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Acute lung injury due to parvovirus pneumonia.

OBJECTIVE: Human parvovirus B19 is responsible for the common childhood exanthematous illness, erythema infectiosum. Adults infected with B19 have been reported to develop a febrile illness associated with arthritis. Life threatening parvovirus infections in non-immunocompromised adults have not been reported to date. We report a previously healthy middle aged female who developed severe parvovirus pneumonia. The patient recovered with supportive care provided in the ICU. Parvovirus may represent an under diagnosed cause of community acquired pneumonia.

Acute Disease↗

A comparative study of a new rapid and one-step test for the detection of parvovirus in faeces from dogs, cats and mink.

A one-step immunochromatographic test, based on the use of monoclonal antibodies, was developed for the detection of canine parvovirus (CPV) in dog faeces. In addition to canine parvovirus the test can also be used for the diagnosis of infections with viruses causing parvovirus enteritis in cats (feline panleukopenia virus) and mink (mink enteritis virus). Four hundred and forty-three faecal samples were evaluated by comparative testing between this one-step test and three different enzyme-linked immunosorbent assays (ELISA) in Sweden, Denmark and The Netherlands. The result of the evaluation showed an overall relative sensitivity and specificity of 95.8 and 99.7%, respectively. Furthermore, the comparative testing of 83 dog samples in Germany between the one-step test and an immune electron microscopy (IEM) agreed to 85.5%. The sensitivity and specificity were 83.9 and 88.9%, respectively. These results show that the one-step test is a rapid, simple, reproducible and sensitive diagnostic test for the detection of parvovirus in faecal samples of dogs, cats and mink.

Animals↗

Intrauterine management of fetal parvovirus B19 infection.

OBJECTIVES: The aim of our study was to determine the outcome of pregnancies after intrauterine management of fetal parvovirus B19 infection. DESIGN: Retrospective study. SUBJECTS: A total of 37 cases of maternofetal parvovirus B19 infection, 35 of which were associated with hydrops fetalis, were referred to our tertiary level center between 1989 and 1996. With regard to fetal hydrops, no apparent cause other than parvovirus B19 infection was found in any patient. METHODS: In all patients, cordocentesis was performed to assess the degree of fetal anemia. When anemia was present, cordocentesis was followed by intrauterine transfusion with packed red cells into the umbilical vein. Further management depended on the degree of fetal anemia and gestational age and included follow-up fetal blood sampling/transfusion as well as ultrasound examinations as deemed appropriate. RESULTS: Packed red cell transfusion was performed in 30 patients with significant fetal anemia (Z-score 1.6-7.8 below the mean for gestational age). The fetal hemoglobin values ranged from 2.1 to 9.6 g/dl. Serum levels of platelets in the transfusion group were 9-228 x 10(9)/l with Z-scores in the range of < 1 to 3.8 below the mean. During treatment and follow-up, there were five intrauterine deaths (13.5%), one neonatal death (2.7%) and 31 live births (83.8%). CONCLUSIONS: Fetal parvovirus infection can lead to marked anemia and hydrops formation. Cordocentesis allows precise assessment of fetal anemia which can then be corrected by intravenous transfusion. Under this regimen, the outcome proved favorable in the majority of fetuses, even those that were severely anemic.

Anemia↗

[Parvovirus B 19 associated hemophagocytic syndrome in a patient with hereditary sperocytosis].

Infections with parvovirus B 19 can cause aplastic crises with a rapid decline of hemoglobin levels in patients with hereditary spherocytosis. Usually, the symptoms and signs of the actual infection are mild. We here report on an eight year old girl with hereditary spherocytosis who was admitted to hospital with high temperature, headache, impaired consciousness and a profound anemia (Hb 2.9 mmol/l). Since she also developed low leukocyte and platelet counts a hematological malignancy was suspected. The bone marrow aspirate showed only 1 % erythroblasts and macrophages with active hemophagocytosis. The serum ferritin was 1381,4 ng/ml. Both, serology and PCR revealed an active infection with parvovirus B 19. Coagulation analysis suggested a low degree of disseminated intravasal coagulation (low fibrinogen, high D-dimers). We diagnosed a parvovirus B 19 associated hemophagocytic syndrome. With only symptomatic treatment the patient's condition and laboratory findings improved during the course of a few days. In accordance with other reported cases, the prognosis of parvovirus B 19 associated hemophagocytic syndrome seems to be better than in hemophagocytic syndrome of other origin.

