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

BACKGROUND: Solid evidence from experimentally infected animals and fragmen tary evidence from naturally infected humans indicate that blood may contai n low levels of the infectious agent of Creutzfeldt-Jakob disease (CJD), ye t blood components have never been identified as a cause of CJD in humans. STUDY DESIGN AND METHODS: Blood components and plasma fractions were prepar ed from the pooled blood of mice that had earlier been infected with a mous e-adapted strain of human transmissible spongiform encephalopathy (TSE). In fectivity bioassays were conducted in healthy mice, and the brains of all a ssay animals dying during the course of the experiments were examined for t he presence of proteinase-resistant protein. RESULTS: Infectivity in the blood during the preclinical phase of disease o ccurred in the buffy coat at infectious unit (IU) levels between 6 and 12 p er mt and was either absent or present in only trace amounts in plasma and plasma fractions. Infectivity rose sharply at the onset of clinical signs t o levels of approximately 100 IU per mt of buffy coat, 20 IU per mt of plas ma, 2 IU per mt of cryoprecipitate, and less than 1 IU per mt of fractions IV and V. Plasma infectivity was not eliminated by either white cell-reduct ion filtration or high-speed centrifugation. Approximately seven times more plasma and five times more buffy coat were needed to transmit disease by t he intravenous route than by the intracerebral route. CONCLUSION: Epidemiologic evidence of the absence in humans of disease tran smission from plasma components can probably be explained by I)the absence of significant plasma infectivity until the onset of symptomatic disease, a nd comparatively low levels of infectivity during the symptomatic stage of disease; 2) the reduction of infectivity during plasma processing; and 3) t he need for at least five to seven times more infectious agent to transmit disease by the intravenous than intracerebral route. These and other factor s probably also account for the absence of transmission after the administr ation of whole blood or blood components.