Acute B19 Infection Research Articles

Prolonged activation of virus-specific CD8+T cells after acute B19 infection.

BackgroundHuman parvovirus B19 (B19) is a ubiquitous and clinically significant pathogen, causing erythema infectiosum, arthropathy, transient aplastic crisis, and intrauterine fetal death. The phenotype of CD8+ T cells in acute B19 infection has not been studied previously.Methods and FindingsThe number and phenotype of B19-specific CD8+ T cell responses during and after acute adult infection was studied using HLA–peptide multimeric complexes. Surprisingly, these responses increased in magnitude over the first year post-infection despite resolution of clinical symptoms and control of viraemia, with T cell populations specific for individual epitopes comprising up to 4% of CD8+ T cells. B19-specific T cells developed and maintained an activated CD38+ phenotype, with strong expression of perforin and CD57 and downregulation of CD28 and CD27. These cells possessed strong effector function and intact proliferative capacity. Individuals tested many years after infection exhibited lower frequencies of B19-specific cytotoxic T lymphocytes, typically 0.05%–0.5% of CD8+ T cells, which were perforin, CD38, and CCR7 low.ConclusionThis is the first example to our knowledge of an “acute” human viral infection inducing a persistent activated CD8+ T cell response. The likely explanation—analogous to that for cytomegalovirus infection—is that this persistent response is due to low-level antigen exposure. CD8+ T cells may contribute to the long-term control of this significant pathogen and should be considered during vaccine development.

Exposure of hematologic patients to parvovirus B19 as a contaminant of blood cell preparations and blood products

Patients with hematologic malignancies often require blood products, and parvovirus B19 is known to be transmitted by this route. Primary infection with parvovirus B19 shows a wide variety of disease manifestation. In immunocompromised patients, symptoms are severe and viral clearance is delayed or missing. A total of 2123 blood products given to all patients of a hematologic ward over a period of 6 months were retrospectively examined for the presence of parvovirus B19 DNA by an in-house real-time polymerase chain reaction (PCR; TaqMan). Patients who had received B19 DNA-positive blood products were further investigated serologically and by PCR for the presence of parvovirus B19 antibodies and DNA. Twenty-one (1%) of 2123 blood products tested positive for the presence of B19 DNA (2% of pooled products, 0.7% of single-donor products, and 17.6% of allogeneic peripheral blood progenitor cells), the median viral load was 700 genome equivalents per mL. During the study period, 114 patients were treated on the ward, and 14 (12%) of them received B19 DNA-positive blood components. None of them developed symptoms of an acute B19 infection, although one had a short low-level viremia. Although B19 DNA was detected in 1 percent of blood products given to hematologic patients, the exposure of 12 percent of patients did not result in symptomatic infections.

CD4+ T‐Cell Responses Against the VP1‐Unique Region in Individuals with Recent and Persistent Parvovirus B19 Infection

To date cellular immune responses against parvovirus B19 (B19) have not been studied extensively. The aim of this study was to examine the T-cell response against the VP1-unique region as the immunodominant part of the viral structural protein VP1 in individuals with different courses of B19 infection. Therefore, a group of 13 parvovirus-positive probands was separated into subgroups characterized for recent or acute, past or persistent infection by means of the presence of specific immunoglobulin (Ig)M and IgG isotypes and of viral DNA in blood and tissue. Transiently transfected B-cells expressing VP1-unique region were used in ELISpot assays to investigate T-cell responses directed against the VP1-unique region in peripheral blood mononuclear cells (PBMC) of individual donors. Significant numbers of interferon-gamma (IFN-gamma) secreting lymphocytes were detectable in PBMC of all individuals with recent, acute or persistent B19 infection, but not in PBMC of donors with past B19 infection and seronegative individuals. A more detailed analysis of IFN-gamma producing cells by intracellular cytokine staining by flow cytometry revealed, that CD4(+) T cells but not CD8(+) cytotoxic lymphocytes (CTL) were the major subpopulation of IFN-gamma producing cells. These data strongly suggest the need of virus protein production for the maintenance of VP1-unique region-specific CD4(+) T-helper cell responses in B19-infected individuals.