Child↗

A rapid and safe method to detect fetal parvovirus B19 infection in amniotic fluid by polymerase chain reaction: report of a case.

Molecular amplification of parvovirus B19 DNA in an amniotic fluid sample was used to confirm the etiologic agent of a case with fetal hydrops. The polymerase chain reaction (PCR) method used is easy and fast to perform. We have a 2-year experience on its use in clinical parvovirus B19 diagnosis. The results are available within 1 day of sampling. In addition to strict laboratory standards, the use of two different sets of PCR primers and probes confirms positive findings. Positive parvovirus PCR on amniotic fluid confirms fetal parvovirus infection in cases of fetal nonimmune hydrops. Intrauterine transfusions may be necessary in cases with severe fetal anemia.

Adult↗

Noninvasive diagnosis by Doppler ultrasonography of fetal anemia resulting from parvovirus infection.

OBJECTIVE: The purpose of this study was to evaluate the feasibility of the middle cerebral artery peak systolic velocity for the detection of fetal anemia in pregnancies that are complicated by parvovirus B19 infection. STUDY DESIGN: Doppler measurements of the middle cerebral artery peak systolic velocity were performed weekly in 32 fetuses at risk for anemia because of maternal parvovirus infection documented by the presence of serum immunoglobulin M antibody. The values of the middle cerebral artery peak systolic velocity and hemoglobin were expressed as multiples of the median. These values were plotted on reference ranges that had been established previously. A cordocentesis was performed either because of fetal ascites or when the middle cerebral artery peak systolic velocity values suggested anemia (middle cerebral artery peak systolic velocity, >1.50 multiples of the median). RESULTS: Gestational age at study entry ranged from 15.1 to 37 weeks. There were 17 fetuses with middle cerebral artery peak systolic velocity of >1.50 MoM (group 1). Sixteen cordocenteses were performed in these fetuses. All 16 fetuses were anemic (15 severely and 1 mildly). Thirteen fetuses had signs of hydrops (12 with severe and 1 with mild anemia). Group 2 included 15 fetuses with the middle cerebral artery peak systolic velocity values <1.50 MoM. Two cordocenteses were performed. One fetus was mildly anemic; the second fetus was not anemic. The remaining 13 fetuses of this group did not have any complications and were not anemic at birth. The sensitivity of the middle cerebral artery peak systolic velocity (>1.50 MoM) for the prediction of anemia because of parvovirus infection was 94.1%; the specificity was 93.3 %; the positive and negative predictive values were 94.1% and 93.3%, respectively. CONCLUSION: Fetal anemia caused by parvovirus infection can be detected noninvasively by Doppler ultrasonography on the basis of an increase in the peak velocity of systolic blood flow in the middle cerebral artery.

Anemia↗

Interfacial enzymology of parvovirus phospholipases A2.

The capsid of parvoviruses proteins were recently shown to contain secreted phospholipase A(2) (sPLA(2))-like activity that is required during host cell entry. Parvoviral PLA(2) domains have little sequence identity with sPLA(2)s and lack disulfide bonds. In the present study, after bacterial expression and purification, the biochemical characterizations of these first PLA(2)s identified in viruses have been investigated, and a comparison has been made with other known PLA(2)s. The specific activities of three viral PLA(2)s differed by 3 orders of magnitude, with porcine parvovirus PLA(2) displaying a specific activity similar to that of the most active sPLA(2)s (e.g. human group IIA) and the human AAV2 and B19 parvoviral enzymes displaying approximately 10(3) lower specific activities (similar to human sPLA(2) groups IIE and XIIA). These differences were not caused by weaker Ca(2+) or interfacial binding. The specific activities of the viral PLA(2)s on zwitterionic or anionic phospholipid vesicles were comparable. The viral PLA(2)s did not display a preference for unsaturated versus saturated sn-2 fatty acyl chains and hydrolyzed all major classes of glycero-phospholipids except phosphatidylinositol. Incubation of mammalian cells with porcine parvovirus PLA(2) led to the release of arachidonic acid into the culture medium. Interestingly, among nine previously known sPLA(2) inhibitors, only a subset showed inhibition of the viral PLA(2)s and with weak potency, indicating that the active sites of these new enzymes are structurally distinct from those of sPLA(2)s. Based on these distinct enzymatic and structural properties, we propose to classify the parvovirus PLA(2)s within the PLA(2) superfamily as group XIII enzymes.

