Aplastic Crisis In Patients Research Articles

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.

Structural Dynamics and Activity of B19V VP1u during the pHs of Cell Entry and Endosomal Trafficking.

Parvovirus B19 (B19V) is a human pathogen that is the causative agent of fifth disease in children. It is also known to cause hydrops in fetuses, anemia in AIDS patients, and transient aplastic crisis in patients with sickle cell disease. The unique N-terminus of Viral Protein 1 (VP1u) of parvoviruses, including B19V, exhibits phospholipase A2 (PLA2) activity, which is required for endosomal escape. Presented is the structural dynamics of B19V VP1u under conditions that mimic the pHs of cell entry and endosomal trafficking to the nucleus. Using circular dichroism spectroscopy, the receptor-binding domain of B19V VP1u is shown to exhibit an α-helical fold, whereas the PLA2 domain exhibits a probable molten globule state, both of which are pH invariant. Differential scanning calorimetry performed at endosomal pHs shows that the melting temperature (Tm) of VP1u PLA2 domain is tuned to body temperature (37 °C) at pH 7.4. In addition, PLA2 assays performed at temperatures ranging from 25–45 °C show both a temperature and pH-dependent change in activity. We hypothesize that VP1u PLA2 domain differences in Tm at differing pHs have enabled the virus to “switch on/off” the phospholipase activity during capsid trafficking. Furthermore, we propose the environment of the early endosome as the optimal condition for endosomal escape leading to B19V infection.

Seroprevalence of human parvovirus B19 immunoglobulin G in children with hematological disorders and healthy children

Objective The aim of this study was to determine the serum levels of anti-parvovirus B19 immunoglobulin-G (IgG) and its prevalence in children with hematological disorders and in apparently healthy children in Menoufia University Hospitals. Background Parvovirus B19 infections can suppress erythropoiesis and induce acute erythroblastopenia, which is often referred to as transient aplastic crisis in patients with chronic hemolytic anemia such as sickle cell anemia, thalassemia, and hereditary spherocytosis. Patients and methods The study was conducted on 60 children with chronic hemolytic anemia (40 children with chronic hemolytic anemia without a history of aplastic crisis and 20 children with chronic hemolytic anemia with a history of aplastic crisis) and 20 age-matched and sex-matched apparently healthy children. All patients were subjected to full history taking, clinical examination, and laboratory investigations. Serum anti-parvovirus B19 IgG levels were measured using anti-parvovirus B19 ELISA kits. Results The prevalence of anti-parvovirus B19 IgG antibodies in the sera of chronic hemolytic anemia children with and without a history of aplastic crisis was 62.5 and 100%, respectively. Seropositivity of anti-parvovirus B19 IgG antibodies was 20% in apparently healthy children. Seropositivity of anti-parvovirus B19 IgG antibodies in children with β-thalassemia major and sickle cell anemia was 78 and 100%, respectively. Significant positive correlations were detected between age of the children, frequency of blood transfusion, and the level of anti-parvovirus B19 IgG. Conclusion The prevalence of anti-parvovirus B19 IgG antibodies was higher in all chronic hemolytic anemia children, particularly in those with a history of aplastic crisis. Furthermore, all children with β-thalassemia major and sickle cell anemia with a history of aplastic crisis had anti-parvovirus B19 IgG antibodies.

The Determinants for the Enzyme Activity of Human Parvovirus B19 Phospholipase A2 (PLA2) and Its Influence on Cultured Cells