Parvovirus B19 viral loads in relation to VP1 and VP2 antibody responses in diagnostic blood samples

Background: Human parvovirus B19 infection is characterised by high peak viral load levels followed by episodes of prolonged viremia. The risk of transmission of parvovirus B19 by blood or blood products has been increasingly recognised and parameters that can predict the risk of transmission are subject of interest. Objectives: This study aimed to study correlations between B19 viral DNA loads and antibody responses to the viral antigens VP1 and VP2 in clinical serum samples. Study design: A panel of 1610 serum samples from patients clinically suspected from acute B19 infection were analysed. Antibodies were measured by the parvovirus anti-VP1 immuno-fluorescence assay (IFA) and the anti-VP2 enzyme immunoassay (EIA) from Biotrin. B19 viral loads were measured by a real-time PCR using the external WHO standard for DNA quantification. Results: Positive IgM responses were found in 154 (9.6%) of the 1610 sera tested. Based on the PCR results in a subset of 312 sera, the anti-VP2 EIA IgM showed a better combination of sensitivity/specificity (91%/94%) compared to the anti-VP1 IFA (66%/97%). B19 DNA levels in the sera strongly correlated with the levels of IgM antibodies, all sera with high viral loads (>10 6 IU/ml) having VP2 EIA IgM ratios above 3.0. Conclusions: The B19 VP2 IgM ELISA is superior to the B19 VP1 IgM IFA if verified by PCR. Anti-VP2 IgM antibodies in sera are indicative for the presence B19 DNA and can be used to predict high levels of B19 DNA in diagnostic sera.

Fetal Morbidity and Mortality After Acute Human Parvovirus B19 Infection in Pregnancy: Prospective Evaluation of 1018 Cases

Between one third and two thirds of pregnant women in different parts of the world are susceptible to human parvovirus B19 (B19) infection. Acute infection by B19 during pregnancy has been associated with fetal anemia, hydrops fetalis, nonhydropic intrauterine fetal death, and asymptomatic fetal infection. The major target cells of B19 are erythroid progenitors. This prospective observational study enrolled 1018 pregnant women living throughout Germany in whom acute B19 infection was confirmed by estimating titers of B19 immunoglobulin G (IgG) and IgM antibodies. Fetal mortality was 6.3% in this study. It was 11.0% when infection occurred in the first 20 months of gestation. Only when maternal B19 infection was detected before 20 completed weeks of gestation did fetal deaths occur. The rate of stillbirth was 0.6%. Three of these 6 cases presented with fetal hydrops, and the overall risk of this condition was 3.9%. Intrauterine transfusions were given in 3 of 17 cases of nonsevere hydrops and to 13 of 23 with severe hydrops. All nontransfused fetuses with severe hydrops died, but 11 of 13 severely affected fetuses (84.6%) survived after fetal transfusion. There was no evident correlation between maternal symptoms and the risk of either hydrops fetalis or nonhydropic fetal death. The findings in this, the largest prospective observational study reported to date, confirms generally favorable fetal outcomes in the presence of maternal B19 infection despite an increased risk of fetal death and hydrops. Fetal deaths are mostly limited to those exposed in the first 20 weeks of gestation. Timely intrauterine transfusion lowers the mortality risk for severely hydropic fetuses. B19-related stillbirths are uncommon in the absence of a hydropic presentation.

High frequency of parvovirus B19 DNA in bone marrow samples from rheumatic patients

Human parvovirus B19 (B19) polymerase chain reaction (PCR) is now a routine analysis and serves as a diagnostic marker as well as a complement or alternative to B19 serology. The clinical significance of a positive B19 DNA finding is however dependent on the type of tissue or body fluid analysed and of the immune status of the patient. To analyse the clinical significance of B19 DNA positivity in bone marrow samples from rheumatic patients. Parvovirus B19 DNA was analysed in paired bone marrow and serum samples by nested PCR technique. Serum was also analysed for B19-specific IgG and IgM antibodies and the results were compared with clinical and epidemiological data. B19 IgG was found in 41 of 50 patients (82%) whereas none was B19 IgM positive. The serologic evaluation showed that none of the patients had acute B19 infection. However, B19 DNA was detected by PCR in 13 of 50 (26%) bone marrow samples from these patients indicating a high frequency of persistent infection compared with previous reports of patient groups and healthy controls. In the study, 22 patients had rheumatoid arthritis (RA) and 7 of these RA patients were B19 DNA positive in bone marrow. Rheumatoid factor was positive in 4 of the 7 B19 DNA positive RA patients as compared with Rheumatoid factor positivity in all of the 15 B19 DNA negative RA patients. Erosive arthritis in X-ray was less common in the B19 DNA positive group than in the B19 DNA negative group. A high frequency of parvovirus B19 DNA was thus detected in bone marrow samples in rheumatic patients. The clinical data does not support a direct association between B19 PCR positivity and rheumatic disease manifestation. Therefore, the clinical significance of B19 DNA positivity in bone marrow samples from rheumatic patients must be interpreted with caution.