Animals↗

Parvovirus B19 in HIV infection: a treatable cause of anemia.

We describe the case of an adult male patient with AIDS who presented with severe anemia and on investigation was found to have red cell aplasia due to parvovirus B19 infection. Bone marrow examination revealed absence of erythroid development and rare giant pronormoblasts. Repeated serological examinations revealed a low level of parvovirus IgM but no IgG. Viremia was demonstrated by electron microscopy and by the polymerase chain reaction (PCR). The patient's initial hemoglobin was 45 g/l and over a four month period he required twenty units of blood. He was treated with intravenous immunoglobulin (Intragam, CSL) at a dose of 400 mg/kg/day for five days. This led to an increase in his hemoglobin to 135 g/l. Parvovirus remained detectable by PCR but not by electron microscopy. Six months later the patient relapsed (Hb 65 g/l). Again he was transfused and treated with intravenous immunoglobulin for five days. His hemoglobin rose to 153 g/l and remained stable. He subsequently received maintenance treatment with 30 g of intagram once a month. We recommend that parvovirus be considered in any HIV infected patient with recurrent anemia.

Adult↗

A case of persistent anemia in a renal transplant recipient: association with parvovirus B19 infection.

We report an unexplained anemia that persisted for 4 months in a renal transplant patient who was receiving immunosuppression therapy that included prednisolone, tacrolimus and azathioprine. A bone marrow biopsy demonstrated pure erythroid hypoplasia and occasional giant pronormoblasts with intranuclear inclusions, characteristic of a parvovirus B19 infection. Both the serum and bone marrow cells were positive by parvovirus B19 DNA PCR. The anemia resolved 6 weeks after the administration of intravenous immunoglobulin (IVIG). Four months later, anemia redeveloped and IVIG was infused again. Hemoglobin levels were, however, still subnormal after 1 month of treatment and tacrolimus was then switched to cyclosporin A, resulting in a clear improvement. A parvovirus B19 infection should be included in the differential diagnosis of renal transplant recipients who present with anemia associated with a low reticulocyte count. Tacrolimus may possibly impair the clearance of a parvovirus B19 infection.

Adolescent↗

Fetal stroke and congenital parvovirus B19 infection complicated by activated protein C resistance.

UNLABELLED: Parvovirus B19 infection in gestation has been associated with severe fetal complications such as anaemia, hydrops and fetal demise. Fetal infection in the first trimester poses the greatest risk for these complications, but infection during the third trimester is more common than previously appreciated and can be associated with severe complications, i.e. fetal death, in the absence of hydrops or classical clinical symptoms. Parvovirus B19 infection has been associated with vasculitis and pathological changes in the central nervous system, which may cause stroke. We report a newborn infant with a rare combination of a recent central nervous system infection with parvovirus B19 and a factor V Leiden mutation, who developed fetal stroke. CONCLUSION: Factor V Leiden mutation leads to activated protein C resistance and increases the risk of thromboembolism. Thromboembolism occurs rarely in newborns with activated protein C resistance, but can be precipitated by dehydration, asphyxia and infection. Although parvovirus B19 infection of the central nervous system may be a precipitant in neonatal and/or fetal stroke, it can also cause stroke independent of a thrombophilic mutation. In this case, both causative factors may have coincided.

Activated Protein C Resistance↗

Quantitative analysis of neutralizing immune responses to human parvovirus B19 using a novel reverse transcriptase-polymerase chain reaction-based assay.

Infection with human parvovirus B19 causes fifth disease, acute and chronic red cell aplasia, fetal hydrops, arthropathy, and other disorders. Antiviral antibodies limit B19 infection in vivo; however, the identification of serologic markers of protection has been hampered by the lack of a quantitative assay for parvovirus neutralization. A novel in vitro test for parvovirus neutralization has been developed using reverse transcriptase-polymerase chain reaction to detect viral transcripts in a B19-permissive cell line. Parvovirus neutralizing activity was measured in sera from naturally infected individuals, and common features of sera with high neutralizing capacity were identified as protection correlates. Sera that suppressed B19 replication in vitro demonstrated IgG reactivity with capsid proteins VP1 and VP2, but no linear relationship between antibody titer and neutralizing capacity was observed. Sera from experimental animals and human volunteers immunized with a virus-like particle vaccine candidate exhibited B19 neutralizing titers equal to or greater than those observed in natural infections.

