Anti-parvovirus B19 Research Articles

A Case of Immunoglobulin Therapy for Pure Red Cell Aplasia Induced by Parvovirus B19

Human parvovirus B19 infection could be manifested as pure red cell aplasia or chronic anemia in im- munocompromised host. The patient was 35-year-old female who had been diagnosed as non-Hodgkin lymphoma, peripheral T-cell unspecified type and had been performed chemotherapy. She complained headache and dizziness that was found to a marked drop in hemoglobin (3.2g/dL). A bone marrow aspira- tion revealed findings consistent with erythroid hypoplasia with maturation arrest. Serum parvovirus B19 PCR and anti parvovirus B19 IgM were positive. After immunoglobulin therapy, it was leading to a marked increase in reticulocyte count and corresponding rise in hemoglobin. To our knowledge, this is the first report to use immunoglobulin in an adult cancer patie nt with pure red-cell aplasia. Human parvo- virus B19 infection should be considered in immunocompromised cancer patients with red cell aplasia and early use of immunoglobulins would be helpful in resolution of anemia and not to delay planned chemotherapy. (Korean J Hematol 2007;42:283-287.)

Prevalence Of IgE Anti-parvovirus B19 Antibodies In Asymptomatic Healthy Adult Humans

RATIONALE: Our previous studies were the first to demonstrate (1) presence of IgE anti-HIV-1 antibodies in HIV-1 infected humans; (2) that IgE has anti-viral function, i.e., suppression of HIV-1 production by IgE mediated cytotoxic activity; and (3) presence and persistence of IgE anti-parvovirus B19 antibodies in infected and IgA deficient patients. Others have described IgE directed against other viruses (RSV, parainfluenza, Puumala, HTLV-1). It could be that an important function of IgE is an anti-viral effect.

Symptoms Associated with Parvovirus B19 Infection in Adults: A Pilot Study

The clinical features of parvovirus B19 infection in adult patients have not been well described. The aim of this prospective study was to clarify the clinical features of adult patients with parvovirus B19 infection in primary care settings. The study subjects were adults over age 18 years who had visited one primary care clinic over a period of one year. They were chosen if they had at least two of the following three symptoms: edema, joint pain, and rash, and if they had contact with children with erythema infectiosum. The diagnosis was confirmed if anti-parvovirus B19 antibodies were identified. The process of these symptoms was recorded until they resolved. Twenty patients met the inclusion criteria, and 14 (70%) patients were diagnosed with parvovirus B19 infection. The 14 adult patients consisted of two men and twelve women ranging from 33 to 63 years (median, 38 years). The patients consisted of two groups. In the first group, they presented with the first phase of infection showing symptoms such as malaise, muscle pain, and fever, and in the second phase presented with edema, rash, and joint pain that developed within two days of the first phase. In the second group, the first and second phases were clearly separated. Parvovirus B19 infection in adults can be efficiently diagnosed in primary care settings by observing clinical symptoms such as edema, joint pain, and rash, and by asking patients about their contact with children who have erythema infectiosum.

Persistent Anemia in a Patient with Diffuse Large B Cell Lymphoma: Pure Red Cell Aplasia Associated with Latent Epstein-Barr Virus Infection in Bone Marrow

We report a case of pure red cell aplasia (PRCA), which was initially suspected as a result of bone marrow involvement of diffuse large B cell lymphoma. Persistent anemia without an obvious cause was observed in a 47-yr-old man diagnosed with relapsed diffuse large B cell lymphoma. The bone marrow study showed only erythroid hypoplasia without the evidence of bone marrow involvement with lymphoma cells, thus PRCA was suggested. However, parvovirus infection was excluded as a potential cause of PRCA because of negative IgM anti-parvovirus B19 antibody and negative parvovirus PCR in the serum. Latent Epstein-Barr virus (EBV) infection of bone marrow was suggested by in situ hybridization with EBV-encoded small RNA (EBER) that showed a strong positive expression in bone marrow cells. Thus, PRCA was thought to be associated with latent EBV infection in bone marrow cells. Although the finding of unexplained anemia is a possible predictor of bone marrow involvement with lymphoma cells, PRCA as a result of a viral infection including EBV should be considered in lymphoma patients. This is the first report of the occurrence of PRCA associated with latent EBV infection in a patient with non-Hodgkin's lymphoma.

