RESUMO
Transmissible spongiform encephalopathies (TSEs) are untreatable, fatal neurologic diseases affecting mammals. Human disease forms include sporadic, familial and acquired Creutzfeldt-Jakob disease (CJD). While sporadic CJD (sCJD) has been recognized for near on 100 years, variant CJD (vCJD) was first reported in 1996 and is the result of food-borne transmission of the prion of bovine spongiform encephalopathy (BSE, 'mad cow disease'). Currently, 230 vCJD cases have been reported in 12 countries, the majority in the UK (178) and France (27). Animal studies demonstrated highly efficient transmission of natural scrapie and experimental BSE by blood transfusion and fuelled concern that sCJD was potentially transfusion transmissible. No such case has been recorded and case-control evaluations and lookback studies indicate that, if transfusion transmission occurs at all, it is very rare. In contrast, four cases of apparent transfusion transmission of vCJD infectivity have been identified in the UK. Risk minimization strategies in response to the threat of vCJD include leucodepletion, geographically based donor deferrals and deferral of transfusion recipients. A sensitive and specific, high-throughput screening test would provide a potential path to mitigation but despite substantial effort no such test has yet appeared. The initial outbreak of vCJD appears to be over, but concern remains about subsequent waves of disease among those already infected. There is considerable uncertainty about the size of the infected population, and there will be at least a perception of some continuing risk to blood safety. Accordingly, at least some precautionary measures will remain in place and continued surveillance is necessary.
Assuntos
Segurança do Sangue/normas , Transfusão de Sangue/normas , Síndrome de Creutzfeldt-Jakob/sangue , Animais , Segurança do Sangue/métodos , Síndrome de Creutzfeldt-Jakob/transmissão , Humanos , Príons/sangueRESUMO
An assay for antibodies to membrane antigens of cells infected by human T-cell leukemia virus was used to examine serum from persons who donated blood to 12 patients with acquired immunodeficiency syndrome (AIDS) associated with blood transfusions. The occurrence of positive results in the assay was significantly greater among donors to the AIDS patients (9 of 117; 7.7 percent) than among random donors (1 of 298; 0.3 percent). Of 12 sets of donors examined, 9 sets included a donor whose serum gave positive results for the presence of the antibodies. In six of these nine sets, the seropositive donor was an individual who was also identified as a possible source of AIDS transmission when epidemiologic and immunologic criteria were used.
Assuntos
Síndrome da Imunodeficiência Adquirida/etiologia , Anticorpos Antivirais/análise , Doadores de Sangue , Deltaretrovirus/patogenicidade , Infecções por Retroviridae/epidemiologia , Retroviridae/imunologia , Reação Transfusional , Síndrome da Imunodeficiência Adquirida/imunologia , Síndrome da Imunodeficiência Adquirida/transmissão , Adulto , Idoso , Antígenos de Superfície/imunologia , Antígenos Virais/imunologia , Deltaretrovirus/imunologia , Feminino , Homossexualidade , Humanos , Masculino , Pessoa de Meia-Idade , RiscoAssuntos
Anticorpos Antiprotozoários/sangue , Doadores de Sangue , Malária/prevenção & controle , Plasmodium/imunologia , Reação Transfusional , Antígenos de Protozoários/imunologia , Brasil/epidemiologia , Portador Sadio/sangue , Portador Sadio/diagnóstico , DNA de Protozoário/sangue , Doenças Endêmicas , Ensaio de Imunoadsorção Enzimática , Europa (Continente)/epidemiologia , Técnica Indireta de Fluorescência para Anticorpo , Humanos , Israel/epidemiologia , Malária/sangue , Malária/diagnóstico , Malária/epidemiologia , Malária/transmissão , Nova Zelândia/epidemiologia , Técnicas de Amplificação de Ácido Nucleico , Estados Unidos/epidemiologiaRESUMO
Interpretation of human immunodeficiency virus (HIV) antibody results that are "indeterminate" rather than clearly positive or negative is problematic for the person delivering the result as well as for the individual being tested. To improve counseling messages for these individuals, we evaluated data collected from a well-characterized cohort of 387 blood donors who had been monitored for up to 2 years. We sought to determine if persons with indeterminate Western blot patterns were infected with HIV, and whether information derived from follow-up monitoring would assist in the development of counseling messages for persons on whom no follow-up information was available. Donors were studied by laboratory assays, clinical evaluation, and assessment of risk for HIV. The absence of HIV infection in 97 of 98 donors with indeterminate Western blot patterns was confirmed by clinical follow-up, Western blot assays of sequential samples, and negative gene amplification results. We propose supplemental guidelines to be used as an adjunct to existing interpretive criteria for counseling individuals when they first present with an indeterminate Western blot finding.
