera were tested. Results agreed in 39/88 (44.3%) sera, whereas 47/88 (53.4%) were discrepant and 2/88 (2.3%) gave an equivocal result. Assay sensitivity ranged from 70.3 to 100% and specificity, from 75.9 to 100%. The best results were obtained with two EIAs (Biotrin, DAKO) using baculovirus-expressed B19 proteins as antigen. This study has shown that baculovirus-expressed B19 antibody tests are suitable tools for detecting anti-B19 IgM.

Antibodies, Viral↗

Higher prevalence of parvovirus B19 in Belgian as compared to Tunisian blood donors: differential implications for prevention of transfusional transmission.

Serious anaemia can be induced by human parvovirus B19 (HPV) infection in immuno-compromised patients or subjects with an haemolytic disorder. Routine inactivation procedures are insufficient to neutralize the virus, but screening for HPV is an effective means to avoid transmission by transfusion of blood components. In the present study, we have compared for the first time the IgG and IgM seroprevalence in a North African (Tunisian) and Western European (Belgian) population of blood donors. The prevalence of HPV-specific IgM was less than 2% in both populations, pointing to the absence of an epidemic. The prevalence HPV IgG was significantly (p < 0.01) higher in Belgium (74%) than in Tunisia (65%), without any relationship with age or sex. This finding may suggest a south-north gradient of this infectious disease. Since the presence or absence of HPV-specific antibodies does not preclude transfusional transmission, screening for the virus itself should be done to avoid iatrogenic infection in HPV-naive subjects at risk. In view of the different transfusion policies in Belgium and Tunisia, a strategy for each of both countries is proposed.

Adolescent↗

Association of parvovirus B19 with plasma cell-rich myocardial infiltrates after heart transplantation.

In this report we describe the development of plasma cell-rich myocardial infiltrates in association with a parvovirus B19 infection in a heart transplant patient. We hypothesize that the virus, either alone or in association with the cardiac allograft, may polarize the immune response in the direction of T helper 2 (Th2) cells rather than the expected Th1 cells. This favors the development of a humoral immune response and infiltration of the graft with plasma cells.

Biopsy↗

Parvovirus B19 and autoimmune diseases.

Parvovirus B19 (B19) causes many clinical disorders, of which the most common are erythema infectiosum, aplastic crisis complicating chronic hemolytic anemia, and hydrops fetalis. In young adults, the skin eruption caused by B19 is accompanied with polyarthritis and polyarthralgia in 60% of the cases. The joint abnormalities predominate in the hands and feet and usually resolve within a week (range 2-21 d). Serological tests show IgM antibodies against B19, confirming the diagnosis of recent infection. Protracted polyarthritis occurs in some patients and seems associated with the DR4 histocompatibility alleles. Rheumatoid factors can be produced transiently in these patients. Other autoantibodies produced in the wake of B19 infection include anti-nuclear antibodies, anti-DNA, anti-SSA/SSB, and anti-phospholipids. Acute B19 infection can simulate early rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) (lupus-like eruption over the cheeks, cytopenia, etc.). In addition, there have been a few reports of erosive RA or SLE developing shortly after a B19 infection, with positive PCR tests for B19 DNA in synovial tissue or blood cells. Studies in large series indicate that B19 is probably an extremely rare cause of RA or SLE. Vasculitides affecting the small vessels (Henoch-Schonlein purpura, Wegener's granulomatosis), medium-sized vessels (periarteritis nodosa), and large vessels (giant cell arteritis) can occur after B19 infection. Here again, the number of clinical cases is small.

Adolescent↗

Baculovirus expression of parvovirus B19 (B19V) NS1: utility in confirming recent infection.

