Surveillance of Erythrovirus B19 (B19V) in patients with acute febrile illness suspected of arboviruses in Mato Grosso do Sul state, Brazil.

Introduction: Human Erythrovirus (parvovirus) B19 infection can produce symptoms similar to those produced by Dengue, Chikungunya, and Zika viruses, making clinical diagnosis difficult. The importance of erythrovirus B19 in human pathology has been increased and reported in numerous studies published globally. Methods: The B19V infection was investigated by real-time PCR in sera samples from patients with signs and symptoms related to classic arboviral symptoms. This study was conducted to provide information on the genetic diversity of Human Erythrovirus B19 (B19V) circulating in the state of Mato Grosso do Sul, Midwest region of Brazil, from 2017 to 2022. A total of 773 sera samples of patients with negative diagnostic results for Dengue, Chikungunya, and Zika, during the study period were analyzed. Results: Erythrovirus DNA was found in 10.6% (82/773) of patients, among them 10 were pregnant women. Four samples were completely sequenced, and the other five partially, to genotype by phylogenetic reconstruction. All samples belong to worldwide dispersed genotype 1, subgenotype 1a. Discussion: The findings of the study demonstrate the importance of including B19V in differential laboratory diagnosis for epidemiological purposes and appropriate patient management. The diagnosis for B19V should be performed, particularly among pregnant women, immunocompromised patients, and individuals with hemolytic diseases, given that the infection is more severe in these cases.

Globoside Is an Essential Intracellular Factor Required for Parvovirus B19 Endosomal Escape.

Human parvovirus B19 (B19V), like most parvoviruses, possesses phospholipase A2 (PLA2) activity, which is thought to mediate endosomal escape by membrane disruption. Here, we challenge this model and find evidence for a mechanism of B19V entry mediated by the glycosphingolipid globoside without endosome disruption and retrograde transport to the Golgi. We show that B19V PLA2 activity requires specific calcium levels and pH conditions that are not optimal in endosomes. Accordingly, endosomal membrane integrity was maintained during B19V entry. Furthermore, endosomes remained intact when loaded with MS2 bacteriophage particles pseudotyped with multiple B19V PLA2 subunits, providing superior enzymatic potential compared to native B19V. In globoside knockout cells, incoming viruses are arrested in the endosomal compartment and the infection is blocked. Infection can be rescued by promoting endosomal leakage with polyethyleneimine (PEI), demonstrating the essential role of globoside in facilitating endosomal escape. Incoming virus colocalizes with Golgi markers and interfering with Golgi function blocks infection, suggesting that globoside-mediated entry involves the Golgi compartment, which provides conditions favorable for the lipolytic PLA2. Our study challenges the current model of B19V entry and identifies globoside as an essential intracellular receptor required for endosomal escape.

Intrauterine transfusion under fetal analgesia: the evaluation of perinatal outcomes.

Introduction: Intrauterine transfusion is the treatment for fetal anemia resulting from maternal alloimmunization, infections (parvovirus B19 and cytomegalovirus), single demise of a monochorionic twin, chorioangioma, and other rare conditions. Fetal analgesia is mandatory to reduce movement and pain perception during the procedure. This study aims to evaluate perinatal outcomes for such procedures, following the routine use of fetal analgesia in our clinical practice. Materials and methods: Retrospective analysis of cases from 2009 to 2022, including all confirmed fetal anemia with fetal blood sampling. After fetal analgesia, Rh-negative concentrated red blood cells were transfused, with ultrasonographic follow-up 24 h and 1 week later. In case of suspected brain lesion, magnetic resonance imaging was performed. Elective delivery was considered in case of persistent anemia after 34 weeks. Post-natal follow-up and comprehensive obstetric and perinatal outcomes data were collected. Results: Altogether 59 anemic fetuses were included, with 34 (57.6%) being hydropic. The causes of anemia were maternal alloimmunization (22, 37.3%), infections (13, 22%), monochorionicity (10, 16.9%), rare conditions (9, 15.3%), and two chorioangiomas (3.4%). The median gestational age at the procedure was 25.2 weeks (18-32 weeks), with no related preterm premature rupture of membranes (<48 h), or side effects from fetal analgesia. Gestational age at delivery was 33 weeks (26-41 weeks), with survival rate of 90%. There were four fetal demises, two termination of pregnancies, and eight neonatal deaths due to persistent severe anemia after preterm delivery. The main contributors to adverse outcome were the type of anemia, and the management with a preterm delivery. Conclusion: Intrauterine transfusion of red blood cells under analgesia is safe, with low incidence of obstetric complication.

