Ensuring Transfusion Safety: Screening Blood Donors for Human Parvovirus B19.

Ensuring the safety of blood and blood products is a vital aspect of healthcare. The potential for transmission of pathogens through blood and blood products makes transfusion safety a significant concern. Despite advancements in testing methodologies, donated blood products still pose a risk for infection transmission. Human parvovirus B19 (B19V) is a small, single-stranded, non-enveloped DNA virus transmissible parenterally by blood transfusion. B19V causes a wide range of clinical manifestations, which is generally harmless in healthy individuals. B19V infection may cause severe complications, such as aplastic crises, as it affects erythrocyte progenitor cells in individuals with increased erythrocyte turnover. Additionally, B19V can be transmitted from pregnant women to their foetus, potentially causing hydrops fetalis and foetal death. The potential for transmission through blood and blood products makes B19V a significant concern for transfusion safety. In response to the growing recognition of B19V's impact on transfusion safety, various international health organisations have introduced guidelines to minimise its transmission through blood and plasma products. However, the implementation of these guidelines varies globally, with some regions, such as India, still lacking formal protocols for B19V monitoring. This review article explores the existing methodologies for screening blood donors for B19V, assesses the associated transfusion risks, and considers the implications for public health and clinical practice. By emphasising advancements in diagnostic techniques and the challenges of their implementation, this article provides a comprehensive overview of efforts to reduce the transmission of B19V through blood transfusions, thereby ensuring safer blood supplies and improved patient outcomes.

Parvovirus B19 Infection Is Associated with the Formation of Neutrophil Extracellular Traps and Thrombosis: A Possible Linkage of the VP1 Unique Region.

Neutrophil extracellular traps (NETs) formation, namely NETosis, is implicated in antiphospholipid syndrome (APS)-related thrombosis in various autoimmune disorders such as systemic lupus erythematosus (SLE) and APS. Human parvovirus B19 (B19V) infection is closely associated with SLE and APS and causes various clinical manifestations such as blood disorders, joint pain, fever, pregnancy complications, and thrombosis. Additionally, B19V may trigger the production of autoantibodies, including those against nuclear and phospholipid components. Thus, exploring the connection between B19V, NETosis, and thrombosis is highly relevant. An in vitro NETosis model using differentiated HL-60 neutrophil-like cells (dHL-60) was employed to investigate the effect of B19V-VP1u IgG on NETs formation. A venous stenosis mouse model was used to test how B19V-VP1u IgG-mediated NETs affect thrombosis in vivo. The NETosis was observed in the dHL-60 cells treated with rabbit anti-B19V-VP1u IgG and was inhibited in the presence of either 8-Br-cAMP or CGS216800 but not GSK484. Significantly elevated reactive oxygen species (ROS), myeloperoxidase (MPO), and citrullinated histone (Cit-H3) levels were detected in the dHL60 treated with phorbol myristate acetate (PMA), human aPLs IgG and rabbit anti-B19V-VP1u IgG, respectively. Accordingly, a significantly larger thrombus was observed in a venous stenosis-induced thrombosis mouse model treated with PMA, human aPLs IgG, rabbit anti-B19V-VP1u IgG, and human anti-B19V-VP1u IgG, respectively, along with significantly increased amounts of Cit-H3-, MPO- and CRAMP-positive infiltrated neutrophils in the thrombin sections. This research highlights that anti-B19V-VP1u antibodies may enhance the formation of NETosis and thrombosis and implies that managing and treating B19V infection could lower the risk of thrombosis.

Parvovirus B19 in Rheumatic Diseases.

Parvovirus B19 (B19V) is a human pathogen belonging to the Parvoviridae family. It is widely diffused in the population and responsible for a wide range of diseases, diverse in pathogenetic mechanisms, clinical course, and severity. B19V infects and replicates in erythroid progenitor cells (EPCs) in the bone marrow leading to their apoptosis. Moreover, it can also infect, in an abortive manner, a wide set of different cell types, normally non-permissive, and modify their normal physiology. Differences in the characteristics of virus-cell interaction may translate into different pathogenetic mechanisms and clinical outcomes. Joint involvement is a typical manifestation of B19V infection in adults. Moreover, several reports suggest, that B19V could be involved in the pathogenesis of some autoimmune rheumatologic diseases such as rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), systemic sclerosis (SSc), systemic lupus erythematosus (SLE), or vasculitis. This review provides basic information on the B19 virus, highlights characteristics of viral infection in permissive and non-permissive systems, and focuses on recent findings concerning the pathogenic role of B19V in rheumatologic diseases.

