Further studies of blood infectivity in an experimental model of transmissible spongiform encephalopathy, with an explanation of why blood components do not transmit Creutzfeldt-Jakob disease in humans

Authors

  • P. Brown,

    1. From the Laboratory of CNS Studies, National Institutes of Neurological Disorders and Stroke; and the Biometric Research Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland; the Jerome H. Holland Laboratory, American Red Cross, Rockville, Maryland; Alliance Pharmaceuticals, Otisville, New York; and the Institute for Basic Research in Developmental Disabilities, Staten Island, New York.
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  • L. Cervenáková,

    1. From the Laboratory of CNS Studies, National Institutes of Neurological Disorders and Stroke; and the Biometric Research Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland; the Jerome H. Holland Laboratory, American Red Cross, Rockville, Maryland; Alliance Pharmaceuticals, Otisville, New York; and the Institute for Basic Research in Developmental Disabilities, Staten Island, New York.
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  • L.M. McShane,

    1. From the Laboratory of CNS Studies, National Institutes of Neurological Disorders and Stroke; and the Biometric Research Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland; the Jerome H. Holland Laboratory, American Red Cross, Rockville, Maryland; Alliance Pharmaceuticals, Otisville, New York; and the Institute for Basic Research in Developmental Disabilities, Staten Island, New York.
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  • P. Barber,

    1. From the Laboratory of CNS Studies, National Institutes of Neurological Disorders and Stroke; and the Biometric Research Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland; the Jerome H. Holland Laboratory, American Red Cross, Rockville, Maryland; Alliance Pharmaceuticals, Otisville, New York; and the Institute for Basic Research in Developmental Disabilities, Staten Island, New York.
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  • R. Rubenstein,

    1. From the Laboratory of CNS Studies, National Institutes of Neurological Disorders and Stroke; and the Biometric Research Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland; the Jerome H. Holland Laboratory, American Red Cross, Rockville, Maryland; Alliance Pharmaceuticals, Otisville, New York; and the Institute for Basic Research in Developmental Disabilities, Staten Island, New York.
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  • W.N. Drohan

    1. From the Laboratory of CNS Studies, National Institutes of Neurological Disorders and Stroke; and the Biometric Research Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland; the Jerome H. Holland Laboratory, American Red Cross, Rockville, Maryland; Alliance Pharmaceuticals, Otisville, New York; and the Institute for Basic Research in Developmental Disabilities, Staten Island, New York.
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  • Address reprint requests to: Paul Brown, MD, Building 36, Room 4A-05, National Institutes of Health, 36 Convent Drive, MSC 4122, Bethesda, MD 20892-4122; e-mail: pwb@codon.nih.gov.

  • Supported in part by the Division of Blood Diseases and Resources, National Heart, Lung, and Blood Institute, National Institutes of Health.

Abstract

BACKGROUND: Solid evidence from experimentally infected animals and fragmentary evidence from naturally infected humans indicate that blood may contain low levels of the infectious agent of Creutzfeldt-Jakob disease (CJD), yet blood components have never been identified as a cause of CJD in humans.

STUDY DESIGN AND METHODS: Blood components and plasma fractions were prepared from the pooled blood of mice that had earlier been infected with a mouse-adapted strain of human transmissible spongiform encephalopathy (TSE). Infectivity bioassays were conducted in healthy mice, and the brains of all assay animals dying during the course of the experiments were examined for the presence of proteinase-resistant protein.

RESULTS: Infectivity in the blood during the preclinical phase of disease occurred in the buffy coat at infectious unit (IU) levels between 6 and 12 per mL and was either absent or present in only trace amounts in plasma and plasma fractions. Infectivity rose sharply at the onset of clinical signs to levels of approximately 100 IU per mL of buffy coat, 20 IU per mL of plasma, 2 IU per mL of cryoprecipitate, and less than 1 IU per mL of fractions IV and V. Plasma infectivity was not eliminated by either white cell-reduction filtration or high-speed centrifugation. Approximately seven times more plasma and five times more buffy coat were needed to transmit disease by the intravenous route than by the intracerebral route.

CONCLUSION: Epidemiologic evidence of the absence in humans of disease transmission from plasma components can probably be explained by 1) the absence of significant plasma infectivity until the onset of symptomatic disease, and comparatively low levels of infectivity during the symptomatic stage of disease; 2) the reduction of infectivity during plasma processing; and 3) the need for at least five to seven times more infectious agent to transmit disease by the intravenous than intracerebral route. These and other factors probably also account for the absence of transmission after the administration of whole blood or blood components.

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