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Recombinant bactericidal/permeability-increasing protein (rBPI21) for treatment of parvovirus enteritis: a randomized, double-blinded, placebo-controlled trial.

We evaluated the ability of an antimicrobial and endotoxin-neutralizing agent, the recombinant amino terminal fragment of bactericidal permeability-increasing protein (rBPI21), to decrease plasma endotoxin concentration and severity of clinical signs of canine parvovirus and to improve survival. This randomized, double-blinded, placebo-controlled clinical trial included 40 client-owned dogs and 9 normal puppies from a closed research colony. Dogs weighing >5 kg (11 lb) with fecal antigen-confirmed parvovirus and clinical signs of vomiting and diarrhea were randomly assigned to receive placebo or rBPI21 infusion over 6 hours. Plasma endotoxin concentration was measured at 0, 3, and 6 hours of infusion. Owners chose continued medical care with either the Veterinary Hospital of the University of Pennsylvania Internal Medicine Service or a local veterinarian. Telephone follow-up was conducted at 14 days. Surviving dogs were reevaluated at >30 days (recovered group), at which time plasma samples for measurement of endotoxin concentration were obtained. Plasma endotoxin concentrations were significantly higher in dogs with parvovirus than in normal or recovered dogs. Despite 90% survival, the rBPI21 treatment did not have a significant effect on outcome, duration of hospitalization, or plasma endotoxin concentrations. Treatment in a tertiary care hospital, however, significantly improved survival but resulted in a significantly increased duration of hospitalization. Endotoxemia occurs in dogs with parvovirus enteritis, but rBPI21 is not associated with improved survival.

Animals↗

Clinical and epidemiological aspects of human parvovirus B19 infection in an urban area in Brazil (Niterói city area, State of Rio de Janeiro, Brazil).

This study was designed to analyse the clinical and epidemiological data from human parvovirus B19 cases in a six-year study of rash diseases conduct in an urban area in Brazil (Niterói city area, State of Rio de Janeiro). A total of 673 patients with acute rash diseases were seen at two primary health care units and at a general hospital. A clotted blood sample was collected from all subjects at the time of consultation. Forty-nine per cent (330 cases) of the patients were negative for dengue, rubella and measles IgM or for low avidity IgG to HHV-6. Of these 330, 105 (31.8%) were identified as IgM positive to parvovirus B19 by using an antibody capture EIA. During the study period, three distinct peaks of parvovirus infection were detected, suggesting that the disease appears to cycle in approximately 4-5 years. B19 infection was characterized by variable combinations of fever, flu-like symptoms, arthropathy, and gastrointestinal symptoms. Frequency of fever and arthropathy was substantially higher in adults, 75% [chi2 (1 D.F.) = 11.39, p = 0.0007] and 62.5% [chi2 (1 D.F.) = 29.89, p = 0.0000], respectively. "Slapped-cheek" appearance and reticular or lace-like rash were seen in only 30.1% of the children. No adult presented this typical rash. The lack of the typical rash pattern in a large proportion of parvovirus B19 and the similarity of clinical manifestations to other rash diseases, specially to rubella, highlight the difficulty of diagnosing B19 infection on clinical grounds alone.

Adolescent↗

The association of pityriasis rosea with cytomegalovirus, Epstein-Barr virus and parvovirus B19 infections - a prospective case control study by polymerase chain reaction and serology.

A viral aetiology is suspected for pityriasis rosea (PR). The objective was to investigate the association of PR with cytomegalovirus (CMV), Epstein Barr virus (EBV) and parvovirus B19 infections. Patients with PR were recruited in a primary care setting over 18 months. Blood was collected at initial presentation and four weeks later. Controls were the next age-and-sex-matched patients requiring blood collection for non-dermatological disease. Polymerase chain reaction was performed for EBV and parvovirus B19 DNA. Serology was done for CMV, EBV and parvovirus B19. 12 patients with PR and 12 control subjects were recruited. No patient had viral DNA or significant antibody rise against any of the viruses investigated. The seroprevalence of all three viruses and Ab titres in the patients with PR were insignificantly different from those of control subjects. Two patients had IgM detectable against CMV and EBV respectively. Based on other investigation results, we believe that both IgM results were caused by cross reactivity. PR is not associated with CMV, EBV or parvovirus B19 infections.