Prevalência de anticorpos IgG antiparvovírus B19 em gestantes durante o atendimento pré-natal e casos de hidropisia fetal não imune atribuídos ao parvovírus B19, na Cidade do Rio de Janeiro

With the aim of measuring the prevalence of anti-parvovirus B19 IgG antibodies during pregnancy up to 24 weeks of gestation and detecting cases of nonimmune hydrops fetalis, 249 sera from pregnant women attending a reference hospital in Rio de Janeiro city, from June 2003 to November 2004 were collected. They were followed-up until the end of pregnancy, with 17 cases of fetal hydrops detected. Four cases were caused by parvovirus B19 and two of them occurred in pregnant women living in the western zone of the city, during February 2005. Anti-parvovirus B19 IgG antibodies were found in 172 (71.6%) pregnant women (CI 95% 65.5%-77.7%); this antibody prevalence is similar to results found for others Brazilian cities. The only variable associated with previous acquisition of IgG antibodies to parvovirus B19 was number of pregnancies greater than one (p= 0.02, CI 95% 0.36-0.94).

Incidence of parvovirus B19 infection among an unselected population of pregnant women in the Netherlands: A prospective study

Objective To evaluate seroprevalence of anti-parvovirus B19 IgG immunoglobulins and the rate of seroconversion in seronegative pregnant women. Design Prospective assessment of anti-parvovirus B19 IgG immunoglobulins in an unselected population of pregnant women booked for antenatal care from 1998 to 2000. Setting Maternity departments of an academic hospital and four affiliated teaching hospitals in the Netherlands. Subjects Two thousand five hundred and sixty seven pregnant women. Main outcome measures Seroprevalence of anti-parvovirus B19 IgG immunoglobulin in the first trimester of pregnancy and subsequent seroconversion in those women who were tested negative for parvovirus B19 antibodies in the first trimester of pregnancy. Results The estimated seroprevalence of anti-parvovirus B19 IgG immunoglobulins among the study population is 70% (95% CI: 68–71) in the first trimester of pregnancy. Seven hundred and seventy nine women tested negative for parvovirus B19 antibodies in the first trimester of pregnancy. Paired testing in these women confirmed 18 seroconversions. Based on these findings the estimated incidence of maternal parvovirus B19 infection in this population among seronegative Dutch women is 2.4% (95% CI: 1.4–3.7). Conclusion Maternal infection with parvovirus B19 is relatively common. However, it is argued that in the Netherlands routine assessment of parvovirus antibodies in pregnant women is not warranted as there is a low risk of adverse fetal outcome and measures to prevent the parvovirus B19 infection and its consequences are very limited.

278 Profile of the anti-Parvovirus B19 humoral response in patients with clinically suspected acute myocarditis, chronic myocarditis and dilated cardiomyopathy

278 Profile of the anti-Parvovirus B19 humoral response in patients with clinically suspected acute myocarditis, chronic myocarditis and dilated cardiomyopathy

IgE, CD8 +CD60 + T Cells and IFN-α in Human Immunity to Parvovirus B19 in Selective IgA Deficiency

Although IgE is implicated in viral immunity, its role in parvovirus B19 immunity and its relationship to other immunological states has not been studied. Total serum immunoglobulin levels, IgG and IgE anti–parvovirus B19, blood lymphocyte numbers, and epsilon and cytokine specific mRNA were determined in pediatric patients with normal serum IgA levels (IgA+) and selective IgA deficiency (IgA−) on days 0 (initial diagnosis) and 14, and 3 years after recovery (nephelometry, Western blot test, flow cytometry, reverse transcriptase–polymerase chain reaction). We found that both patients had serum IgM, IgG, IgE, and IgA levels within normal ranges on day 0 to 3 years, excluding IgG 1 and IgA in the IgA− patient, which were elevated and negative, respectively, and IgE in the IgA+ patient, which was elevated (>100 IU/ml). The serum IgA+ and IgA− patients made IgE (and IgG) anti–parvovirus B19 at all time points. Excluding CD8 +CD60 + T cells, determinations of T, B, and NK lymphocyte subsets always were within normal ranges. In both patients, CD8 +CD60 + T-cell numbers were within normal ranges on day 0, but dramatically increased on day 14 (more than fivefold). At 3 years, they had returned to normal in the IgA+ patient, but remained high in the IgA− patient. On day 0 to 3 years, peripheral blood mononuclear cells of both patients expressed epsilon- and interferon (IFN)-α–specific mRNA. On day 0, the IgA+ patient expressed interleukin (IL)-4 and IL-10, but not IL-2, IFN-γ, or IL-6 mRNA; the IgA− patient expressed IL-6 and IL-10 mRNA, but not IL-4, IL-2, or IFN-γ mRNA. At 3 years, the IgA+ patient expressed mRNA for all cytokines, but the IgA− patient did not express mRNA for any of these cytokines. Our results suggest that IgE is important in parvovirus B19 immunity, and that IFN-α and CD8 +CD60 + T cells may regulate IgE memory responses and isotype switching.

