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PubMed2001

Reconstituted immunity against persistent parvovirus B19 infection in a patient with acquired immunodeficiency syndrome after highly active antiretroviral therapy.

We discovered a patient with AIDS with persistent B19 infection who had slow resolution of anemia after he commenced receiving HAART without intravenous immunoglobulin. The patient's anemia recurred when the initial course of HAART failed, but it remitted slowly after salvage therapy was instituted. However, circulating B19 was still detectable by nested polymerase chain reaction 1 year after commencement of salvage therapy. Immunoglobulin G and immunoglobulin M antibodies against B19 were not detected by means of enzyme-linked immunosorbent assay when the anemia initially resolved, but they were detected after the patient commenced receiving salvage therapy. The absence of antibody response after the initial remission of parvovirus B19 infection suggested that cellular immunity was an important component of reconstituted immune function against B19 after the patient received HAART. The humoral response that was restored later was abnormal; it had strong reactivity to nonstructural protein NS-1 and poor generation of neutralizing antibodies against linear epitopes unique to minor capsid protein VP1.

AIDS-Related Opportunistic Infections↗
PubMed2002

Human parvovirus Bb19 detection in asymptomatic blood donors: association with increased neopterin concentrations.

Serum neopterin concentrations were determined in 20,000 blood donations. For the 400 donations with neopterin concentrations above the 98 th percentile and another 1200 donations with neopterin concentrations in the lower range, results of human parvovirus (HPV) B19 tests were compared. Infectious specimens were identified by dot blot hybridization assay and polymerase chain reaction (PCR) that used the outer primers and detected 1 pg of HPV B19 DNA, corresponding to approximately 10(5) copies of the genome, in the specimens and by a nested PCR that detected 1-10 fg of DNA, corresponding to 10(2)-10(3) copies of the genome. Of 400 specimens with neopterin concentrations > or =12 nmol/L (98th percentile, current cutoff), 10 tested positive by dot blot hybridization assay (9 of these were confirmed by nested PCR). Among 1200 specimens with low neopterin concentrations (<12 nmol/L), no specimen containing HPV B19 DNA was detected. These findings suggest an association between elevated neopterin concentrations and HPV B19 infectivity.

Blood Donors↗
PubMed2003

Severe prolonged red blood cell aplasia and thrombocytopenia induced by parvovirus B19 infection in a patient with sarcoidosis.

We describe an acromegalic patient who developed a parvovirus B19 (PVB19) infection concomitantly with sarcoidosis, which was complicated by chronic red blood cell aplasia and severe thrombocytopenia, despite disappearance of the virus from serum and the production of high levels of specific polyclonal antibodies to PVB19. Mitogen stimulation of the patient's peripheral blood mononuclear cells induced oversecretion of interferon-gamma (IFN-gamma). Because hematopoietic suppression by IFN-gamma has been reported, a possible mechanism underlying reticulocytopenia and thrombocytopenia could involve IFN-gamma.

Adult↗
PubMed2004

Persistent parvovirus B19 infection without the development of chronic anemia in HIV-infected and -uninfected children: the Women and Infants Transmission Study.

We evaluated the prevalence of persistent parvovirus B19 (B19) infection and associated anemia in human immunodeficiency virus (HIV)-infected and HIV-uninfected children. B19 persistence was defined as B19 DNA detected in specimens collected >16 weeks apart. Of 182 children, 3 HIV-infected children and two HIV-uninfected children had evidence of persistent B19 infection. Of the 5 children, none had evidence of B19-associated anemia. Our data suggest that B19 infections can persist in children without the development of symptomatic anemia.

AIDS-Related Opportunistic Infections↗
PubMed2004

B cell memory is directed toward conformational epitopes of parvovirus B19 capsid proteins and the unique region of VP1.

