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Parvovirus B19-antibody serosurvey in 500 developmentally disabled subjects.

Sera of 500 residents were screened for parvovirus B19 immunoglobulin M (IgM) and immunoglobulin G (IgG) by enzyme-linked immunosorbent assay. Positive IgM and equivocal IgG or IgM results were confirmed by immunofluorescent antibody and Western blot. IgM was detected in 13 sera (2.6%), and IgG was detected in 285 (57%). Records of IgM-positive residents contained no evidence of erythema infectiosum or polyarthropathy.

Adult↗

Acute bilateral carpal tunnel syndrome associated with human parvovirus B19 infection.

Human parvovirus B19 has been described as a causative agent of erythema infectiosum (a disease common in children), aplastic crisis in patients with hemolytic disorders, and arthralgias and arthritis. Joint involvement may be a prominent clinical feature of parvovirus B19 infection and may last for several weeks. We describe three cases of acute bilateral carpal tunnel syndrome associated with parvovirus B19 infection as evidenced by serological data and, in one case, by detection of parvovirus B19 DNA in blood with use of PCR.

Acute Disease↗

Experimental parvoviral infection in humans.

Healthy adult volunteers were inoculated intranasally with human parvovirus obtained from an asymptomatic blood donor. One week after inoculation, intense viremia was observed in seronegative volunteers, accompanied by a mild illness with pyrexia, malaise, myalgia, itching, and excretion of virus from the respiratory tract. In the following week hematologic studies revealed reticulocytopenia with an associated slight drop in hemoglobin concentration, lymphopenia, neutropenia, and a drop in platelet counts. At 17-18 days after inoculation a second-phase illness with rash and arthralgia lasting three to four days occurred in three of four infected volunteers. This study confirms the etiologic role of human parvovirus in erythematous rash illness, with the second-phase illness being consistent with adult cases of erythema infectiosum. Moreover, the hematologic changes associated with infection support the hypothesis that the same virus is responsible for the temporary arrest of erythropoiesis that leads to aplastic crisis in persons with chronic hemolytic anemia.

Anemia, Hemolytic↗

Risk of adverse outcomes of pregnancy after human parvovirus B19 infection.

Human parvovirus B19 (B19) infection during pregnancy has been associated with fetal deaths. We conducted several studies to develop data needed to make recommendations for preventing fetal death associated with infection. In the first study, after an outbreak of B19 infection, specimens of cord blood from 47 infants with congenital anomalies, 10 with suspected intrauterine infection, and gestational age-matched controls were tested for IgG and IgM antibodies to B19. None had evidence of recent infection. Next, 192 women with unknown exposure to B19 who had stillbirths or spontaneous abortions were studied. Two patients and two controls had evidence of recent B19 infection. In a second case-control study of women who had stillbirths after outbreaks of erythema infectiosum in area schools, none of the 20 patients or 26 controls were IgM positive at the time of delivery. The rate of infection, as demonstrated by IgM positivity, among 267 pregnant control subjects was approximately 1%. These studies suggest that among pregnant women unselected for exposure to B19, neither infection nor stillbirths are common.

Antibodies, Viral↗

Occupational risk factors for infection with parvovirus B19 among pregnant women.

To identify exposures associated with parvovirus B19 infection during pregnancy, two groups of pregnant women were studied during an outbreak of erythema infectiosum (EI). Of 796 pregnant women from Connecticut who were tested serologically because of perceived exposure to B19, 53% (419/796) had serologic evidence of previous B19 infection, and 6% (23/376) of the rest had evidence of recent infection. Of 121 pregnant women who had not requested testing but who lived in a community where a large outbreak of EI had occurred among schoolchildren, 36% (43/121) had serologic evidence of previous infection, and only 3% (2/78) of the rest had had a recent infection. In the exposed group, 479 women returned a supplemental exposure questionnaire. The highest infection rates among susceptible women were for schoolteachers (16%, 10/64), followed by day care workers (9%, 2/22) and homemakers (9%, 4/46). Women working outside the home but not in school or day care settings had the lowest risk (4%, 3/80). This study suggests that there is risk for B19 infection in selected occupational settings and in households.

Child Day Care Centers↗

The "fourth disease" of childhood: reevaluation of a nonexistent disease.