Adolescent↗

The presence of parvovirus B19 VP and NS1 genes in the synovium is not correlated with rheumatoid arthritis.

OBJECTIVE: To amplify both NS1 and VP genes of Parvovirus B19 DNA in synovial membrane (SM) and serum obtained from patients with rheumatoid arthritis (RA) and to analyze whether the presence of viral DNA is correlated with synovitis. METHODS: DNA obtained from 30 SM and 24 serum samples from RA patients was analyzed using single round-polymerase chain reaction (PCR) and nested PCR for both VP and NS1 genes of parvovirus B19. Twenty-four SM and serum samples from sex and age matched subjects with osteoarthritis (OA) or joint trauma served as controls. RESULTS: The first round PCR was negative for NS1 in RA samples. After nested PCR, NS1 was detected in the SM of 6/30 patients and of 10/24 controls and in the serum of 4/24 patients and controls. Nested PCR for the VP gene detected viral DNA in the SM of 7/30 patients with RA and of 7/24 of the controls and in the serum of 5/24 patients and of 2/24 controls. Altogether parvovirus DNA was found in the SM of 11/30 (36.6%) patients and of 12/24 (50%) controls and in the serum of 8/24 (33.3%) patients with RA and of 5/24 (20.8%) controls. CONCLUSION: Our results suggest that the amplification by nested PCR of both NS1 and VP genes is necessary to define the presence of viral DNA in tissue samples and confirm that the presence of parvovirus B19 DNA is similar in RA and control SM, suggesting that simple detection of viral DNA is not sufficient to confirm a link between the virus and RA.

Adult↗

[Exanthematous outbreak caused by human parvovirus B19 in a school in Banderaló, Argentina].

We report an exanthematic outbreak in a school of Banderaló town, located in the district of General Villegas, Buenos Aires province, Argentina. This outbreak affected 21 individuals, with a wide range of age (out of a total population of 1400). The observed clinical manifestations were exanthema and in some cases fever, asthenia, arthropathies and myalgia. The presence of specific IgM antibodies against measles, rubella and human parvovirus B19 were investigated. Analysis of IgM antibodies to parvovirus B19 by ELISA was positive in 90.8% of the cases and viremia was detected in 66.7% of the patients by nested PCR. These results indicate that human parvovirus B19 was the etiologic agent of the outbreak and they confirm its circulation in Argentina. Moreover, this study demonstrates that PCR may be useful for the study of transmission foci and of individuals with prolongued clinical manifestations. We consider that it is necessary to include the differential diagnosis of human parvovirus B19 in the surveillance of exanthematic virosis.

Adolescent↗

Polymyalgia rheumatica is not seasonal in pattern and is unrelated to parvovirus b19 infection.

OBJECTIVE: To prospectively analyze seasonal distribution in the onset of symptoms of polymyalgia rheumatica (PMR) and its relationship to parvovirus B19 infection. METHODS: Over a 4-year period (September 1997 to September 2001), 68 patients were prospectively diagnosed with PMR in an outpatient rheumatology department, of which only 55 patients (38 women, 17 men) aged 50 to 90 years (mean 74.1 +/- 8.1) were able to specify the month of onset of symptoms. During the last year parvovirus B19 IgM serologies were determined in all new cases. RESULTS: No significant seasonal variation in disease onset was observed during the 4-year period; 17 cases were observed in spring, 10 in summer, 15 in autumn, and 13 in winter (p = 0.625). Nevertheless, almost 50% of all cases of PMR were diagnosed in the months of May, February, and August. All of the evaluated patients (14 of 14) had negative parvovirus B19 IgM serologies. CONCLUSION: Onset of symptoms in PMR is unrelated to seasonal pattern. Yet almost 50% of cases occurred in the months of May, February, and August. Parvovirus B19 infection was unrelated to the onset of PMR.

Aged↗

[Detection of human parvovirus B19 nonstructural protein DNA by nested- polymerase chain reaction in pregnant women].