Circulating cytokines and chemokines in acute symptomatic parvovirus B19 infection: negative association between levels of pro-inflammatory cytokines and development of B19-associated arthritis.

The aim of the study was to characterise the profile and clinical correlates (arthritis, rash, and fatigue) of cytokines, chemokines, and other mediators in symptomatic acute parvovirus B19 infection. Serum was examined from cases of acute B19 infection (as defined by serum anti-B19 IgM positivity) (n = 84), and in normal persons (n = 43) for B19 markers (serum B19 antibodies and DNA), rheumatoid factor (RF), and antinuclear antibody (ANA). A panel of cytokines/chemokines was measured in duplicate using the Bioplex Protein Array system (BioRad Hemel Hempstead, UK). These included interleukin-1 beta (IL-1 beta), IL-4, IL-5, IL-6, IL-8, IL-13, tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), macrophage chemoattractant protein-1 (MCP-1), granulocyte-monocyte colony stimulating factor (GM-CSF), transforming growth factor-beta1 (TGF-beta 1), endothelin-1 (ET-1), and neopterin. Acute symptomatic infection was characterised by specific IgG positivity (83%), serum B19 DNA positivity (96%), and raised levels of IL-4, IL-6, IL-8, TNF-alpha, IFN-gamma, MCP-1, GM-CSF, TGF-beta 1, and ET-1. Patients with acute B19-associated arthritis were found to have lower levels of IL-6, TNF-alpha, and GM-CSF than patients without arthritis, while those with rash had lower levels of TGF-beta 1. It is concluded that cytokine levels following acute symptomatic infection with parvovirus B19 indicate a state of immune activation. The profile of circulating mediators may provide insights into the possible pathogenesis of particular clinical manifestations of this infection.

Fetal morbidity and mortality after acute human parvovirus B19 infection in pregnancy: prospective evaluation of 1018 cases.

To determine more precisely the incidence of fetal complications following maternal parvovirus B19 infection at various gestational ages. An observational prospective study of 1018 pregnant women whose acute B19 infection was serologically confirmed in our laboratory. The observed rate of fetal death throughout pregnancy was 6.3% (64/1018) (95% confidence interval [CI]: 4.9, 8.0). The fetal death rate for those infected within the first 20 weeks of gestation (WG) was 64/579 (11.0%). Fetal death was only observed when maternal B19 infection occurred before the completed 20 WG. The observed stillbirth proportion was 0.6% (6/960). Three of six stillbirth cases presented with fetal hydrops. The overall risk of hydrops fetalis was 3.9% (40/1018) (95% CI: 2.8, 5.3). Three of 17 cases with non-severe hydrops and 13 of 23 cases with severe hydrops received intrauterine transfusion(s). The proportion of fetuses with severe hydrops that survived following fetal transfusions was 11/13 (84.6%). All of the non-transfused fetuses with severe hydrops died. Our data demonstrate a relevant B19-associated risk of fetal death, which is largely confined to maternal B19 infection in the first 20 WG. Timely intrauterine transfusion of fetuses with severe hydrops fetalis reduces the risk of fetal death. Parvovirus B19-associated stillbirth without hydropic presentation is not a common finding.