Viral Myocarditis as a Factor Leading to the Development of Heart Failure Symptoms, Including the Role of Parvovirus B19 Infection-Systematic Review.

Myocarditis (MC) is defined as an immunological inflammatory reaction with various etiologies, clinical presentations and prognoses within the myocardium. Currently, parvovirus B19 (PVB19) has become the main factor leading to this disease, replacing the previously dominant viruses A and B. In the case of chronic heart failure with subsequent dilated cardiomyopathy, approximately 67% have a viral etiology, and most of them are the result of PVB19 infection. However, the analysis showed a correlation between PVB19 infection and the risk of developing inflammatory dilated cardiomyopathy (DCMi). PVB19 is detected in 23% of patients with DCMi. Chronic infection may also contribute to progressive left ventricular failure in patients with a history of MC. The above effect suggests the active replication of PVB19 only in heart biopsies with inflammation due to MC or DCMi. Moreover, the supply of IFN-ß to suppress the active transcription of PVB19 accompanied by DCMi over a period of 6 months results in the normalization of NT-proBNP and an improvement in LVEF along with NYHA performance. The small number of reports on this topic and inaccuracies resulting from constantly conducted research and ongoing changes make it impossible to clearly answer the question of whether PVB19 is a factor inducing de novo MC and DCM or only accompanies the above conditions. However, large clinical cohort studies lead to the perception of PVB19 as a viral etiological agent capable of causing de novo MC together with DCMi.

Adult-Onset Still's Disease: An Atypical Presentation Refractory to Standard Treatment.

A previously healthy young female of Southeast Asian descent presented with a two-week history of polyarthritis, urticarial rash, sore throat, and 8.6 kg of unintentional weight loss. The initial workup revealed a positive parvovirus B19 polymerase chain reaction with hyperferritinemia. The patient was diagnosed with adult-onset Still's disease (AOSD) secondary to parvovirus B19 infection. Bone marrow biopsy also showed evidence of hemophagocytic lymphohistiocytosis. Viral and bacterial infections may trigger AOSD in genetically susceptible hosts either via an unknown mechanism or by direct cytotoxic effect. This case shows an atypical presentation of AOSD, as well as the challenge in diagnosing and treating AOSD complicated by macrophage activation syndrome refractory to standard treatment.

Lymphocytic Myocarditis in Children with Parvovirus B19 Infection: Pathological and Molecular Insights.

BACKGROUND: This study aims to evaluate the role of parvovirus B19 (B19V) in the pathogenesis of myocarditis in a paediatric population, including post-mortem samples from two children. METHODS: From 2004 to 2023, endomyocardial biopsies (EMBs) from children under 16 years of age were analyzed using histology, immunohistochemistry, and molecular pathology. A total of 306 children with acute and 1060 children with chronic lymphocytic myocarditis were identified. RESULTS: B19V infection was more frequent in acute myocarditis than in chronic myocarditis (43% vs. 14%), with higher viral loads in acute cases regardless of age. The most prominent cardiac CD3+ T cell infiltration was noted in children < 2 years, correlating with high cardiac B19V loads. In two male infants who died from B19V infection, B19V DNA was localized in the endothelial cells of multiple organs using in situ hybridization. Virus replication was found in the endothelial cells of small cardiac arterioles and venules but not in capillaries. B19V DNA/mRNA was also detected in immune cells, especially in the spleen and lymph nodes, revealing virus replication in B lymphocytes. CONCLUSIONS: B19V can induce severe lymphocytic myocarditis, especially in young children. The simultaneous histopathological and molecular assessment of EMBs is important for early diagnosis of viral myocarditis, preventing severe disease, and ensuring appropriate therapy.

Viral myocarditis: From molecular mechanisms to therapeutic prospects.