Human parvovirus B19 (B19V) is the causative agent of erythema infectiosum in humans. B19 infection also causes severe disease manifestations, such as chronic anemia in immunocompromised patients, aplastic crisis in patients with a high turnover rate of red blood cells, and hydrops fetalis in pregnant women. Although a secreted phospholipase A2 (PLA2) motif has been identified in the unique region of the B19V minor capsid protein VP1(VP1u), the determinants for its enzyme activity and its influences on host cells are not well understood. The purpose of this study was to investigate the contribution of the PLA2 motif and other regions of the VP1u to the PLA2 activity, to determine the cellular localization of the VP1u protein, and to examine the effects of VP1u on cellular cytokines. We found that in addition to the critical conserved and non-conserved amino acids within the VP1u PLA2 motif, amino acid residues outside the VP1u PLA2 motif are also important for the PLA2 activity. VP1u and various mutants all revealed a nucleo-cytoplasmic distribution. UT7-Epo cells treated with prokaryotic expressed VP1u or mutant proteins with PLA2 activity released a large amount of free fatty acid (FFA), and the cell morphological change occurred dramatically. However, neither free fatty acid nor cell morphology change occurred for cells treated with the mutants without PLA2 activity. The wild type and the VP1u mutants with the PLA2 activity also activated TNF-α promoter and upregulated the transcription activity of NF-κB in transfected cells. In addition, we found that the amino acids outside the PLA2 domain are critical for the viral PLA2 activity, and that these tested VP1u mutants did not affect the localization of the VP1u protein.

Risk of Transfusion-Transmitted Human Parvovirus B19 Infection in Anyigba and Lokoja, Kogi State – Nigeria

Risk of Transfusion-Transmitted Human Parvovirus B19 Infection in Anyigba and Lokoja, Kogi State – Nigeria

Acute Parvovirus B19 Infection Leading to Severe Aplastic Anemia in a Previously Healthy Adult Female

Human Parvovirus B19 has been linked to a variety of diseases. One of the most common complications is transient aplastic crisis in patients with chronic hemolytic anemia. Very few case reports have implicated this virus as a putative etiology behind hepatitis and severe aplastic anemia in immuno competent individuals. We report a case of severe aplastic anemia in a previously healthy adult female due to acute parvovirus B19 infection. Laboratory examination showed pancytopenia in peripheral blood and severe hypoplastic bone marrow on biopsy. Serological analysis (ELISA) revealed acute Parvovirus B19 infection. In the face of unavailable HLA matched bone marrow donor, immuno-supressive therapy was contemplated, but could not be given because of financial constraints. Pancytopenia persists till date, 4months after the diagnosis, with the patient requiring repeated packed red cell and irradiated platelet transfusions. Thus, acute infection with this virus must be considered a cause of acquired aplastic anemia even in individuals without underlying disease.

Human bocavirus is not detectable in bone marrow from patients with myelodysplastic syndromes

To the editor: The human bocavirus (HBoV) was discovered in 2005 and, depending on the subtype, is associated mainly with respiratory infections and gastrointestinal disorders. 1 , 2 , 3 However, the final proof that HBoV is in fact a pathogen is still missing. It also remains unclear if HBoV modifies the pattern of other diseases. 4 Human bocavirus is the second‐known human pathogenic parvovirus and as such related to parvovirus B19, which has been known for decades and can cause severe clinical complications such as hydrops fetalis. Parvovirus B19 has a marked tropism for erythropoietic progenitor cells and can trigger aplastic crisis in patients with chronic hemolytic anemia. In this context, parvovirus B19 has also been shown to be present and eventually persist in multiple tissues including bone marrow (reviewed in Ref. 5). Based on the relationship between HBoV and B19, the fact that HBoV particles can be found in the lung but also in the serum as they are released from infected tissues, 6 , 7 , 8 and the observation that HBoV infection may be most severe in patients with haemato‐oncological disease, 9 , 10 we addressed the question whether HBoV is associated with a group of hematological disorders typically presenting with anemia attributable to inefficient erythropoiesis. These disorders, called myelodysplastic syndromes (MDS), are clonal bone marrow diseases which are characterized by ineffective hematopoiesis and a risk of leukemic transformation. 11 Although the MDS clone often carries acquired genetic and epigenetic abnormalities, a disturbed bone marrow microenvironment is thought to contribute to disease pathology, and infectious triggers have also been suspected. 12 We investigated 25 patients with different types of MDS (Table 1). Total DNA was isolated from bone marrow aspirates as previously described and subjected to a PCR specific for human bocavirus, using a previously published protocol. 10 Table 1 Patients with myelodysplastic syndromes (MDS) included in the analysis Human bocavirus DNA was detected in nasal swabs previously tested HBoV positive but not in any of the MDS samples. Therefore, although a causative role in myelodysplastic syndromes appears unlikely as the virus was not detected in bone marrow, a ‘hit‐and‐run’ mechanism remains possible. This conclusion is supported by the fact that in 2007 Manning et al. 13 have also not detected HBoV‐DNA in the bone marrow of HIV positive and HIV negative patients, which in turn may allow the conclusion that HBoV lacks a tropism for bone marrow. Clinical relevance of HBoV in the field of hematology may be restricted to its possible role as a cause of pneumonia in patients whose general condition is weakened by a hematological malignancy.