BACKGROUND: The presence of anti-parvovirus B19 (B19V) IgM against viral capsid proteins (VP1 and VP2) has long been used to detect recent infection. The utility of antibodies directed against B19V NS1 protein has received less attention as a serological indicator of recent infection, although anti-B19V NS1 IgG has been associated with persistent infection. OBJECTIVES: To elucidate the role of anti-B19V NS1 antibody detection in recent infection, full-length B19V NS1 was expressed and purified. The resultant antigen was used to develop both Western blot assays and microplate ELISA for the detection of NS1 antibodies. STUDY DESIGN: Serum specimens were obtained from individuals recently infected with B19V (children (n=16), adults (n=40)) and from 17 individuals with no evidence of recent B19V infection. All specimens were screened for anti-B19V NS1 IgG and IgM. RESULTS: It was observed that 68.8% (11/16) of children recently infected with B19V were anti-B19V NS1 IgG seropositive. Furthermore, 27.5% (11/40) anti-B19V VP2 IgM positive specimens also contained anti-B19V NS1 IgM when tested by ELISA, while no reactivity was observed following Western blot analysis, possibly due to the absence of conformational epitopes. CONCLUSIONS: Anti-B19V NS1 IgM detection may have utility in the confirmation of recent infection with B19V.

Adult↗

Simultaneous IgM reactivity by EIA against more than one virus in measles, parvovirus B19 and rubella infection.

BACKGROUND: A clinical diagnosis of rash-causing infections is not always possible and reliance has to be placed on serological evidence of infection, especially on the presence of specific immunoglobulin (Ig)M. However, despite the use of modern serological methods and validated commercial kits, reports appear in the literature of simultaneous IgM reactivity against more than one virus in cases of Epstein Barr virus, rubella, cytomegalovirus, human parvovirus B19 (HPV B19) and measles infections, all with implications for the pregnant woman. OBJECTIVES: We decided to evaluate the extent of the problem in rubella, measles and HPV B19 infections in a routine diagnostic laboratory. STUDY DESIGN: We tested sera from cases with initial clinical and serological evidence of infection with measles, HPV B19 or rubella for evidence of simultaneous IgM reactivity against more than one virus. We confirmed primary infections with specific-IgG antibody avidity tests, and subjected sera with IgM reactivity against more than one virus to avidity tests to identify which, if any, of the three viruses was the cause of the primary infection. Groups of monoreactive IgM sera were randomly selected from the presented sera to demonstrate that the avidity of the IgG specific for the other two viruses would be of high avidity compared with the low avidity of the IgG specific for the virus against which specific IgM had been detected. RESULTS: Our results confirm that simultaneous IgM reactivity against more than one virus does occur in these three infections, and that this is unlikely to be caused by the presence of rheumatoid factor. CONCLUSIONS: In the absence of seroconversion, reliance on specific IgM results alone for diagnosis of these infections should be avoided and tests such as specific IgG antibody avidity should also be employed. The simultaneous occurrence of IgM reactivity against more than one virus is also important for epidemiological and surveillance reasons as the widespread use of the mumps, measles and rubella vaccine makes its impact on the population. Falsely diagnosed cases of apparent measles or rubella could throw into question the efficacy of the vaccine.

Antibodies, Viral↗

Human parvovirus B19 infection within a family and risk for pregnant women.

During an outbreak of parvovirus B19 infection among four related families at least 70% of the household contacts, including a woman at the 33rd week of pregnancy, became infected. Twins were born at the 39th week of pregnancy, both with B19 infection. B19 DNA was detected in their sera by a nested PCR, anti-B19 IgM was detectable only by an immunofluorescence assay, and low levels of maternal anti-B19 IgG were demonstrable by an immunoenzymatic test in the serum of both children. All the haematological parameters were normal at birth and 6 months later, when B19 DNA and anti-B19 antibody were no longer detectable in serum samples. This observation emphasizes the high risk of B19 infection among household contacts and the possibility of a favourable outcome of the foetal infection, possibly related to infection late in the pregnancy.

Adult↗

A school outbreak of parvovirus B19 infection investigated using salivary antibody assays.

