Mark P. Dagleish and Amy L. Robinson Chronic wasting disease (CWD), originally called CWD of deer and elk (North American elk [Cervus elaphus canadensis], in contrast to the European elk/moose Alces alces), is found throughout North America and is probably the greatest disease threat to free-ranging, park and farmed deer in Europe, should it become established. The threat is exacerbated in the United Kingdom due to the exceptionally high population densities of various deer species, including native, deliberately introduced and those escaped from zoological collections. White-tailed deer and CWD are discussed in Chapter 32. Along with scrapie in sheep and goats, Creutzfeldt-Jakob disease (CJD) in humans and bovine spongiform encephalopathy (BSE, syn. mad-cow disease, the cause of variant CJD [vCJD]), CWD belongs to the transmissible spongiform encephalopathies (TSEs) group of diseases. All TSEs are invariably fatal and, typically, have long incubation periods prior to overt clinical signs developing. Pathogenesis is dependent on the conversion of the normal host-encoded membrane-bound prion protein (PrPC) to the abnormal disease-associated isoform (PrPd, PrPSc or PrPCWD). The latter is an infectious agent and is extremely environmentally resistant, persisting for decades under some circumstances. PrPd accumulates in the nervous system causing dysfunction that results in clinical signs. Additionally, depending on the host species and the TSE agent involved, PrPd accumulates in lymphoid tissues and some other viscera including kidney, muscle and adrenal glands. Detection of PrPd, by one of the several available methods (enzyme-linked immunosorbent assay [ELISA], Western blot and immunohistochemistry), is required for a definitive diagnosis. The existence of different prion strains is a highly complex topic in prion biology but nonetheless has important implications for understanding prion diseases. For example, there is evidence that the CWD strains present in cases in Europe differ from those in North America; therefore, the progress made in understanding CWD pathogenesis, genetic susceptibility, environmental persistence and potential for cross-species transmission in North America may not necessarily apply. Classical signs of CWD include behavioural changes (including loss of fear of humans often resulting in road traffic accidents), excess salivation (Figure 13.1), polydipsia, polyuria, severe progressive weight loss, ataxia, incoordination and recumbency prior to death. No treatment or vaccine is available. Figure 13.1 Excess salivation in an elk (Cervus elaphus canadensis) with CWD. Source: Mark Dagleish with permission from the late Elizabeth ‘Beth’ Williams. An important determinant of susceptibility to prion disease in many species is the sequence of the prion protein gene (PRNP), which encodes the normal cellular form of the prion protein (PrPC). In North America, changes in the PRNP gene (polymorphisms) have been shown to influence disease susceptibility, incubation period and phenotype in CWD-affected deer. PRNP polymorphisms have been studied by various methods, including genotyping of clinical cases of naturally acquired CWD and unaffected conspecific animals in endemic areas, in vivo experimental transmission studies (deer and transgenic mice) and using in vitro models. In Rocky Mountain elk (Cervus canadensis nelsoni), polymorphism at codon 132 for methionine or leucine (M132L) has been associated with reduced susceptibility and/or slower disease progression in elk homozygous for leucine (132LL). Interestingly, this polymorphism in elk corresponds to codon 129 in humans, which is critically important in human prion disease susceptibility. In white-tailed deer, polymorphisms in multiple codons have been identified that alter disease susceptibility, incubation period and/or phenotype, such as G96S, Q95H, A116G, Q226K and, in mule deer, S225F. Although no PRNP polymorphism has been identified in any deer species that is completely protective against CWD, the S138N polymorphism identified in fallow deer and some North American reindeer populations may be significant because fallow deer are resistant to developing CWD even when subjected to long-term exposure to infected mule deer and in an environment heavily contaminated with the CWD agent. As all fallow deer are homozygous for asparagine (N) at codon 138, suggesting this genotype may be protective. Additional evidence of a partially protective effect has been demonstrated in experimental CWD transmission to reindeer both heterozygous (138NS) and homozygous (138NN) at this codon and in experimental transmission to transgenic mice expressing the 138N-cervid PrP gene. However, both fallow deer and reindeer expressing the homozygous 138N
Chapter 13
Notifiable Diseases in Deer – Chronic Wasting Disease
Introduction
Cause
Clinical Signs
Genetics of Susceptibility
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