OBJECTIVE: To explore the sensitivity and specificity of the new nested-polymerase chain reaction (nested-PCR) assay in the detection of human parvovirus B19 (HPV B19) nonstructural protein DNA and the applicability of this technique in detecting the gravida infected with parvovirus B19. METHODS: Evaluating the new nested-polymerase chain reaction assay by routine process, and compared with the general nested-PCR in detecting structural protein DNA. Then, the two techniques were used to detect human parvovirus B19 structural protein and nonstructural protein DNA in gravida serum and pregnant tissue of 30 cases. RESULTS: The sensitivity of the new method was 0.005 fg which was similar to the general nested-polymerase chain reaction assay, and the detection results of other viruses and human genome DNA were all negative. The positive rates of structural protein DNA and nonstructural protein DNA in gravida sera were 26.7% and 33.3%, respectively. And the difference was non significant in statistics. At the same time, both of these two positive rates in placenta and villus were 26.7%. CONCLUSIONS: The new nested-polymerase chain reaction assay was a sensitive, specific and convenient method in detecting human parvovirus B19 infection, and the detection of nonstructural protein DNA paves the way for the following study on the disease mechanisms of B19.

Female↗

[Tubulointerstitial nephritis associated with parvovirus beta19 infection].

A previously healthy 9 year old girl developed nephrotic syndrome with hypertension, microhematuria and normal renal function. The patient evolved as steroid resistant nephrotic syndrome whose initial renal biopsy was consistent with diffuse proliferative mesangial glomerulonephritis with focal segmental glomerulosclerosis. At the time of cyclophosphamide and prednisone treatment, she developed a prolonged febrile syndrome. She also had severe anemia following an aplastic crisis induced by human parvovirus B19 infection and acute renal failure secondary to a severe tubulointersticial disease. Bone marrow and renal tissue, tested by polimerase chain reaction were positive for parvovirus, while the patient's blood was negative. The renal involvement did not improve requiring chronic dialysis support. We believe that the initial glomerular disease could have been due to a parvovirus infection followed by un unexpected acute tubular interstitial nephritis, rapidly progressing to chronic renal disease. This case represents, to our knowledge, the first time that a direct relationship between parvovirus infection and acute tubulointerstitial disease has been demonstrated.

Biopsy↗

Erythema infectiosum following generalized petechial eruption induced by human parvovirus B19.

Parvovirus B19 is a DNA virus responsible for a wide spectrum of clinical illnesses. Among dermatological manifestations, the most common is erythema infectiosum, also known as the fifth disease. In 1990 Harms et al first described a papular-purpuric gloves and socks syndrome (PPGSS) due to parvovirus B19. It is an acute acral dermatosis characterized by an eruption of petechiae and small purpuric papules affecting the hands and feet in a gloves-and-socks distribution. Recently it was observed that PPGSS may be associated with involvement of the peri-oral region and the chin (acropetechial syndrome) and other sites provoking unusual presentation of the rash. We describe a patient with an acral purpura with the features of the "acropetechial syndrome" involving the buttocks, genital and axillary regions who subsequently developed a maculopapular eruption with the characteristics of the fifth disease. Parvovirus B19 DNA was detected by polymerase chain reaction (PCR) both in skin vasculitic lesions and in the serum during the petechial eruption, before the onset of antibodies. The immune response coincided with the development of the exanthem, suggesting a direct role of parvovirus B19 in the pathogenesis of endothelial cell injury.

Adult↗

[Aplastic crisis caused by Parvovirus B-19. Response to treatment with low doses of gammaglobulin].

BACKGROUND: Parvovirus B19 is the etiologic agent of transient aplastic crisis, an acute episode of bone marrow failure in persons with underlying hemolysis. Successful administration of gammaglobulin in some chronic cases and immunocompromised patients infected with parvovirus B-19, resulting in the elimination of this virus has been reported. However little is known about the evolution of acute aplastic crisis in treated patients with chronic hemolysis nor about the minimal effective dose of immunoglobulin. METHODS: We report a family infected by Parvovirus B 19, discovered when a pure red blood-cell aplasia broke out in one family member who was suffering from a chronic haemolytic disease. The diagnosis was considered by presence of giant proerythroblasts in bone marrow and later confirmed by DNA viral detection using PCR technique. RESULTS: The patient was treated with a small dose of polivalent intravenous gammaglobulin, with a temporary disappearance of the virus from his serum during treatment. CONCLUSION: The usefulness, doses and length of immunoglobulin treatment in patients with transient aplastic crisis is discussed. Our results show that treatment with low doses of I.V. gammaglobulin able to control viremia and probably shorten the episode of anemia and acute aplastic crisis in this patient with chronic hemolytic anemia and parvovirus B-19 infection. This observation could be useful and cost saving also in chronic cases and in immunocompromised.