Mapping of the Ex Vivo Cellular Immune Response Against the Complete Human Parvovirus B19 Genome During Acute Infection

Background: Human parvovirus B19 (B19) is a ubiquitous pathogen, normally causing a mild self‐limiting disease, but also capable of causing both significant pathology and long‐term persistence. The small size and stability of the virus makes it suitable for mapping of the full breath and the kinetics of the cellular immune responses following acute viral infection. Methods: Five patients with acute primary B19 infection were included in the study and followed consecutively for up to 200 weeks. Cellular immune responses were mapped by IFNγ enzyme‐linked immunospot to overlapping peptides spanning the whole B19 genome. Results: In all five acutely infected patients, we were able to monitor the kinetics of a strong specific cellular immune reaction. Responses peaked at levels of 850–1850 SFC/million PBMCs, roughly corresponding to 0.3–0.6% B19‐specific CD8+ cells circulating in peripheral blood at 10–80 weeks post‐infection. The responses in individual patients were directed to three or four different peptide pools, and the specificity was confined to the same CD8 epitopes present in the pools throughout the follow‐up period. The majority of responses were directed to the virus nonstructural protein, only two patients showed any response to the capsid proteins, elicited by the same epitope in both cases. Conclusion: The cellular immune responses to acute B19 infection are surprisingly narrow in distribution and remain at high levels for up to 80 weeks post‐infection. The initial epitope specificity is maintained, and the majority of responses target the virus nonstructural protein, which is not included in vaccine preparations, evaluated against the infection.

Parvovirus B19 infection in medical students during a hospital outbreak.

From March to May 2002, a parvovirus B19 (B19) outbreak was identified at a general hospital that serves as a teaching facility for the Universidad Autónoma de San Luis Potosí, Mexico. Medical students attending the hospital presented with symptoms suggestive of B19 infection. Previous studies have suggested that apparent hospital-related B19 outbreaks may be a reflection of B19 infection in the community. A study was undertaken to assess whether exposure to the hospital was a risk factor for B19 infection and to determine to what extent medical students were infected during this outbreak. The incidence of B19 infection in medical students attending the teaching hospital during the outbreak (n=211) was determined and compared to students not attending the hospital (n=96). To assess if a community-wide outbreak had occurred, 80 blood donors were also evaluated for the presence of B19 antibodies. Acute B19 infection was identified in 40 of 119 (33.6%) susceptible students attending the hospital and in 20 of 47 (42.6%) susceptible students not attending the hospital. The frequency of acute infection among susceptible blood donors was lower (9.5%) than in students, but higher than the rate expected during non-epidemic periods. Most infections (68.3%) were asymptomatic. Symptoms reported by infected subjects were not specific for B19 infection. Only 11.7% of subjects with acute infection fulfilled the clinical surveillance definition used to detect cases during the outbreak. In conclusion, hospital exposure was not associated to increased risk of B19 infection among medical students. Medical students may be at increased risk for acquiring and transmitting B19 infection during outbreaks.

The mantra of blood safety: time for a new tune?

The mantra of blood safety: time for a new tune?

Lack of association between B19 or V9 erythrovirus infection and ANCA-positive vasculitides: a case-control study.

To examine the potential association of human B19 or V9 erythrovirus infection and onset of ANCA-positive vasculitides. We tested the sera of 13 adults with newly diagnosed ANCA-positive vasculitides. Each was age- and sex-matched to three sera obtained from healthy controls. All samples were tested for B19- and V9-specific immunoglobulin (Ig) G and IgM antibodies (Ab) (third-generation ELISA), and B19 or V9 DNA was sought with the polymerase chain reaction. Statistical analysis was performed by conditional logistic regression. Patient diagnoses comprised six cases of Wegener's granulomatosis, six of microscopic polyangiitis and one of Churg-Strauss syndrome. IgG Ab to B19 were detected equally in patient and control sera (77 and 79% respectively) (odds ratio=0.84, P=0.84). All 13 cases and 39 controls were negative for IgM Ab and viral DNA. These results suggest that neither acute nor chronic B19 or V9 infection is an aetiological factor in ANCA-associated vasculitides.

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.

Association of symptomatic acute human parvovirus B19 infection with human leukocyte antigen class I and II alleles.

