Virus pb19

This is not very common but can be serious for people with weakened immune systems sickle cell disease or similar long-lasting anemia. Fifth disease commonly affects children. Links with this icon indicate that you are leaving the CDC website. Linking to a non-federal website does not constitute an endorsement by CDC or any of its employees of the sponsors or the information and products presented on the website.

You will be subject to the destination website's privacy policy when you follow the link. CDC is not responsible for Section compliance accessibility on other federal or private website.

Cancel Continue. Parvovirus B19 PB19 is an important human pathogen that results in a wide spectrum of clinical outcomes, from mild, self-limiting erythema infectiosum in immunocompetent children and arthralgia in adults to lethal cytopenia in immunocompromised patients and intrauterine fetal death.

However, there have been few reports of PB19 infection in neonates or young infants aged 28—90 days , and no previous reports contained descriptions of PB19 infection as a cause of sepsislike syndrome in this age group.

We report a case of sepsislike syndrome caused by PB19 infection in a day-old infant whose mother had polyarthralgia at the time of his admission. PB19 infection was diagnosed on the basis of positive polymerase chain reaction results for PB19 DNA in the serum and cerebrospinal fluid. Positive immunoglobulin M and negative immunoglobulin G for PB19 suggested acute infection. He was admitted to the ICU because of poor peripheral circulation, but fully recovered without antibiotic administration.

After excluding other possible pathogens, PB19 should be suspected as a cause of sepsislike syndrome in young infants, especially those who have close contact with PBinfected individuals. Parvovirus B19 PB19 infection is common in childhood, but its clinical manifestations vary considerably in relation to patient age and immunologic status.

Arthralgia is the most common manifestation in adults, particularly in women. PB19 can cause fetal hydrops when mothers develop intrauterine infections. Herein, we report a case of sepsislike syndrome caused by PB19 infection in a young infant. A term day-old boy with a birth weight of g was admitted to our hospital in January because of high fever and poor sucking. Perinatal history was unremarkable. In addition, his mother reported systemic joint pain, a sign of PB19 infection, on the day of his admission.

In the emergency department, his vital signs were as follows: body temperature, Physical examination revealed significant abdominal distension. Capillary refilling time was prolonged up to 5 seconds , and his extremities were cold. He had no bulging anterior fontanelle, rash, petechiae, vesicular lesions, hepatosplenomegaly, or abnormal neurologic signs.

Laboratory findings on admission were a white blood cell count of 3. A blood smear revealed no evidence of atypical lymphocytes or abnormal red blood cell morphology. No abnormal findings were observed in cerebrospinal fluid CSF or urine. The patient did not present with any obvious source of fever on admission. He was critically ill with poor circulation and was admitted to an ICU. Bacterial infection was excluded on the basis of negative results for blood, urine, and CSF cultures. Real-time reverse transcription PCR was used to test serum and CSF samples for herpes simplex virus, enteroviruses, human parechoviruses, and adenovirus, but all tests yielded negative results.

As stated above, the boy had close contact with family members with erythema infectiosum. His mother developed rash on her extremities a few days after she developed arthritis. Because we suspected an outbreak of PB19 among his family members, PB19 was considered as a possible cause of his condition. Ultimately, sepsislike syndrome due to PB19 infection was diagnosed.

During hospitalization, fever persisted for 2 days but resolved with supportive care. He was well enough to be transferred from the ICU to the pediatric ward on hospital day 2 and was discharged from the hospital on day 6 without sequelae. At the time of discharge, white blood cell count No additional measurement of viral load was performed during his hospitalization. Findings of a 2-month follow-up examination were all normal.

Written informed consent was obtained from his parents, and they were informed that the case would be submitted for publication as a case report. Bspecific DNA has been detected in respiratory secretions at the time of viremia, suggesting that virus is generally spread in the community by a respiratory route.

