Asymptomatic deer excrete infectious prions in faeces

Abstract
Chronic wasting disease (CWD) is a highly contagious prion disease that causes neurodegeneration in several species in the deer family, including the elk and moose. The precise mechanisms of natural CWD transmission are unresolved. It is known that once an animal shows signs of the disease, its excretions can contain contagious prions. Stanley Prusiner and colleagues show that mule deer infected with CWD begin to excrete infectious prions in faeces long before they develop visible signs of the disease. This suggests a plausible, natural mechanism that could explain the high incidence and efficient horizontal transmission of CWD among deer — and may also be relevant for the similarly contagious scrapie in sheep. Infectious prion diseases are transmitted naturally within affected host populations, for example of sheep and deer. Once an animal is symptomatic its excretions may contain contagious prions, but the biological importance of these sources in sustaining epidemics remains unclear. Here it is shown that asymptomatic mule deer infected with chronic wasting disease excrete infectious prions in their faeces long before they develop clinical signs of prion disease. Infectious prion diseases1—scrapie of sheep2 and chronic wasting disease (CWD) of several species in the deer family3,4—are transmitted naturally within affected host populations. Although several possible sources of contagion have been identified in excretions and secretions from symptomatic animals5,6,7,8, the biological importance of these sources in sustaining epidemics remains unclear. Here we show that asymptomatic CWD-infected mule deer (Odocoileus hemionus) excrete CWD prions in their faeces long before they develop clinical signs of prion disease. Intracerebral inoculation of irradiated deer faeces into transgenic mice overexpressing cervid prion protein (PrP) revealed infectivity in 14 of 15 faecal samples collected from five deer at 7–11 months before the onset of neurological disease. Although prion concentrations in deer faeces were considerably lower than in brain tissue from the same deer collected at the end of the disease, the estimated total infectious dose excreted in faeces by an infected deer over the disease course may approximate the total contained in a brain. Prolonged faecal prion excretion by infected deer provides a plausible natural mechanism that might explain the high incidence and efficient horizontal transmission of CWD within deer herds3,4,9, as well as prion transmission among other susceptible cervids.