Myocarditis is characterized as local or diffuse inflammatory lesions in the myocardium, primarily caused by viruses and other infections. It is a common cause of sudden cardiac death and dilated cardiomyopathy. In recent years, the global prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the widespread vaccination have coincided with a notable increase in the number of reported cases of myocarditis. In light of the potential threat that myocarditis poses to global public health, numerous studies have sought to elucidate the pathogenesis of this condition. However, despite these efforts, effective treatment strategies remain elusive. To collate the current research advances in myocarditis, and thereby provide possible directions for further research, this review summarizes the mechanisms involved in viral invasion of the organism and primarily focuses on how viruses trigger excessive inflammatory responses and in result in different types of cell death. Furthermore, this article outlines existing therapeutic approaches and potential therapeutic targets for the acute phase of myocarditis. In particular, immunomodulatory treatments are emphasized and suggested as the most extensively studied and clinically promising therapeutic options.

Pancytopenia Concurrent With Metabolic Encephalopathy.

Pancytopenia is a decrease in the number of cells in all peripheral blood cell lines and has been associated with anemias, cancers, chemotherapy, infections, and nutritional deficiencies. However, pancytopenia concurrent with encephalopathy is rare and not well-studied. We present a case of pancytopenia concurrent with metabolic encephalopathy. An 81-year-old female patient presented to the emergency department for two weeks of increased fatigue and hypersomnolence. The patient had trouble staying awake during the initial physical exam, and her laboratory results were significant for pancytopenia, hypercreatinemia, hypernatremia, hypermagnesemia, and alkalemia. She was admitted to the floor, diagnosed with metabolic encephalopathy and acute kidney injury, and treated with medication withholding, fluid resuscitation, and electrolyte repletion. She also received a comprehensive workup for pancytopenia, iron replacement, and red blood cell transfusion therapy. After her metabolic encephalopathy was resolved, she was discharged with plans to follow up with hematology/oncology for stable but unresolved pancytopenia. We hypothesize that the patient's metabolic encephalopathy was likely due to acute kidney injury-induced uremia or dehydration. We further hypothesize that parvovirus B19 and myelodysplastic syndrome are possible etiologies for pancytopenia. Our case highlights the importance of closely monitoring patients taking Sodium-glucose co-transporter-2 (SGLT-2) inhibitors and loop diuretics for dehydration and subsequent organ failure.

Prenatal parvovirus B19 infection.

Parvovirus B19 (B19V) causes erythema infectiosum, a.k.a., fifth disease. This disease primarily affects children. It is generally self-limiting and subsides after 1-2 weeks. In pregnancy, the virus can cross the placenta and result in a fetal infection. This may lead to severe fetal anemia, hydrops fetalis, a miscarriage, or intrauterine fetal death. The risk of long-term sequelae also appears to be increased. About one-third of pregnant women are not immune to B19V and, therefore, are at risk to contract a primary infection. The seroconversion rate during pregnancy is generally around 1-2%. During a primary infection, maternal-fetal transplacental transmission of B19V occurs in about 30-50% of the cases and the risk of fetal infection increases with advancing gestational age. The risk of severe fetal anemia or hydrops is around 3-4% overall and is around 6-7% if the primary infection occurs before 20 weeks' gestation. Fetal monitoring in women with a primary B19V infection includes regular ultrasound examinations looking for evidence of hydrops fetalis and Doppler measurements of the middle cerebral artery peak velocity. Fetal blood sampling is performed if a significant anemia is suspected and, if such is found, an intrauterine blood transfusion is needed. This article provides an overview of the epidemiology, pathogenesis, clinical manifestations, diagnostic methods, and management of B19V infection during pregnancy.

Metronidazole-Induced Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Syndrome With Parvovirus B19 Reactivation: A Pediatric Case.

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe and rare syndrome that causes life-threatening organ dysfunctions. Here, we present the case of a 10-year-old child who developed a pruritic erythematous eruption, fever, facial edema, and lymphadenopathy seven days after receiving intravenous metronidazole (20 mg/kg/day), vancomycin (50 mg/kg/day), and cefotaxime (200 mg/kg/day). Laboratory tests showed eosinophilia and liver damage as well as positive parvovirus B19 IgM and IgG indicating viral reactivation. Vancomycin was initially discontinued and later reintroduced with no ill effects. The patient was managed with topical corticosteroid emollients and cetirizine and improved within seven days of metronidazole withdrawal. Treatment with cefotaxime was continued and showed no adverse effects.