Infections par des virus transmissibles par le sang chez des hémophiles en Tunisie

In this work, we proposed to evaluate prevalences of hepatitis B and C viruses and Parvovirus B19 among 70 Tunisian haemophiliacs treated with clotting factors imported from Europe and/or locally produced cryoprecipitate; among them 6 (8.6%) are known HIV positive patients. HBs antigen, anti-HBc antibodies and anti-Parvovirus B19 antibodies were detected in 7.1%, 52.9% and 91.8%, respectively. HCV prevalence, defined as positive ELISA with positive Immunoblot and/or PCR was 50.0%. Prevalences of these viral infections in haemophiliacs are higher than prevalences detected among general population and in the control group of the study. HCV infection is less frequent in haemophiliacs born after 1985, the year of introduction of the inactivation procedures in the production of coagulation factors concentrates; it decreases more considerably after 1994, date of introduction of systematic screening of HCV among blood donors. In contrast, despite the inactivation of the factors concentrates and the systematic screening of the blood donations against HBs antigen, since 1973, the risk of HBV infection contamination remains high in the Tunisian haemophiliacs. The introduction in 1995 of hepatitis B vaccination in the national schedule of new-born vaccination may resolve in the future the problem of HBV infection in haemophiliacs and in the other categories of the Tunisian population.

Agranulocytosis associated with parvovirus B19 infection in otherwise healthy patients

In the course of 6 years, 23 otherwise healthy patients with acute febrile illness and leukopenia were diagnosed as having acute parvovirus B19 infection. Five of these patients had agranulocytosis associated with acute parvovirus B19 infection and one had chronic agranulocytosis due to persistent parvovirus B19 infection. The diagnosis was made after positive anti-parvovirus B19 IgM antibodies were found in all of the patients and viral DNA was detected by PCR in four patients. Neutropenia and agranulocytosis appear to be much more frequently associated with parvovirus B19 infection than previously reported.

Differential Transmission of Parvovirus B19 in a Twin Gestation: A Case Report

Maternal infection with parvovirus B19 during pregnancy can cause aplastic anemia in the fetus. Severe anemia may lead to nonimmune hydrops or fetal demise. In the case reported, the demise of one twin was diagnosed by ultrasonography in an asymptomatic 21-year-old para 1-0-2-1 African American at the gestational age of 25 weeks. The deceased twin (A) was grossly hydropic with anasarca, ascites, pleural and pericardial effusions, and a thickened placenta. Parvovirus B19 DNA was found in the amniotic fluid of Twin A using the polymerase chain-reaction technique. Serial scans of Twin B showed normal growth and no evidence of hydrops. The pregnancy was managed expectantly until 29 weeks when delivery was indicated by maternal disseminated intravascular coagulation. Maternal IgM antiparvovirus B19 antibodies were detected at the time of delivery. Antiparvovirus B19 IgM antibodies were not present in Twin B. These serologic studies suggest a recent acute maternal infection and refute such an infection in Twin B. We present a case of differential transmission of parvovirus B19 in a twin pregnancy with in utero death of the infected twin and subsequent maternal disseminated intravascular coagulation.