An outbreak of parvovirus B19 infection at a primary school was investigated using saliva samples. Antibody capture immunoassays for salivary B19 IgG and IgM were developed using a recombinant B19 antigen and monoclonal antibody to B19 virus. Evaluation of the salivary IgG assay using paired serum and saliva samples from 43 staff at St Thomas' Hospital showed that it had a sensitivity of 100% and a specificity of 95%. Evaluation of the salivary B19 IgM assay using 87 paired blood and saliva samples from a study of general practitioner rubella notifications showed it had a sensitivity of 60% and a specificity of 98%. Using the salivary assay the level of B19 IgG within 2 weeks of the start of the outbreak ranged from 5-33% in children and 29% in staff. By detecting salivary B19 IgM and/or B19 IgG seroconversions, attack rates of 8-50% in children in different classes and 47% in staff were observed. Household transmission was also studied and an attack rate of 45% was recorded in 11 susceptibles. After the outbreak, the level of B19 IgG in children with the highest attack rates was 60-70%, similar to that seen in adults in the UK. This study highlights the risk of B19 infection in an institutional setting and shows that saliva samples are a useful alternative to blood.

Adolescent↗

Current epidemiological aspects of human parvovirus B19 infection during pregnancy and childhood in the western part of Germany.

This investigation was undertaken to provide detailed information on the epidemiology of human parvovirus B19 (B19) infection during pregnancy and childhood in the western part of Germany. Between 1997 and 2004, 40,517 sera from pregnant women aged 17-45 years and 6060 sera from children and young adults were tested for B19 IgG and IgM in our laboratory. In pregnant women, both the history of a 'specific' (OR 7.7, 95% CI 5.2-11.4) and a 'non-specific' rash (OR 3.3, 95% CI 1.5-7.1) was predictive for B19 IgM positivity. The B19 IgG prevalence was 69.2% (4097/5924) in a subgroup of asymptomatic pregnant women screened for B19 antibodies. In children, the age-specific IgG-positivity rate increased from 12.2% (66/541) at 2 years of age to 71.9% (396/551) in those older than 10 years. In conclusion, the prevalence of B19 IgG in pregnant women from the western part of Germany is higher then previously reported. Contact with children aged 3-10 years is a major risk factor for exposure to B19. Pregnant women with the history of a 'non-specific' rash should also be evaluated for acute B19 infection.

Adolescent↗

Detection of challenge virus in fetal tissues by nested PCR as a test of the potency of a porcine parvovirus vaccine.

To estimate the potency of a porcine parvovirus (PPV) vaccine, three vaccinated and three non-vaccinated pregnant gilts were infected with PPV and the distribution of the virus was studied in the tissues of their 51 fetuses. Virus detection was attempted using haemagglutination (HA) and immunofluorescence (IF) assays, as well as by standard (single) and nested polymerase chain reactions (PCR). None of the detection methods yielded positive results when used to test for the presence of virus in suspensions of organs from the fetuses from the vaccinated gilts. However, the virus was detected in the fetuses from non-vaccinated gilts as follows: HA was positive in 14 cases out of 23 (60.8%), IF in 16/23 (69.5%), standard PCR in 12/20 (60%), and the nested PCR in 19/23 (82.6%). Although the correlation among the results of various methods of virus detection was rather close (r < 0.83), the sensitivity of the nested PCR was the highest, both when testing dilutions of PPV and when analysing the fetal organs. The nested PCR therefore provides a reliable approach for studies of virus distribution in fetal organs, with special reference to potency tests on vaccines.

Animals↗

Detection of porcine circovirus type 2, porcine parvovirus and porcine pseudorabies virus from pigs with postweaning multisystemic wasting syndrome by multiplex PCR.

Multiplex PCR was established to detect porcine circovirus type 2 (PCV-2), porcine parvovirus (PPV) and porcine pseudorabies virus (PRV) and applied to samples from 137 piglets exhibiting clinical signs of postweaning multisystemic wasting syndrome (PMWS). PCV-2 DNA was detected from all samples. Moreover, 43 samples were positive for PPV but negative for PRV; 11 samples were positive for PRV but negative for PPV; and 35 samples were positive both for PPV and PRV. These results suggests that PCV-2 co-infection with PRV and PPV may play an important role in PMWS. Also, multiplex PCR is an appropriate candidate method for diagnosis of PCV-2, PRV and PPV simultaneously in field cases.

Animals↗

Human parvovirus B19 infection in organ transplant recipients.