Chronic hepatitis caused by persistent parvovirus B19 infection

BackgroundHuman infection with parvovirus B19 may lead to a diverse spectrum of clinical manifestations, including benign erythema infectiosum in children, transient aplastic crisis in patients with haemolytic anaemia, and congenital hydrops foetalis. These different diseases represent direct consequences of the ability of parvovirus B19 to target the erythroid cell lineage. However, accumulating evidence suggests that this virus can also infect other cell types resulting in diverse clinical manifestations, of which the pathogenesis remains to be fully elucidated. This has prompted important questions regarding the tropism of the virus and its possible involvement in a broad range of infectious and autoimmune medical conditions.Case PresentationHere, we present an unusual case of persistent parvovirus B19 infection as a cause of chronic hepatitis. This patient had persistent parvovirus B19 viraemia over a period of more than four years and displayed signs of chronic hepatitis evidenced by fluctuating elevated levels of ALAT and a liver biopsy demonstrating chronic hepatitis. Other known causes of hepatitis and liver damage were excluded. In addition, the patient was evaluated for immunodeficiency, since she had lymphopenia both prior to and following clearance of parvovirus B19 infection.ConclusionsIn this case report, we describe the current knowledge on the natural history and pathogenesis of parvovirus B19 infection, and discuss the existing evidence of parvovirus B19 as a cause of acute and chronic hepatitis. We suggest that parvovirus B19 was the direct cause of this patient's chronic hepatitis, and that she had an idiopathic lymphopenia, which may have predisposed her to persistent infection, rather than bone marrow depression secondary to infection. In addition, we propose that her liver involvement may have represented a viral reservoir. Finally, we suggest that clinicians should be aware of parvovirus B19 as an unusual aetiology of chronic hepatitis, when other causes have been ruled out.

Acute Ophthalmoparesis Associated with Human Parvovirus B19 Infection

Parvovirus B19 infection (PVB19) has been linked with a broad spectrum of clinical syndromes. In addition to erythema infectiosum and asymptomatic infection, other less common manifestations include transient aplastic crisis in patients with hemoglobinopathies, pure red cell aplasia and pancytopenia in immunocompromised persons, nonimmune hydrops fetalis, chronic arthritis, myocarditis, and hepatitis. Only 19% of patients had peripheral nervous system damage, mainly including brachial plexitis and carpal tunnel syndrome. Two cases of cranial nerves palsies have been described in children in the literature, including one case of peripheral facial nerve palsy and one case of velopalatine hemiparalysis. We report the first case of acute ophthalmoparesis associated with PVB19 infection. We present a 40-year-old man with PVB19 with acute sixth cranial nerve palsy, diagnosed on the basis of serology and polymerase chain reaction carried out both on serum and cerebrospinal fluid. Clinicians should be aware of this possible clinical presentation.

