Catherine Botteron

Diversity in neuroanatomical distribution of abnormal prion protein in atypical scrapie.

Scrapie is a transmissible spongiform encephalopathy (TSE) in sheep and goats. In recent years, atypical scrapie cases were identified that differed from classical scrapie in the molecular characteristics of the disease-associated pathological prion protein (PrPsc). In this study, we analyze the molecular and neuropathological phenotype of nine Swiss TSE cases in sheep and goats. One sheep was identified as classical scrapie, whereas six sheep, as well as two goats, were classified as atypical scrapie. The latter revealed a uniform electrophoretic mobility pattern of the proteinase K–resistant core fragment of PrPsc distinct from classical scrapie regardless of the genotype, the species, and the neuroanatomical structure. Remarkably different types of neuroanatomical PrPsc distribution were observed in atypical scrapie cases by both western immunoblotting and immunohistochemistry. Our findings indicate that the biodiversity in atypical scrapie is larger than expected and thus impacts on current sampling and testing strategies in small ruminant TSE surveillance.

Atypical Scrapie in a Swiss Goat and Implications for Transmissible Spongiform Encephalopathy Surveillance

Different types of transmissible spongiform encephalopathies (TSEs) affect sheep and goats. In addition to the classical form of scrapie, both species are susceptible to experimental infections with the bovine spongiform encephalopathy (BSE) agent, and in recent years atypical scrapie cases have been reported in sheep from different European countries. Atypical scrapie in sheep is characterized by distinct histopathologic lesions and molecular characteristics of the abnormal scrapie prion protein (PrPsc). Characteristics of atypical scrapie have not yet been described in detail in goats. A goat presenting features of atypical scrapie was identified in Switzerland. Although there was no difference between the molecular characteristics of PrPsc in this animal and those of atypical scrapie in sheep, differences in the distribution of histopathologic lesions and PrPsc deposition were observed. In particular the cerebellar cortex, a major site of PrPsc deposition in atypical scrapie in sheep, was found to be virtually unaffected in this goat. In contrast, severe lesions and PrPsc deposition were detected in more rostral brain structures, such as thalamus and midbrain. Two TSE screening tests and PrPsc immunohistochemistry were either negative or barely positive when applied to cerebellum and obex tissues, the target samples for TSE surveillance in sheep and goats. These findings suggest that such cases may have been missed in the past and could be overlooked in the future if sampling and testing procedures are not adapted. The epidemiological and veterinary public health implications of these atypical cases, however, are not yet known.

Neuropathological survey of fallen stock: Active surveillance reveals high prevalence of encephalitic listeriosis in small ruminants

This paper describes the prevalence of brain lesions in the Swiss fallen stock population of small ruminants. 3075 whole brains (75% sheep, 25% goats) were collected as part of a year-long active survey of transmissible spongiform encephalopathies (TSEs) in small ruminants conducted by the Swiss authorities between July 2004 and July 2005. All fallen stock brains were systematically examined by histopathology to obtain reliable data on histologically identifiable brain lesions. Lesions were found in an unexpectedly high number of animals (8.1% of all examined brains). A wide spectrum of diseases was detected showing that this approach provides an excellent opportunity to screen for the prevalence of neurological diseases. Encephalitic listeriosis was by far the most frequent cause of CNS lesions in both species and its prevalence was unexpectedly high when compared to notified confirmed cases. In conclusion, the prevalence of listeriosis as estimated by passive surveillance based on the notification of clinical suspects has been underestimated in the past.

Spongiform Encephalopathy in a Miniature Zebu

The first case of spongiform encephalopathy in a zebu (Bos indicus) was identified in a zoo in Switzerland. Although histopathologic and immunohistochemical analyses of the central nervous system indicated a diagnosis of bovine spongiform encephalopathy (BSE), molecular typing showed some features different from those of BSE in cattle (B. taurus).

Canine distemper virus-immune complexes induce bystander degeneration of oligodendrocytes

SummaryDemyelination in chronic canine distemper encephalitis may be the result of a bystander effect in which the antiviral immune response is involved. In the present report we demonstrate that canine distemper virus-antiviral antibody immune complexes induce oligodendroglial degeneration in mixed brain cell cultures, particularly at the level of the cell processes. The involvement of macrophages as effector cells in this process was confirmed by depletion of these cells from the cultures which prevented the immune complex-mediated oligodendroglial degeneration. Canine distemper virus-immune complex-induced oligodendroglial pathology is thought to be mediated by toxic factors released from stimulated macrophages. this bystander effect demonstrated here in vitro may be relevant to the mechanisms of demyelination in vivo, in which virus persistence plays an important role.

Neuropathological and molecular comparison between clinical and asymptomatic bovine spongiform encephalopathy cases

Interest in the proper neuropathological and molecular characterization of bovine spongiform encephalopathy (BSE) has increased since asymptomatic and atypical cases were detected in the cattle population by active disease surveillance. In this respect we investigated a total of 95 confirmed BSE cases originating from different active and passive surveillance categories (clinical suspects, emergency-slaughter, fallen stock and routinely slaughter) in Switzerland for their neuropathological and molecular phenotype. We looked for measurable differences between these categories in lesion profile, severity of spongiform change, degree of astrocytosis as well as immunohistochemical and molecular patterns of the disease-associated isoform of the prion protein (PrPd) in the caudal brainstem. Our results indicate significantly higher intensities of spongiform change in clinically affected compared to asymptomatic BSE cases. Similar effects were in trend observed for the intensities of PrPd deposition and astrocytosis, whereas the frequencies of morphological PrPd types and the molecular patterns in Western immunoblot were not different. Importantly, none of the animals included in this study revealed features of atypical BSE. Taken together, this study suggests that both clinically affected as well as asymptomatic Swiss BSE cases in cattle share the neuropathological and molecular phenotype of classical BSE and that asymptomatic classical BSE cases are at a pre-clinical stage of the disease rather than representing a true sub-clinical form of BSE.