We report a 61-yr-old kidney transplant recipient with human Parvovirus B19 (HPV B19) infection presenting as a severe pancytopenia 1 month after transplantation. Bone marrow aspiration revealed severe erythroid hypoplasia with giant and dystrophic proerythroblasts. Bone marrow cells were positive for HPV B19 DNA detected by polymerase chain reaction (PCR). Pancytopenia resolved shortly after administration of intravenous immunoglobulins. Nineteen cases of HPV B19 infection in organ transplant recipients have been so far reported in the literature. Immunocompromised patients should be considered at risk from developing symptomatic HPV B19 infections. In such patients, specific anti-HPV B19 IgM and IgG antibodies may be absent or transient and therefore their negativity cannot rule out the diagnosis of HPV B19 infestation. Bone marrow smear morphological findings may suggest the diagnosis but testing for viral DNA by PCR is mandatory. Patients may spontaneously recover. However, since specific anti-viral therapy is not currently available, intravenous immunoglobulin administration appears to be the more efficacious treatment.

DNA, Viral↗

Pure red cell aplasia caused by Parvovirus B19 infection in solid organ transplant recipients: a case report and review of literature.

Human Parvovirus B19 (PV B19) is one of the several recently described 'emerging viruses' and has been identified as the etiological agent of 'fifth disease' in childhood. Human PV B19, which is the etiological agent of transient erythroblastopenia in hemolytic anemia, is also a recognized rare cause of red cell aplasia in immunocompromised patients, including transplant recipients. To date, 26 cases of PV B19-induced red cell aplasia have been reported in solid organ transplant recipients. Twelve patients had cyclosporine-based immunosuppression and 14 had tacrolimus-based immunosuppression. Sixteen of these patients required treatment with commercial intravenous immunoglobulin alone, 1 required treatment with intravenous immunoglobulin and plasmapheresis, 4 required intravenous immunoglobulin and erythropoietin, 1 required treatment with intravenous immunoglobulin and conversion of tacrolimus to cyclosporine, 1 had improvement in hematocrit with erythropoietin alone and in 3 patients the disease was self-limiting. Herein, we report a case of pure red cell aplasia caused by acute PV B19 infection in a renal transplant recipient in whom the immunosuppressive regimen included prednisone, mycophenolate mofetil and tacrolimus and the red cell aplasia resolved with discontinuation of mycophenolate mofetil.

Acute Disease↗

Treatment of parvovirus B-19 (PV B-19) infection allows for successful kidney transplantation without disease recurrence.

Parvovirus B 19 (PV-B19) has emerged as a cause of glomerulopathy in native and transplanted kidneys. Disease recurrence is less well described. The clinical and pathological spectrum of PV-B19 infection can be quite variable and therefore easily missed. There are no data regarding the safety of transplantation in PV-B19-infected patients. We diagnosed a kidney transplant patient with recurrent PV-B19 infection and collapsing glomerulopathy (CG) on renal biopsy. Retrospective analysis of stored serum showed that PV-B19 DNA was present prior to the transplant. The patient was treated with intravenous immunoglobulin (IVIG), and eventually the virus was successfully eradicated after allograft loss and discontinuation of immunosuppressive medications. The patient subsequently received her fourth kidney transplant. Polymerase chain reaction (PCR) for PV-B19 DNA was negative on multiple occasions for approximately 1 year prior to her transplant. The patient is now 22 months post transplantation, quarterly serum PCRs continue to be negative for PV-B19 DNA despite reinstitution of immunosuppressive therapy. The patient's renal function remains stable with a serum creatinine of 0.9 mg/dL and a serum albumin of 4.2 g/dL. Successful diagnosis and treatment of PV-B19 viremia appears to allow for successful transplantation without evidence of disease recurrence. Since PV-B19 can cause significant morbidity post transplant, it is important to screen potential transplant candidates at risk for PV-B19 infection pre transplant. Careful surveillance post transplantation is necessary to identify disease recurrence so that early treatment can be initiated.

Acute Kidney Injury↗

A rare case of acute 'infective' myocardial infarction triggered by acute parvovirus B19 myocarditis.