Observed and described between 1884 and 1900, "fourth disease" (Dukes disease) followed measles, scarlet fever, and rubella as the fourth clinically characterized childhood exanthem. Like rubella ("third disease") and erythema infectiosum ("fifth disease"), accepted by the medical community at about the same time, the existence of fourth disease was initially controversial. Over the following decades descriptions of hundreds of cases, outbreaks, and laboratory studies were published in the indexed medical literature. Unlike rubella and fifth disease, however, fourth disease was not subsequently proven to exist by either epidemiologic criteria or isolation of an etiologic agent. By the 1930s, it was infrequently recognized and by the 1960s had been dropped from textbooks. In this study, the authors use epidemiologic methods to reevaluate published data on English schoolchildren from 1892 to 1900 upon which the original fourth disease claim of Dukes was based. The authors conclude that fourth disease never existed. Reinterpretation of the original data suggests that cases can be completely explained as misdiagnosed rubella and scarlet fever. Misidentification of fourth disease is attributed to failures in the critical abilities of the medical and scientific communities at the time. The implications of erroneously identifying a nonexistent disease suggest that modern scientific approaches to disease identification are sound.

Child↗

Human parvovirus B19 infection in patients with systemic lupus erythematosus.

OBJECTIVE: The clinical significance of the presence of B19 DNA in patients with SLE was studied. METHODS: Sera from 72 patients with systemic lupus erythematosus (SLE), 23 patients with rheumatoid arthritis (RA), 18 patients with Sjögren's syndrome (SS), eight patients with Raynaud's phenomenon (RP), five patients with primary biliary cirrhosis (PBC), five patients with polymyositis (PM), four patients with erythema infectiosum (EI) and 22 normal controls were examined for parvovirus B19 (B19) infection by serological assays, nested PCR and Southern blotting. RESULTS: Parvovirus B19 DNA was detected in 17 of 72 patients with SLE and in three of four patients with EI, but not in patients with other systemic rheumatic diseases. Of the 17 patients with B19 DNA, only one had IgG anti-B19 antibody and two had IgM anti-B19 antibodies, whereas IgG and IgM anti-B19 antibodies were detected in 27 (49.1%) and 21 (38.2%) of 55 SLE patients without B19 DNA respectively. All sera from the patients with EI contained both IgG and IgM anti-B19 antibodies. B19 DNA was found more commonly in sera from SLE patients without anti-B19 antibodies than in those with anti-B19 antibodies (P<0.05). CONCLUSIONS: B19 infection in patients with SLE may be due to lack of anti-B19 antibodies because of either the immunocompromised nature of the host or the use of immunosuppressive drugs. There was a higher prevalence of hypocomplementaemia and RP in patients with parvovirus B19 viraemia than in those without parvovirus B19 viraemia.

Adult↗

Human parvovirus-associated red cell aplasia in the absence of underlying hemolytic anemia.

Human parvovirus (HPV) infection has recently been implicated as the cause of aplastic crisis in patients with hemolytic anemias such as congenital spherocytosis and sickle cell anemia. The virus causes a transient red cell aplasia which, in patients with a shortened red cell life span, is manifested as a rapid worsening of the anemia and an absence of peripheral reticulocytosis. Recovery is associated with the presence of giant pronormoblasts in the bone marrow, and several days later, a brisk peripheral reticulocytosis. In normal subjects, HPV causes erythema infectiosum (fifth disease) but is not associated with symptomatic anemia, probably because of the duration of the normal red blood cell life span. A case of HPV infection producing severe anemia in an immunocompromised patient without an underlying hemolytic anemia is presented here. Infection in this patient, a 3-year-old boy with acute lymphoblastic leukemia in remission, may have been prolonged by immunosuppression, leading over a 4-week period to a severe anemia. The immunosuppressed appear to be another group of patients at risk of developing symptomatic anemia when infected by HPV.

Anemia, Hemolytic↗

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

BACKGROUND: 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. OBJECTIVES: To determine whether human parvovirus B19 DNA can be detected in SSc skin tissue specimens. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Adult↗

Severe parvovirus B19 encephalitis after renal transplantation.