Assuntos
Síndrome da Imunodeficiência Adquirida/epidemiologia , Western Blotting , Soropositividade para HIV , HIV-1/isolamento & purificação , Síndrome da Imunodeficiência Adquirida/diagnóstico , Doadores de Sangue , Estudos de Coortes , Aconselhamento , Seguimentos , Humanos , Técnicas Imunoenzimáticas , Prevalência , Estudos Prospectivos , Fatores de Risco , Fatores de TempoRESUMO
Blood safety is a global public health priority. However, the degree to which blood is, or is not free of infection risk varies greatly around the world. The major determinants of this variation in risk are the availability of resources to support blood safety measures such as testing and the qualitative and quantitative epidemiological patterns of blood-borne infections. These factors are outlined and examples are presented.
Assuntos
Saúde Global , Segurança , Reação Transfusional , Doadores de Sangue , Prioridades em Saúde , HumanosRESUMO
Controlled pore glass (CPG) adsorbs hepatitis B surface antigen (HBsAg) from whole plasma with a high degree of specificity. The resultant complex is stable at acid pH and in the presence of high concentrations of sodium thiocyanate. The adsorbed HBsAg is qualitatively and quantitatively similar to the soluble material in its ability to bind antibodies to HBsAg (anti-HBs). The HBsAg in 1 ml of strongly reactive plasma is adsorbed by 100 mg of CPG, which can then specifically bind 32,000 passive hemagglutination units of anti-HBs. Bound antibody can be eluted in 77% yield by acid or by chaotropic ions and the CPG-HBsAg complex can be reused in further adsorption-elution cycles. Antibody to HBsAg can be purified 144-fold in a single step by using this technique. The preparation of monospecific subtyping reagents for HBsAg and of immunochemically purified anti-HBs is described.
Assuntos
Especificidade de Anticorpos , Complexo Antígeno-Anticorpo , Antígenos de Superfície da Hepatite B , Imunoadsorventes , Adsorção , Anticorpos Antivirais , Antígenos Virais , Vidro , Humanos , Concentração de Íons de Hidrogênio , Imunoeletroforese , Indicadores e Reagentes , Tiocianatos/farmacologiaRESUMO
A highly sensitive technique for determining the subtype specificity of antibody to hepatitis B surface antigen (anti-HBs) is described. Immunoadsorbent consisting of controlled pore glass coated with subtype specific HBsAg was used to remove homologous antibody from the test samples before testing them for residual antibody by a commercially available radioimmunoassay (RIA). A total of 73 anti-HBs-positive samples from asymptomatic blood donors were tested. In nearly 80% of these samples the subtype reactivity could be determined by this technique. Only 67% could be typed by conventional liquid phase absorption RIA and 22% by passive hemagglutination inhibition techniques. Among the samples with low anti-HBs titer, ad and ay subtypes were found with equal frequency; however, with the increase in anti-HBs titer, considerably higher proportion of ad specificity was detected.
Assuntos
Anticorpos Antivirais/análise , Anticorpos Anti-Hepatite B/análise , Antígenos de Superfície da Hepatite B/imunologia , Testes de Inibição da Hemaglutinação , Humanos , Radioimunoensaio/métodosRESUMO
The results of hepatitis B surface antigen (HBs-Ag) testing in a large volunteer blood donor population are described. Counterelectrophoresis and three versions of solid-phase radioimmunoassay technic are compared and evaluated. Initial results suggested that the radioimmunoassay technic are compared and evaluated. Initial results suggested that the radioimmunoassay technic detected more than five times as many reactive donors as did counterelectrophoresis. The specificity of the radioimmunoassay technic has been increased by successive modifications, and recent results show that the technic detects 73 percent more reactive donors than does counterelectrophoresis. Not all of these reactions are specific, and it is estimated that the true gain in detection of HBsAg carriers is 49 percent of the value found by counterelectroesis. The incidence of HBsAg carriers in the America Red Cross donor population is about 1.25 per 1,000.