Adolescent↗

In vitro erythroid effects of human stem cell factor in a case of human immunodeficiency virus-related chronic parvovirus B19 induced anemia.

Chronic B19 parvovirus infection in patients infected with human immunodeficiency virus type 1 (HIV-1) is one cause of reversible anemia in this patient group. This report describes a case of concurrent HIV-1 and B19 parvovirus infection with pure red cell aplasia in which the anemia resolved with gammaglobulin treatment. When cultured in vitro with recombinant human stem cell factor, the red blood cell precursors from this patient demonstrated increases in both number and size, suggesting that simultaneous infection with B19 parvovirus and HIV-1 does not preclude a response to erythroid-acting growth factors. Although rare, persistent B19 parvovirus infection has become an increasingly recognized treatable cause of anemia in HIV-infected patients. Further in vitro and in vivo studies are required to determine whether cytokines such as stem cell factor have a consistent effect in these anemic states.

AIDS-Related Complex↗

[Parvovirus B19-induced arthritis/arthropathy--an important differential diagnosis of chronic polyarthritis].

INTRODUCTION/AIMS: The differential diagnosis of rheumatoid arthritis (RA) and parvovirus-B19-induced arthritis/arthropathy (PBA) can be difficult, but is of importance because of the different therapeutic implications. The purpose is to describe characteristic features serving to differentiate between chronic PBA and RA, based on 6 personal cases and the literature. METHODS/PATIENTS: 6 patients presenting with acute (3 cases) or chronic PBA (3 cases) over the last 5 years are described. RESULTS/CONCLUSIONS: The demonstration of anti-parvovirus-B19-immunoglobulins (Ig)M in addition to anti-parvovirus-B19-IgG is the most important diagnostic finding. Measurement of IgM must be done within the first months after onset, as it disappears later on. Furthermore, history of disease (exposure, prodromi and acute onset of arthritis), clinical examination (rash) and further investigations (normal ESR and CRP, typical hematologic findings, examination of synovial tissue and fluid without inflammatory changes, demonstration of the genome of parvovirus B19 by polymerase chain reaction, no erosions on radiographs) support the diagnosis of PBA. 2 of the 3 patients with chronic PBA fulfilled the criteria for classification of RA. Therapeutic approaches in PBA are discussed. In contrast to the favourable effect in RA, immunosuppressive agents may prolong persistence of virus and disease in PBA.

Adult↗

[Laboratory diagnosis of parvovirus B 19 infection: comparison of ten commercial IgG- and IgM-antibody tests].

Seven ELISAs, two westernblots and one immunofluorescence assay for serological detection of parvovirus-B19-infection were compared with regard to their sensitivity and specificity. All ten assays are commercially available and use recombinant proteins (VP1, VP2) from bacterial and eukaryotic expression systems and synthetic viral peptides as antigens. The ELISA assays comprise indirect ELISA and mu-capture systems. All assays were tested for their sensitivity with follow-up sera from 21 patients with acute parvovirus B19 infections. The specificity was analysed by 194 sera from pregnant women and from patients with acute other virus infections or rheumatoid factors, but without acute parvovirus infection. Only three ELISAs, both westernblots and the immunofluorescence assay can be recommended for the IgG-measuring (prevalence). For the detection of an acute parvovirus infection, especially during pregnancy, two ELISAs show good IgG- and IgM-results, one ELISA is less recommendable and all other assays show only a poor IgM-specificity.

Antibodies, Viral↗

[Detection by PCR of genomic markers in canine parvovirus and feline panleukopenia virus].

The NS1 and VP1/VP2 genes of canine parvovirus and feline panleukopenia virus were amplified by the polymerase chain reaction (PCR). The restriction cleavage patterns of the amplified DNA fragments were compared among these parvoviruses including vaccine strains. Differences of the restriction site in the NS1 portions were observed between the vaccine strain and the wild type strain as well as between canine parvoviruses and feline panleukopenia viruses. The restriction patterns of feline panleukopenia viruses were distinct from those of canine parvoviruses, and showed differences between the vaccine strain and its wild type strain. This PCR-based restriction cleavage can be used for ecological study of such viruses.

Feline Panleukopenia Virus↗

[Description of 31 pediatric cases of infection caused by human Parvovirus B 19].