The case-to-case interval is 6 to 11 days irrespective of the type of Brelated disease. Vertical transmission occurs in one-third of cases involving serologically confirmed primary maternal infections Nosocomial transmission has been described infrequently 98 , , , and transmission has also been reported among staff in laboratories handling native virus 69 , ; Cohen and Brown, letter.

Conversely, as a large number of blood donations make up the plasma pools used to produce plasma derivatives, clotting-factor concentrates may very often be contaminated. B19 DNA has also been detected in all of 25 solvent- or detergent-treated plasma batches B19 may also infrequently be transmitted by BM and blood-derived products such as platelets 66 , intravenous immunoglobulin 93 , and fibrin products , and B19 infection and seroconversion have been observed in patients after receiving solvent- or detergent-treated plasma units 17 , Although the presence of giant pronormoblasts in either BM or peripheral blood is suggestive of B19 infection, their presence or absence should not be used alone to make a diagnosis of B19 infection.

These cells are often absent in patients with human immunodeficiency virus HIV infection or other chronic infections. Although B19 can be detected in serum by EM, B19 antigen enzyme-linked immunosorbent assays, and even hemagglutination, B19 virus is usually detected by isolation of viral DNA by direct hybridization or PCR. Direct hybridization, usually as a slot blot or dot blot format, generally employs an almost-full-length viral DNA probe labeled with 32 P, digoxigenin, or biotin to bind to DNA in clinical specimens 10 , Although direct hybridization is sensitive enough to detect B19 levels in acute transient aplastic crisis and pure red cell aplasia due to B19 infection in immunosuppressed patients, lower levels of viremia will be missed.

The advent of PCR has greatly increased the sensitivity of DNA detection in serum and tissue samples, although it possesses a great propensity for contamination , , , , , DNA may be detectable for extended periods of time in serum 54 , , , synovial membranes , and BM 52 , even in healthy individuals. Therefore, the presence of low levels of B19 DNA alone cannot be used to diagnose acute B19 infection. In addition, although most primer pairs based on the pvbaua isolate are able to detect temporally and geographically diverse B19 isolates 89 , most primer pairs would not have detected the V9 variant, and ideally two sets of primers should be used to ensure that B19 has not been missed.

Although B19 DNA-based assays are crucial for the diagnosis of B19 infection presenting as transient aplastic crisis before the antibody response and in chronic infections in immunosuppressed individuals who fail to make an immune response , diagnosis of B19 infection in immunocompetent individuals presenting with erythema infectiosum or Binduced arthropathy is by detection of Bspecific antibody.

Due to the inability of B19 to efficiently replicate in culture systems, viral capsids were initially purified from serum with high virus titer and used for antibody tests 6 , B19 antigen can be expressed in bacteria, in cell lines 24 , or as peptides, but currently most antigen is produced in insect cell lines with recombinant baculovirus These recombinant antigens are noninfectious, and serologic results correlate well with those using native virus IgM capture assays will reliably detect a current or recent infection in immunocompetent persons 48 , 52 , , Tests using an indirect method of detection are less useful for diagnosis due to reduced specificity and sensitivity.

In contrast, for detection of IgG both capture assays and indirect assays may be used. Two weeks following infection IgG is usually present and persists for life. Sequential sera may show a decline in IgG titer, but detection of IgG is generally not useful for diagnosis of acute infection, apart from detecting a seroconversion in immunocompromised patients, who may not be able to produce IgM.

However, a significant correlation between the relative amounts of low-avidity specific IgG antibodies and time after onset of illness has been documented , but is probably of minor clinical use. The significance of detecting NS1-specific IgG has been continuously discussed and contested since this antibody was suggested to be associated with an altered course of disease , One group has repeatedly argued that NS1-specific IgG is primarily found in patients with arthritis or persistent B19 infection , , , It is believed that prolonged viremia may lead to infection of cells outside the erythroid lineage nonpermissive cells in which gene expression shifts towards the preferential transcription of the NS1 gene rather than the VP1 and VP2 genes , , The cytotoxic and apoptotic effects of NS1 84 , , , , may result in cell lysis and the release of NS1 protein, thereby rendering this nonstructural viral component accessible to the immune system of the host.