Assuntos
Doadores de Sangue , Antígenos da Hepatite B/isolamento & purificação , Hepatite B/prevenção & controle , Radioimunoensaio , Portador Sadio , Eletroforese , Hepatite B/imunologia , Humanos , Estados UnidosRESUMO
A comparative evaluation of six licensed radioimmunoassay kits for the detection of hepatitis B surface antigen (HBsAg) has been performed. Each method met the federal licensure requirements for the test. The performance of the kits varied considerably, however, when they were challenged to the limits of their sensitivities. During the period December 1978 through March 1979, four kits were judged to be of equivalent high sensitivity, whereas two were less sensitive. Three of the kits, including two of those with high sensitivity, generated a high (6%--7%) proportion of false reactive results. The sensitivities of all kits decreased during the shelf lives of the reagents.
Assuntos
Antígenos de Superfície da Hepatite B/análise , Radioimunoensaio/métodos , Kit de Reagentes para Diagnóstico/normas , Estudos de Avaliação como AssuntoRESUMO
Human immunodeficiency virus-1 (HIV-1) screening programs currently are based primarily on the detection of specific HIV-1 antibodies by the commercially available enzyme immunoassay (EIA) combined with highly specific confirmation procedures. Factors to be considered in establishing a screening program include test performance characteristics, economy, confidentiality and notification procedures, legal and regulatory issues, proficiency and quality control measures, and laboratory safety. Commercial EIA screening in conjunction with a licensed Western blot assay permits the classification of all but a few serum samples into HIV-1-positive and HIV-1-negative categories. The occasional indeterminate results often can be resolved by following a defined retesting/resampling algorithm or by using research-level test procedures that may become available for diagnostic use in the future. Although screening of patient populations with an increased risk of HIV-1 exposure will improve the predictive accuracy of an initial screening assay, confirmation testing should nonetheless be performed for all EIA reactive sera regardless of the source. Local HIV-1 screening programs that meet minimum-volume requirements can result in considerable savings and flexibility for a moderate-size institution. However, before this type of program is undertaken, numerous technical and ethical considerations need to be addressed.
Assuntos
Soropositividade para HIV/diagnóstico , Programas de Rastreamento/métodos , Algoritmos , Western Blotting , Humanos , Estudos ProspectivosRESUMO
We have used a death-record search to define the frequency of lethal outcomes of hepatitis B virus infection among a population of more than 15,000 overtly healthy blood donors found positive in routine HBsAg testing. We have compared the study population with a control group of some 18,000 donors selected on the basis of a negative test result. The index and control groups were observed for periods reflecting a total of 55 and 59 thousand person-years, respectively. Twenty percent of the 134 deaths identified among HBsAg positive donors were in some way liver related, including seven deaths due to hepatitis, seven to cirrhosis and six to hepatoma. In contrast, only one of the 95 deaths in the control population was liver related, and was due to fatty degeneration of the liver. The majority (four) of the hepatoma deaths occurred among blacks, three of whom were less than 35 at the time of death. In contrast, deaths from cirrhosis were all among whites. We conclude that there is significant mortality associated with the HBsAg positive state, even though the affected individuals may be asymptomatic and well enough to give blood at some stage. We estimate the standardised mortality ratio for hepatoma among HBsAg-positive persons in the United States is at least 27, confirming the association observed in other populations. The risk for hepatoma among young, HBsAg positive black males appears to approach that reported for HBsAg positive males in Taiwan. Data on the feasibility of AFP testing for early detection of hepatoma are included and discussed.
Assuntos
Doadores de Sangue , Carcinoma Hepatocelular/mortalidade , Hepatite B/mortalidade , Cirrose Hepática/mortalidade , Neoplasias Hepáticas/mortalidade , Carcinoma Hepatocelular/complicações , Portador Sadio , Causas de Morte , Feminino , Hepatite B/complicações , Antígenos de Superfície da Hepatite B , Humanos , Cirrose Hepática/complicações , Neoplasias Hepáticas/complicações , Masculino , Fatores de Risco , Software , Estados Unidos , alfa-Fetoproteínas/análiseRESUMO
A technique (Ig-EIA) for the detection of CMV-specific IgG, IgM and IgA in human blood is described. Ig-EIA utilizes alkaline phosphatase-labeled goat anti-human IgG, IgM and IgA as a detection probe and CMV antigen-coated solid phase from commercial kits. Ig-EIA is compared to indirect fluorescent assay (IFA) and indirect hemagglutination (IHA) for sensitivity and specificity. On sequential samples of blood from a set of patients, Ig-EIA clearly demonstrated seroconversion in CMV-specific IgG and IgM. A test of 332 blood donors by Ig-EIA showed 177 (53%) had CMV-specific IgG and 17 (5%) had CMV IgM. Only two of the 17 donors with CMV IgM were nonreactive for CMV-IgG. The potential of CMV-IgM as an indicator of CMV infectivity is discussed.