Reconstruction of the historic time course of blood-borne virus contamination of clotting factor concentrates, 1974-1992.

Factor VIII and IX clotting factor concentrates manufactured from pooled plasma have been identified as potent sources of virus infection in persons with hemophilia (PWHs) in the 1970s and 1980s. To investigate the range and diversity of viruses over this period, we analysed 24 clotting factor concentrates for several blood-borne viruses. Nucleic acid was extracted from 14 commercially produced clotting factors and 10 from nonremunerated donors, preserved in lyophilized form (expiry dates: 1974-1992). Clotting factors were tested by commercial and in-house quantitative PCRs for blood-borne viruses hepatitis A, B, C and E viruses (HAV, HBV, HCV, HEV), HIV- types 1/2, parvoviruses B19V and PARV4, and human pegiviruses types 1 and 2 (HPgV-1,-2). HCV and HPgV-1 were the most frequently detected viruses (both 14/24 tested) primarily in commercial clotting factors, with frequently extremely high viral loads in the late 1970s-1985 and a diverse range of HCV genotypes. Detection frequencies sharply declined following introduction of virus inactivation. HIV-1, HBV, and HAV were less frequently detected (3/24, 1/24, and 1/24 respectively); none were positive for HEV. Contrastingly, B19V and PARV4 were detected throughout the study period, even after introduction of dry heat treatment, consistent with ongoing documented transmission to PWHs into the early 1990s. While hemophilia treatment is now largely based on recombinant factor VIII/IX in the UK and elsewhere, the comprehensive screen of historical plasma-derived clotting factors reveals extensive exposure of PWHs to blood-borne viruses throughout 1970s-early 1990s, and the epidemiological and manufacturing parameters that influenced clotting factor contamination.

Parvovirus B19 Infection in Adults: A Case Series.

Parvovirus B19 infection, typically associated with erythema infectiosum in children, presents variably in adults, often leading to misdiagnosis. This case series describes three adult patients diagnosed with parvovirus B19 infection in an internal medicine outpatient clinic in March 2024. Symptoms included fatigue, joint pain, swelling, and skin rash, with misdiagnoses including early rheumatoid arthritis. The diagnosis was confirmed via positive parvovirus antibodies and polymerase chain reaction (PCR). All patients received supportive care, and symptoms resolved within an average of 18 days. This series underscores the need for heightened clinical suspicion and timely serological testing for parvovirus B19 in adults presenting with flu-like symptoms, joint pain, and rash, especially during mini-outbreaks and following contact with infected children.

Conjugation with the Carrier Helped to Reveal acidification-Induced Structural Shift in the Peptide from Phospholipase Domain of Parvovirus B19.

Spectroscopic studies on domains and peptides of large proteins are complicated because of the tendency of short peptides to form oligomers in aquatic buffers, but conjugation of a peptide with a carrier protein may be helpful. In this study we approved that a fragment of SK30 peptide from phospholipase A2 domain of VP1 Parvovirus B19 capsid protein (residues: 144-159; 164; 171-183; sequence: SAVDSAARIHDFRYSQLAKLGINPYTHWTVADEELLKNIK) turns from random coil to alpha helix in the acidic medium only in case if it had been conjugated with BSA (through additional N-terminal Cys residue, turning it into CSK31 peptide, and SMCC linker) according to CD-spectroscopy results. In contrast, unconjugated SK30 peptide does not undergo such shift because it forms stable oligomers connected by intermolecular antiparallel beta sheet, according to IR-spectroscopy, CD-spectroscopy, blue native gel electrophoresis and centrifugal ultrafiltration, as, probably, the whole isolated phospholipase domain of VP1 protein does. However, being a part of the long VP1 capsid protein, phospholipase domain may change its fold during the acidification of the medium in the endolysosome by the way of the formation of contacts between protonated His153 and Asp175, promoting the shift from random coil to alpha helix in its N-terminal part. This study opens up a perspective of vaccine development, since rabbit polyclonal antibodies against the conjugate of CSK31 peptide with BSA, in which the structure of the second alpha helix from the phospholipase A2 domain should be reproduced, can bind epitopes of the complete recombinant unique part of VP1 Parvovirus B19 capsid (residues: 1-227).

