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Deer cohorts 1 (blood), 2 (saliva), and 3 (urine and feces) were electively euthanized at 18 months pi to permit whole-body examination
for PrPCWD. The greatest scrutiny was directed toward those tissues previously established to have highest frequency of PrPCWD deposition in infected deer and generally regarded as the most sensitive indicators of infection—medulla oblongata and other brainstem regions, tonsil, and retropharyngeal lymph node. We found unequivocal evidence of PrPCWD in brain and lymphoid tissue of all six tonsil biopsy–positive deer in cohorts 1 (blood) and 2 (saliva), whereas all deer in cohorts 3 and 5 were negative for PrPCWD in all tissues (Table 2 and Figs. 1 and 2).  The transmission of CWD by a single blood transfusion from two symptomatic and one asymptomatic CWDþ donor is important in at least three contexts: (i) It reinforces that no tissue from CWD-infected cervids can be considered free of prion infectivity; (ii) it poses the possibility of hematogenous spread of CWD, such as through insects; and (iii) it provides a basis for seeking in vitro assays sufficiently sensitive to demonstrate PrPCWD or alternate prion protein conformers in blood—one of the grails of prion biology and epidemiology.  The identification of blood-borne prion transmission has been sought before with mixed results (9–11). Bovine spongiform encephalopathy and scrapie have been transmitted to naBve sheep through the transfer of 500 ml of blood or buffy coat white blood cells from infected sheep (12, 13). In addition, limited but compelling evidence argues for the transmission of variant
Creutzfeldt-Jakob disease (vCJD) through blood from asymptomatic donors (14–16). Even in sporadic CJD, PrPres has been found in peripheral organs of some patients (17). The present work helps establish that prion diseases can be transmitted through blood. The presence of infectious CWD prions in saliva may explain the facile transmission of CWD. Cervid-to-cervid interactions (SOM text),
especially in high density and captive situations, would be expected to facilitate salivary crosscontact (11, 18, 19). Salivary dissemination of prions may not be limited to CWD. Proteaseresistant prion protein has been demonstrated in the oral mucosa, taste buds, lingual epithelium, vomeronasal organ, and olfactory mucosa of hamsters infected with transmissible mink encephalopathy (19) and ferrets infected with CWD (20). Although no instance of CWD transmission to humans has been detected, the present results emphasize the prudence of using impervious gloves during contact with saliva or blood of cervids that may be CWD-infected. Environmental contamination by excreta from infected cervids has traditionally seemed the most plausible explanation for the dissemination of CWD (21). However, we could not detect PrPCWD in cohort 3 deer inoculated repeatedly with urine and feces from CWDþ deer and examined up to 18 months pi (Table 2). There are several reasons to view this negative finding cautiously, including small sample size, elective preclinical termination, and potential variation in individual susceptibility that may be associated with the 96 G/S polymorphism in the PRNP gene (7, 22). Although no genotype of white-tailed deer is resistant to CWD infection, PRNP genotypes S/S or G/S at codon 96
appear to have reduced susceptibility manifest by longer survival (7). Both deer in cohort 3 (urine and feces) were subsequently shown to
be of the PRNP 96 G/S genotype. Thus, it is possible, although we think unlikely, that these deer had a prolonged incubation period (918
months pi) before the amplification of PrPCWD became detectable in tissues. Recent studies have shown that PrPres is poorly preserved
after incubation with intestinal or fecal content (23, 24). Further research using cervid and surrogate cervid PrP transgenic mice (25) are indicated to continue to address the presence of infectious CWD prions in excreta of CWDþ deer and to provide a more substantial basis for reconsideration of the assumption that excreta are the chief vehicle for CWDdissemination and transmission. The results reported here provide a plausible basis for the efficient transmission of CWD in nature. We demonstrate that blood and saliva in particular are able to transmit CWD to naBve deer and produce incubation periods consistent with those observed in naturally acquired infections (3, 26). The time from exposure to first detection of PrPCWD by tonsil biopsy was variable—as short as 3 months but as long as 18 months (likely
underestimates due to sampling frequency). The results also reinforce a cautious view of the exposure risk presented by body fluids, excreta, and all tissues from CWDþ cervids...

http://www.sciencemag.org/cgi/content/abstract/314/5796/133