Assuntos
Anticorpos Antivirais/análise , Citomegalovirus/imunologia , Imunoglobulinas/análise , Adulto , Idoso , Especificidade de Anticorpos , Reações Falso-Positivas , Feminino , Imunofluorescência , Testes de Hemaglutinação , Humanos , Técnicas Imunoenzimáticas , Imunoglobulina A/análise , Imunoglobulina G/análise , Imunoglobulina M/análise , Masculino , Valor Preditivo dos Testes , Kit de Reagentes para DiagnósticoRESUMO
A modified and improved technique for the detection of hepatitis B virus-specific DNA polymerase activity is described. DNA polymerase is released from Dane particles by mixing samples with the detergent Nonidet P-40 and beta-mercaptoethanol. After incubation of pretreated samples with a reaction mixture containing tritiated thymidine-methyl-5'-triphosphate (3H-TTP), DNA is precipitated onto a trichloroacetic acid (TCA)-treated paper. Unincorporated 3H-TTP is then chromatographically eluted with a 5% TCA solution and precipitated counts are determined. A sample is considered positive for DNA polymerase if the incorporated counts are significantly higher than the counts of a group of negative control samples. The modifications include pretreatment of the paper with TCA, chromatographic elution of unincorporated 3H-TTP with TCA solution, prefiltration of the sample through bacteriological filters, and use of sound statistical methods for evaluation of data. These changes have led to a highly reproducible, reliable and sensitive technique. The coefficient of variation of negative control samples from various test runs was in the range of 2.7-8.5%. A linear relationship between incorporated counts and DNA polymerase concentration was shown. A total of 419 serum samples from asymptomatic HBsAg-carrying blood donors were tested. Twenty-three (5.5%) of these were found to contain detectable DNA polymerase activity. All 23 samples also contained HBeAg.
Assuntos
DNA Polimerase Dirigida por DNA/metabolismo , Vírus da Hepatite B/enzimologia , Técnicas Microbiológicas , Precipitação Química , Antígenos de Superfície da Hepatite B , Antígenos E da Hepatite B , Humanos , Nucleotídeos de Timina/metabolismoRESUMO
For many years, viral hepatitis has been considered to be a frequent and serious adverse outcome of blood transfusion. The majority of cases have been due to hepatitis B and C viruses, which, respectively, are DNA and RNA viruses. Both are lipid enveloped and are susceptible to viral inactivation procedures. Careful donor screening and the use tests for HBsAg and anti-HBc have essentially eliminated the risk of transfusion-transmitted HBV infection.
