RESUMO
Glomerulonephritis with proteinuria of sufficient degree to manifest the nephrotic syndrome followed aplastic crises induced by human parvovirus (B19) in seven patients with homozygous sickle-cell disease, within 7 days in five patients and 6-7 weeks in two. Segmental proliferative glomerulonephritis was found in all four patients who underwent acute renal biopsies and focal segmental glomerulosclerosis was found in the fifth patient who had a biopsy 4 months later. One patient recovered completely, one died in chronic renal failure after 3 months, and the others had impaired creatinine clearance, four with continuing proteinuria.
Assuntos
Anemia Falciforme/genética , Eritema Infeccioso/complicações , Glomerulosclerose Segmentar e Focal/etiologia , Adolescente , Adulto , Anemia Falciforme/complicações , Anticorpos Antivirais/análise , Biópsia , Criança , DNA Viral/análise , Feminino , Glomerulosclerose Segmentar e Focal/patologia , Homozigoto , Humanos , Rim/patologia , Masculino , Síndrome Nefrótica/etiologia , Parvovirus B19 Humano/genética , Parvovirus B19 Humano/imunologia , Proteinúria/etiologiaRESUMO
We studied the epidemiology of human parvovirus B19 infection in 308 children with homozygous sickle cell (SS) disease and 239 controls with a normal haemoglobin (AA) genotype followed from birth in a cohort study. Annual serum samples identified the time and frequency of B19 infection, which did not differ between SS and AA children, about 40% of each group developing specific IgG by age 15. B19 infection followed an epidemic pattern similar to that observed for aplastic crises; accounted for all 91 aplastic crises that occurred; and was found in an additional 23 SS patients, of whom 10 showed mild haematological changes and 13 no changes. The magnitude or duration of IgG response did not differ between these groups. No patient had 2 attacks of aplasia and no patient nor control had 2 attacks of B19 infection. Following B19 infection, serial specific IgG concentrations remained high after 5 years in only 45% of SS patients, although the rarity of recurrent aplasia suggests lifelong immunity. B19 infection accounts for most if not all aplastic crises in SS disease, but at least 20% of infections do not result in aplasia. An effective vaccine against B19 might make an important contribution to the management of sickle cell disease.
Assuntos
Anemia Aplástica/etiologia , Anemia Falciforme/complicações , Eritema Infeccioso/complicações , Adolescente , Anemia Aplástica/epidemiologia , Anemia Aplástica/imunologia , Criança , Pré-Escolar , Estudos de Coortes , Eritema Infeccioso/epidemiologia , Eritema Infeccioso/imunologia , Seguimentos , Genótipo , Hemoglobinas/genética , Humanos , Imunoglobulina G/análise , Incidência , Lactente , Recém-Nascido , Índias Ocidentais/epidemiologiaRESUMO
The presence of B19 parvovirus in plasma from blood donors is seldom demonstrable, but clotting factor concentrates, prepared from large plasma pools, may be able to transmit B19 virus infection, and the effectiveness of different chemical and physical treatment to inactivate this virus is not yet known. In this study we report on the detection of B19 DNA in 25 clotting factor concentrates, prepared by a variety of procedures of purification and inactivation; dot blot hybridization and Southern blot hybridization assays, as well as a 'nested' polymerase chain reaction (PCR) have been employed. Nine out of 25 products were B19 DNA positive by PCR, whereas only two gave positive results by hybridization techniques. B19 DNA positive concentrates have been found in 'untreated' products but also in some solvent/detergent or steam-treated products and even in monoclonal purified concentrates. PCR may be useful for the screening of blood products to be used in immunocompromised haemophiliacs, particularly in HIV positive subjects, at risk of severe chronic anaemia following B19 infection.
Assuntos
Fatores de Coagulação Sanguínea/genética , DNA Viral/genética , Parvovirus B19 Humano/genética , Parvovirus B19 Humano/isolamento & purificação , Sequência de Bases , Southern Blotting , DNA Viral/análise , Eritema Infeccioso/genética , Humanos , Dados de Sequência Molecular , Reação em Cadeia da PolimeraseRESUMO
The seroprevalence of antibodies against parvovirus B19 in 308 Norwegians with coagulation factor defects of different types and severities was assessed by an IgG antibody capture radioimmunoassay (GACRIA). The overall seroprevalence was 62%. The seroprevalence among subjects with different types of coagulation factor defects was related to the type and severity of the coagulation factor defect: severe hemophilia A 64%, moderate and mild hemophilia A 58%, severe hemophilia B 88%, moderate and mild hemophilia B 73%, and von Willebrand's disease 52%. The prevalence of parvovirus B19 antibodies among household contacts and blood donors was 49% and 42% respectively. This study confirms that replacement therapy with coagulation factors is accompanied by an increased risk for acquiring parvovirus B19 infection. However, the prevalence of parvovirus B19 antibodies among Norwegian hemophiliacs is well below the prevalence reported from other countries and probably reflects the small numbers of donors in plasma pools used for the preparation of coagulation factor concentrates.