Role of clinical, molecular, and serological features in the diagnosis of parvovirus B19 infection in children.

BACKGROUND: Parvovirus B19(B19) is a DNA virus. The most common B19 disease is erythema infectiosum (fifth-disease). PCR and ELISA are sensitive for detecting of acute disease. However, it is not clear which test better and the relationship between laboratory tests and clinical findings. OBJECTIVE: To discuss the clinical and laboratory characteristics of pediatric patients infected with B19. STUDY DESIGN: 236 children were examined. Children with at least one positive molecular or serological test were included. Positive serum B19-DNA and/or B19-IgM was considered an acute B19 infection. RESULTS: B19DNA was detected in 80.8 % of acute cases. Serological tests were less positive. Acute B19 infection was observed in 24 patients. Only 17 patients were positive for B19 DNA, 3 for IgM and 4 for both. The sensitivity of B19 DNA is 87.5 %. However, this rate is 29.2 % for B19 IgM. CONCLUSION: B19-DNA and IgM together provide a better, highly accurate diagnosis.

A Multiplex Fluorescence of Loop Primer Upon Self-Dequenching Loop-Mediated Isothermal Amplification Assay for the Detection of Epstein-Barr Virus and Human Parvovirus B19 in Clinical Transplant Samples.

Viral infections are major causes of mortality in solid-organ and hematopoietic stem cell transplant recipients. Epstein-Barr virus (EBV) and Parvovirus B19 (B19V) are among the common viral infections after transplantation and were recommended for increased screening in relevant guidelines. Therefore, the development of rapid, specific, and cost-effective diagnostic methods for EBV and B19V is of paramount importance. We applied Fluorescence of Loop Primer Upon Self-Dequenching Loop-mediated Isothermal Amplification (FLOS-LAMP) for the first time to develop a novel multiplex assay for the detection of EBV and B19V; the fluorophore attached to the probe are self-quenched in unbound state. After binding to the dumbbell-shaped DNA target, the fluorophore is dequenched, resulting in fluorescence development. The novel multiplex FLOS-LAMP assay was optimized by testing various ratios of primer sets. This novel assay, with great specificity, did not cross-react with the common virus. For the detection of EBV and B19V, the limits of detection could reach 969 and 798 copies/µL, respectively, and the assay could be completed within 25 min. Applying this novel assay to detect 200 clinical transplant individuals indicated that the novel assay had high specificity and good sensitivity. We developed multiplex FLOS-LAMP assay for the detection of EBV and B19V, which has the potential to become an important tool for clinical transplant patient screening.

TCRαß-depleted hematopoietic stem cell transplant and third-party CD45RA+ depleted adoptive cell therapy for treatment of post-transplant parvovirus B19 aplastic crisis.

This is a case report of a 6-year-old girl with relapsed B cell acute lymphoblastic leukemia in which adoptive cell therapy was applied successfully to treat refractory human parvovirus (HPV) B19 infection. Allogenic chimeric antigen receptor (CAR) T-cell therapy (bispecific CD19/CD22) was bridged to hematopoietic stem cell transplantation (HSCT) using a haploidentical paternal donor. However, HPV B19 DNAemia progressed and transfusion-related graft versus host disease occurred. After finding a third-party related donor with a better HLA match, haploidentical HPV B19-seropositive CD45RA+ depleted cells (16.5 × 106/kg) were administered and paternal TCRαß+ depleted stem cell were retransplanted. The HPV B19 DNAemia became negative within 1 week and the reticulocyte, neutrophil, hemoglobin, and platelet counts gradually normalized. The patient remained stable during the 1-year outpatient follow-up period. Thus, our case report highlights that persistent B19 infection can lead to pancytopenia, aplastic crisis, and graft rejection and TCRαß+ depleted haplo-HSCT is an effective means of hematopoiesis recovery. CD45RO memory T-cell therapy is the key to treating and preventing the development of refractory severe HPV B19 infection.

Seroepidemiology of Human Parvovirus B19 Infection among the Population of Vojvodina, Serbia, over a 16-Year Period (2008-2023).