Hence, viral persistence may be a precondition for the formation of NS1-specific antibodies , Conversely, others have found no evidence of NS1 IgG representing a marker of persistent infection or contributing to pathogenesis , , , In addition, detection of B19 DNA has been linked to a heterogeneous group of diseases in which the causality is unconfirmed. Subclinical B19 infection is a common finding in both children and adults.

Asymptomatic seroconversion following recent transfusion in patients with hemolytic anemia suggests that symptoms may be masked by transfusion of erythrocytes with a longer life span than the defective erythrocytes of the host 7. In some cases nonspecific symptoms indistinguishable from the common flu may be noted. Following an outbreak of erythema infectiosum an association with B19 was made by the discovery of specific IgM in specimens from the involved patients Anderson et al.

This disease entity was well known prior to the discovery of B19 19 , which is now recognized as the only etiologic agent of erythema infectiosum 13 , , Prodromal symptoms often go unnoticed but may include fever, coryza, headache, and nausea.

Erythema infectiosum is characterized by a facial erythema of medium intensity involving the cheeks, but with relative circumoral pallor slapped cheek appearance beginning 18 days after infection Fig. A second stage consisting of a rash involving the trunk and limbs occurs 1 to 4 days later.

The rash is frequently lacy or reticular and consists of pink maculae that usually undergo a central fading, which causes the rash to take on a festooned appearance. The rash may be transient or recurrent, and fluctuations of intensity can be linked to environmental factors such as exposure to sunlight and heat Other symptoms include itching, vesicles, and scaly dermatitis , In an association between arthropathy and B19 infection was made , Among the latter persistent arthritis for 2 to 13 months, which would fulfill criteria for the diagnosis of juvenile rheumatoid arthritis, was observed.

The arthropathy is presumably immunologically mediated since the onset coincides with the appearance of circulating antibodies. It has been postulated that B19 is involved in the initiation and perpetuation of rheumatoid arthritis leading to joint lesions , but these results have not been reproduced by other groups and Brown, unpublished observations.

Recently, an experimental in vitro system was established in which healthy primary human synovial fibroblasts were treated with or without Bcontaining human sera and then tested for their ability to degrade reconstituted cartilage matrix Incubation with B19 induced an invasive phenotype in the fibroblasts, and preincubation of viremic serum with a neutralizing antibody to B19 eliminated the observed effect.

It seems unlikely, though, that B19 plays a role in classic erosive rheumatoid arthritis, but understanding the pathogenesis of B19 arthropathy may provide insight into the mechanisms by which rheumatoid arthritis develops Accordingly, during long-term follow-up none of 54 patients with Bassociated arthralgia reported persistence of joint swelling or restricted motion, and no evidence of inflammatory joint disease was found In conclusion, despite B19 mimicking rheumatoid arthritis in the acute stage and detection of B19 DNA in synovial fluid 83 and synovial biopsy specimens , a convincing link to chronic erosive arthropathy has yet to be demonstrated The discovery of B19 causing nonimmune hydrops fetalis has led to significant public concern It has since been found that fetal B19 infection may also cause fetal or congenital anemia, abortion, or stillbirth or result in an asymptomatic self-limiting episode.

A few case reports have speculated on B19 causing congenital malformations , ; Weiland et al. The pathogenesis of fetal damage appears to be similar to that of patients with aplastic crisis in which the erythrocytes have a reduced life span.