To determine the effect of the major histocompatibility complex on the development of symptoms during acute human parvovirus B19 infection, we compared human leukocyte antigen (HLA) class I and II alleles in 36 patients with symptomatic acute B19 infection with those in >900 control subjects from northwestern England. The frequency of each of HLA-DRB1*01 (P=.016), DRB1*04 (P=.007), and DRB1*07 (P<.0001) alleles was significantly higher in parvovirus B19 patients than in control subjects. In the parvovirus group, 63.9% carried the rheumatoid arthritis-associated shared epitope sequence, compared with 45% of control subjects (odds ratio [OR], 2.2; 95% confidence interval [CI], 0.97-4.8; P=.04), and carriage was associated with fatigue during the acute phase (OR, 4.2; 95% CI, 0.8-23.9; P=.047). All symptomatic parvovirus-associated HLA-DRB1 molecules carry a neutrally charged glutamine at position 10 and a positively charged lysine at position 12 of the first hypervariable region. HLA-B49 was associated with parvovirus infection independently of HLA-DRB1*01, DRB1*04, and DRB1*07.

Study of chronic hemolytic anaemia patients in Rio de Janeiro: prevalence of anti-human parvovirus B19 IgG antibodies and the development aplastic crises.

The prevalence of anti-human parvovirus B19 IgG antibodies was determined in sera from 165 chronic hemolytic anemia patients, receiving medical care at Instituto Estadual de Hematologia (IEHE), Rio de Janeiro, during the year of 1994. This sample represents around 10% of the chronic hemolytic anemia patients attending at IEHE. Most of these patients (140) have sickle cell disease. Anti-B19 IgG antibodies were detected in 32.1% of patients. No statistically significant difference (p > 0.05) was seen between IgG antibody prevalence in male (27.8%) and female (35.5%) patients. Anti-B19 IgG antibodies were more frequent in older (37.6%) than younger (28.2%) than 20 years old patients, although this difference had no statistical significance (p > 0.05). Anti-B19 IgG antibody prevalence showed that 67.9% of patients enrolled in the study were susceptible to B19 acute infection. With the aim to detect acute B19 infection, patients follow up continued until February 1996. During this period four patients presented transient aplastic crisis due to human parvovirus B19 as confirmed by the detection of specific IgM antibodies. All four patients were younger than 20 years old, and 3 were younger than 10 years old. Three of them were sickle cell disease patients. Three of the four acute B19 infection occurred during 1994 springtime.

Antibodies to parvovirus B19 non-structural protein are associated with chronic but not acute arthritis following B19 infection.

To determine the incidence and significance of antibodies to the parvovirus B19 non-structural (NS1) protein in B19-infected persons during acute infection and convalescence. The B19 NS1 protein was expressed in SF9 cells using the baculovirus expression system and was used to prepare immunofluorescence slides. These were used in a fluorescent antibody test to determine anti-B19 NS1 IgG in a well-characterized cohort of 53 persons at the time of acute B19 infection and again after a follow-up period of 26-85 months. Results were examined for statistical significance by the use of Fisher's exact test. NS1 antibodies were detected in five of 32 persons with acute B19 infection (four with arthritis) and 10 of 53 persons with past B19 infection (six with chronic arthritis and two with chronic arthritis and chronic fatigue syndrome). Regarding the correlation of NS1 antibodies and arthritis, at the time of acute infection four of 24 persons with arthritis had NS1 antibodies detected compared with one of eight persons with any other symptoms (P: = 1). During convalescence, eight of 20 persons with chronic arthritis had NS1 antibodies compared with two of 33 with symptoms of any other category (all except one were asymptomatic) (P: = 0.007). All 10 patients with NS1 antibodies during convalescence had arthritis during acute infection, which persisted in eight persons until the time of follow-up. Antibodies to parvovirus B19 NS1 protein are associated with chronic but not with acute arthritis after B19 infection.

An epidemic of parvovirus B19 in a population of 3,596 pregnant women: a study of sociodemographic and medical risk factors.