Assuntos
Anticorpos Antivirais/sangue , Produtos Biológicos/uso terapêutico , Transtornos da Coagulação Sanguínea/complicações , Eritema Infeccioso/etiologia , Parvovirus B19 Humano/imunologia , Adulto , Fatores Etários , Produtos Biológicos/efeitos adversos , Transtornos da Coagulação Sanguínea/congênito , Transtornos da Coagulação Sanguínea/terapia , Eritema Infeccioso/epidemiologia , Hemofilia A/complicações , Hemofilia A/terapia , Hemofilia B/complicações , Hemofilia B/terapia , Humanos , Noruega/epidemiologia , Prevalência , Viremia/etiologia , Doenças de von Willebrand/complicações , Doenças de von Willebrand/terapiaRESUMO
We have expressed a number of polypeptides derived from the capsid proteins of the human parvovirus B19 in Escherichia coli. These include native VP1 (84K) and VP2 (58K) proteins and also fusions to beta-galactosidase containing differing amounts of the amino terminus of the VP1/2 polypeptide. Although each of these was expressed at high levels and the majority were produced as full-length proteins, only one was soluble. This soluble polypeptide, p132, is a beta-galactosidase fusion protein that includes 145 amino acids from B19 which are entirely derived from the region unique to VP1. Despite containing such a small portion of VP1, which itself constitutes only 4% of total capsid protein, p132 reacted with all our known anti-B19 IgM-positive human serum samples. We conclude that this region contains epitopes which must be prominently exposed on the intact virus. We have demonstrated the use of this recombinant antigen in a simple diagnostic assay for B19-specific antibodies which can be used for initial screening of human serum samples. In a survey of 103 serum specimens, our ELISA positively identified all samples (19/19) which were positive by IgM antibody capture radioimmunoassay. The recombinant p132 antigen is efficiently produced and readily purified from E. coli, and its use as a diagnostic antigen should increase the availability of routine clinical testing for human parvovirus infection.
Assuntos
Antígenos Virais/imunologia , Capsídeo/genética , Escherichia coli/genética , Parvoviridae/metabolismo , Sequência de Bases , Capsídeo/imunologia , Proteínas do Capsídeo , Clonagem Molecular , Reações Cruzadas , Ensaio de Imunoadsorção Enzimática , Epitopos , Humanos , Imunoglobulina M/imunologia , Óperon Lac , Dados de Sequência Molecular , Parvoviridae/genética , Parvoviridae/imunologia , Plasmídeos , Proteínas Recombinantes/imunologia , beta-Galactosidase/genéticaRESUMO
B19 virus infection is common in the population and is frequently asymptomatic. However, a viraemia and prompt antibody response occurs in normal individuals and this is associated with mild, non-specific respiratory tract symptoms at the time of the viraemia and/or a rash-illness a week or ten days later. Infection of red cell precursors is a regular occurrence and this leads to aplastic crisis if B19 virus infection occurs in an individual with chronic heamolytic anaemia. Fetal infection sometimes takes place if infection occurs during pregnancy and some fetuses fail to clear the infection, develop anaemia leading to heart failure and hydrops fetalis. Some immunocompromised patients also fail to clear the viraemia and this results in a persistent or relapsing anaemia.
Assuntos
Infecções por Parvoviridae/fisiopatologia , Feminino , Doenças Fetais/fisiopatologia , Humanos , Hidropisia Fetal/fisiopatologia , Infecções por Parvoviridae/etiologia , GravidezRESUMO
Methods were established for the detection of parvovirus DNA in human serum using single-stranded RNA probes. The sensitivity of detection of virus using 32P-radiolabelled RNA versus non-radiolabelled biotinylated RNA probes using a streptavidin-polyalkaline phosphatase detection system was compared. Virus was detected using 32P-labelled and biotinylated RNA probes at serum dilutions of 10(-3), equivalent to approx. 3 pg of viral DNA. Using biotinylated RNA probes and a dot-blot system, diagnosis of numerous serum samples could be performed within 8 h of receipt of samples, using an RNA probe which was synthesised and stored at -20 degrees C for up to 12 months without loss of sensitivity. Our work demonstrates the potential of biotinylated RNA probes in the routine analysis of viral sequences in serum.
