Intrauterine transfusion in 103 fetuses with severe anemia caused by parvovirus infection. A multicenter retrospective study.

PURPOSE: Evaluating procedure-related complications and perinatal outcomes after intrauterine transfusion (IUT) before or after 20+0 weeks of gestation in fetuses with severe anemia due to intrauterine human parvovirus B19 infection. METHODS: A retrospective study investigating fetuses requiring IUT for fetal Parvo B19 infection in two tertiary referral centers between December 2002 and December 2021. Procedure-related complications, intrauterine fetal death (IUFD), and perinatal outcome were correlated to gestational age (GA) at first IUT, the presence of hydrops and fetal blood sampling results. RESULTS: A total of 186 IUTs were performed in 103 fetuses. The median GA at first IUT was 19+3 (13+0-31+4) weeks of gestation. IUFD occurred in 16/103 fetuses (15.5%). Overall survival was 84.5% (87/103). Hydrops (p = 0.001), lower mean hemoglobin at first IUT (p = 0.001) and low platelets (p = 0.002) were strongly associated with IUFD. There was no difference observed in fetuses transfused before or after 20+0 weeks of gestation. CONCLUSION: IUT is a successful treatment option in fetuses affected by severe anemia due to parvovirus B19 infection in specialized centers. In experienced hands, IUT before 20 weeks is not related to worse perinatal outcome.

Fetal Brain Injury Associated with Parvovirus B19 Congenital Infection Requiring Intrauterine Transfusion.

BACKGROUND: Infection with parvovirus B19 (B19V) during pregnancy may cause severe fetal anemia, hydrops, and fe tal death. Furthermore, neurodevelopmental impairment among survivors may occur despite appropriate prenatal management, including intrauterine transfusion (IUT). OBJECTIVES: Our primary objective was to describe cerebral lesions on MRI in fetuses with severe anemia requiring IUT for B19V infection. Our secondary objective was to search for clinical and biological characteristics associated with the occurrence of such lesions. STUDY DESIGN: We performed a retrospective review of data on fetuses infected with B19V and requiring at least one IUT between 2005 and 2016. Fetuses with abnormal cerebral MRI results in the 3rd trimester were compared to those with normal MRI results. RESULTS: Of 34 transfused fetuses, 26 children were born at full term. Five intrauterine fetal deaths, 1 neonatal death, and 2 terminations of pregnancy occurred. Cerebral anomalies were observed in 7/27 fetuses on MRI, including cerebellar hemorrhage or a small cerebellum. Only viral load in fetal blood appeared to be associated with brain lesions (11.5 log10 copies/mL [10.5-12.5] in case of abnormal MRI results vs. 9.5 log10 copies/mL [7.8-10.0]; p = 0.05). CONCLUSIONS: Among the fetuses transfused for B19V infection, 26% presented with prenatal abnormal cerebral imaging results. In our study, viral load in fetal blood appeared to be the only factor associated with fetal brain lesions.

TREATMENT STRATEGIES AND OUTCOME OF PARVOVIRUS B19 INFECTION IN KIDNEY TRANSPLANT RECIPIENTS: A CASE SERIES AND LITERATURE REVIEW OF 128 PATIENTS.

BACKGROUND: There is no specific antiviral treatment for parvovirus B19 (PVB19) infection. OBJECTIVE: The objective of this study was to study the treatment and outcome of PVB19 infection in kidney transplant recipients (KTR) at our institution, and cases published in the medical literature. METHODS: We conducted a retrospective review of PVB19 infection in KTR at an academic medical center over a 16-year period and summarized the data on its treatment and outcome in 120 KTR in the medical literature. RESULTS: In our cohort of eight patients, the median time to the onset of PVB19 disease was 7.2 weeks after transplantation. All patients had severe aregenerative anemia (mean hemoglobin (Hb) of 6.2 ± 1.0 g/dl); all were treated with a reduction in their immunosuppressive regimen and the administration of single-dose intravenous immunoglobulin (IVIG) (mean total dosage of 0.87 ± 0.38 g/kg). The median time to anemia improvement (Hb >10 g/dl) was 3-week post-treatment. No recurrences were documented during follow-up (median 25 months). Among 128 patients (including our cohort of 8 and 120 reported in literature), therapeutic strategies included: 43% IVIG alone, 39% IVIG and reduced immunosuppression, 9% reduction of immunosuppression, and 9% conservative therapy. Clinical relapses were observed in 35% of 71 reported cases. CONCLUSIONS: In KTR, decreasing immunosuppression and the administration of low-dose immunoglobulin seem to be not worse than the standard dose in PVB19 infection.