Epidemic of parvovirus B19 and disease severity in pregnant people, Denmark, January to March 2024.

We report an epidemic of parvovirus B19 infections in Denmark during the first quarter of 2024, with a peak incidence 3.5 times higher than during the most recent epidemic in 2017. In total, 20.1% (130/648) of laboratory-confirmed cases were pregnant. Severe adverse outcomes were observed among 12.3% (16/130) of pregnant people and included foetal anaemia, foetal hydrops and miscarriage. Parvovirus B19 infection is not systematically monitored, but a national laboratory-based surveillance system is currently being established in Denmark.

Splenic Sequestration Induced by Parvovirus B19: A Case Report.

Splenic sequestration crisis is a life-threatening complication of sickle cell disease (SCD), characterized by a sudden and huge accumulation of blood in the spleen, leading to rapid enlargement and may lead to organ failure. This case report discusses an unusual case of a splenic sequestration crisis in an adult with SCD. The patient's age, Parvovirus B19 infection, and concurrent retrocardiac pneumonia are all things that differentiate this case from our usual presentation. We will be discussing the clinical presentation, diagnostic methods, and management.

An unusual outbreak of parvovirus B19 infections, France, 2023 to 2024.

From April 2023 to May 2024, an unusual epidemic of parvovirus B19 (B19V) infections occurred in France. The number of B19V IgM-positive serologies was four times higher than in the previous epidemic in 2019. Clinical data from emergency networks corroborated this observation. Morbidity and mortality consequences were observed in children through all data sources. In adults, the increase was only observed in laboratory-confirmed data. Physicians and decisionmakers should be informed in order to better prevent, diagnose and manage at-risk patients.

Backbone NMR resonance assignments for the VP1u N-terminal receptor-binding domain of the human parvovirus pathogen B19.

Parvovirus B19 (B19V) is a human pathogen that is the causative agent of several diseases in infants and adults. Due to a lack of antivirals against this virus, treatment options are limited. The minor capsid protein of B19V has a unique N terminus, named VP1u, which is essential for infection. The VP1u encodes a receptor binding domain (RBD), necessary for host cell entry, and a phospholipase A2 (PLA2) domain, crucial for endosomal escape during cellular trafficking. Both domains are indispensable for infection, making the RBD a plausible drug target for inhibitors against B19V, as it is located on the exterior surface of the virus. To date, no experimental structural information has been available for the VP1u component for any Parvovirus. Here we report the backbone NMR resonance assignments for the RBD of B19V and demonstrate it forms a stable structure. The backbone chemical shifts are in good agreement with a structure predicted by AlphaFold, validating that the RBD contains three helices connected by tight turns. This RBD construct can now be used for further NMR studies, including assignment of full-length VP1u, determination of protein-protein interaction interfaces, and development of B19 antivirals specific to the RBD domain. Database: BMRB submission code: 52440.

Backbone NMR resonance assignments for the VP1u N-terminal receptor-binding domain of the human parvovirus pathogen B19.

Parvovirus B19 (B19V) is a human pathogen that is the causative agent of several diseases in infants and adults. Due to a lack of antivirals against this virus, treatment options are limited. The minor capsid protein of B19V has a unique N terminus, named VP1u, which is essential for infection. The VP1u encodes a receptor binding domain (RBD), necessary for host cell entry, and a phospholipase A2 (PLA2) domain, crucial for endosomal escape during cellular trafficking. Both domains are indispensable for infection, making the RBD a plausible drug target for inhibitors against B19V, as it is located on the exterior surface of the virus. To date, no experimental structural information has been available for the VP1u component for any Parvovirus. Here we report the backbone NMR resonance assignments for the RBD of B19V and demonstrate it forms a stable structure. The backbone chemical shifts are in good agreement with a structure predicted by AlphaFold, validating that the RBD contains three helices connected by tight turns. This RBD construct can now be used for further NMR studies, including assignment of full-length VP1u, determination of protein-protein interaction interfaces, and development of B19 antivirals specific to the RBD domain.