Differential Transmission of Parvovirus B19 in a Twin Gestation: A Case Report

Maternal infection with parvovirus B19 during pregnancy can cause aplastic anemia in the fetus. Severe anemia may lead to nonimmune hydrops or fetal demise. In the case reported, the demise of one twin was diagnosed by ultrasonography in an asymptomatic 21-year-old para 1-0-2-1 African American at the gestational age of 25 weeks. The deceased twin (A) was grossly hydropic with anasarca, ascites, pleural and pericardial effusions, and a thickened placenta. Parvovirus B19 DNA was found in the amniotic fluid of Twin A using the polymerase chain-reaction technique. Serial scans of Twin B showed normal growth and no evidence of hydrops. The pregnancy was managed expectantly until 29 weeks when delivery was indicated by maternal disseminated intravascular coagulation. Maternal IgM antiparvovirus B19 antibodies were detected at the time of delivery. Antiparvovirus B19 IgM antibodies were not present in Twin B. These serologic studies suggest a recent acute maternal infection and refute such an infection in Twin B. We present a case of differential transmission of parvovirus B19 in a twin pregnancy with in utero death of the infected twin and subsequent maternal disseminated intravascular coagulation.

Quantification of Parvovirus B19 DNA Using COBAS AmpliPrep Automated Sample Preparation and LightCycler Real-Time PCR

The COBAS AmpliPrep instrument (Roche Diagnostics GmbH, D-68305 Mannheim, Germany) automates the entire sample preparation process of nucleic acid isolation from serum or plasma for polymerase chain reaction analysis. We report the analytical performance of the LightCycler Parvovirus B19 Quantification Kit (Roche Diagnostics) using nucleic acids isolated with the COBAS AmpliPrep instrument. Nucleic acids were extracted using the Total Nucleic Acid Isolation Kit (Roche Diagnostics) and amplified with the LightCycler Parvovirus B19 Quantification Kit. The kit combination processes 72 samples per 8-hour shift. The lower detection limit is 234 IU/ml at a 95% hit-rate, linear range approximately 10(4)-10(10) IU/ml, and overall precision 16 to 40%. Relative sensitivity and specificity in routine samples from pregnant women are 100% and 93%, respectively. Identification of a persistent parvovirus B19-infected individual by the polymerase chain reaction among 51 anti-parvovirus B19 IgM-negative samples underlines the importance of additional nucleic acid testing in pregnancy and its superiority to serology in identifying the risk of parvovirus B19 transmission via blood or blood products. Combination of the Total Nucleic Acid Isolation Kit on the COBAS AmpliPrep instrument with the LightCycler Parvovirus B19 Quantification Kit provides a reliable and time-saving tool for sensitive and accurate detection of parvovirus B19 DNA.

Detection of IgE anti-parvovirus B19 and increased CD23+ B cells in parvovirus B19 infection: relation to Th 2 cytokines

The immune profile of a parvovirus B19-infected patient (male, 8 years old) was studied on day 0 (initial presentation) and on days 14 and 210 post symptom presentation (psp). Before infection, the patient was skin test positive to various allergens, including ragweed and tree and grass pollens, and had a serum IgE level of 150 IU/mL. On day 0, the patient was diagnosed as parvovirus B19 infected, as judged by the presence of IgG anti-parvovirus Abs in serum (EIA) and presentation of “slap cheek” rash. The patient’s serum IgE level increased from 150 IU/mL before infection to 256 IU/mL on day 0, was 233 IU/mL on day 14, and returned to preinfection levels on day 210. In contrast, there was little change in the levels of serum IgM, IgG, or IgA (nephelometry). IgE anti-parvovirus B19 protein (VP-N) was detected in serum (Western blot) on days 0, 14, and 210, despite the decrease in total IgE on day 210. Although there was no increase in total numbers of blood CD23+ B cells on day 0, by day 14 the numbers of these cells increased dramatically (93%), remaining high on day 210. In contrast, there were virtually no changes in total numbers of CD4+ and CD8+ T cells or CD16/56+ NK precursor cells on days 0–210. On day 0, when IgG and IgE anti-parvovirus were detected in serum, patient’s peripheral blood mononuclear cells (PBMC) expressed mRNA for the Th2 cytokines IL-4 and IL-10, but not for the Th1 cytokines IFN-γ or IL-2. However, by day 14 psp, PBMC expressed mRNA for the Th1 cytokines IFN-γ and IL-2, as well as for IL-4 and IL-10. This is the first demonstration of the existence of IgE anti-parvovirus B19 Ab. The presence of IgE anti-parvovirus B19 Ab in serum on day 0 and its persistence in serum 7 months psp suggests that IgE anti-parvovirus may be useful in prognosis of parvovirus B19 infection. Our results reinforce the idea that IgE, in general, may play a major role in anti-viral immunity, perhaps in conjunction with CD23+ cells. The results further suggest that clearance of this infection is accompanied by a switch to Th1 cytokines.

