Acute Human Parvovirus B19 Infection Research Articles

Adult acute respiratory distress syndrome due to human parvovirus B19 infection after cardiac surgery: a case report

BackgroundInfection with human parvovirus B19 (PB19) is very common in pediatric patients. Symptoms and signs depend on the infected patient’s immune and hematopoietic status and can range from an asymptomatic condition to life-threatening disease.Case presentationA 69-year-old man received elective mitral valvular replacement and tricuspid valvuloplasty under cardiopulmonary bypass and suffered acute respiratory distress syndrome on postoperative day 8. Through the detection of positive serum IgM and human PB19-specific nucleic acids in serum and bronchoalveolar lavage fluid via metagenomic next-generation sequencing (mNGS), acute human PB19 infection was confirmed. The patient was ventilated and the pulmonary infiltration was attenuated six days later.ConclusionA combination of serum human PB19 DNA by mNGS and positive serum human PB19 IgM could provide higher diagnostic sensitivity for acute human PB19 infection. The method of mNGS may be a new choice for detecting rare or atypical pathogens in severe complicated pneumonia. The infection of human PB19 was possibly self-limited.

Acute human parvovirus B19 infection in a 6-year old girl with sickle cell disease: a case report

A 6-year-old girl with Sickle-cell disease was hospitalized because of fever and arthralgia. During hospitalization she developed a splenic sequestration with the need of three successive red packed-cell transfusions. Microbiological investigations revealed positive HPVB19 IgM and IgG and HPVB19 DNA in blood. Given the diagnosis of HPVB19 infection and persistent fever, she received intravenous immunoglobulins (IVIg) with progressive clinical improvement and discharge after 24 days of hospitalization. This is the first case of acute HPVB19 infection in a child with Sickle cell disease and more than 20 days fever, associated with splenic sequestration. IVIg may represent an effective therapy.

Rhabdomyolysis Associated With Human Parvovirus B19 Infection in a Patient With Fukuyama-Type Congenital Muscular Dystrophy

Patients with Fukuyama-type congenital muscular dystrophy sometimes experience transient exacerbations of muscle weakness. We took care of a 9-year-old boy with Fukuyama-type congenital muscular dystrophy who presented with acute respiratory failure and decreased exercise ability with marked elevation of serum creatine kinase indicating rhabdomyolysis. At that time, his younger sister suffered from erythema infectiosum. Although he had no particular symptoms, he was tested and proven to have acute human parvovirus B19 infection based on detection of anti-B19 IgM and parvovirus B19 DNA in his serum. His acute rhabdomyolysis was possibly triggered by human parvovirus B19 infection.

Molecular and clinical evaluation of the acute human parvovirus B19 infection: comparison of two cases in children with sickle cell disease and discussion of the literature

Human parvovirus B19 is a well-known cause of severe conditions in patients with sickle cell disease, but the molecular mechanisms of the infection are insufficiently understood. The different clinical outcome of the acute parvovirus B19 infection in two pediatric patients with sickle cell disease has been examined. One of them developed life-threatening condition requiring emergency transfusions, while the other had asymptomatic infection, diagnosed occasionally. Both cases had high viral load and identical subgenotype, indicating that the viral molecular characteristics play a minimal role in the infection outcome.

Coinfection with Parvovirus B19 and Epstein Barr Virus in An Adolescent with Sickle Cell Disease Manifesting As Septic Shock