Parvovirus B19 Infection Associated With Acute Hepatitis in Infant

To the Editors: Human parvovirus B19 (B19) infection shows a wide spectrum of cutaneous manifestations and systemic involvements, especially in adults. Acute hepatitis and hepatic disorders are rare, however, and there are only 2 reports of B19 infection associated with acute hepatitis in adults in the English literature.1,2 To our knowledge, the case reported in this article is the first case of B19 infection associated with acute hepatitis in an infant. A 9-month-old female infant presented at our hospital with high-grade intermittent fever (39°C) for 6 days, associated with erythematous maculopapular nonpruritic rash. Her parents denied any drug intake or exposure to children or adults with exanthematous diseases. Erythematous maculopapular rashes were present over the entire body, excluding the palms and soles. The rash first appeared on the face within 12 hours of the onset of fever, and later spread to the trunks and limbs. After 7 to 10 days, a central clearing appeared in the rash that had a lace-like or reticular appearance especially on the cheeks, which looked like “slapped-cheek.” There was no hepatosplenomegaly or palpable lymph nodes. As the symptoms and signs suggested erythema infectiosum, we asked for the consent of the parents of the patient to perform further evaluations to determine the causative agent. We conducted normal tests such as a full blood count, measurement of the prothrombin time and the muscle enzymes, and urinalysis. The serum alanine aminotransferase level was 4745 U/L (normal level: 10–35), the aspartate aminotransferase level was 3428 U/L (normal level: 5–38), and the lactate dehydrogenase level was 825 U/L (normal level: 106–211). The serologic tests for cytomegalovirus, Epstein-Barr virus, herpes simplex virus, and hepatitis A, B, C, and E viruses were all negative. Enzyme-linked immunosorbent assay revealed anti-B19 IgM 5.77 (normal level: <0.8) and IgG 0.61 (normal level: <0.8) antibodies. Using the polymerase chain reaction (Chung-Ang University Hospital Laboratory, Seoul, Korea), the serum was positive for B19. Based on these clinical features and investigations, the patient was finally diagnosed to have erythema infectiosum with acute hepatitis. The patient was treated with antipyretics and rest. The skin eruption cleared in 10 days without desquamation, and the aminotransferase values became normal within 14 days. Three weeks later, the anti-B19 enzyme-linked immunosorbent assay had changed to IgM 0.41 (normal level: <0.8) and IgG 9.40 (normal level: <0.8). B19 infection has a worldwide distribution, with school outbreaks in late winter and early spring. It affects primarily the 4- to 10-year age group. Although the disease is self-limiting, systemic features with B19 infection make its diagnosis important.3 Systemic features are severe in adults, including arthralgia with synovitis and rarer manifestations such as aplastic crisis in patients with chronic hemolytic anemia, bone marrow failure in immunocompromised hosts, a transient febrile myasthenia-like syndrome, myositis, and acute heart failure. These occur rarely in infants.4 B19 infection is associated with a wide spectrum of clinical manifestations, including erythema infectiosum, rubilliform rashes, the Gianotti-Crosti syndrome, Henoch-Schönlein purpura, the papular purpuric gloves-and-socks syndrome, and erythema multiforme. The best known of these is erythema infectiosum, or fifth disease, which classically occurs with childhood infections.3,4 Erythema infectiosum is characterized by confluent erythematous and edematous patches or plaques on the cheeks, which spare the nasal bridge and periorbital regions. The rash spreads to the trunk and extensor extremities, which undergo patchy clearing that results in a lace-like reticular pattern. Occasionally, mild prodromal symptoms precede the rash, which include low-grade fever, headache, pharyngitis, malaise, myalgias, nausea, diarrhea, and joint pain.5 To our knowledge, there are only 2 reports of B19 infection, both in adults, associated with acute hepatitis in the English literature.1,2 We documented a case of erythema infectiosum with acute hepatitis in a 9-month-old infant associated with B19 infection. This is the first report of such infection in an infant in English literature. Beom Joon Kim, MD Kwang Ho Yoo, MD Kapsok Li, MD Myeung Nam Kim, MD Department of Dermatology College of Medicine Chung-Ang University Seoul, Korea

Seroprevalence of parvovirus B19 among pregnant women in Tripoli, Libya

Human parvovirus B19 has been implicated as a primary etiologic agent of erythema infectiosum (fifth disease) and aplastic crisis in patients with chronic haemolytic anemias. Human parvovirus B19 is known to be associated with adverse effects on fetuses such as hydrops fetalis, intrauterine fetal death, and chronic anaemia in immunocompromized individuals. The objective of this study was to assess the seroprevalence of human parvovirus B19 among the pregnant women in Tripoli, Libya. A total number of 150 participants were included in the study, consisting of women of child-bearing age ranging from 18 to 41 years, and divided into age groups as follows: < or = 21 years, 22-27, 28-32, 33-37, and > or = 38 years. Specific IgM and IgG antibodies were measured using a commercial ELISA kit. IgG was observed to be prevalent (61%) among the women of child-bearing age. The sero-prevalence of IgM was found to be 5% overall and there was no detectable IgM in the age group between 33 and 37. The presence of IgG and absence of IgM indicate immunity to primary infection, but a significant percentage of child-bearing aged women are at risk of primary infection with parvovirus B19 which could adversely affect their pregnancy.

