Prions' travels--feces and transmission of prion diseases.

The epidemiological profile of prion disease varies strikingly among different mammalian species. The overwhelming majority ( 90%) of prion diseases in humans are sporadic, with most of the remaining cases due to inherited mutations in the gene (PRNP) encoding the prion protein. Lateral transmission of disease between humans is extraordinarily rare. Most documented cases have been due to direct inoculation of infected material, as is exemplified (1) by transplantation of dural grafts or injection of either human growth hormone or gonadotropins derived from pools of cadaveric pituitary glands, or (2) as in the case of variant Creutzfeldt-Jakob disease (vCJD), by transfusion of infected blood. Similarly, bovine spongiform encephalopathy (BSE) is almost always acquired through consumption of prion-infected food supplements, and lateral transmission within cattle herds appears to be rare or nonexistent. In contrast to human prion diseases and BSE, both chronic wasting disease (CWD) in cervids and scrapie in sheep are laterally transmitted with high efficiency. In wild populations of deer, 15% of animals may be infected, and, in captive herds, rates of infection can approach 100% [2]. Neither how prion disease spreads easily through herds of sheep or deer nor, conversely, why prion disease fails to spread through herds of cattle or human populations is known. One explanation for variations in the epidemiological profile of disease may be the differences in how prions spread within infected hosts and are subsequently shed into the environment. Hamsters infected by intracerebral inoculation will accumulate the disease-causing isoform of the prion protein (PrPSc) in taste and olfactory receptors [3]. These cells are shed and can contaminate saliva or mucous. White-tailed deer with oral exposure to the saliva of CWDinfected deer develop CWD [4]. Transfusion of blood from infected donors transmits BSE and scrapie to sheep, CWD to deer, and vCJD to humans [4–6]. Initial reports indicating that urine contained levels of PrPSc that were detectable by immunoblotting have not been reproducibly confirmed, but infectious prions have been found, at least transiently, in the urine of infected animals [7–9]. In this issue of the Journal, Safar et al. [10] report investigations of prions in the feces of Syrian hamsters (SHas) experimentally infected with a hamster-adapted Sc237 prion strain. Prion levels were determined both by bioassay and by a highly sensitive immunoassay. A careful histological analysis of representative animals was performed, and excretion of prions in feces was studied in hamsters infected orally, intraperitoneally, or intracerebrally. For oral inoculations, animals were fed “one-half of the brain from a Sc237-infected SHa in a petri dish.” This is an extremely high oral inoculum of 10 log10 ID50 per hamster. High titers of infectious prions (6.6 log10 ID50/g) were detected in the feces of orally challenged hamsters in the first week, and then titers decreased to low levels ( 2.3 log10 ID50/g; incubation time, 165–314 days), which persisted to 106 days after inoculation. The capacity of these animals to transmit disease to uninoculated cage mates showed an interesting triphasic pattern. Uninfected cage mates that cohabited with an infected index animal within hours of inoculation of the index animal developed disease rapidly (after 150 days), reflecting exposure to relatively high doses of PrPSc. Animals that cohabited 24–48 h after oral feeding of the index hamster developed disease more slowly (after 192–254 days), reflecting exposure to lower PrPSc doses. However, animals exposed to the index hamster at 7–14 days after its oral challenge again had relatively short disease incubation times (140– 165 days). These results could be explained if the initial short incubation times reflected exposure to the initial challenge inoculum that had been rapidly excreted, with later rates reflecting exposure to PrPSc that had replicated in and was being shed endogenously from the intestinal tract of the index animal. Low levels of prions, detectable by Received 9 January 2008; accepted 9 January 2008; electronically published 27 May 2008. Potential conflicts of interest: The authors report that they have no conflicts of interest regarding prions and prion disease. Reprints or correspondence: Dr. K. L. Tyler, Neurology B-182, University of Colorado Health Sciences Center, 4200 East 9th Ave., Denver, CO 80262 ([email protected]). The Journal of Infectious Diseases 2008; 198:8 –9 © 2008 by the Infectious Diseases Society of America. All rights reserved. 0022-1899/2008/19801-0004$15.00 DOI: 10.1086/588194 E D I T O R I A L C O M M E N T A R Y