Identification of putative atypical scrapie in sheep in Portugal

Abstract

Experimental transmission of bovine spongiform encephalopathy to sheep has prompted the implementation of a surveillance plan of scrapie in small ruminants by the European Union in all member states. Since its start over 30 000 animals have been tested, and the first seven cases of sheep with detectable PrP res deposition in the central nervous system have been identified in Portugal. Notably, the pattern of PrP res distribution in the brainstem was different from that previously described for scrapie and consistent in all seven animals. Moreover, the profile of the electrophoretic mobility of PrP res after proteinase K treatment was equivalent in all cases analysed but distinct from that observed for scrapie. Notably, four animals had genotypes rarely associated with scrapie, including one animal homozygous for A 136 R 154 R 171. There were no cases found to exhibit vacuolation, a pattern of PrP res distribution or PrP res electrophoretic mobility corresponding to scrapie. These data reveal a putative atypical scrapie strain in Portugal not linked to specific Prnp genotypes. Scrapie affects sheep and goats and is the most common natural form of a group of diseases designated transmissible spongiform encephalopathies, which include Creutzfeldt-Jakob disease (CJD) of humans and bovine spongiform encephalopathy (BSE). Scrapie is endemic in several European Union (EU) countries and has been recognized, as a disease identity, for over 250 years (McGowan, 1922). To date, there are no apparent clinical or epidemiological data linking scrapie to human disease. However, since it has been shown that sheep could be experimentally infected with BSE (Foster et al., 1993), the possibility has been raised that BSE could have been accidentally introduced in this species. This would constitute a grave problem in terms of public health, since, in contrast to scrapie, BSE has been directly linked with a new form of CJD (Bruce et al., 1997; Collinge et al., 1996). Furthermore, it has been proposed that like scrapie, BSE in sheep could be naturally transmitted and thus become endemic (Foster et al., 2001). Clinically both diseases are indistinguishable (Foster et al., 2001). These possibilities prompted the EU to implement a surveillance scheme for scrapie in small ruminants.

Atypical/Nor98 scrapie: properties of the agent, genetics, and epidemiology

“…In the brainstem, some cases have been described as totally negative at the level of the obex [5,9,10,16,32] while other cases display minimal staining restricted only to the spinal tract nucleus of the trigeminal nerve [5,31,33,37,41]. The primary structure affected in classical scrapie, the dorsal motor nucleus of the vagus (DMNV) was never affected.…”

“…Evidence so far indicates that atypical scrapie affects animals with PrP genotypes different from classical scrapie [2,3,9,26,27,29,30,33,36]. The appearance of atypical/Nor98 scrapie and classical scrapie in the same flock has not been reported as a common event, although there is no apparent genetic reason for this: indeed the separation of susceptible genotypes would perfectly permit infection with both diseases in an infected flock.…”

“…II). Importantly, they described ARR/ARR carriers with atypical scrapie [2,9,27,33,36]. The susceptibility of RR 171 homozygotes has been a major concern because national breeding and eradication plans for classical scrapie in EU member states are inadvertently creating a high frequency of ARR/ARR animals.…”

“…The vast majority of these atypical cases are similar if not identical to Nor98 cases, but they are designated outside Norway as "Nor98", "Nor98-like", or "atypical scrapie". The authors therefore choose to the majority of the European countries [9,13,15,16,[31][32][33]37], with also one case in the Falkland Islands [14] and in the USA [12]. A case was recently retrospectively found in UK archive material dating from 1989 [7].…”

Prion agent diversity and species barrier

“…Furthermore, confirmatory neuropathological methods were often inconclusive [18]. Atypical scrapie has been diagnosed in sheep carrying various PrP genotypes, including those homozygous for ARR [40,137,141] Analyses of brain PrP res from natural scrapie cases revealed that scrapie molecular features are not uniform, consistent with the existence of distinct strains. Three major types of PrP res profiles have been identified, with unglycosylated forms (see Fig.…”