The distribution of infectivity in blood components and plasma derivatives in experimental models of transmissible spongiform encephalopathy.
BACKGROUND
The administration of blood components from donors who subsequently develop Creutzfeldt-Jakob disease has raised the issue of blood as a possible vehicle for iatrogenic disease.


METHODS
We examined infectivity in blood components and Cohn plasma fractions in normal human blood that had been "spiked" with trypsinized cells from a scrapie-infected hamster brain, and in blood of clinically ill mice that had been inoculated with a mouse-adapted strain of human transmissible spongiform encephalopathy. Infectivity was assayed by intracerebral inoculation of the blood specimens into healthy animals.


RESULTS
Most of the infectivity in spiked human blood was associated with cellular blood components; the smaller amount present in plasma, when fractionated, was found mainly in cryoprecipitate (the source of factor VIII) and fraction I+II+III (the source of fibrinogen and immunoglobulin); almost none was recovered in fraction IV (the source of vitamin-K-dependent proteins) and fraction V (the source of albumin). Mice infected with the human strain of spongiform encephalopathy had very low levels of endogenous infectivity in buffy coat, plasma, cryoprecipitate, and fraction I+II+III, and no detectable infectivity in fractions IV or V.


CONCLUSIONS
Convergent results from exogenous spiking and endogenous infectivity experiments, in which decreasing levels of infectivity occurred in cellular blood components, plasma, and plasma fractions, suggest a potential but minimal risk of acquiring Creutzfeldt-Jakob disease from the administration of human plasma protein concentrates.
Brown
P
P
Laboratory of CNS Studies, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA.
Rohwer
R G
RG
Dunstan
B C
BC
MacAuley
C
C
Gajdusek
D C
DC
Drohan
W N
WN
D000818:Animals; D001781:Blood Component Removal; D016913:Blood Component Transfusion / Q000009:adverse effects*; D001782:Blood Donors; D007562:Creutzfeldt-Jakob Syndrome / Q000635:transmission; D006224:Cricetinae; D006801:Humans; D051379:Mice; D010949:Plasma; D017096:Prion Diseases / Q000635:transmission*; D018570:Risk Assessment; D012608:Scrapie / Q000635:transmission