BACKGROUND: Loss of antibody reactivity against linear epitopes of parvovirus B19 (B19) capsid proteins VP1 and VP2 occurs after infection; however, it is unclear whether B cell memory is established against linear epitopes. METHODS: B cell enzyme-linked immunospot assay was used to evaluate B19-specific B cell memory in volunteer donors (n=22). RESULTS: B cell memory is maintained against conformational epitopes of VP2 and is absent against linear epitopes of VP2. Individuals seronegative for IgG against the unique region of VP1 have detectable B cell memory, with the potential to mount a humoral response on reexposure to B19. Conversely, in mice immunized with VP2, long-lasting IgG against linear epitopes of VP2 and a strong B cell-memory response are observed. CONCLUSIONS: B cell memory is established and maintained against conformational epitopes of VP2 and against linear epitopes of VP1 but not against linear epitopes of VP2. These findings further our understanding of the immune response to B19 and suggest that analysis of B19-specific B cell memory merits consideration for future B19-vaccine studies.

Adult↗
PubMed2005

Slow clearance of human parvovirus B19 viremia following acute infection.

Parvovirus B19 is a common, clinically significant pathogen. Reassessment of the viral kinetics after acute infection showed that the virus is not rapidly cleared from healthy hosts, despite early resolution of symptoms. These findings challenge our current conception of the virus' pathogenesis and have implications for the management of the infection.

Adult↗
PubMed2006

Parvovirus B19 infection after transplantation: a review of 98 cases.

BACKGROUND: Infections with parvovirus B19 (PVB19) can cause significant morbidity in transplant recipients. METHODS: To characterize the epidemiology and clinical spectrum of posttransplant PVB19 infection, we reviewed all cases at our institution during a 16-year period, summarized the data from 91 cases published in the medical literature, and performed longitudinal molecular surveillance for PVB19 DNAemia among 47 solid organ and hematopoietic stem cell transplant recipients. RESULTS: The median time to onset of PVB19 disease was 7 weeks after transplantation. Anemia, leukopenia, and thrombocytopenia were present in 98.8%, 37.5%, and 21.0% of patients, respectively. Hepatitis, myocarditis, and pneumonitis were also reported in association with PVB19 disease. Allograft tissue loss or dysfunction was observed at the time of PVB19 disease in 10% of cases. At the onset of disease, PVB19 IgM serological test results were negative in 29% of cases. Almost all patients (96%) with anti-PVB19 IgM had a positive PVB19 polymerase chain reaction assay result. Intravenous immunoglobulin was the most commonly used treatment modality. Three of 98 patients died of myocarditis and cardiogenic shock associated with PVB19 disease. Molecular surveillance throughout the first year after transplantation did not reveal PVB19 DNAemia in 47 anemic solid organ and hematopoietic stem cell transplant patients. CONCLUSIONS: PVB19 is a rare but clinically significant infection that manifests as refractory anemia during the posttransplantation period. The use of polymerase chain reaction for diagnosis is particularly helpful in immunosuppressed transplant patients who may fail to mount antibodies against PVB19 during active infection.

Adult↗
PubMed2006

The immune response to parvovirus B19 exposure in previously seronegative and seropositive individuals.

Little information is available on the immune response to parvovirus B19 after the administration of contaminated blood products. In the present study, we found that levels of B19 IgG in B19-seropositive recipients protect against reinfection and, after transfusion with pooled plasma containing B19 DNA (1.6 x 10(8) IU/mL), increase from 19-39 IU/mL to 50-100 IU/mL. We found that, in the presence of 1.6-2.2 x 10(8) IU of B19 DNA/mL in B19-seronegative recipients, a pooled-plasma B19 IgG level of 59.5 IU/mL is insufficient to prevent B19 transmission and subsequent seroconversion. These data should lead to improvements in the assessment of blood-product safety.

Antibodies, Viral↗
PubMed2006

Parvovirus B19 empty capsids as antigen carriers for presentation of antigenic determinants of dengue 2 virus.