Pure red cell aplasia.

Pure red cell aplasia (PRCA) is a syndrome defined by a normocytic normochromic anemia with severe reticulocytopenia and marked reduction or absence of erythroid precursors from the bone marrow. Diamond-Blackfan anemia is a congenital form of PRCA. Acquired PRCA may be either a primary disorder or secondary to some other disorder or agent. Primary acquired PRCA is an autoimmune disorder that is frequently antibody-mediated. Myelodysplastic syndromes may also present with the morphologic appearance of PRCA. Secondary acquired PRCA may be associated with collagen vascular/autoimmune disorders such as systemic lupus erythematosus; lymphoproliferative disorders such as chronic lymphocytic leukemia or large granular lymphocyte leukemia; infections, particularly B19 parvovirus; thymoma and other solid tumors; or a variety of other disorders, drugs, or toxic agents. The therapeutic approach to PRCA typically involves immunosuppression, but specific pathogenic subtypes are associated with specific therapeutic approaches. Cyclosporine A, with or without concurrent corticosteroids, appears to be the single most effective immunosuppressive agent.

Common Skin Rashes in Children.

Because childhood rashes may be difficult to differentiate by appearance alone, it is important to consider the entire clinical presentation to help make the appropriate diagnosis. Considerations include the appearance and location of the rash; the clinical course; and associated symptoms, such as pruritus or fever. A fever is likely to occur with roseola, erythema infectiosum (fifth disease), and scarlet fever. Pruritus sometimes occurs with atopic dermatitis, pityriasis rosea, erythema infectiosum, molluscum contagiosum, and tinea infection. The key feature of roseola is a rash presenting after resolution of a high fever, whereas the distinguishing features in pityriasis rosea are a herald patch and a bilateral and symmetric rash in a Christmas tree pattern. The rash associated with scarlet fever usually develops on the upper trunk, then spreads throughout the body, sparing the palms and soles. Impetigo is a superficial bacterial infection that most commonly affects the face and extremities of children. Erythema infectiosum is characterized by a viral prodrome followed by the "slapped cheek" facial rash. Flesh-colored or pearly white papules with central umbilication occur with molluscum contagiosum, a highly contagious viral infection that usually resolves without intervention. Tinea is a common fungal skin infection in children that affects the scalp, body, groin, feet, hands, or nails. Atopic dermatitis is a chronic, relapsing inflammatory skin condition that may present with a variety of skin changes.

Fetal Intracardiac Transfusions in Hydropic Fetuses with Severe Anemia.

INTRODUCTION: Fetal anemia can have significant perinatal morbidity and mortality, particularly with onset prior to 20 weeks of gestation. MATERIALS AND METHODS: We detail a case-cohort study (n = 8) of all women who underwent fetal in-utero, intracardiac transfusion prior to 24 weeks of gestation (7 women before 20 + 1 weeks), between March 2004 and September 2014, in a supraregional Fetal Medicine Center in the United Kingdom, comprising 2.2% of all transfusions performed during this period. All the fetuses were hydropic, with high maternal BMI, and had severe anemia as an indicator for transfusion. It was an attempt to perform intravascular transfusion when other common routes of fetal vascular access had failed. RESULTS: There were 2 intrauterine deaths (25%), both of which were associated with in-utero transfusion and fulminant parvovirus B19 infection. The perinatal survival rate was 75% (6/8). DISCUSSION: Fetal in-utero, intravascular transfusion by the intracardiac route may be used to correct severe early-onset anemia. It is particularly useful when technical issues of fetal size, early gestation (<20 weeks), maternal adiposity, and hydrops fetalis make umbilical cord or intrahepatic vein puncture technically difficult. Survival rates appear comparable to other series of pregnancies where in-utero transfusion is performed at early gestation.

