title: 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.
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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Laboratory of CNS Studies, National Institutes of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-4122, USA. pwb@codon.nih.gov
authors.forename: P
authors.initials: P
authors.lastname: Brown
authors.forename: L
authors.initials: L
authors.lastname: Cervenáková
authors.forename: L M
authors.initials: LM
authors.lastname: McShane
authors.forename: P
authors.initials: P
authors.lastname: Barber
authors.forename: R
authors.initials: R
authors.lastname: Rubenstein
authors.forename: W N
authors.initials: WN
authors.lastname: Drohan
mesh_terms: D000818:Animals; D002498:Centrifugation; D007562:Creutzfeldt-Jakob Syndrome / Q000635:transmission*; D004195:Disease Models, Animal; D006801:Humans; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D007937:Leukapheresis / Q000379:methods; D051379:Mice; D010956:Plasmapheresis / Q000379:methods; D017096:Prion Diseases / Q000097:blood*