Abstract 4854Patients with Sickle Cell Disease (SCD) are at an increased risk of serious and life-threatening infections. Epstein Barr Virus (EBV) and Human Parvovirus B19 (HPV-B19) are common viral infections that are usually asymptomatic or self-limiting in healthy children. However, SCD patients can have significant morbidity and mortality caused by these infections. In patients with SCD, EBV can cause splenic rupture, thrombocytopenia, agranulocytosis, hemolytic anemia and hemophagocytic lymphocytosis while HPV-B19 can cause severe aplastic crisis, stroke, nephrotic syndrome, myocardial infarction and splenic sequestration. Coinfection with EBV and HPV-B19 has not been reported in SCD patients and there are no reports of EBV or HPV B19 causing septic shock.A 15 year old male with SCD presented with a one day history of fever, oliguria, and hypotension caused by simultaneous viremia with EBV and HPV-B19. He had been discharged 2 days previously after an admission for a vaso-occlusive crisis. He did not have pharyngitis, rash hepatosplenomegaly (spleen likely autoinfarcted) or lymphadenopathy. Peripheral smear did not show lymphocytosis, atypical lymphocytes or features of microangiopathic hemolytic anemia. Fluid resuscitation with normal saline and then with red cell transfusion was done and he was transferred to pediatric intensive care unit. He received supportive therapy for septic shock with fluids, antibiotics and red cell transfusions. Blood and urine bacterial cultures were negative and blood quantitative DNA PCR was positive for EBV (3300 copies/ml) and HPV-B19 (2.3×107 copies/ml). His EBV titers were positive for viral capsid antigen (VCA)-IgM and IgG and Epstein Barr nuclear antigen (EBNA)-IgG. He had EBV titers done 2 years previously which were positive for VCA-IgG and EBNA-IgG documenting previous primary EBV infection. The patient gradually improved with supportive therapy and was discharged on Day 8. The patient returned to Pediatric Hematology clinic on Day 19 and had resolution of signs and symptoms. Table 1 shows an overview of his blood counts and transfusion requirements. [Display omitted] Coinfection with EBV and HPV-B19 in healthy adults has rarely been reported. Severe aplastic anemia caused by EBV and HPV-B19 infections was reported in a previously healthy 22-year-old male. He was treated with immunosuppressive therapy followed by allogeneic bone marrow transplant (Kaptan K et al, Am J Hematol 2001). Acute HPV-B19 infection and concomitant EBV reactivation causing moderate hemophagocytic syndrome was reported in a previously healthy 37-year-old-male (Larroche C et al, Eur J Clin Microbiol Infect Dis 2002). HPV-B19 infection with EBV reactivation has not been reported in children.Sepsis from viremia is not common with either EBV or HPV-B19, however together this co-infection can be life-threatening as seen in our patient. HPV-B19 infection has been reported to produce false positive EBV VCA-IgM serology assay. Our patient had a true coinfection because he had viremia documented by EBV DNA PCR.This is the first report of viremia and septic shock associated with an acute HPV-B19 infection and EBV reactivation in a patient with SCD.WBC- White Blood Cell Count, ANC- Absolute Neutrophil Count, ALC- Absolute Lymphocyte Count, Plt- Platelet Count, Hgb- Hemoglobin, HCT- Hematocrit, Retic: Corrected Reticulocyte Count, U- Units, PRBC- Packed red blood cells, ER- Emergency room Disclosures:No relevant conflicts of interest to declare.

Acute human parvovirus B19 infection and nephrotic syndrome in patients with sickle cell disease

Acute Human Parvovirus B19 (HPV B19) infection is the major cause of transient red cell aplasia (TRCA) and acute anaemia in patients with sickle cell disease (SCD). We report three cases of patients who developed nephrotic syndrome (NS) with chronic sequelae after initially presenting with HPV B19-associated TRCA. There was no correlation between evidence of HPV B19 infection and impaired renal function in our cohort of adult sickle cell patients. This is consistent with a view that although NS is potentially a rare complication of symptomatic acute HPV B19 infection, exposure to HPV B19 is not associated with an increased risk of renal disease.

Acute Human Parvovirus B19 Infection and Nephrotic Syndrome in Patients with Sickle Cell Disease

Human Parvovirus B19 (HPV B19) infection has previously been thought to be a trigger of nephrotic syndrome. The virus is associated with significant morbidity in patients with sickle cell disease (SCD) and a major cause of transient red cell aplasia (TRCA). We report three patients with SCD who presented with TRCA secondary to acute HPV B19 infection who subsequently developed significant proteinuria and nephrotic syndrome (NS) on outpatient follow up. There were 37 cases of acute HPV B19 infection in SCD patients admitted to King's College Hospital between November 2002 and July 2008. 29 cases were in children below the age of 16 years, eight in patients over the age of 16 years. The average age of the cohort was just over 11 years at diagnosis. Three patients developed NS within 4 months of acute HPV B19 infection and TRCA. Two of these patients were aged 17 and 26 years at diagnosis (patient 1 and 2 respectively), whereas the third was a child aged 11 (patient 3). Renal histology demonstrated the collapsing variant of focal segmental glomerulosclerosis (FSGS) in the acute phase of NS in patient 1, a characteristic finding associated with HPV B19-associated nephrotic syndrome. A subsequent biopsy in the same patient two years later demonstrated non-collapsing FSGS and marked interstitial fibrosis. Patient 2 had a renal biopsy performed 4 months after the onset of NS. This demonstrated non-collapsing FSGS, acute sickle nephropathy and significant chronic tubular atrophy. Patient 3 also had a renal biopsy 1 year after her acute HPV B19 infection which demonstrated the cellular variant of FSGS. Patient 1 was treated with immunosuppression and although the NS has improved slowly he continues to have significant proteinuria and progressive renal impairment. Patient 2 has not received immunosuppressive therapy and has also slowly improved from her NS but continues to have significant proteinuria; her estimated GFR has fallen from 169 ml/min to 104 ml/min six months after the acute HPV B19 infection. Patient 3 was treated with corticosteroids with subsequent improvement in serum albumin and symptoms but proteinuria persists with normal renal function. Consistent with previous reports, we observe that NS is a relatively rare complication of HPV B19 infection in young children with SCD (one case in 29 in our cohort). However, two out of eight patients older than 16 years developed this complication. Proteinuria in patients with SCD is common and gradual in onset, and eventually may progress to NS. Nephrotic syndrome of acute onset in adults with SCD is rare, only two cases were observed during a 6-year period among our cohort of over 400 adult patients with SCD. In both cases, they were associated with recent HPV B19 infection. It has previously been noted that acute HPV B19 infection in older patients with HbSC SCD have a more severe clinical course than younger children (Smith-Whitley et al., 2004). Our data, though limited by small numbers in the cohort, suggest that older SCD patients with acute HPV B19 infection may be more susceptible to chronic complications including the development of NS and progressive renal fibrosis. A correct diagnosis of the aetiology of NS is vitally important as the HPV B19-associated condition may not be responsive to corticosteroids, unlike other aetiologies of NS in this age group. It is possible that antiviral therapy may be of benefit in the acute setting but this needs further investigation. Furthermore, immunisation of older children and young adults who are HPV B19-naïve may be effective in preventing an important contributor of chronic renal disease in SCD patients.

