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Human infection with parvovirus B19 causes a range of clinical manifestations, including benign erythema infectiosum in children, arthralgias in adults, aplastic crisis in patients with bone marrow failure, and potentially fatal congenital hydrops fetalis. Persistent parvovirus B19 infection is a rare disease presentation mostly seen in adult women or immunocompromised individuals. Treatment options include corticosteroids and intravenous immunoglobulin; however, viral clearance is difficult to obtain and rarely maintained. In this Grand Round, we report the case of a 43-year-old man with persistent parvovirus B19 infection and anaemia, who was refractory to standard treatment regimens, and whom we successfully treated with pegylated interferon alfa-2a. Initial treatment led to viral clearance and remission of anaemia, although secondary recurrence of virus required treatment extension. Despite extensive genetic and immunological evaluations, no underlying primary or secondary immunodeficiency was identified in the patient. We propose interferon alfa-2a as a treatment option for persistent parvovirus B19 infection and advocate long-term follow-up of patients and potentially repeated treatment. [ABSTRACT FROM AUTHOR]

• ⊿PLA2 B19 VLPs-immunization did not cause inflammation in mice. • B19 PLA2 domain does not constitute an important human CD4+ T cell epitope. • ⊿PLA2 B19 VLPs induced neutralizing antibodies against B19. • ⊿PLA2 B19 VLPs could be a safe and effective vaccine candidate against B19. Parvovirus B19 (B19) belongs to the Erythroparvovirus genus and is known to cause the fifth disease in children. Primary infection of pregnant women is associated with a high risk of hydrops fetalis and stillbirth due to severe fetal anemia. Virus-like particle (VLP) vaccine candidates for B19 have been developed, although none have been approved so far. The B19 phospholipase A2 domain (B19 PLA2), located in the VP1 unique region, is believed to be associated with adverse inflammatory reactions, and previous effective attempts to improve this vaccine modality inserted a mutation to impair the PLA2 activity of VLPs. In this study, we designed VLPs with a deletion mutant of PLA2 (⊿PLA2 B19 VLP), devoid of PLA2 activity, and confirmed their immunogenicity and safe use in vivo. These results were supported by the lack of histological inflammatory reactions at the site of immunization or the production of IL-6 in ⊿PLA2 B19 VLP-immunized mice, that were observed in mice immunized with B19 VLPs. CD4+ T cells from mice vaccinated with VLPs and B19-seropositive human samples were not activated by B19 PLA2 stimulation, suggesting that the B19 PLA2 domain does not constitute a major CD4+ T cell epitope. Most importantly, the ⊿PLA2 B19 VLPs induced neutralizing antibodies against B19, in levels similar to those found in B19-seropositive human samples, indicating that they could be used as a safe and effective vaccine candidate against B19. [ABSTRACT FROM AUTHOR]

Parvovirus B19 is a small, non-enveloped, single-stranded DNA virus with global distribution. It is primarily known for being the causative agent of fifth disease, also known as erythema infectiosum, a common self-limiting childhood disease characterized by the development of a rash. During infection, it targets erythroid progenitor cells in bone marrow, where it replicates and ultimately induces cellular apoptosis. In the correct patient population, it may be responsible for the development of arthropathy, aplastic crisis, nonimmune hydrops fetalis, viral-associated hepatitis, and myocarditis. However, most infections are asymptomatic and remain undetected. Here, we review the nature of this virus to provide information about its biology; interactions with the human host; how those interactions shape the clinical presentation; and, finally, the available diagnostic approaches. [ABSTRACT FROM AUTHOR]

Parvovirus B19 (B19V) is a widespread infection that may affect 1-5% of pregnant women, mainly with normal pregnancy outcome. Vertical transmission occurs in 33-51% of cases of maternal infection. B19V infection is an important cause of fetal morbidity (fetal anaemia and non-immune hydrops) and mortality, predominantly in the second trimester. Diagnosis of B19V infection requires a multi-method approach using mainly serology and PCR techniques. Severe fetal anaemia is managed with intrauterine transfusion with perinatal survival rates following intrauterine transfusion ranging from 67% to 85%. If fetal anaemia is mild, and considering that hydrops can spontaneously resolve, invasive therapy is not recommended and B19V complicated pregnancy may be non-invasively monitored by serial ultrasound examination and MCV-PSV measurements. As an alternative, intrauterine IVIG therapy has been described with successful treatment of fetal hydrops. No specific antiviral therapy or vaccine is presently available for B19V infection but efforts in the search for compounds inhibiting B19V replication are now being pursued. New virus-like-particle based parvovirus B19 vaccine candidates, produced by co-expressing VP2 and either wild-type VP1 or phospholipase-negative VP1 in a regulated ratio from a single plasmid inSaccharomyces cerevisiae have been developed and show sufficient promise to test in humans. [ABSTRACT FROM AUTHOR]