For the production of dengue-vaccine candidates, empty capsids, or virus-like particles (VLPs), of parvovirus B19 that carry dengue 2-specific epitopes were employed as antigen carriers. Two epitopes (comprising amino acids 352-368 and 386-397) of domain BIII of the envelope glycoprotein were chosen to produce recombinant B19 VLPs for immunization of BALB/c mice. Serum samples from immunized mice revealed that recombinant B19 VLPs elicited strong humoral immune responses. In summary, this B19 VLP-vaccine platform produced high (> or =2.0 x 10(5)) anti-dengue 2 titers and robust (< or =1 120) 50%-plaque-reduction neutralization test (PRNT(50)) titers, which effectively neutralized live dengue 2 virus in PRNT(50) assays.

Animals↗
PubMed2006

Maternal-fetal transmission of human parvovirus B19 genotype 3.

Plasma samples obtained at delivery from 885 pregnant Ghanaian women were tested for human parvovirus B19 DNA and B19-specific antibodies. Maternal-fetal transmission was evaluated by testing paired maternal plasma and umbilical cord blood samples, as well as newborn whole-blood samples when they were available. The B19 DNA seroprevalence rate in women was 1.8% (94% had genotype 3 strains), and the immunoglobulin G (IgG) seroprevalence rate in women was 81%. Two of 3 cases of primary maternal B19 infection resulted in fetal transmission. Coexistence of B19 DNA and B19-specific IgG (persistence) was detected in 13 women (1.5%), but no transmission of the virus was observed. Contrary to the situation in pregnant women with primary B19 infection and high viral loads, pregnant women with low viral loads and B19-specific IgG do not appear to be vertically infectious.

DNA, Viral↗
PubMed1998

Parvovirus B19-induced anemia as the presenting manifestation of X-linked hyper-IgM syndrome.

Parvovirus B19 (B19) can cause chronic anemia due to persistent infection in immunocompromised hosts who cannot produce neutralizing antibody necessary for clearing B19. Three patients with X-linked hyper-IgM syndrome (XHIM), who were all asymptomatic until they developed B19-induced chronic anemia at the ages of 8, 14, and 17 years, respectively, were found to have mutations of the CD40L gene, including a missense mutation (T254M), a nonsense mutation resulting in a new initiation codon and loss of the intracellular domain (R11X), and a splice site mutation (nt 309+2t-->a). Antibody responses to the T cell-dependent antigen, bacteriophage phiX174, were impaired, but neutralizing antibody titers were higher than in XHIM patients with classic phenotype. All 3 patients responded to intravenous immune globulin (IVIG) treatment. Certain mutations of the CD40L gene result in a mild XHIM phenotype that may become apparent following B19 infection in patients not on IVIG therapy and therefore not protected from B19 infection.

Adolescent↗
PubMed1997

Nosocomial exposure to parvovirus B19: low risk of transmission to healthcare workers.

OBJECTIVE: To evaluate the risk of nosocomial transmission of parvovirus B19 (B19) infection to healthcare workers (HCWs) exposed to patients with transient aplastic crisis (TAC) caused by acute B19 infection. DESIGN: Cohort study. SETTING: 1,000-bed, urban teaching hospital in Atlanta, Georgia. PARTICIPANTS: Eighty-seven exposed HCWs who cared for two patients with TAC prior to the time they were isolated and a comparison group of 88 unexposed HCWs from wards or clinics where the patients did not receive care. INTERVENTION: Self-administered questionnaire on hospital contact with index patients, B19 community risk factors, and signs and symptoms suggestive of B19 disease. Serology for B19-specific IgM and IgG antibodies measured by antibody-capture enzyme-linked immunosorbent assay. RESULTS: 1 (3.1%) of the 32 nonimmune exposed HCWs had serologic evidence of recent B19 infection compared to 3 (8.1%) of the 37 nonimmune HCWs in the comparison group (P = .6). In a subgroup analysis of exposed HCWs who cared for index patients during the time when the virus load was expected to be greatest, a recent infection rate of 5.8% (1/17) was found among nonimmune HCWs. CONCLUSIONS: The finding of similar rates of recent infection in nonimmune exposed and unexposed HCWs suggests that transmission to HCWs did not occur, despite failure to place the patients in isolation at the onset of hospitalization.