Intravenous immunoglobulin therapy for severe arthritis associated with human parvovirus B19 infection

Symptoms caused by acute human parvovirus B19 (HPV-B19) infection can vary considerably, from asymptomatic to severely symptomatic. A 39-year-old Japanese woman complained of sudden, severe arthralgia with edematous limbs coincident with an outbreak of HPV-B19 infection at the elementary school attended by her daughter. A diagnosis of acute HPV-B19 infection was made by the detection of serum antibody to HPV-B19 IgM and HPV-B19 DNA. Magnetic resonance imaging revealed bilateral synovitis of the cubital joints. The patient was immunocompetent and suffered from severe arthralgia associated with persistent HPV-B19 viremia for more than 4 months after the diagnosis of acute HPV-B19 infection. The administration of high-dose intravenous immunoglobulin resulted in remission, with little change in the serum HPV-B19 DNA level. Even in our immunocompetent patient, severe and prolonged arthritis was found to be associated with persistent viremia.

Acute Human Parvovirus B-19 Infection in Hospitalized Children

The extent and clinical manifestations of acute human parvovirus B19 (B19) infection were assessed in previously healthy hospitalized children admitted with clinical syndromes potentially associated the virus. The study was prospective and was conducted between October 2002 and August 2004 in the pediatric departments of 3 hospitals in Israel. The survey included previously healthy children who were hospitalized with 1 or more of the following acute diseases: acute nonallergic exanthema, fever for >1 week, aplastic anemia or pancytopenia, acute nonbacterial arthropathy, immune thrombocytopenic purpura (ITP), Henoch-Schönlein purpura (HSP) and aseptic meningitis. A control group of children with a proven, non-B19 infection was also studied. Serum samples obtained from each child on admission were tested for B19 DNA by real-time PCR and B19 IgM by ELISA. Acute B19 infection was defined by the following criteria: positive serum B19-DNA and/or B19 IgM, negative serum B19 IgG, and no other proven infection. Overall, 167 children were included in the study. The mean age was 5.5 +/- 4.6 years (range, 0.5-17), males and females equally divided. Acute B19 infection was demonstrated in 12.6% (n = 21) of the children. Both tests were performed in 19 children and were positive in 10 (53%). In 7 and 2 children, only B19-DNA or B19 IgM, respectively, was positive. Acute B19 infection was documented in 27% (10/39) of children who presented with a variety of acute exanthema diseases; 9% (5/57) of children with acute arthropathy (all 5 had transient synovitis); 10% (2/21) of children with fever >1 week, both presented as mononucleosis syndrome; and in 44% (4/9) of children with transient pancytopenia or aplastic anemia. No acute B19 infection was demonstrated in 15 children with ITP, 9 with HSP, and 6 with aseptic meningitis and among 70 children in the control group. By logistic regression analysis, manifestations significantly associated with acute B19 infection were exanthema (OR 2.9; 95% CI = 1.1-7.5), anemia (OR 6.35; 95% CI = 2.2-18.2) and leucopenia (OR 4.14; 95% CI =1.2-14.2). Acute B19 infection was documented among 12.6% of children hospitalized with clinical syndrome potentially associated with the virus. Clinical and laboratory features associated with acute B19 infection were exanthema, anemia and leucopenia. Determination of both serum B19-DNA and serum B19 IgM should be performed for the accurate diagnosis of acute B19 infection.

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.

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.