Erythroblasts in the fetal liver exhibit signs of B19 infection, including pathognomic cytopathology, viral DNA, and antigen 3 , In utero infection is persistent and characterized by severe anemia, high-output cardiac failure, and death Impaired circulation due to fetal myocarditis may contribute to the accumulation of fluids Fig. B19 might also be associated with cases of nonhydropic intrauterine fetal death The chance of an adverse fetal outcome after infection seems to be greatest between 11 and 23 weeks of gestation, which correlates with the hepatic period of hematopoietic activity , Cordocentesis allows precise assessment of fetal anemia, which might then be corrected by intravenous transfusion of erythrocytes Hematologic evaluation has revealed anemia in each of the examined Bassociated hydropic fetuses reported , , , , although no cases of congenital anemia have been found in prognostic studies on outcome of series of hydropic fetuses following B19 infection , , , However, three infants with hydrops and congenital anemia due to transplacental B19 infection have been described One infant died, and the others remained persistently anemic despite continued treatment with immunoglobulin.

The Bpositive children were the only children who experienced a remission, while the seven surviving Bnegative patients remained on steroid treatment. In another report, an infant developed congenital anemia due to a possible B19 infection At the age of 10 months immunoglobulin therapy was commenced, and 8 months later the anemia gradually resolved.

Recently, B19 infection causing severe hydrops fetalis and subsequent congenital anemia, which was corrected by multiple intrauterine transfusions and postnatal immunoglobulin, was described Despite frequent reports of intrauterine B19 infection and hydrops, the risk of associated congenital anemia is apparently low.

This may be explained by B19 causing severe disease in only the first two trimesters , Ordinarily, infection probably leads to one of two outcomes: lethal hydrops or a milder course of disease in which the virus is eradicated and the ill effects ameliorated before term. However, the paucity of cases of congenital anemia may also reflect underdiagnosis. In children, unlike in adults, most cases of idiopathic thrombocytopenic purpura ITP are of acute onset and are often preceded by a specific viral infection 22 , Accordingly, B19 infection may result in subclinical or overt thrombocytopenia in volunteers and patients 8 , , , ; Foreman et al.

Among the Bpositive children, duration of disease was brief in three children treated with immunoglobulin but chronic in the remaining three patients given high-dose steroids. Binduced thrombocytopenia seems to consist of a central and a peripheral type Thrombocytopenia of central origin is due to BM suppression , and the possible cytopathologic effect is underlined by the finding that the NS1 protein, produced by B19, has been found to inhibit the megakaryocytic colony formation , This indicates tissue tropism of B19 beyond the erythroid progenitor cell and shows that viral proteins may be toxic to cell populations that are nonpermissive for viral DNA replication.

Destructive thrombocytopenia of peripheral origin may result from immunologically mediated antiplatelet antibody production with subsequent excessive platelet clearance in the reticuloendothelial system ; Foreman et al. Transient erythroblastopenia of childhood TEC is a disorder of young children, ages 3 to 4 years, characterized by anemia, reticulocytopenia, and decreased red blood cell precursors in the BM aspirate.

TEC is the most common single cause of red cell aplasia in immunocompetent children, and other cytopenias are increasingly being recognized in these patients , , B19 has been a prime viral suspect in TEC patients due to its hematopoietic effects and has been implicated in a number of cases , , ; Muir and Fitzsimons, Letter, Br.

Review of the literature, however, indicates that B19 is not the cause of anemia in young patients with typical features of TEC , ; Bhambhani et al. Rather, B19 infection may occasionally cause a protracted anemia, often with thrombocytopenia, which erroneously may be diagnosed by some as TEC, leaving the etiology of TEC unresolved.

Primary autoimmune neutropenia is caused by granulocyte-specific autoantibodies and occurs predominantly in infancy.

Encouraged by initial case reports 85 , , , , and volunteer studies 8 , the BM of children with neutropenia was examined for B19 DNA Results indicated that B19 infection may be a common cause of immune-mediated neutropenia in childhood 15 of 19 patients , but larger, more recent studies have not been able to verify this 49 ; Hartman et al. Prior to the advent of specific virologic techniques, neurologic symptoms associated with erythema infectiosum were reported in a few cases 20 , Neuropathy Faden et al.