To estimate the incidence of human parvovirus B19 among pregnant women before and during an epidemic, to elucidate possible sociodemographic and medical risk factors during pregnancy and to estimate the association between parvovirus B19 infection and negative pregnancy outcome. Prospective study among pregnant women followed from their first antenatal visit before 24 full weeks of gestation until delivery. Department of Obstetrics and Gynaecology, Odense University Hospital, Denmark, November 1992 to February 1994. 3,596 pregnant women were invited to participate. The women were examined at first antenatal visit in the period from November 1992 to February 1994 and at delivery. The last delivery was in August 1994 and samples were thus collected before and during a large parvovirus B19 epidemic in Denmark January to September 1994. A blood sample for parvovirus B19 serology was taken at enrollment and from the umbilical cord at delivery. Three questionnaires were completed during 2nd and 3rd trimesters and a registration form at delivery. In total, 3,174 (87.6%) were enrolled and 79.5% completed the study. The prevalence of B19 IgG seropositivity at the first antenatal visit before 24 full weeks of gestation was 66% . The cumulative prevalence proportion of acute parvovirus B19 infection during pregnancy among IgG negative women was found to be 10.3% (IgM seropositivity and/or IgG seroconversion). The IgG seroconversion incidence increased significantly from 1.0% to 13.5% among 932 seronegative pregnant women before and during the epidemic, respectively (P < 0.001). Independent risk factors related to increased risk of B19 infection during pregnancy, adjusted for other sociodemographic and medical factors, were: children at home (adjusted OR 2.1, 95% CI 1.3-3.2); serious medical disease (adjusted OR 3.0, 95% CI 1.0-8.5); and a stressful job (adjusted OR 1.8, 95% CI 1.0-3.3). Parvovirus B 19 IgM seropositivity was associated with events of late spontaneous abortions and stillbirths (crude OR 9.9; 95% CI 3.3-29.4). Before and during an epidemic of acute B19 infection incidences were measured among pregnant women to be 1.0% and 13.5%, respectively. Three factors, significantly increasing the risk of acute B19, were identified as: having children at home; suffering from serious medical diseases; and having a stressful job. IgM positivity for parvovirus B19 was associated with negative outcome of pregnancy.

Acute-phase-specific heptapeptide epitope for diagnosis of parvovirus B19 infection.

The major capsid protein VP2 of human parvovirus B19, when studied in a denatured form exhibiting linear epitopes, is recognized exclusively by immunoglobulin G (IgG) antibodies of patients with acute or recent B19 infection. By contrast, conformational epitopes of VP2 are recognized both by IgG of the acute phase and by IgG of past immunity. In order to localize the VP2 linear epitope(s) specific for acute-phase IgG, the entire B19 capsid protein sequence was mapped by peptide scanning using well-characterized acute-phase and control sera. A unique heptapeptide epitope showing strong and selective reactivity with the acute-phase IgG was detected and characterized. By using this linear epitope (VP2 amino acids 344 to 350) and virus-like particles exhibiting conformational VP2 epitopes, an innovative approach, second-generation epitope-typing enzyme immunoassay, was set up for improved diagnosis of primary infections by human parvovirus B19.

Novel human erythrovirus associated with transient aplastic anemia.

Erythrovirus (formerly parvovirus) B19 causes a wide range of diseases in humans, including anemia due to aplastic crisis. Diagnosis of B19 infection relies on serology and the detection of viral DNA by PCR. These techniques are usually thought to detect all erythrovirus field isolates, since the B19 genome is known to undergo few genetic variations. We have detected an erythrovirus (V9) markedly different from B19 in the serum and bone marrow of a child with transient aplastic anemia. The B19 PCR assay yielded a product that hybridized only very weakly to the B19-specific probe and whose sequence diverged more from those of 24 B19 viruses (11 to 14%) than the divergence found within the B19 group (</=6.65%). Restriction enzyme analysis of the V9 genome revealed that this genetic divergence extended beyond the amplified region. Interestingly, serological tests failed to demonstrate a response characteristic of acute B19 infection. V9 could be a new erythrovirus, and new diagnostic tests are needed for its detection.

Genetic heterogeneity of the immunogenic viral capsid protein region of human parvovirus B19 isolates obtained from an outbreak in a pediatric ward

Whereas human parvovirus B19 commonly infects children and causes erythema infectiosum, it causes more severe diseases when it infects adults. In order to examine whether different clinical outcomes of B19 infection can be ascribed to the viral genetic heterogeneity, we have determined the nucleotide sequence of highly immunogenic portions of the B19 genome obtained from six patients with various clinical manifestations in a single outbreak. Our observations demonstrated that although the B19 sequences showed a significant heterogeneity, it was not correlated with the clinical manifestation. It was thus suggested that the host immune response to B19 infection may be a major determinant of clinical presentations associated with acute B19 infection.