Tumor necrosis factor (TNF)α and its soluble receptor (sTNFR) p75 during acute human parvovirus B19 infection in children

Human parvovirus B19 (HPV) has been shown to be involved in the pathogenesis of various connective tissue and autoimmune diseases. In order to gain more information on HPV possible role in these diseases, we have investigated some immune responses in patients with acute HPV infection, mainly the secretion of the proinflammatory cytokine tumor necrosis factor (TNF)α and it's antagonist—the soluble TNF receptor (sTNFR) p75. Thirteen children with acute HPV infection and 13 healthy volunteers were investigated for the presence of autoantibodies, lymphocyte subpopulation counts, levels of total immunoglobulins, IgG subclasses and complement. The levels of TNFα and sTNFR p75 were determined in serum and conditioned medium (CM) from unstimulated and LPS stimulated peripheral blood mononuclear cell (PBMC) cultures. There was no difference between patients and controls regarding autoantibodies, lymphocytes, immunoglobulins, IgG subclasses and complement. A significant imbalance between TNFα and sTNFR p75 was found in the patients group. TNFα concentrations were significantly higher both in sera and in CM from the patients as compared with the controls. The levels of sTNFR concentrations were either similar (in sera) or significantly lower (in CM) in the patients compared with the controls. The TNF index, representing the biologically available TNFα, was significantly higher in patient's sera and CMs. In view of these results, it is conceivable that infection with human HPV in otherwise healthy children may lead to a proinflammatory state. The presence of high levels of biologically available TNFα, in susceptible individuals, may in turn play a role in the pathogenesis of systemic autoimmune diseases in HPV infected individuals.

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.

Human parvovirus B19 infection mimicking systemic lupus erythematosus

Although several recent reports have discussed the similarities between human parvovirus B19 (HPV-B19) infection and systemic lupus erythematosus (SLE), the relationship between these conditions has not been established owing to the small number of patients investigated. In 1998–1999, an outbreak of Erythema infectiosum occurred close to our hospital, enabling us to investigate the clinical, hematological, and serological findings, including serum complement and antinuclear antibodies (ANA), in 22 patients with acute HPV-B19 infection. The principal symptoms included rash (86.3%), edema (59%), arthralgia (45.4%) and fever (31.8%). Lymphadenopathy was seen in three of the 22 cases. The laboratory findings showed high incidences of leukopenia (50%), hypocomplementemia (95%), and ANA (64.7%). At the time of disease onset, patients with acute HPV-B19 infection presented with features which were similar to those of SLE. The possibility of HPV-B19 infection should therefore be considered in patients presenting with SLE-like features.

Human parvovirus B19 infection mimicking systemic lupus erythematosus

Although several recent reports have discussed the similarities between human parvovirus B19 (HPV-B19) infection and systemic lupus erythematosus (SLE), the relationship between these conditions has not been established owing to the small number of patients investigated. In 1998–1999, an outbreak of Erythema infectiosum occurred close to our hospital, enabling us to investigate the clinical, hematological, and serological findings, including serum complement and antinuclear antibodies (ANA), in 22 patients with acute HPV-B19 infection. The principal symptoms included rash (86.3%), edema (59%), arthralgia (45.4%) and fever (31.8%). Lymphadenopathy was seen in three of the 22 cases. The laboratory findings showed high incidences of leukopenia (50%), hypocomplementemia (95%), and ANA (64.7%). At the time of disease onset, patients with acute HPV-B19 infection presented with features which were similar to those of SLE. The possibility of HPV-B19 infection should therefore be considered in patients presenting with SLE-like features.

Anti-VP1 and anti-VP2 antibodies detected by immunofluorescence assays in patients with acute human parvovirus B19 infection.

Acute human parvovirus B19 infection is followed by an antibody response to the structural proteins of the viral capsid (VP1 and VP2). We used 80 sera collected from 58 erythema infectiosum and 6 transient aplastic crisis patients to test IgM and IgG antibodies against these two proteins in an immunofluorescence assay (IFA) using Sf9 cells infected with recombinant baculovirus expressing either VP1 or VP2 antigen. Although less sensitive than IgM capture enzyme immunoassay using native antigen (MACEIA), we could detect anti-VP1 or anti-VP2 IgM antibodies by IFA in 49 patients with acute infection (76.6%). Detection of IgG anti-VP1 and anti-VP2 by IFA, however, was as sensitive as IgG detection by indirect enzyme immunoassay. By applying IgG avidity IFA to sera of the 15 IgM IFA negative patients we were able to confirm acute infection in further 12 cases by IFA. Overall, acute infection was confirmed by IFA in 61 (95.3%) of the 64 patients.

Erythema multiforme in a patient with acute human parvovirus B19 infection

Erythema multiforme in a patient with acute human parvovirus B19 infection