Psychiatry , ; Pellas et al. Detection of IgM Tsuji et al. One patient suffering from seizures received successful immunoglobulin therapy The mechanism for the neurological symptoms is unknown, but frequently rash or arthralgia is also present, suggesting that the neuropathy may be immune mediated. Histologic examination and the finding of specific DNA in the nuclei of fetal myocytes demonstrate the cardiac tropism of B19 30 , , , , , ; Anderson et al.

Clinically significant myocarditis and perimyocarditis have been diagnosed in a few children 32 , 92 ; Beghetti et al. In addition, in pediatric cardiac transplant recipients B19 infection has been noted to cause general disease , as well as possible myocarditis , The finding of myocarditis is puzzling since B19 is thought to replicate only in rapidly dividing cells of hematopoietic origin but may be explained by the tissue distribution of the viral receptor P antigen involving myocytes 40 or from immunological cross-reaction to epitopes shared between the virus and the myocardium Considering that B19 is a common infectious agent, and that resulting myocarditis is currently believed to be a rare event, either the virus is only mildly cardiotropic or other unknown concerted factors are required to cause clinical disease.

The role of B19 in hepatitis remains unclear. Although transient elevation of liver transaminases is not uncommon in B19 infection, and B19 was originally identified in a sample sent for hepatitis testing, frank hepatitis associated with B19 infection has only rarely been reported , , ; Drago et al.

Studies of blood donors with raised transaminases do not suggest that B19 is a major cause of seronegative hepatitis Similarly, B19 has been suggested as a possible causative agent of fulminant liver failure and associated aplastic anemia based on PCR studies ; Naides et al. However, in both studies the numbers are small and other studies in this area have not confirmed the association ; Brown et al.

B19 has been suggested as the causative agent in a variety of clinical syndromes, but given the common nature, causality is often difficult to infer. Severe pneumonia , conjunctivitis , Behcet's disease Kiraz et al. In immunocompromised patients unable to mount a neutralizing antibody response due to a persistent BM insufficiency, B19 infection may cause chronic anemia.

Predisposing conditions include Nezelof's syndrome , acute lymphatic leukemia ALL , , acute myeloid leukemia Weiland et al. Patients have absent or low levels of specific antibodies, with persistent or recurrent viremia being detected Clinical hallmarks include fatigue and pallor, while immune-mediated symptoms rash and arthralgia are generally not present , Infection may serve as a prodrome of an underlying disease ; Murray et al.

Temporary cessation of maintenance chemotherapy has also led to resolution of anemia However, the prevalence of Binduced anemia in HIV-seropositive patients may be underestimated ; Vernazza et al.

The presence of IgM to B19, the clinical circumstance under which anemia developed, and the marrow morphology were poor predictors of chronic B19 infection. Chronic B19 infection has been described in case reports of adult 96 , , ; Hitchins and Sloots, Letter, Aust. Though no conclusions can be drawn on the basis of these single observations, the reported cases indicate that ALL patients with B19 infection typically present with persistent anemia, while rash or arthropathy is commonly absent.

Children with leukemia share the chief age of B19 infections and may be particularly vulnerable to the ill effects of B19 due to immunosuppression. B19 infection was able to mimic a leukemic relapse or therapy-induced cytopenia and contributed to the development of chronic anemia and profound thrombocytopenia in the majority of infected individuals. Infrequently, isolated thrombocytopenia or transient pancytopenia preceding ALL has also been observed. Virus-associated hemophagocytic syndrome VAHS is characterized by histiocytic hyperplasia, marked hemophagocytosis, and cytopenia, in association with a systemic viral illness In contrast to malignant histiocytosis, VAHS is usually a benign self-limiting illness, in which histiocytic proliferation is reversible.

Hemophagocytosis is not uncommon and occurs in the setting of a wide range of infections, not only viral, but also in the context of bacterial, rickettsial, fungal, and parasitic infections However, in many patients there is underlying immunosuppression, usually iatrogenic, so that the role of the incriminated pathogen as the etiological agent or a coincidental opportunistic infection remains unclear.