This study aimed to estimate the serological status and dynamic changes in the prevalence of Parvovirus B19 (PVB19) antibodies within the general population residing in the northern part of the Republic of Serbia (Province of Vojvodina) during a 16-year period. Serum samples were analyzed for Human PVB19-specific IgM and IgG antibodies using enzyme-linked immunosorbent assay (ELISA). Throughout the study period, the overall seroprevalence was 49.51%. Approximately 10% of patients exhibited a serologic profile positive for PVB19 IgM antibodies. Notably, seroprevalence varied significantly, ranging from 9.12% in the pediatric cohort (ages 1-4 years) to 65.50% in the adult demographic (40-59 years old). Seroprevalence was higher (51.88%) among women compared to men (42.50%). Immunologically naive pregnant women in the age groups 26-36 and 36-45 years had 45% (OR = 0.55, 95% CI: 0.31-1.00) and 52% (OR = 0.48; 95% CI: 0.24-0.94) lower odds of having negative IgM and IgG compared to those in age group 16-25 years old. Improved knowledge of the epidemiology of PVB19 may assist clinicians in the differential diagnosis of PVB19 clinical manifestations. The PVB19 detection is particularly important for monitoring individuals in risk groups such as women of reproductive age, medical staff, patients with hematological disorders, and those with immunodeficiency.

An Outbreak of Parvovirus B19 in Israel.

Human parvovirus B19 (B19V) has a wide clinical spectrum, ranging from an asymptomatic infection to a life threatening one. During pregnancy, it can lead to fetal loss and hydrops fetalis. This retrospective study examined the incidence rates of B19V in Israel, analyzing anonymized electronic medical records of 2.7 million individuals between January 2015 and September 2023. A generalized linear model with a Poisson distribution was fit to the data, adjusting for potential confounders. A marked increase in B19V was observed in 2023, with an adjusted incidence rate ratio (IRR) of 6.6 (95% CI 6.33-6.89) when comparing 2023 to previous years. When specifically comparing 2023 to COVID-19 years (2020-2022), adjusted IRR climbs to 9.21 (8.66-9.80). Moreover, in 2023, previously existing seasonality has largely disappeared. High SES characterized most infected individuals with a marked discrepancy in social sectors; the Arab population was significantly less likely to be found B19V positive, even when adjusting for SES. Most infections occurred in school-aged children (6-11 years old). Pregnant women experienced the most significant rise in B19V, with an adjusted IRR of 11.47 (9.44-13.97) in 2023 compared to previous years; most cases were diagnosed in the first trimester. This study demonstrates that Israel is currently experiencing the largest and longest reported outbreak of B19V to date. Policymakers should consider setting screening policies in place, at least for populations at risk, while specifically studying and potentially targeting low socioeconomic populations and specific social sectors to avoid health inequalities.

Effect of the Functional VP1 Unique Region of Human Parvovirus B19 in Causing Skin Fibrosis of Systemic Sclerosis.

Human parvovirus B19 (B19V) is a single-stranded non-enveloped DNA virus of the family Parvoviridae that has been associated with various autoimmune disorders. Systemic sclerosis (SSc) is an autoimmune connective tissue disorder with high mortality and has been linked to B19V infection. However, the precise mechanism underlying the B19V contribution to the development of SSc remains uncertain. This study investigated the impacts of the functional B19V-VP1 unique region (VP1u) in macrophages and bleomycin (BLE)-induced SSc mice. Cell experimental data showed that significantly decreased viability and migration of both B19V-VP1u-treated U937 and THP-1 macrophages are detected in the presence of celastrol. Significantly increased MMP9 activity and elevated NF-kB, MMP9, IL-6, TNF-α, and IL-1ß expressions were detected in both B19V-VP1u-treated U937 and THP-1 macrophages. Conversely, celastrol revealed an inhibitory effect on these molecules. Notably, celastrol intervened in this pathogenic process by suppressing the sPLA2 activity of B19V-VP1u and subsequently reducing the inflammatory response. Notably, the administration of B19V-VP1u exacerbated BLE-induced skin fibrosis in mice, with augmented expressions of TGF-ß, IL-6, IL-17A, IL-18, and TNF-α, ultimately leading to α-SMA and collagen I deposits in the dermal regions of BLE-induced SSc mice. Altogether, this study sheds light on parvovirus B19 VP1u linked to scleroderma and aggravated dermal fibrosis.