Field performance of two rapid screening tests in active surveillance of transmissible spongiform encephalopathies in small ruminants

Recently, screening tests for monitoring the prevalence of transmissible spongiform encephalopathies specifically in sheep and goats became available. Although most countries require comprehensive test validation prior to approval, little is known about their performance under normal operating conditions. Switzerland was one of the first countries to implement 2 of these tests, an enzymelinked immunosorbent assay (ELISA) and a Western blot, in a 1-year active surveillance program. Slaughtered animals (n = 32,777) were analyzed in either of the 2 tests with immunohistochemistry for confirmation of initial reactive results, and fallen stock samples (n = 3,193) were subjected to both screening tests and immunohistochemistry in parallel. Initial reactive and false-positive rates were recorded over time. Both tests revealed an excellent diagnostic specificity (> 99.5%). However, initial reactive rates were elevated at the beginning of the program but dropped to levels below 1% with routine and enhanced staff training. Only those in the ELISA increased again in the second half of the program and correlated with the degree of tissue autolysis in the fallen stock samples. It is noteworthy that the Western blot missed 1 of the 3 atypical scrapie cases in the fallen stock, indicating potential differences in the diagnostic sensitivities between the 2 screening tests. However, an estimation of the diagnostic sensitivity for both tests on field samples remained difficult due to the low disease prevalence. Taken together, these results highlight the importance of staff training, sample quality, and interlaboratory comparison trials when such screening tests are implemented in the field.

[TSE surveillance in small ruminants and pigs: a pilot study].

Switzerland is controlling Transmissible Spongiform Encephalopathies (TSE) in cattle (BSE) and small ruminants (scrapie). Since BSE is potentially transmissible to sheep, goats or pigs through feeding of contaminated meat and bone meal, implementation of an active surveillance programme for TSE in these species is discussed. The aim of this pilot study was to obtain preliminary data on the prevalence ofTSE and other neurological disorders in these populations. For that purpose, a total of 398 perished and 825 slaughtered adult small ruminants and pigs was examined for the presence of neuropathological changes. None of these animals revealed positive for TSE. However, the investigations demonstrated that perished sheep and goats exhibited a higher prevalence of relevant neuropathological changes when compared with slaughtered animals. From these results, it is concluded that perished small ruminants are probably a risk population for TSE and should be considered as target populations for an active surveillance programme.

Scrapie-Überwachung in der Schweiz. I. Klinische Aspekte von neurologischen Erkrankungen bei Schaf und Ziege

Die Traberkrankheit (Scrapie) der Kleinwiederkauer manifestiert sich klinisch sehr uneinheitlich. Die Hauptsymptome Bewegungsstorungen, Sensibilitatsstorungen, Verhaltensstorungen und Auszehrung kommen selten gemeinsam vor. Es sind Scrapie-Falle beschrieben, bei denen nur einer dieser Symptomkomplexe zu finden ist. Entsprechend problematisch ist die klare Definition eines klinischen Verdachtsfalles. Auch Tiere mit anderen das ZNS beeinflussenden Erkrankungen wie Listeriosis, Polioenzephalomazie, Zerebrospinale Nematidiasis und Enterotoxamie zeigen bei sorgfaltiger klinisch-neurologischen Untersuchung Scrapie-Symptome und sind als Verdachtsfalle anzusehen. Eines von 22 in unserer Studie intensiv klinisch untersuchten Kleinwiederkauern, eine Ziege mit Gliomatosis cerebri und Haarlingen, zeigte die meisten Scrapie-Symptome. Der Befund des einseitigen Kopfnervenausfalles konnte als quasi-Ausschlusskriterium dienen. Die Resultate zeigen die Bedeutung der postmortalen Untersuchungen des Gehirns von neurologisch...

Papillary Tumor of the Pineal Region of a Dog

A 3-year-old, intact, male Beagle dog developed clinical signs of pleurothotonus and altered head position to the right, neck pain, nystagmus, hyperreflexia of the left forelimb, and hyperextension of both forelimbs. Magnetic resonance imaging enabled a tentative diagnosis of thalamic neoplasia with incidental hydromyelia at the level of the second cervical vertebra. The animal was euthanatized due to the poor prognosis, and a necropsy was performed. A large, well-demarcated, nonencapsulated, and focally infiltrative mass was present in the approximate location of, and effacing, the pineal gland. The mass was composed of densely packed polyhedral neoplastic cells that exhibited epithelial characteristics, such as intercellular junctions, and contained carbohydrate granules and occasionally melanin granules. Immunohistology confirmed that neoplastic cells expressed neuron-specific enolase and, in a small proportion, cytokeratin. These combined findings led to the diagnosis of a papillary tumor of the pineal region, a tumor not previously described in dogs.