In two reported cases of VAHS, pure red cell aplasia was concurrent , B19 infection has been detected in cases of hemophagocytosis syndrome among children and adults , , , , , , ; Toyoshige and Takahashi et al. Although the majority of patients reported to have VAHS were previously healthy, several patients were immunosuppressed by drug therapies. Transient aplastic crisis, the first disease to be associated with B19, refers to a brief self-limited episode of pure red cell aplasia and was originally described in patients with hemolytic anemia.

However, any person suffering from decreased red cell production or increased destruction or loss will be in danger of developing aplastic crisis following B19 infection. Cessation of the production of erythrocytes for 10 to 15 days, as seen during infection in healthy individuals, will in hemolytic patients lead to a marked drop in hemoglobin due to the underlying decrease in red cell survival in these patients.

Conditions associated with decreased red cell production, thereby rendering patients susceptible to Binduced aplastic crisis, include iron deficiency Graeve and Elliott, Letter, J. Infection may also cause transient aplastic crisis in patients with increased red cell destruction or loss, including hereditary spherocytosis 59 , , , , hereditary stomatocytosis , hereditary elliptocytosis Lortholary et al.

The aplasia may also be associated with hemophagocytic syndrome Severe anemia associated with B19 can also rarely affect apparently healthy subjects with no underlying hematologic disorder ; Hamon et al. Although the erythrocytes are predominantly affected, with presentation often of a pure red cell aplasia, concurrent thrombocytopenia, neutropenia, or pancytopenia is found infrequently , , , , While the anemia may be lethal, the aplastic crisis itself is usually terminated by the appearance of specific antibodies and thus rarely lasts for more than 2 weeks.

Aplastic crisis usually presents with pallor, weakness, and lethargy, and patients are highly viremic, thereby posing a risk of transmission to others 7 , 26 , In most cases erythema infectiosum requires no treatment, while some patients with Binduced arthralgia may need symptomatic treatment i. In cases of transient aplastic crisis caused by B19, prognosis is excellent once a satisfactory hemoglobin concentration is obtained by erythrocyte transfusion B19 infection in pregnant seronegative women should be monitored by weekly ultrasound examinations, and cordocentesis and intrauterine transfusions are effective in lowering the mortality in cases of hydrops fetalis Effective therapy of persistent B19 infection pure red cell aplasia consists of infusion of immunoglobulin 0.

This treatment is usually ameliorative and very often curative , , , , leading to a marked increase in reticulocyte count and corresponding rise in hemoglobin. On a more experimental note, generation of neutralizing human monoclonal antibodies directed against B19 proteins have been proposed as an immunotherapy of chronically infected individuals and acutely infected pregnant women Though there is insufficient evidence to recommend universal testing, especially for single units, it has been proposed that B19 screening of blood components destined for children with malignancies be implemented When germane, testing BM donors should also be considered prior to transplantation In addition, assaying of B19 is essential at diagnosis of ALL and HIV to avoid subsequent diagnostic uncertainty and during treatment in other Bseronegative immunocompromised patients exhibiting unexplained cytopenia.

The presence of VP1 protein is important for elicitation of potent virus-neutralizing activity, and results indicate that VP1-enriched empty capsids could serve as candidates of a recombinant vaccine Sera from experimental animals and human volunteers immunized with such a VLP vaccine candidate exhibit titers of neutralizing antibody equal to or greater than those observed in natural infections Phase I trial results appear promising, and phase II trials are planned.

Although currently B19 is the only member of the Erythrovirus genus, three primate parvoviruses which are similar to the human B19 parvovirus at the genome level and in their predilection for host BM in vitro have been identified , , The identification of theses viruses, and especially the simian parvovirus, originally isolated from cynomolgus monkeys, has allowed the development of an animal model for B19 infection.