Adolescent↗
PubMed1997

Parvovirus B19-antibody serosurvey in 500 developmentally disabled subjects.

Sera of 500 residents were screened for parvovirus B19 immunoglobulin M (IgM) and immunoglobulin G (IgG) by enzyme-linked immunosorbent assay. Positive IgM and equivocal IgG or IgM results were confirmed by immunofluorescent antibody and Western blot. IgM was detected in 13 sera (2.6%), and IgG was detected in 285 (57%). Records of IgM-positive residents contained no evidence of erythema infectiosum or polyarthropathy.

Adult↗
PubMed2001

Identification of an immunodominant peptide in the parvovirus B19 VP1 unique region able to elicit a long-lasting immune response in humans.

The immune response against parvovirus B19 is mainly directed against the two structural proteins, VP1 and VP2. The amino terminal half of the VP1 unique region has been shown to elicit a dominant immune response in humans, more effective than other linear epitopes and also it has been seen to contain significant neutralizing linear epitopes. Three overlapping recombinant peptides corresponding to amino acids 2-40 (VP1-A), amino acids 32-71 (VP1-B), and amino acids 60-100 (VP1-C) of the VP1 unique region were produced by a procaryotic expression system. These peptides were used as antigens in a Western blot assay to detect specific immunoglobulin G (IgG) in serum samples from blood donors of different age groups with documented signs of a past B19 infection. Fragment VP1-C appeared significantly immunodominant over the other peptides, reacting with specific IgG in 86% of serum samples. The fragment VP1-C corresponds to a sequence with a known neutralizing activity and seems able to elicit a long-lasting immune response because specific IgG were present in blood donors of all age groups. VP1-C would therefore appear to be an attractive candidate as a component of a subunit vaccine.

Adult↗
PubMed2002

A longitudinal study of cell-mediated immunity in pigs infected with porcine parvovirus.

Porcine parvovirus (PPV) is an ubiquitous pathogen causing reproductive failure in swine. Protection against reproductive failure caused by acute PPV infection has commonly been related to the presence of specific antibodies in the dam. However, the role of cell-mediated immunity during chronic PPV infection remains to be elucidated, and may be relevant to the pathogenesis of novel diseases such as postweaning multisystemic wasting syndrome (PMWS), which may be triggered by coinfection with PPV and porcine circovirus type 2 (PCV2). To investigate whether pigs infected with PPV generate a cell-mediated immune response, a longitudinal infection experiment was performed, using swine leukocyte antigens (SLA) class I characterized growing pigs (haplotype H7/H7). Pigs were intranasally inoculated with PPV at 0, 80, and 136 days. At predetermined time points, peripheral blood mononuclear cells (PBMC) were isolated, and virus-specific lymphoproliferative responses and the cytolytic activities of cytotoxic T-lymphocytes (CTL) and natural killer (NK) cells were examined. Cytolytic assays were performed by the chromium release method, using as targets a syngeneic porcine kidney cell line established for the purpose (CTL assays) and K562 cells (NK assays). A specific proliferative response of PBMC from virus-infected pigs to PPV was observed from day 101 onwards. In contrast, PBMC from mock-infected pigs did not proliferate in response to PPV. Flow cytometric analysis indicated that the CD4+CD8+ T-cell subset of PBMC proliferated in response to virus antigen, in keeping with the assumed role for these cells in immunological memory. This is, to our knowledge, the first indication of a cellular immune response following PPV infection. A weak CTL activity, which peaked on days 80 and 87, was observed in PPV-infected pigs. In vitro restimulation of PBMC with live PPV did not induce further CTL activity. A pronounced NK cell activity was detected in both virus-infected and control pigs throughout the experiment, and may have negatively affected the sensitivity of the CTL assay. In conclusion, the findings of a late lymphoproliferative response together with weak CTL activity are in keeping with an effective control of acute PPV infection by humoral immunity, but open the possibility that cellular immunity may play a role in controlling PPV reinfection. Finally, we find that the established experimental model using SLA characterized pigs may constitute a valuable tool for future studies of CTL activity in pigs.