Assuntos
DNA Viral/sangue , Infecções por Parvoviridae/diagnóstico , Parvoviridae/isolamento & purificação , Humanos , Hibridização de Ácido Nucleico , Infecções por Parvoviridae/sangue , Infecções por Parvoviridae/microbiologia , RNA ViralRESUMO
Infection of normal individuals with human parvovirus (B19) results in a mild disease (erythema infectiosum) but gives rise to aplastic crises in patients with chronic hemolytic anemias. The effects of this disease on hemopoiesis were investigated following intranasal inoculation of the virus into three volunteers. A typical disease ensued with a viremia peaking at 9 d. Marrow morphology 6 d after inoculation appeared normal but at 10 d there was a severe loss of erythroid precursors followed by a 1-2-g drop in hemoglobin, and an increase in serum immunoreactive erythropoietin. Erythroid burst-forming units (BFU-E) from the peripheral blood were considerably reduced, starting at the time of viremia and persisting for 4-8 d depending on the individual. Granulocyte-macrophage colony-forming units (CFU-GM) were also affected but the loss started 2 d later. Both CFU-GM and BFU-E showed a sharp overshoot at recovery. In the marrow, BFU-E and CFU-E were reduced at 6 and 10 d in the individual having the longest period of peripheral progenitor loss. In contrast, there was an increase in BFU-E and CFU-E in the subject with least change in peripheral progenitors. In the third subject, with an intermediate picture, there was a loss at 6 d but an increase at 10 d of erythroid progenitors. It is suggested that the architecture of the marrow might partially isolate progenitors from high titers of virus in the serum and individual variation in this respect might give the results observed.
Assuntos
Células da Medula Óssea , Eritroblastos/microbiologia , Células-Tronco Hematopoéticas/microbiologia , Parvoviridae , Adulto , Ensaio de Unidades Formadoras de Colônias , Eritropoetina , Humanos , Masculino , Infecções por Parvoviridae/sangueRESUMO
B19 virus is the first human virus to be shown to be a member of the parvovirus genus. This review is concerned with the diseases associated with B19 virus, their nature, pathogenesis and diagnosis. The virus was discovered by chance in blood donors but has been shown to be a common infection of childhood. Infection may be asymptomatic or associated with mild, non-specific symptoms. The most common specific clinical manifestation is an erythematous rash illness which often has the classical features of erythema infectiosum. Often, however, it is described simply as rubelliform and only laboratory tests can distinguish B19 and rubella virus infections. Joint involvement is the most common complication of B19 virus infection occurring especially in adult females. It often involves the joints of the hands and wrists, clears rapidly in most patients but may persist for months or years in a few. B19 virus is also the principle cause of the transient aplastic crisis which complicates chronic haemolytic anaemia. This has been demonstrated repeatedly in sickle cell anaemia and hereditary spherocytosis and in individual cases of other haemolytic anaemias. The pathogenesis of the aplastic crisis is related to the ability of B19 virus to infect and damage early erythroid progenitor cells. Volunteer studies in normal individuals have demonstrated that this is a regular event occurring about a week after infection via the respiratory tract. Rash illness and joint involvement occur 7 to 10 days later and are presumably immune mediated. Diagnosis of B19 virus infection can be achieved by detection of the viraemia (aplastic crisis) or by detection of virus specific IgM antibody (all diseases).(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Infecções por Parvoviridae/etiologia , Humanos , Parvoviridae/patogenicidade , Infecções por Parvoviridae/diagnósticoRESUMO
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.
Assuntos
Infecções por Parvoviridae/etiologia , Anemia Hemolítica/complicações , Feminino , Hemoglobinas/análise , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Parvoviridae/isolamento & purificação , Infecções por Parvoviridae/sangue , Infecções por Parvoviridae/complicações , Contagem de Plaquetas , Reticulócitos , Fatores de Tempo , Viremia/etiologiaRESUMO
Mice from lines genetically selected for the production of either high or low affinity antibody to protein antigens and which differ in their susceptibility to chronic immune complex disease were infected with Trypanosoma musculi. The parasite became patent in both lines by day 5 and no significant differences in the levels of parasites during the infection were observed between the two lines. Serum levels of both antigen non-specific and T. musculi antigen specific immune complexes were determined during the infection by the solid phase conglutinin and Clq binding assays. In both lines, antigen non-specific complexes were detected by day 15 after infection with maximum levels observed by day 30. At this time, low affinity line mice had significantly higher levels than did high line mice as determined by the Clq assay but not by the conglutinin assay. The deposition of immune complex like material in glomeruli, assessed by immunofluorescence, was associated with the clearance of the parasite and the presence of circulating antigen specific complexes. The pattern of localization of complexes in both lines was predominantly mesangial with some deposition in the capillaries. The intensity of fluorescence increased during the infection. Initially (day 10) only IgM was observed in the glomeruli but IgG1 and IgG2b were detected from day 20 to day 40. IgG2a was only detected on day 40. However, in none of the animals was this deposition of complexes associated with proteinuria. Hence, the data presented here show that the low affinity line mice produce higher levels of smaller circulating complexes following T. musculi infection than do high affinity mice. However, this does not result in significant differences in localization and induction of renal disease as seen following chronic antigen injection.