Assuntos
Hepatite Viral Humana/transmissão , Reação Transfusional , Doadores de Sangue , Anticorpos Anti-Hepatite/sangue , Hepatite B/sangue , Hepatite B/epidemiologia , Hepatite B/prevenção & controle , Hepatite B/transmissão , Hepatite C/sangue , Hepatite C/epidemiologia , Hepatite C/prevenção & controle , Hepatite C/transmissão , Vírus de Hepatite/classificação , Vírus de Hepatite/imunologia , Vírus de Hepatite/isolamento & purificação , Hepatite Viral Humana/sangue , Hepatite Viral Humana/epidemiologia , Hepatite Viral Humana/prevenção & controle , Humanos , Programas de Rastreamento , Prevalência , Estudos Soroepidemiológicos , Estados Unidos/epidemiologia , Viremia/virologiaRESUMO
Psoralens and UVA light have been used in the laboratory to study the inactivation of viruses that may be infrequently present in platelet concentrates that are prepared for transfusion. In order to evaluate safety aspects of the treatment of platelet suspensions with 4'-aminomethyl-4,5',8-trimethylpsoralen (AMT), we have investigated the residual levels and mutagenic potential of AMT after UVA phototreatment. 4'-aminomethyl-4,5',8-trimethylpsoralen, at a final concentration of 40 micrograms/mL, was added to platelet suspensions which contained 16% plasma and a synthetic medium. Platelet suspensions containing AMT were irradiated with up to 7.2 J/cm2 UVA light under normal oxygen levels. Residual levels of AMT were determined by HPLC and a bioassay based on bacteriophage phi 6 inactivation. The photodestruction of AMT or its activity by UVA was characterized by a D37 value of 0.6 and 0.3 J/cm2 with HPLC or bioassay, respectively. At 2.4 J/cm2 UVA, which results in approximately 5 log10 inactivation of vesicular stomatitis virus (VSV) and retention of platelet in vitro properties, 12% (HPLC) to 9% (bioassay) AMT remained. Like other psoralens, AMT was found to bind to serum proteins as shown by ultrafiltration. Results are consistent with approximately 36% of the initial drug load binding primarily to serum albumin. It was determined using 3H-AMT that 9 to 18% of radioactivity was bound to platelets in the absence of irradiation. Similar fractions (13 to 18%) of AMT were bound to platelets after 3.6 J/cm2 UVA irradiation, and 8 to 10% of total AMT was associated with saline-washed irradiated platelets and is presumably tightly bound.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Plaquetas/efeitos dos fármacos , Mutagênicos/toxicidade , Fármacos Fotossensibilizantes/toxicidade , Trioxsaleno/análogos & derivados , Raios Ultravioleta , Bacteriófagos/efeitos dos fármacos , Sangue , Plaquetas/efeitos da radiação , Humanos , Testes de Mutagenicidade/métodos , Salmonella typhimurium/efeitos dos fármacos , Albumina Sérica/farmacologia , Trioxsaleno/toxicidade , Ensaio de Placa ViralRESUMO
Despite the low risk of transfusion-transmitted infection currently present in the blood supply, processes to inactivate contaminating viruses and bacteria may improve the safety of transfusion even further. A variety of techniques, using both physical and chemical processes, are being explored. Particularly promising is adaptation of the solvent/detergent technique (already in use for plasma derivatives) to plasma for transfusion. Inactivation of viruses in cellular components may require a combination of techniques, possibly including leukocyte depletion filtration, photoactive compounds, and subsequent washing. Concerns about potential toxicity of the agents employed and retention of component efficacy after treatment and storage remain unresolved, however.
Assuntos
Transfusão de Componentes Sanguíneos , Sangue/microbiologia , Desinfecção/métodos , Bactérias/efeitos dos fármacos , Bactérias/efeitos da radiação , Detergentes/farmacologia , Filtração , Humanos , Luz , Vírus/efeitos dos fármacos , Vírus/efeitos da radiaçãoRESUMO
The safety of blood and blood products is based on three interdependent activities: selection of safe donors, laboratory testing, and, where applicable, treatment of the product to reduce residual infectivity. Posttransfusion hepatitis has provided both the initial stimulus and the model for these procedures. The procedures have resulted in a progressive increase in the safety of the blood supply, which is continuing, as evidenced by a 50% decrease in the frequency of reported posttransfusion hepatitis over the past two years.
Assuntos
Hepatite Viral Humana/prevenção & controle , Reação Transfusional , Bancos de Sangue , Doadores de Sangue , Antígenos de Superfície da Hepatite B/análise , Hepatite Viral Humana/transmissão , Humanos , SegurançaRESUMO
Natural history studies conducted over the past 15 years have shown that parenterally transmitted non-A non-B hepatitis infection frequently results in an indolent chronic disease with serious long-term consequences. The recent identification of nucleic acid sequences comprising the genome of hepatitis C virus (HCV) has allowed the development of a serological assay based upon recombinant viral proteins specifically associated with the major agent of non-A, non-B hepatitis infection. The HCV antibody assays have now been applied to sera from blood donors worldwide, as well as various population samples with increased hepatitis risk in the course of clinical trials conducted in both Europe and the United States. Data from these studies provide further encouragement that assays based on the hepatitis C virus recombinant proteins are highly specific for the major agent of non-A non-B hepatitis and will provide a firm basis for blood donor screening and future diagnostic tests.