Infection of immunosuppressed macaques with simian parvovirus leads to persistent anemia, whereas in immunocompetent animals there is a transient drop in reticulocytes And as in B19, infection of the immunologically immature fetus leads to the development of hydrops fetalis M. O'Sullivan, D. Feeney, et al. This animal model is currently being used to learn more about the pathophysiology of Binduced hydrops and to develop better methods for treating infected fetuses. National Center for Biotechnology Information , U.

Journal List Clin Microbiol Rev v. Clin Microbiol Rev. Erik D. Heegaard 1 and Kevin E. Kevin E. Author information Copyright and License information Disclaimer. Phone: Fax: E-mail: vog. This article has been cited by other articles in PMC. Abstract Parvovirus B19 B19 was discovered in and is the only member of the family Parvoviridae known to be pathogenic in humans. TABLE 1. Genus Virus Natural host s Clinical spectrum Parvovirus Aleutian mink disease virus Mink, ferret, skunk, raccoon Immune complex disease and fetal death Canine parvovirus Dog Enteritis, myocarditis Mice minute virus Mouse, rat No known disease Porcine parvovirus Pig Abortion, fetal death Dependovirus Adeno-associated virus 1 to 6 Human No known disease Avian adeno-associated virus Birds No known disease Canine adeno-associated virus Dog No known disease Bovine adeno-associated virus Cow No known disease Erythrovirus Parvovirus B19 Human Erythema infectiosum, aplastic crisis, arthritis, hydrops fetalis, etc.

Parvovirus V9 a Human Aplastic crisis? Chipmunk parvovirus a Chipmunk No known disease Simian parvovirus a Cynomolgus monkeys Anemia Pig-tailed macaque parvovirus a Pig-tailed macaques Anemia and immunosuppression Rhesus parvovirus a Rhesus monkeys Anemia. Open in a separate window. Morphology The B19 virion has a simple structure composed of only two proteins and a linear, single-strand DNA molecule Genomic Structure and Organization The single-stranded genome contains 5, nucleotides nt , composed of an internal coding sequence of 4, nt flanked by the terminal repeat sequences of nt each 80 Fig.

Sequence Variability The nucleotide sequence of B19 was originally established by sequencing a viral isolate designated pvbaua obtained from the serum of a child with homozygous sickle cell disease Capsid and Nonstructural Proteins Capsid proteins.

Nonstructural proteins. Culture There is no animal model for B19, and virus can only be grown in culture with difficulty. Cytopathology The cytopathic effect of infection of erythroid progenitor cells with B19, both in vivo and in vitro, is manifested as giant pronormoblasts alternately referred to as lantern cells , first recognized in in the BM of patients with transient aplastic crisis Giant pronormoblast. Arrowheads indicate dog-ear projections. TABLE 2. Prevalence of B19 DNA in blood donors.

Reference No. Seasonal Changes and Contagiousness The peak incidence of erythema infectiosum shows seasonal variation, occurring mainly during the months of late winter and early spring. Transmission Transmission of infection occurs via the respiratory route, through blood-derived products administered parenterally, and vertically from mother to fetus.

Detection of Antibodies Although B19 DNA-based assays are crucial for the diagnosis of B19 infection presenting as transient aplastic crisis before the antibody response and in chronic infections in immunosuppressed individuals who fail to make an immune response , diagnosis of B19 infection in immunocompetent individuals presenting with erythema infectiosum or Binduced arthropathy is by detection of Bspecific antibody.

Detection of NS1-specific antibodies. TABLE 3. Summary of clinical manifestations following B19 infection. Psychiatry , ; Oeda et al. Heart J. Infection in the Healthy Host Asymptomatic infection. Erythema infectiosum.

Erythema infectiosum with a reticular rash of the legs A and slapped cheeks B. B19 infection in pregnancy. TEC and neutropenia. Neurologic disease. Putative associations. Infection in the Immunodeficient Host Chronic pure red cell aplasia.