Assuntos
Afinidade de Anticorpos , Complexo Antígeno-Anticorpo/análise , Antígenos de Protozoários/imunologia , Glomérulos Renais/imunologia , Trypanosoma/imunologia , Tripanossomíase/imunologia , Animais , Formação de Anticorpos , Feminino , Imunoglobulina G/análise , Imunoglobulina M/análise , Córtex Renal/imunologia , Camundongos , Fatores de Tempo , Trypanosoma/crescimento & desenvolvimento , Tripanossomíase/genética , Tripanossomíase/parasitologiaRESUMO
Infection with either a pathogenic species of trypanosome (Trypanosoma brucei brucei) or a non-pathogenic trypanosome (Trypanosoma musculi) had differing effects on the response of mice to a soluble protein antigen (human serum albumin, HSA) injected in either Freund's incomplete adjuvant or in saline. T. brucei suppressed the response to HSA to a level undetectable by ammonium sulphate globulin precipitation, irrespective of the mode of immunization, whereas T. musculi did not suppress the amount of antibody produced in response to either form of antigen presentation. The affinity of the antibody produced in response to antigen in adjuvant was unaffected, but antibody affinity was significantly reduced in infected animals in which the antigen was given in saline. This depression of antibody affinity was related to the period of infection and arose as a result of a delay in the normal maturation of affinity. Furthermore, the depression was only observed when infection preceded the exposure to antigen. Possible mechanisms which may lead to a depression of affinity without a corresponding effect upon antibody levels are discussed in context of current knowledge of immunosuppression in trypanosome infections.
Assuntos
Afinidade de Anticorpos , Tripanossomíase Africana/imunologia , Animais , Formação de Anticorpos , Feminino , Imunização , Camundongos , Camundongos Endogâmicos , Albumina Sérica/imunologia , Fatores de TempoAssuntos
Anticorpos Antivirais/análise , Infecções por Coxsackievirus/diagnóstico , Enterovirus Humano B/imunologia , Imunoglobulina M/análise , Especificidade de Anticorpos , Contraimunoeletroforese , Reações Cruzadas , Enterovirus Humano B/classificação , Humanos , Imunodifusão , Técnicas Imunoenzimáticas , Testes de Neutralização , Radioimunoensaio , SorotipagemRESUMO
From 1980 to 1982 seven adults with chronic hemolytic anemia were admitted to Cook County Hospital, Chicago, with aplastic crisis. Six of these patients had sickle cell anemia, the seventh patient had beta thalassemia intermedia. Virologic studies showed that six patients had acute infection with the human parvovirus-like virus; in the remaining patient the lack of appropriate specimens precluded viral diagnosis. We describe the features of the virus infection and accompanying erythroid aplasia, and discuss the role of parvovirus-like virus as the etiologic agent in the arrest of erythrocyte production.
Assuntos
Anemia Aplástica/etiologia , Anemia Falciforme/complicações , Talassemia/complicações , Viroses/complicações , Adolescente , Adulto , Anemia Falciforme/sangue , Anticorpos Antivirais/análise , Antígenos Virais/análise , Feminino , Humanos , Masculino , Parvoviridae/imunologia , Talassemia/sangue , Viroses/sangueRESUMO
The occurrence of infection with a parvovirus-like agent during the period April 1979-May 1981 in children attending a single sickle cell clinic in London was investigated. Virus was detected in serum by counter-current immunoelectrophoresis (CIE) and immunoelectron microscopy (IEM). Viral antibody was detected by CIE and specific IgM antibody by an IgM-antibody capture assay. Of the 68 children studied nine presented in aplastic crisis and evidence of infection with the parvovirus-like agent at the time of the crisis was found in all nine. Eighteen of the other children were antibody-positive at some time during the study. In 11 children there was no evidence of recent infection; however, two of these had a history of aplastic crisis in previous years. The other seven seroconverted during the course of the study but did not show any haematological effects. Five of these had a primary infection, one appeared to have reinfection and in the seventh there were insufficient data to distinguish between the two. Possible explanations for the difference between those presenting with aplastic crisis and those with asymptomatic seroconversion are discussed.