Animals↗

Successful intravenous immunoglobulin therapy in 3 cases of parvovirus B19-associated chronic fatigue syndrome.

Three cases of chronic fatigue syndrome (CFS) that followed acute parvovirus B19 infection were treated with a 5-day course of intravenous immunoglobulin (IVIG; 400 mg/kg per day), the only specific treatment for parvovirus B19 infection. We examined the influence of IVIG treatment on the production of cytokines and chemokines in individuals with CFS due to parvovirus B19. IVIG therapy led to clearance of parvovirus B19 viremia, resolution of symptoms, and improvement in physical and functional ability in all patients, as well as resolution of cytokine dysregulation.

Adult↗

Recurrent erythema in patients with long-term parvovirus B19 infection.

We describe 3 patients with long-term parvovirus B19 infection (defined as detectable parvovirus B19 DNA load for >6 months after the onset of symptoms), which we monitored by serial testing for parvovirus B19 load and the presence of parvovirus B19-specific antibodies in blood. The patients showed recurrent erythema at intervals of several months.

Adult↗

Papular-purpuric gloves and socks syndrome associated with acute parvovirus B19 infection: case report and review.

The papular-purpuric gloves and socks syndrome (PPGSS) was first described in 1990. This syndrome is characterized by fever, acral pruritus, edema, petechiae, and oral erosions. Subsequently, parvovirus B19 has been implicated, in most cases, as the causative agent of this syndrome. To date, with two exceptions, all published cases of PPGSS have been from Europe and the Middle East and have been mainly reported in the dermatology literature. Herein, we report what we believe to be only the second case of documented parvovirus B19-associated PPGSS occurring in the United States. The patient presented with the typical clinical syndrome, and the diagnosis of acute parvovirus B19 infection was documented by serial serologies that demonstrated development of IgM antibody to virus during the acute phase of infection and seroconversion to IgG antibody in the convalescent period. We then review the existing literature on this unusual syndrome and its association with parvovirus B19.

Acute Disease↗

Life-threatening parvovirus B19-associated myocarditis and cardiac transplantation as possible therapy: two case reports.

Parvovirus B19 infection can cause a wide spectrum of disease syndromes. Two cases of parvovirus B19 infection were identified that resulted in life-threatening myocarditis shortly after acute infection in immunocompetent individuals. The diagnosis was made with serological and polymerase chain reaction techniques. One patient was successfully treated by heart transplantation. Sequence analysis showed that the parvovirus B19 cloned from the patients' sera had 99% homology with the prototype sequence. Clinicians should be alerted to the possible role of parvovirus B19 in myocarditis presenting in immunocompetent patients.

Adolescent↗

Juvenile dermatomyositis in a child infected with human parvovirus B19.

We report a case of juvenile dermatomyositis in which clinical onset occurred soon after infection with human parvovirus B19. To the best of our knowledge an association between juvenile dermatomyositis and human parvovirus B19 has not been previously reported. Parvovirus infection has been associated with several autoimmune diseases, and the findings in the case we describe raise the possibility that parvovirus may induce juvenile dermatomyositis, although we could not demonstrate a causal relationship.

Anti-Inflammatory Agents↗

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↗

Accurate serodiagnosis of B19 parvovirus infections by measurement of IgG avidity.

In an attempt to improve diagnosis of illnesses caused by parvovirus B19 and to discriminate primary from secondary infections, a protein-denaturing assay for avidity of parvovirus-specific IgG antibodies was developed. The assay used three types of purified recombinant antigens: a fusion protein containing the unique portion of the structural protein VP1, entire capsids made up of the major structural protein VP2 alone, or VP2 plus VP1. The avidity assays were evaluated by testing sequential acute-phase serum samples from 61 well-characterized patients (34 were followed > or = 6 months), sera from 38 controls with evidence of past infection, and sera from 388 seropositive patients studied for evidence of B19 infection during an epidemic. Parvovirus capsids consisting of VP2 alone yielded unusual IgG avidity and IgG antibody responses. Three different IgG avidity assays based on VP1 protein antigens were highly sensitive and specific and were considered suitable for identification of recent primary infections by human parvovirus B19.

Antibodies, Viral↗