Parvovirus B19 in Pregnancy.

Importance: Although the risk of parvovirus B19 infection during pregnancy and subsequent risk of adverse fetal outcome are low, understanding management practices is essential for proper treatment of fetuses with nonimmune hydrops fetalis. In addition, continued investigation into delivery management, breastfeeding recommendations, and congenital abnormalities associated with pregnancies complicated by parvovirus B19 infection is needed. Objective: This review describes the risks associated with parvovirus B19 infection during pregnancy and the management strategies for fetuses with vertically transmitted infections. Evidence Acquisition: Original articles were obtained from literature search in PubMed, Medline, and OVID; pertinent articles were reviewed. Results: Parvovirus B19 is a viral infection associated with negative pregnancy outcomes. Up to 50% of people of reproductive age are susceptible to the virus. The incidence of B19 in pregnancy is between 0.61% and 1.24%, and, overall, there is 30% risk of vertical transmission when infection is acquired during pregnancy. Although most pregnancies progress without negative outcomes, viral infection of the fetus may result in severe anemia, congestive heart failure, and hydrops fetalis. In addition, vertical transmission carries a 5% to 10% chance of fetal loss. In pregnancies affected by fetal B19 infection, Doppler examination of the middle cerebral artery peak systolic velocity should be initiated to surveil for fetal anemia. In the case of severe fetal anemia, standard fetal therapy involves an intrauterine transfusion of red blood cells with the goal of raising hematocrit levels to approximately 40% to 50% of total blood volume. One transfusion is usually sufficient, although continued surveillance may indicate the need for subsequent transfusions. There are fewer epidemiologic data concerning neonatal risks of congenital parvovirus, although case reports have shown that fetuses with severe anemia in utero may have persistent anemia, thrombocytopenia, and edema in the neonatal period. Conclusions and Relevance: Parvovirus B19 is a common virus; seropositivity in the geriatric population reportedly reaches 85%. Within the pregnant population, up to 50% of patients have not previously been exposed to the virus and consequently lack protective immunity. Concern for parvovirus B19 infection in pregnancy largely surrounds the consequences of vertical transmission of the virus to the fetus. Should vertical transmission occur, the overall risk of fetal loss is between 5% and 10%. Thus, understanding the incidence, risks, and management strategies of pregnancies complicated by parvovirus B19 is essential to optimizing care and outcomes. Further, there is currently a gap in evidence regarding delivery management, breastfeeding recommendations, and the risks of congenital abnormalities in pregnancies complicated by parvovirus B19. Additional investigations into optimal delivery management, feeding plans, and recommended neonatal surveillance are needed in this cohort of patients.

Ballantyne syndrome and congenital anaemia associated with Parvovirus B19 infection: case report and review.

Acute maternal Parvovirus B19 infection affects about 1% of all pregnancies worldwide. Diaplacental transmission of Parvovirus B19 during the second trimester can cause complications like foetal hydrops, premature delivery or foetal loss in about 20-30% of these pregnancies, whereas the majority of maternal infections remain clinically silent. In individual cases, foetoplacental hydrops (of various origins) can trigger a rare form of Preeclampsia in the pregnant woman. The developing maternal oedema in this situation apparently "mirrors" the hydropic state of the foetus. The symptom triad of foetal hydrops, foetoplacental oedema and maternal anasarca defines Ballantyne syndrome. We report a case of Parvovirus-induced Ballantyne syndrome including a 10-year follow-up of mother and child. While the mother recovered rapidly after (preterm) delivery, the infection complicated the first months of life of the neonate. Congenital transfusion-dependent red cell aplasia and cholestatic hepathopathy took a chronic course but resolved under IVIG treatment. Follow-up now finds both the former neonate and the mother entirely recovered. Current knowledge on Ballantyne syndrome as well as perigestational Parvovirus infections including congenital anaemia is briefly reported and pathophysiological hypotheses are discussed.