ヒトパルボウイルスＢ１９感染症の様々な病態

Human parvovirus B19 infection causes erythema infectiosum in child, aplastic crisis in patients with chronic hemolytic anemia, chronic pure red cell aplasia in immunocompromised patients and hydrops fetalis. Human parvovirus B19 causes arthritis and acute glomerulonephritis due to immunological mechanism. Other disorders, rheumatoid arthritis, vasculitis and thrombotic microangiopathy, are linked in human parvovirus B19 infection. Parvovirus B19 infection causes choronic rheumatoid-like arthropathy. Autoantibody and low complement were seen in acute human parvovirus infection, and parvovirus B19 infection present clinically lupus like tableau.

Parvovirus-B19-associated complications in renal transplant recipients

Parvovirus B19 is a common human pathogen, causing erythema infectiosum in children, hydrops fetalis in pregnant women, and transient aplastic crisis in patients with chronic hemolytic anemia. Immunosuppressed patients can fail to mount an effective immune response to B19, resulting in prolonged or persistent viremia. Renal transplant recipients can develop symptomatic B19 infections as a result of primary infection acquired via the usual respiratory route or via the transplanted organ, or because of reactivation of latent or persistent viral infection. The most common manifestations of B19 infection in immunosuppressed patients are pure red cell aplasia and other cytopenias. Thus, this diagnosis should be considered in transplant recipients with unexplained anemia and reticulocytopenia or pancytopenia. Collapsing glomerulopathy and thrombotic microangiopathy have been reported in association with B19 infection in renal transplant recipients, but a causal relationship has not been definitively established. Prompt diagnosis of B19 infection in the renal transplant recipient requires a high index of suspicion and careful selection of diagnostic tests, which include serologies and polymerase chain reaction. Most patients benefit from intravenous immunoglobulin therapy and/or alteration or reduction of immunosuppressive therapy. Conservative therapy might be sufficient in some cases.

An Adult with Aplastic Crisis induced by Human Parvovirus B19 as an Initial Presentation of Hereditary Spherocytosis

The association between aplastic crisis and human parvovirus (HPV) B19 infection is well described in patients with sickle cell anemia. This association has also been described, although much less frequently, in patients with hereditary spherocytosis (HS). However, most cases of aplastic crises in patients with HS and induced by HPV B19 have been reported in children or adolescents. In this paper, we describe an aplastic crisis induced by HPV B19 in an adult with HS. A 34-year-old female presented with presyncope, febrile sensation, and myalgia. The complete blood counts showed severe anemia. The peripheral blood smear revealed spherocytosis with reticulocytopenia and pancytopenia. The direct Coombs' test was negative; the osmotic fragility test was positive. In the bone marrow aspirates, a few giant pronormoblasts with deep blue cytoplasm, pseudopods, and intracellular inclusion bodies were observed. The patient was given eight units of packed red blood cells. HPV B19 infection was proven by the presence of IgM antibodies to HPV B19 and the detection of viral DNA using the PCR technique. To the best of our knowledge, this is the first report in Korea that describes an adult with aplastic crisis presenting initially with HS.

Parvovirus B19 Infection Presenting as Pre-B-Cell Acute Lymphoblastic Leukemia: A Transient and Progressive Course in Two Children.

Parvovirus B19 is the causative agent of various forms of hematologic diseases such as aplastic crisis in patients with hemolytic anemia, aplastic anemia, hypoplastic anemia, and idiopathic thrombocytopenic purpura. In addition, parvovirus B19 infection may precede or be associated with acute lymphoblastic leukemia (ALL). The authors present two cases of parvovirus B19 infection and bone marrow infiltration with pre-B-cell lymphoblasts; one patients was diagnosed as having ALL, and the other patient, with neurologic findings, showed total resolution of the blastic morphology and phenotype.

Increased prevalence of human parvovirus B19 DNA in systemic sclerosis skin.

