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The distribution of infectivity in blood components and plasma derivatives in experimental models of transmissible spongiform encephalopathy
Author(s) -
Brown P.,
Rohwer R. G.,
Dunstan B. C.,
MacAuley C.,
Gajdusek D. C.,
Drohan W. N.
Publication year - 1998
Publication title -
transfusion
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.045
H-Index - 132
eISSN - 1537-2995
pISSN - 0041-1132
DOI - 10.1046/j.1537-2995.1998.38998408999.x
Subject(s) - infectivity , transmissible spongiform encephalopathy , virology , bovine spongiform encephalopathy , distribution (mathematics) , encephalopathy , medicine , prion protein , virus , mathematics , scrapie , disease , mathematical analysis
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. STUDY DESIGN AND 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. CONCLUSION: 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.