Successful use of interferon alfa-2a for persistent parvovirus B19 infection.

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.

Intrauterine transfusion for parvovirus B19 infection: long-term neurodevelopmental outcome.

OBJECTIVE: To evaluate long-term neurodevelopmental outcome of children treated with intrauterine transfusions for fetal anemia because of parvovirus B19 infection. STUDY DESIGN: Children treated with intrauterine transfusions for fetal anemia because of parvovirus B19 infection underwent standardized age-appropriate neurodevelopmental testing. Main outcome was the incidence of neurodevelopmental impairment. RESULTS: Twenty-eight children were evaluated at a median age of 5 years (range, 1.5-13 years). Neurodevelopmental impairment was diagnosed in 3 of 28 (11%) children, including 1 child with combined cerebral palsy and severe developmental delay and 2 children with isolated severe developmental delay. CONCLUSION: Neurodevelopmental impairment in children treated with intrauterine transfusion for parvovirus B19 infection is increased compared with the general population. Large long-term follow-up studies are required to determine potential risk factors.

The detection, treatment of parvovirus B19 infection induced anemia in solid organ transplants: A case series and literature review of 194 patients.

BACKGROUND: There are no optimal diagnostic, treatment and post-infection surveillance strategies for parvovirus B19 infection in solid organ transplantation (SOT) recipients. METHODS: We conducted a retrospective review of all PVB19 infected cases confirmed by qPCR among SOT recipients at our institution over a 3-year period and reviewed the literature from 1990 to 2021. RESULTS: Eight kidney and two heart transplant patients with refractory anemia had PVB19 infection. The viral DNA load in peripheral blood ranged from 2.62×102 to 8.31×106 copies/mL. Two patients with the lowest PVB19 DNA load only reduced the use of immunosuppressants and anemia was relieved. Eight received intravenous immunoglobulin (IVIG) (ranging from 0.25 to 0.5g/kg/day). The median time to anemia improvement (hemoglobulin>100g/L) was 16days (8-70days) after treatment. One patient had a PVB19 relapse and viral DNA load>1.00×108 copies/mL at diagnosis. A total of 86 studies involving 194 SOTs were screened from the literature, and the most common symptom was anemia and low reticulocyte count. PVB19 DNA was detected in all cases. Of that, 91.4% of cases received IVIG, 53.8% received IVIG and immunosuppression reduction, 6.5% of cases showed reduced immunosuppression without IVIG, and 2.1% did not receive any special treatment. The recurrence rate was 17.5%. CONCLUSION: PVB19 infection is a cause of anemia after SOT, and treatment mainly relies on IVIG and/or immunosuppression reduction.

Parvovirus B19 infection in human pregnancy.

Human parvovirus B19 infection is widespread. Approximately 30-50% of pregnant women are nonimmune, and vertical transmission is common following maternal infection in pregnancy. Fetal infection may be associated with a normal outcome, but fetal death may also occur without ultrasound evidence of infectious sequelae. B19 infection should be considered in any case of nonimmune hydrops. Diagnosis is mainly through serology and polymerase chain reaction. Surveillance requires sequential ultrasound and Doppler screening for signs of fetal anaemia, heart failure and hydrops. Immunoglobulins, antiviral and vaccination are not yet available, but intrauterine transfusion in selected cases can be life saving.

Parvovirus B19 infection in pregnancy: new insights and management.

In this article, we review the virology, pathology, epidemiology and clinical spectrum of intrauterine human parvovirus B19 (B19V) infection, including intrauterine fetal death, non-immune hydrops fetalis, thrombocytopenia and neurological manifestations such as pediatric stroke and perivascular calcifications. In addition, we discuss the new insights into the neurodevelopmental outcome of intrauterine B19V infection. Current diagnosis and management of B19V infection is summarized, including a diagnostic and follow-up flowchart for practical clinical use.