Human parvovirus B19 is a common cause of benign erythema infectiosum (fifth disease) in otherwise healthy children. Immunocompromized patients are at risk of developing chronic infections leading to chronic hyporegenerative anemia. We report the case of a nine-year-old boy who presented five days after renal transplantation with seizures and signs of encephalitis on MRI. The clinical course was characterized by anemia and seroconversion for parvovirus B19 accompanied by a high viral load (>10(9) copies per milliliter). A transfusion of red blood cells that the patient required after transplantation was found to be negative for parvovirus B19, leaving the donated organ as the most likely source of infection. Reduction of the immunosuppressive regimen led to complete recovery of the patient with a stable RBC count upon discharge. Parvovirus B19 infections should be considered in the differential diagnosis of seizures after solid organ transplantation.

Anemia↗

A case of prolonged human parvovirus B19 DNA-emia associated with polyclonal B cell activation.

The current paper reports an 8 year old girl with arthralgia and polyclonal B cell activation induced by human parvovirus B19 infection (HPV B19). The infection was diagnosed by the presence of the virus genome in sera. The patient presented with transient arthritis in the wrist, ankle joint and neck and elevation of immunoglobulin IgM antibodies to HPV B19 and rubella, antibodies to Mycoplasma and antistreptolysin O but without the typical clinical features of erythema infectiosum. The polyclonal B cell activation was paralleled by the presence of the virus genome of HPV B19 in sera. In some children with arthralgia, it is important to examine the genomes of viruses that may cause arthritis as well as the antibody titers to the viruses.

Arthralgia↗

Characterization and molecular cloning of a human parvovirus genome.

The genome of the small human virus serologically associated with erythrocyte aplasia and erythema infectiosum (fifth disease) is shown to be a linear, nonpermuted, single-stranded DNA molecule with self-priming hairpin termini, properties which are characteristic of the genomes of the family Parvoviridae. This human parvovirus chromosome was molecularly cloned into bacterial plasmid vectors and the cloned DNA was used to explore its relatedness to other mammalian parvovirus serotypes by DNA:DNA hybridization. It is not related to the human adeno-associated viruses but does show a distant evolutionary relationship to genomes of the helper-independent parvoviruses of rodents. This strongly suggests that it is an autonomous parvovirus, and as such is the first example of a member of this group of common animal pathogens to cause disease in man.

Base Sequence↗

Human parvovirus B19.

Parvovirus B19 (B19) was discovered in 1974 and is the only member of the family Parvoviridae known to be pathogenic in humans. Despite the inability to propagate the virus in cell cultures, much has been learned about the pathophysiology of this virus, including the identification of the cellular receptor (P antigen), and the control of the virus by the immune system. B19 is widespread, and manifestations of infection vary with the immunologic and hematologic status of the host. In healthy immunocompetent individuals B19 is the cause of erythema infectiosum and, particularly in adults, acute symmetric polyarthropathy. Due to the tropism of B19 to erythroid progenitor cells, infection in individuals with an underlying hemolytic disorder causes transient aplastic crisis. In the immunocompromised host persistent B19 infection is manifested as pure red cell aplasia and chronic anemia. Likewise, the immature immune response of the fetus may render it susceptible to infection, leading to fetal death in utero, hydrops fetalis, or development of congenital anemia. B19 has also been suggested as the causative agent in a variety of clinical syndromes, but given the common nature, causality is often difficult to infer. Diagnosis is primarily based on detection of specific antibodies by enzyme-linked immunosorbent assay or detection of viral DNA by dot blot hybridization or PCR. Treatment of persistent infection with immunoglobulin reduces the viral load and results in a marked resolution of anemia. Vaccine phase I trials show promising results.

Animals↗

Evaluation of a synthetic-peptide enzyme-linked immunosorbent assay for immunoglobulin M to human parvovirus B19.

A synthetic peptide corresponding to a part of the virus protein 1-virus protein 2 overlapping region of human parvovirus B19 was used in an indirect enzyme-linked immunosorbent assay. Antibodies of the immunoglobulin (Ig) M class were measured in serum samples from patients with erythema infectiosum and controls. In comparison with an IgM assay using native B19 viral antigen, the peptide antigen assay was 92% sensitive and 87% specific. B19 IgM reactivities were seen in a limited number of children with other viral diseases. Specific IgM reactivities to short synthetic viral peptides have previously been reported only with Epstein-Barr virus. Since other sources of viral antigen are limited, the peptide antigen assay may be a useful alternative for the diagnosis of B19-associated disease in human beings.