BACKGROUND: A 25-year-old obese male (BMI 31.9 kg/m(2)) presented with atypical chest pain of sudden onset that was indistinguishable from acute myocardial infarction. He had tachycardia (104 beats/min) and dyspnea at a low level of exercise. He had no previous cardiac history, but his cardiovascular risk profile included a familial predisposition, smoking and hypertension. INVESTIGATIONS: Electrocardiogram, laboratory testing, chest radiography, echocardiography, coronary angiography, intravascular ultrasonography and endomyocardial biopsy. DIAGNOSIS: Acute myocardial infarction and parvovirus-B19-positive myocarditis. MANAGEMENT: Percutaneous transluminal coronary angioplasty with intracoronary abciximab, heparin and nitroglycerin infusion.

Acute Disease↗

Quantitative real-time detection of parvovirus B19 DNA in plasma.

BACKGROUND: As of 2004, the European Pharmacopoeia demands that plasma pools for production of anti-D immunoglobulin should not contain more than 104 IU per mL of parvovirus B19 (B19V) DNA. Hence, before pooling, highly viremic donations have to be identified, and after pooling the level of B19V DNA must be determined. The performance of a new real-time B19V DNA PCR test (Roche, Mannheim, Germany) was studied, using a DNA extractor (NucliSens, bioMerieux, Boxtel, the Netherlands) for isolation of nucleic acid, and using a DNA quantification test (LightCycler apparatus, Roche, Mannheim, Germany) for amplification and detection. STUDY DESIGN AND METHODS: Dilutions of the international B19V DNA standard and reference preparations were tested to determine the precision, linear range, and accuracy of the assay and to calculate the factor for conversion of B19V DNA copies to IUs. The internal control signals, invalid test results, and the effect of cryo-poor plasma were studied as a measure for robustness. Routine performance was assessed by testing 164 manufacturing pools (not screened for B19V) and 1048 test pools of 480 donations each. RESULTS: The copies-to-IU conversion factor was calculated to be 3.34 (95% CI, 3.07-3.63). The assay appears linear between 10(3) and 10(7) IU per mL. Between 10(3) and 10(5) IU per mL, the test can discriminate samples differing a factor two in B19V DNA content. Overall, 0.78 percent of the test results were invalid. Of 127 B19V DNA negative control plasma samples, 7 were contaminated with low levels of B19V DNA. Of 164 nonscreened manufacturing plasma pools, 92 contained B19V DNA (56%); 13 contained more than 10(4) IU per mL. Of 503,040 donations, 29 contained more than 5 x 10(6) IU per mL B19V DNA (1:17,346). CONCLUSION: The B19V DNA quantification test (LightCycler, Roche ) is suitable for quantitative, routine, in-process measurement of B19V DNA levels in plasma pools, using the DNA extractor (NucliSens, bioMerieux) for nucleic acid isolation.

Blood Donors↗

Prevalence of human parvovirus B19 in blood donors as determined by a haemagglutination assay and verified by the polymerase chain reaction.

BACKGROUND AND OBJECTIVES: Transmission of human parvovirus B19 (PV B19) by transfusion of blood and blood products is well documented. Although PV B19 infection is connected with severe complications in some recipients, donor screening is not yet mandatory. In this study the prevalence of PV B19, as detected by a haemagglutination assay (the Human PV B19 Antigen-Test), was assessed. In addition, the persistence of B19 DNA and the serological status of blood donors was also assessed. The specificity and utility of the Human PV B19 Antigen-Test for donor screening was investigated and compared with other screening strategies. MATERIALS AND METHODS: The prevalence of PV B19 viraemia was assessed in 28 972 donations from 15,660 remunerated donors by means of the haemagglutination assay. Reactive results were confirmed by the polymerase chain reaction (PCR). RESULTS: Overall, 255 donations gave reactive or indeterminate results in the screening assay. Four donations/donors detected by the haemagglutination assay were confirmed as positive for B19 DNA by PCR. Therefore, a frequency was detected of 1:7243 B19-positive donations and 1:3915 positive donors. Specificity was determined to be 99.1%. Follow-up showed the persistence of viraemia in low concentrations for prolonged time-periods. CONCLUSION: Blood donations with a high level of human PV B19 viraemia can be detected by the haemagglutination assay, which is rapid and easy to perform. The presence of neutralizing antibody may inhibit specific haemagglutination.

Adolescent↗