Long term follow up of serostatus after maternofetal parvovirus B19 infection

Background: Maternofetal parvovirus B19 infection may result in fetal hydrops or abortion. Chronic infection has been associated with long term complications (polyarthritis, persistent aplastic anaemia, hepatitis). In pregnancy maternal immunosuppression...

Evaluation of anti-parvovirus B19 activity in sera by assay using quantitative polymerase chain reaction

Human parvovirus B19 (B19) infects cells of erythroid lineage. Production of neutralizing antibodies (Abs) is indispensable for recovery from B19-related disease state. In this study, we used a convenient method to measure neutralizing activities in human sera by using a real-time quantitative PCR based assay. Erythroid cell line KU812Ep6 was incubated with test sera before infection with B19 virus. The copy number of B19-DNA in cultures was decreased in the presence of the sera from patients who recovered from acute B19 infection, whereas no decrease in B19-DNA was in cultures incubated with sera from healthy volunteers who had no B19 infection. The decrease in B19-DNA copy number was calculated and the inhibition percentage was expressed as neutralizing activity to B19. A clinical study showed that the levels of neutralizing ability were high in patients who recovered soon after acute B19 infection, but were low in some patients with a prolonged clinical course for recovery from B19 infection. This method is simple and convenient compared with methods described previously, showing its usefulness to evaluate the neutralizing activity to B19.

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

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. 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. 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. 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. Anti-B19V NS1 IgM detection may have utility in the confirmation of recent infection with B19V.

Human parvovirus B19 in cord blood of premature infants.

We investigated whether intrauterine parvovirus B19 infection is associated with premature birth by evaluating parvovirus B19 antibodies and DNA in umbilical cord blood from 76 premature infants. We performed enzyme-linked immunoadsorbent (ELISA) and polymerase chain reaction (PCR) assays to detect B19-specific IgM antibodies and parvovirus DNA. No parvovirus DNA was detected in cord blood sera, and no sample was positive for anti-parvovirus B19 IgM antibodies. Parvovirus appears unlikely to lead to premature birth.

Viral safety of blood derivatives by immune neutralization.

Despite careful donor selection and virus inactivation procedures, transmission of viruses by transfusion of blood and blood derivatives is still a threat. Outbreaks of hepatitis A among hemophiliacs having received highly purified, immune globulin depleted coagulation factor concentrates, put the importance of immune neutralization of viruses in blood derivatives in focus. Neutralizing antibodies may block several steps in the virus infection of a cell, from binding of virus to the cellular receptor to the uncoating of virus after uptake in the cell. The efficacy of antibody neutralizing activity depends on the availability and stability of the neutralizing epitopes. Hepatitis A and B viruses are very efficiently neutralized by antibodies and immune escape mutants rarely emerge. Anti-parvovirus B19 antibodies do not fully inactivate the virus, at least in low concentrations, but may prevent development of disease. The neutralizing epitopes on hepatitis C virus and human immunodeficiency virus are located on hypervariable regions of virus membrane proteins. The effects of neutralizing antibodies are thus marginal as immune escape mutants emerge at a relatively high frequency for both viruses. The neutralizing activity of anti-cytomegalovirus antibodies is also questionable as persons may become reinfected with cytomegolvirus despite high levels of antibodies. Plasma and plasma derivatives produced from large donor pools have the potential of being very efficient transmitters of viruses. Neutralizing antibodies are Nature's own, and very important barriers against the spread of many known and unknown viruses contaminating the plasma pools.

Detection of parvovirus B19 in macerated fetal tissue using in situ hybridisation.

AIMS: To compare the application of a non-radioactive in situ hybridisation (ISH) technique with an immunocytochemical technique for the detection of human parvovirus B19 in formalin fixed, paraffin wax embedded...