• B19 RBD alone could not induce neutralizing antibodies due to poor T cell-activation. • RBD-PspA enhanced immunogenicity of RBD, generating parvovirus B19-neutralizing IgG. • RBD-PspA induced PspA-specific protective immunity against pneumococcal infection. • PspA-specific T cells, promoted production of both RBD- and PspA-specific antibodies. • RBD-PspA is a potent bivalent vaccine against parvovirus B19 and S. pneumoniae. Parvovirus B19 (B19) is a well-known cause of fifth disease in children, but infection during pregnancy may cause hydrops fetalis and stillbirth. The receptor-binding domain (RBD) of the VP1 unique capsid plays a pivotal role in infection. Here, we aimed to improve the immunogenicity of an RBD-based vaccine by genetically fusing it with Streptococcus pneumoniae surface protein A (PspA). Mice were intramuscularly injected with RBD-based vaccines. Antigen-specific antibodies and neutralizing activity against B19 were measured. Protective immunity against S. pneumoniae was evaluated by monitoring the survival of mice nasally challenged with bacteria and determining antigen-specific T cell activation in splenic cells. RBD alone failed to generate neutralizing antibodies against B19, but fusion with PspA induced higher levels of neutralizing IgG compared to B19 virus-like particles. Furthermore, a comparable level of PspA-specific IgG was induced by RBD-PspA and PspA alone, which was sufficient to protect mice against pneumococcal infection. Stimulation with PspA, but not RBD, induced cytokine production in splenic cells from mice immunized with RBD-PspA, suggesting that PspA-specific T cells supported immunoglobulin class switching of both RBD- and PspA-specific B cells. RBD-PspA should be an effective bivalent vaccine against B19 and S. pneumoniae infections. [ABSTRACT FROM AUTHOR]

Highlights • Maternal parvovirus B19 infection during pregnancy increased the risk of fetal loss, spontaneous abortion and stillbirth. • The incidence of fetal loss in B19 infectious pregnant women was 7.6% (95% CI: 5.5-9.5). • The incidence of fetal hydrops in B19 infectious pregnant women was 9.3% (95% CI: 5.6-13.0). Abstract Background Human parvovirus B19 (B19) is widespread infection in humans, yet the impact on adverse pregnancy outcomes is controversial. Objective to evaluate the impact of B19 infection during pregnancy on adverse pregnancy outcome, and investigated the incidence of fetal loss and fetal hydrops after maternal B19 infection during pregnancy. Study design A systematic literature search was performed using Embase, Medline, PubMed, Web of science, and the Cochrane Library database for relevant publications up to 10th August 2018. Cohort studies and case-control studies were included in analyses. Results In total, 36 eligible studies were included. Of these, 18 studies reported the risk of maternal B19 infection during pregnancy on fetal loss and 20 studies reported the incidence of fetal loss or fetal hydrops after maternal B19 infection. Collectively, the results indicated that maternal B19 infection increased the risk of fetal loss, spontaneous abortion, and stillbirth with ORs of 2.68 (95% CI: 2.02–3.55), 2.42 (95% CI: 1.76–3.33), and 3.53 (95% CI: 1.91–6.54), respectively, when compared with uninfected pregnant women. In addition, the incidence of fetal loss and fetal hydrops in B19 infected pregnant women was 7.6% (95% CI: 5.5–9.5) and 9.3% (95% CI: 5.6–13.0), respectively. Conclusions maternal parvovirus B19 infection during pregnancy increased the risk of fetal loss, spontaneous abortion, and stillbirth. A high incidence of fetal loss and fetal hydrops was observed in pregnant women with parvovirus B19 infection. [ABSTRACT FROM AUTHOR]

Objective To study modalities and complications of intrauterine exchange transfusion (IUET) for the management of severe fetal anaemia. Study design Retrospective study of all IUET procedures performed between January 1999 and January 2012 at a regional centre. Characteristics of each procedure were studied to identify risk factors for complications. Survival rates according to the different aetiologies of anaemia were evaluated. Results In total, 225 IUET procedures were performed in 96 fetuses. Major indications were feto-maternal erythrocyte alloimmunization (n = 80/96, 83.3%) and parvovirus B19 infection (n = 13/96, 13.5%). Twenty-six percent of the fetuses (25/96) had hydrops fetalis before the first IUET. Intrauterine fetal death occurred after 2.7% (6/225) of procedures, premature rupture of the membranes occurred after 0.9% (2/225) of procedures, and emergency caesarean section was required after 3.6% (8/225) of procedures. Fetal bradycardia [odds ratio (OR) 37, 95% confidence interval (CI) 8.3-170; p < 0.01] and gestational age up to 32 weeks (OR 3.67; 95% CI, 1.07-12.58; p = 0.038] were significantly associated with complications after IUET. Complications occurred in 17.7% of pregnancies (17/96) and 7.5% of IUET procedures (17/225). The overall survival rate in the study cohort was 87.5% (84/96): 90% (72/80) in the alloimmunization group and 76.9% (10/13) in the parvovirus-infected group (NS). Conclusion IUET has a higher complication rate than simple intrauterine transfusion, and should be performed by well-trained specialists. [ABSTRACT FROM AUTHOR]

Abstract: The aim of the present study was to determine whether there is an association between Parvovirus B19 infection and hydrops fetalis setting in fetus and neonate. Twenty-nine samples were analyzed by three methods. Each sample was histologically examined for viral nuclear inclusions in fetal organs and placenta, then immunohistochemical study using Parvovirus B19 antibody that recognized the VP2 protein of the Parvovirus B19 capsid was done in tissue embedded in paraffin (lungs, liver, thymus, kidneys, heart and placenta). Nested-PCR analysis was done after DNA extraction from paraffin blocks and using specific primers of the Parvovirus B19 VP1 gene. Apparent causes of hydrops were eliminated such as metabolic diseases, cardiac failure or malformation. The standard histological study objectivates viral inclusion in one case (lung tissue). However, the immunohistochemical study was negative in all cases. Nested-PCR demonstrates the presence of the viral DNA in five cases. Our study demonstrates that the implication of Parvovirus B19 in hydrops fetalis must be affirmed by the use of more than one method. Nested-PCR is the most sensitive method in our study and can be easily used for the detection of Parvovirus B19 in formalin-fixed paraffin-embedded tissues. [Copyright &y& Elsevier]