Animals↗
PubMed2000

Parvovirus B19-related anemia in HIV-infected patients.

Persistent infection with parvovirus B19 (B19) is an important treatable cause of anemia in HIV-infected patients. B19 has a tropism for erythroid progenitors and causes pure red cell aplasia (PRCA). The failure to produce neutralizing antibodies to the virus following B19 infection in immunodeficient persons may result in persistent viremia and chronic PRCA (B19-PRCA). The seroprevalence rates for B19 in unselected persons with HIV infection are high, similar to those seen in the general population. Reports of B19-related anemia in HIV infected patients, however, are infrequent. A partial explanation may be that B19-PRCA is predominantly a complication associated with advanced immunodeficiency. The condition is probably underdiagnosed as well. The finding of an unexplained normocytic anemia with absent reticulocytes, in an afebrile HIV-infected patient without renal dysfunction suggests a diagnosis of B19-PRCA. The diagnosis is established when the following criteria are met: (1) bone marrow biopsy showing PRCA, (2) serum or bone marrow positivity for B19 DNA by PCR or dot-blot hybridization, and (C) no alternate explanation for the PRCA. Serological methods are unreliable for the diagnosis because these patients often lack IgM and IgG antibodies to B19. Nearly all patients with B19-PRCA respond to treatment with intravenous immunoglobulin (IVIg) with a rise in the hemoglobin to levels appropriate for the clinical condition of the patient. An alternative explanation for the anemia must be sought in patients not responding to IVIg. Most patients with CD4+ T-lymphocyte counts of < or = 100 cells/mm3 relapse to anemia, usually within 6 months of IVIg therapy. Such patients must be retreated with IVIg 2 g/kg given over 2 to 5 days. The routine use of maintenance IVIg 0.4 g/kg q 4wk may be considered in these patients to prevent relapse.

Adult↗
PubMed1993

Risk of human parvovirus B19 infections among school and hospital employees during endemic periods.

Because human parvovirus B19 (B19) infections are common in children, and maternal infection of pregnant women may cause fetal death, risk factors for B19 infections for hospital and school employees were identified during an endemic period. By serologic testing, 2730 employees of 135 schools in three school systems and 751 employees of a hospital were monitored. Of these, 60% were initially seropositive. After adjusting for age, race, and gender, risk factors for seropositivity were contact with children 5-18 years old at home (odds ratio [OR] = 1.2), at work (OR = 1.2), and employment in elementary schools in school system 2 (OR = 1.4). Over 42 months, 1 of 198 susceptible hospital employees seroconverted versus 62 of 927 school employees. Four factors associated with seroconversion were employment at elementary schools in system 2, contact with children 5-11 years old at home or with children 5-18 years old at work, and age < 30 years. Those in daily contact with school-age children had a fivefold increased annual occupational risk for B19 infection.

Adult↗
PubMed1995

Parvovirus B19 clearance from peripheral blood after acute infection.

The clearance of B19 parvovirus from peripheral blood was followed after acute infection to determine how long the virus is present in blood, even at low titer. The presence of B19 DNA in serum was investigated with dot blot hybridization during an epidemic. Fourteen patients positive for B19 DNA were followed for up to 1 year for its presence in samples taken monthly, using both dot blot hybridization and nested polymerase chain reaction (PCR). All patients examined showed medium to high viremic titers (detectable with hybridization assay) only at the beginning of observation; later the virus titer decreased and was detectable only by nested PCR. Of the 14 patients followed, 13 were positive for B19 DNA by nested PCR for 2-6 months; 1 patient showed a persistent infection associated with chronic arthritis and was positive for B19 DNA for 1 year without clearance of the virus.

Acute Disease↗