FUNDAMENTALS: [corrected] Human Parvovirus B19 has been identified as the etiological agent implicated in several clinical forms of disease. The aim of this study was to define the clinical aspects observed in the children with human parvovirus infection in our hospital. METHODS: A retrospective study was done in 31 pediatric cases observed in our hospital from January-92 to July-94; all had positive IgM against Parvovirus (determined by enzymoinmunoanalysis). RESULTS: The most frequent signs and symptoms were fever in 66.6% of the cases and skin findings in 48%, manifested as typical infectious erythema in 26% and polimorphic nonspecific exanthema in the rest. There were variable blood manifestations, observed in 11 children (35%): Immune Thrombocytopenic purpura, Chronic anemia in immunocompromised hosts, bone marrow erithrophagocytosis and hemolytic crises in non-hemolytic anemia patients. The abnormal blood findings were mostly observed in children with compromised immunity. Articular disease was presented in four children (12%). Long lasting fever was observed in only one case. CONCLUSIONS: In our sample the diversity of clinical forms of presentation of Parvovirus B19 infection is well documented as it is reported by several authors. Although other studies as polymerase chain reaction (PCR), nucleic acid hybridization, direct visualization of the virus or its particles, or viral antigen detection are desirable to confirm the serologic studies.

Adolescent↗

[Evolution of canine parvovirus: loss and gain of the feline host].

Canine parvovirus is a newly emerged virus that was first isolated in 1978. As with all new viruses CPV continues to show active evolution, demonstrated by the appearance of new antigenic types. These new types termed CPV-2a and CPV-2b have replaced the original type CPV-2 throughout the world. The reason for the evolutionary advantage of the new viruses was most likely the acquisition of a new host, the cat. The new types are in contrast to CPV-2 able to infect and replicate in cats. Interestingly, about 10 per cent of the parvovirus isolates made from routine diagnostic cat materials were found to be canine parvovirus type 2a or 2b. The relevance of these findings for the epizootiology of parvovirus infection of dogs and cats and also for the vaccination are discussed.

Animals↗

Parvovirus B19 infection in a liver transplant recipient: case report and review in organ transplant recipients.

We report an adult liver transplant recipient with parvovirus B19 infection, presenting as chronic transfusion-dependent anemia ensuing 1 month post-transplantation. Both serum and bone marrow cells were positive for parvovirus B19 DNA detected by polymerase chain reaction. The bone marrow biopsy revealed erythroid hypoplasia with a selective decrease of nucleated red cell precursors, and giant pronormoblasts with prominent intranuclear inclusions, characteristic of parvovirus B19 infection. Anemia and viremia resolved shortly after administration of immunoglobulin, suggesting a therapeutic role. This case and several similar ones in the literature provide justification for a controlled clinical trial of immunoglobulin for parvovirus-induced anemia in transplant recipients.

Adult↗

Constitutive activation of U937 promonocytic cell clones selected for their resistance to parvovirus H-1 infection.

The human promonocytic cell line U937 is highly sensitive to the lytic effect of the autonomous parvovirus H-1. Rare cell variants that resisted H-1 virus infection could be isolated, of which four (RU1, RU2, RU3, and RU4) were further characterized. In contrast to parental cells, the RU clones sustained an abortive H-1 virus infection. Three of the clones showed a significant decrease in the accumulation levels of the c-Myc oncoprotein and in their capacity for forming tumors in immunodeficient mice. Surprisingly, all RU clones resisted the suppressing effect of 12-O-tetradecanoylphorbol-13-acetate (TPA) on c-myc oncogene expression and cell proliferation. In contrast, RU clones exhibited the TPA-induced changes in membrane surface antigens and nonspecific esterase activities that are characteristic of monocytic differentiation. Studies of the activation steady-state of RU cells demonstrated the constitutive production of significant amounts of nitric oxide (NO) and superoxide anion (O-.2). Inhibitors of NO and O-.2, production sensitized all RU cells to the killing effect of parvovirus H-1 and increased the production of infectious viral particles. These data argue for the participation of active oxygen species in macrophage defence mechanisms against parvovirus infection. Moreover, the use of parvovirus H-1 as a selective agent in a cell-colony formation assay allowed us to show that expression of defined markers of monocytic differentiation can be uncoupled from suppression of proliferation.

Animals↗