Human parvovirus B19 is a small, single-stranded DNA virus encoding two structural capsid proteins and a nonstructural protein. It is the aetiological agent of erythema infectiosum and transient aplastic crisis in patients with haemolytic anaemia, and has been associated with fetal death, arthritis and chronic anaemia. In recent years, the possible involvement of parvovirus B19 in systemic sclerosis (SSc) has been reported. To determine whether human parvovirus B19 DNA can be detected in SSc skin tissue specimens. Normal subjects (n = 97) and patients with SSc (n = 48), systemic lupus erythematosus (n = 16), dermatomyositis (n = 8), morphoea (n = 6) and graft-versus-host disease (n = 8) were studied. Crude DNA was extracted from skin tissue specimens. We attempted to determine whether human parvovirus B19 could be detected in the skin of SSc using nested polymerase chain reaction (PCR). PCR amplification was performed with specifically designed first and second primer pairs for parvovirus B19 DNA. After the first PCR, the occurrence rate of parvovirus B19 DNA in SSc skin tissues (36 of 48, 75%) was significantly elevated in comparison with that in normal controls (50 of 97, 52%) (P < 0.01). After the second PCR, the occurrence rate of parvovirus B19 DNA in SSc skin tissues (36 of 48, 75%) was significantly elevated compared with that in normal controls (53 of 97, 55%) (P < 0.02). The occurrence rates in the other diseases showed no significant difference from that in normal controls. The increased prevalence of human parvovirus B19 DNA in SSc skin showed the possibility that the virus may be involved in the formation of skin tissue abnormalities in the disease.

Parvovirus B19.

Parvovirus B19 is the cause of fifth disease in children and can trigger transient arthropathy in adults. It can also provoke transient aplastic crises in patients with sickle cell disease or other chronic hemolytic anemias and cause pure red-cell aplasia. This article reviews the features of the virus, the host response to it, and ways of preventing and treating the infection.

Parvovirus B19: Characteristics, diseases and diagnosis

Abstract Parvovirus B19 is small, unenveloped, single-stranded DNA virus. It is the causative agent of fifth disease and is capable of causing severe fetal infections and illnesses in adults ranging from arthropathy to chronic anemia. It has been shown to be the cause of transient aplastic crises in patients with an underlying hemolytic disease. Detection methods for a parvovirus B19 infection include antibody serology studies; DNA-based methods, such as PCR; and various methods based on antigen detection. This review explores the basic biology of parvovirus B19 and the clinical pathologies of the human diseases it can cause. Some of the current and most popular diagnostic methods are discussed in light of which method would be the best choice for establishing diagnoses in particular clinical situations.

Haematological response to parvovirus B19 infection in homozygous sickle-cell disease

Infection with human parvovirus B19 is known to cause aplastic crises in patients with homozygous sickle-cell disease. We studied the haematological consequences of parvovirus B19 infection in 280 such patients who had been followed up from birth in Jamaica. Evidence of seroconversion was routinely sought with a baculovirus-based, enzyme immunoassay in serum samples taken during aplastic crises and in all stored annual serum samples. 70% of patients had seroconverted by age 20 years; of 177 infections, haematological change was typical of aplastic crises in 118 (67%), minor in 16 (9%), and not discernible in 43 (24%). This assay increased the detection of unsuspected seroconversion-an observation important in planning a strategy for parvovirus B19 immunisation.

Cerebrovascular complications and parvovirus infection in homozygous sickle cell disease

Human parvovirus B19 infection causes most clinically defined aplastic crises in homozygous sickle cell (SS) disease. With transfusion support, the outcome is generally benign; however, cerebrovascular complications in close temporal association with B19-induced aplastic crises have been described. We carried out a retrospective review, between 1978 and 1999, of 346 aplastic crises in patients with SS disease attending the Sickle Cell Clinic of the University Hospital of the West Indies, Kingston, Jamaica. Six cerebrovascular episodes, 5 with hemiplegia, occurred within 2 days of aplastic crises; and 4, all with features of encephalitis, occurred within 2 to 5 weeks. Hemiplegia in 2 children resolved completely, one is improving, and one persists 20 years later; one patient died from recurrent strokes. Of the 4 children whose events occurred later, all had seizure disorders and 2 had transient cortical blindness. The crude risk of cerebrovascular episodes in the 5-week interval after B19 infection was calculated as 58 times greater than expected, which is suggestive of a causal association. (J Pediatr 2001;139:438-42)