Stem cell transplantation in 6 children with parvovirus B19- induced severe aplastic anaemia or myelodysplastic syndrome.

Parvovirus B19 (PVB19) induced severe aplastic anaemia (SAA) or myelodysplastic syndrome (MDS) is rare, and haematopoietic stem cell transplantation (HSCT) in this condition has not been reported so far. 6 children with SAA (n=4) or MDS (n=2) caused by acute PVB19 infection underwent HSCT under the protection of intravenous immunoglobulines. The 4 children with SAA received matched HLA bone marrow from a sibling (n=3) or peripheral unrelated blood stem cells (n=1). 1 patient had delayed erythrocyte engraftment, whereas 3 patients had an uneventful transplantation course. HSCT in one of the 2 children with MDS was complicated by poor graft function, the other patient engrafted without complications. In conclusion, HSCT in children with PVB19 induced SAA or MDS is feasible, even though some patients may develop delayed engraftment or prolonged poor graft function.

Parvovirus b19 infection in pregnancy - A review.

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.

Myocarditis and inflammatory cardiomyopathy: current evidence and future directions.

Inflammatory cardiomyopathy, characterized by inflammatory cell infiltration into the myocardium and a high risk of deteriorating cardiac function, has a heterogeneous aetiology. Inflammatory cardiomyopathy is predominantly mediated by viral infection, but can also be induced by bacterial, protozoal or fungal infections as well as a wide variety of toxic substances and drugs and systemic immune-mediated diseases. Despite extensive research, inflammatory cardiomyopathy complicated by left ventricular dysfunction, heart failure or arrhythmia is associated with a poor prognosis. At present, the reason why some patients recover without residual myocardial injury whereas others develop dilated cardiomyopathy is unclear. The relative roles of the pathogen, host genomics and environmental factors in disease progression and healing are still under discussion, including which viruses are active inducers and which are only bystanders. As a consequence, treatment strategies are not well established. In this Review, we summarize and evaluate the available evidence on the pathogenesis, diagnosis and treatment of myocarditis and inflammatory cardiomyopathy, with a special focus on virus-induced and virus-associated myocarditis. Furthermore, we identify knowledge gaps, appraise the available experimental models and propose future directions for the field. The current knowledge and open questions regarding the cardiovascular effects associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are also discussed. This Review is the result of scientific cooperation of members of the Heart Failure Association of the ESC, the Heart Failure Society of America and the Japanese Heart Failure Society.

Parvovirus B19-induced persistent pure red cell aplasia in a child with T-cell immunodeficiency.

Persistent pure red cell aplasia can be a manifestation of parvovirus B19 infection in immunocompromised hosts. Failure of the humoral immune response to clear parvovirus B19 in such patients results in persistent pure red cell aplasia. The authors describe a child who had T-cell immunodeficiency and persistent pure red cell aplasia due to parvovirus B19 infection. Interestingly, they detected human parvovirus B19 genome by polymerase chain reaction (PCR) not in the peripheral blood, but in the bone marrow specimen of the patient. In their patient, T-cell immunodeficiency may have caused impaired B-cell activation and failure of effective humoral immune response to neutralize the virus. Additionally, before the diagnosis of pure red cell aplasia, IVIG treatment given at a dosage of 400 mg/kg/day with 3-week intervals may result in sufficient neutralization of peripheral blood parvovirus B19, whereas it may not be sufficient for the neutralization of parvovirus B19 genome in bone marrow. Thus, peripheral blood parvovirus B19 serology (IgM and IgG) and PCR were negative, whereas bone marrow aspiration sample was positive for parvovirus B19 PCR in this patient. Reticulocytopenia and severe anemia may warn the physicians of parvovirus B19 infection, especially in immunocompromised children. Diagnosis may require demonstration of absence of late erythroid precursors in the bone marrow as well as serologic testing and detection of parvovirus B19 genome by PCR in the serum and/or bone marrow samples of the patient.