Amino Acid Sequence↗

Prevalence of parvovirus B19 and parvovirus V9 DNA and antibodies in paired bone marrow and serum samples from healthy individuals.

Parvovirus B19 (hereafter referred to as B19) exhibits a marked tropism to human bone marrow (BM), and infection may lead to erythema infectiosum, arthropathy, hydrops fetalis, and various hematologic disorders. Recently, a distinct parvovirus isolate termed V9 with an unknown clinical spectrum was discovered. In contrast to the many studies of B19 serology and viremia, valid information on the frequency of B19 or V9 DNA in the BM of healthy individuals is limited. To develop a reference value, paired BM and serum samples from healthy subjects were tested for the presence of B19 and V9 DNA and specific antibodies. Immunoglobulin M (IgM) was not found in any of the serum samples. The prevalence of IgG showed a gradual and steady increase from 37% in children aged 1 to 5 years to 87% in people aged >50 years. When 190 well-characterized subjects were examined, B19 DNA was detected in the BM of 4 individuals (2.1%; 95% confidence interval, 0.58 to 5.3%) while none of the paired serum samples showed evidence of circulating viral DNA. V9 DNA was not found in any of the BM or serum samples. The finding of B19 DNA probably indicated a primary infection in one 7-year-old individual and reinfection or reactivation of persistent infection in the remaining three persons, aged 47 to 58 years. Serving as a benchmark for future studies, these findings are useful when interpreting epidemiologic data, performing BM transplantation, or considering clinical implications of parvovirus infection.

Adolescent↗

The VP1 unique region of parvovirus B19 and its constituent phospholipase A2-like activity.

Parvovirus B19 is the causative agent of erythema infectiosum. In addition, parvovirus B19 infection may be associated with other disease manifestations, namely, thrombocytopenia or granulocytopenia, spontaneous abortion or hydrops fetalis in pregnant women, acute and chronic arthritis, and systemic lupus erythematosus. Based on sequence homology data, a phospholipase A2 motif has been identified in the VP1 unique region of parvovirus B19. (Y. Li et al., J. Gen. Virol. 82:2821-2825, 2001; Z. Zadori et al., Dev. Cell 1:291-302, 2001). We have established a new in vitro assay based on electrospray ionization tandem mass spectroscopy to show that phospholipase A2 activity is present in the VP1 unique region produced in Escherichia coli and in virus-like particles consisting of combinations of VP1 and VP2 proteins expressed by recombinant baculovirus. The enzyme activity of the VP1 unique region showed typical Ca(2+) dependency and could be inhibited by manoalide and 4-bromophenacylbromide, which bind covalently to lysine and histidine residues, respectively, as part of the active center of the enzyme. By using subfragments, we demonstrated an association between the phospholipase A2-like activity and the carboxy-terminal domain of the VP1 unique region.

Amino Acid Sequence↗

Human parvovirus infections.

The B19 strain of parvovirus causes several distinct and important clinical diseases in humans. Aplastic crisis in patients with chronic hemolytic anemia, persistent bone marrow depression in immunocompromised individuals, and hydrops fetalis all result from direct infection of hematopoietic cells by the virus. Erythema infectiosum, arthritis, and purpuric vasculitis are postinfectious manifestations of B19 parvovirus infection.

Female↗

[Erythrovirus B19 infection].

Erythrovirus B19 has been associated with an expanding range of clinical disorders since its identification as the etiological agent of erythema infectiosum, or fifth disease of childhood: acute arthropathy, dermatologic manifestations, chronic anemia in immunocompromised patients, and transient aplastic crisis in individuals with underlying chronic hemolytic disorders. Furthermore, exposure to and infection by B19 virus can lead to serious complications during pregnancy, which may result in fetal anemia, spontaneous abortion, and hydrops fetalis. Consequently, the B19 immune status of pregnant women should be routinely determined. Because many immunocompromised patients with chronic anemia will respond positively to intravenous immunoglobulin therapy, laboratory confirmation of B19 infection is required. Since Erythrovirus B19 cannot be routinely grown in vitro, diagnostic methods for detecting the presence of B19 by molecular techniques or by investigating the specific immune response should be considered in clinical microbiology laboratories.

Humans↗