Virus-associated hemophagocytic syndrome. Animal Models of B19 Infection Although currently B19 is the only member of the Erythrovirus genus, three primate parvoviruses which are similar to the human B19 parvovirus at the genome level and in their predilection for host BM in vitro have been identified , , Abkowitz, J.

Brown, R. Wood, N. Kovach, S. Green, and N. Clinical relevance of parvovirus B19 as a cause of anemia in patients with human immunodeficiency virus infection. Agbandje, M. Kajigaya, R. McKenna, N. Young, and M. The structure of human parvovirus B19 at 8 A resolution. Virology : Anand, A. Gray, T. Brown, J. Clewley, and B. Human parvovirus infection in pregnancy and hydrops fetalis. Anderson, L.

Role of parvovirus B19 in human disease. Gillespie, T. Torok, E. Hurwitz, C. Tsou, and G. Risk of infection following exposures to human parvovirus B Behring Inst. Tsou, R. Parker, T. Chorba, H. Wulff, P. Tattersall, and P. Detection of antibodies and antigens of human parvovirus B19 by enzyme-linked immunosorbent assay. Anderson, M. Davis, J.

Hodgson, S. Jones, L. Murtaza, J. Pattison, C. Stroud, and J. Occurrence of infection with a parvovirus-like agent in children with sickle cell anaemia during a two-year period. Higgins, L. Willman, S. Jones, I. Kidd, J. Pattison, and D. Experimental parvoviral infection in humans.

Jones, and A. Diagnosis of human parvovirus infection by dot-blot hybridization using cloned viral DNA. Lewis, I. Kidd, S. Hall, and B. An outbreak of erythema infectiosum associated with human parvovirus infection. London 93 : Astell, C. Terminal hairpins of parvovirus genomes and their role in DNA replication, p.

Tijssen ed. CRC Press, Inc. Azzi, A. Fanci, S. Ciappi, K. Zakrzewska, and A. Human parvovirus B19 infection in bone marrow transplantation patients.

Macchia, C. Favre, M. Nardi, K. Zakrzewska, and O. Aplastic crisis caused by B19 virus in a child during induction therapy for acute lymphoblastic leukemia. Haematologica 74 : Morfini, and P. The transfusion-associated transmission of parvovirus B Balfour, H. Erythema infectiosum fifth disease. Clinical review and description of 91 cases seen in an epidemic.

Philadelphia 8 : Schiff, and J. Encephalitis associated with erythema infectiosum. Bansal, G. Hatfield, F. Dunn, A. Kramer, F. Brady, C. Riggin, M. Collett, K. Yoshimoto, S. Kajigaya, and N. Candidate recombinant vaccine for human B19 parvovirus. Baranski, B. Hematologic consequences of viral infections. Baurmann, H. Schwarz, J. Oertel, S. Serke, M. Roggendorf, and D.

Acute parvovirus B19 infection mimicking myelodysplastic syndrome of the bone marrow. Beard, C. Amand, and C. Bell, L. Naides, P. Stoffman, R. Hodinka, and S. Human parvovirus B19 infection among hospital staff members after contact with infected patients.

Berns, K. Parvoviridae : the viruses and their replication, p. Fields, D. Knipe, P. Howley, R. Chanock, J. Melnick, T. Monath, B. Roizman, and S. Straus ed. Lippincott-Raven, Philadelphia, Pa. Adeno-associated viruses: an update. Virus Res. Berry, P. Gray, H. Porter, and P. Parvovirus infection of the human fetus and newborn. Borreda, D. Palomera, B. Gilbert, A. Lienhardt, and L. Paris 39 : In French.

Bostic, J. Brown, N. Young, and S. Quantitative analysis of neutralizing immune responses to human parvovirus B19 using a novel reverse transcriptase-polymerase chain reaction-based assay. Breese, C. Encephalopathy with erythema infectiosum. Broliden, K.