Cats, Pumas, Cheetahs
Mice, Guinea Pigs, Hamsters
Goats, Pigs
Mule Deer, Elk, Kudus, Oryx, Elands
Marmosets, Squirrel Monkeys
Mink
Ostrich
Spongiform encephalopathies in captive wild animals in the British Isles


Animals Dead from Bovine Spongiform Encephalitis

NZ Veterinary Correspondent
Tue, 2 July 1996

[Over 50 house cats have died from FSE in England.There is an issue on the extent of the infection, maternal trnasmission, passage by fleas, early onset, geography of infection, whether US and Canadian cats have been getting it as well.]

"Paul Brown recently commented on the cat situation. [] The situation is probably underrecorded because of the nature of cats. If one's cat does not return it is presumed to have gone astray or hit by a car. If one brings their cat to the vet with ataxia, it's automatically diagnosed as Feline Vestibular Disease and put down. The situation could be far more extensive than it is and as a result of our current veterinary practices, we would not know. Special attention to the dairy states might prove interesting.


* Pearson, G. R.; Wyatt, J. M.; Gruffydd-Jones, T. J.; Hope, J.; Chong, A.; Higgins, R. J.; Scott, A. C.; Wells, G. A. H. Feline spongiform encephalopathy: fibril and PrP studies. Veterinary Record 1992 131 14 307-310

The brains from 18 cats were examined for the presence of the fibrils and modified PrP protein which are molecular diagnostic markers for scrapie-like diseases. Thirteen cats were referred with clinical neurological signs potentially indicative of feline spongiform encephalopathy (FSE). Of these, 5 had histopathological changes of FSE, 5 had other lesions of the central nervous system, and in 3 the brain was normal. The remaining 5 cats had no clinical neurological signs and were selected as controls. Fibrils and modified PrP protein were found in the brains of the 5 cats with FSE and in one of the cats with neurological signs but no histopathological changes in the central nervous system. Fibrils were present in the absence of modified PrP in the brains of 2 cats, one with neurologi* Bratberg, B.; Ueland, K.; Wells, G. A. H. Feline spongiform encephalopathy in a cat in Norway. Veterinary Record 1995 136 17 444 Norway

A 6-year-old female domestic shorthaired cat from the Oslo area was presented with ataxia of gait with dysmetria and hypermetria of the extremities, hyperaesthesia was a constant feature. The neurological signs progressed despite treatment and the cat was humanely destroyed. At PM examination no gross lesions were found. Histopathological examination revealed spongiform change in the brain and spinal cord grey matter. Neuronal vacuolation was present in the spinal cord and the red nucleus of the midbrain. Immunostaining using the mouse monoclonal anti-hamster PrP antibody, 3F4 demonstrated extensive immunolabelling in the grey matter neuropil of the head of the caudate nucleus, putamen and the cerebral cortex as obtained previously in cases of feline spongiform encephalopathy (FSE). This appears to be the first case of FSE in a domestic cat outside the UK. The cat had been fed several imported commercial dry cat food products. There was no genetic link or any form of contact with FSE cases in the UK.

* Wyatt, J. M.; Pearson, G. R.; Smerdon, T.; Gruffydd-Jones, T. J.; Wells, G. A. H. Spongiform encephalopathy in a cat. [Correspondence]. Veterinary Record 1990 126 20 513 UK

A 5-year-old neutered male Siamese cat was presented with a 6-week history of progressive forelimb and hindlimb ataxia. Hypermetria of the forelimb and hindlimb gait and postural difficulties were noted. After a few days the cat became quiet and depressed and there was no response to treatment. Euthanasia was carried out. There were no macroscopic post mortem changes. Histopathological examination revealed a spongiform encephalopathy characterised principally by grey matter neuropil spongiosis, vacuolation of neuronal perikarya and an astrocytic response. There were no significant changes in liver, kidney, lung or spleen. This is the first report of a naturally occurring disease in a domestic cat with microscopic changes consistent with the transmissible spongiform encephalopathies due to unconventional viruses.

* Pearson, G. R.; Wyatt, J. M.; Henderson, J. P.; Gruffydd-Jones, T. J. Feline spongiform encephalopathy: a review. Veterinary Annual 1993 33 1-10

A novel scrapie-like spongiform encephalopathy was first seen in a domestic cat in 1990 and since then 23 further cases have been recorded in the UK. This review covers clinical signs, pathology, the presence of fibrils and prion proteins and transmission.

This paper reviews the recently recognised condition of feline spongiform encephalopathy and its importance as a neurological disorder of cats. Its possible origin and relationship to other transmissible spongiform encephalopathies are discussed.

* Feline Practice 1993 21 3 7-9 UK

Between April 1990 and February 1992, a total of 24 cases of feline spongiform encephalopathy (FSE) was reported in the UK. Most affected cats were between 4 and 9 years of age. There were more males than females but this finding is not significant due to small number of involved individuals. Most cats were non-pedigree and came from a wide range of geographical locations throughout the UK. Clinical signs developed gradually over several weeks in all cases. The first signs to be noted were often changes in behaviour. These were either manifested with unprovoked attacks on family members or other household pets or as increased timidity with cats, with a tendency to hide and avoid contact. Locomotor abnormalities developed in all cases and generally affected hindlimbs before forelimbs. The cats became ataxic and often further developed a rapid, crouching, hypermetric gait. Other signs included hyperaesthesia to touch and sound, decreased grooming behaviour. The cats were killed on humane grounds. Significant gross lesions were not observed. Changes were found only in the central nervous system and consisted of vacuolation of grey matter neurophil and neuronal perikarya with neuronal loss and gliosis. Similar lesions were also found in the spinal cord of some cats. All affected cats have been fed a variety of foods ranging from proprietary cat foods to table scraps. So far no cases of FSE have been reported in domestic cats outside the UK.

* Leggett, M. M.; Dukes, J.; Pirie, H. M. A spongiform encephalopathy in a cat. Veterinary Record 1990 127 24 586-588 UK

In 1990 a 7.5 year-old cat which developed a change of temperament, with muscle tremors, ataxia and pupillary dilatation was suspected and later confirmed histopathologically to have a spongiform encephalopathy. The cat had been fed throughout life on a proprietary canned diet, supplemented with dry cat food and fresh cooked chicken and had never been boarded in a cattery. This is the fourth case of spongiform encephalopathy in a British cat which has been confirmed by the Central Veterinary Laboratory. The case is of special interest in view of the widespread concern about spongiform encephalopathies as a result of the recent epidemic of bovine spongiform encephalopathy.

*Fleetwood, A. J.; Furley, C. W. Spongiform encephalopathy in an cats. [Correspondence]. Veterinary Record 1990 126 16 408-409 UK

An eland (Taurotragus oryx) born at a zoo in England in April 1987 and kept on the zoo premises on a grass enclosure developed clinical signs on 12 December, 1989 when the animal was 3 months pregnant. Initially the disease was characterized by high stepping of the hind limbs, fine muscular tremors and loss of weight. Three to four days later signs of circling and head pressing were seen. The animal became increasingly dull, developed a clear nasal discharge, hypersalivation, became recumbent and died on 20 December, 1989. No significant lesions were evident on gross PM examination but histopathological examination of the brain revealed a spongiform encephalopathy. The animal may have been exposed to the causal agent of bovine spongiform encephalopathy or scrapie through processed animal protein fed in the diet. This appears to be the first report of a spongiform encephalopathy in an eland.

* Pearson, G. R.; Gruffydd-Jones, T. J.; Wyatt, J. M.; Hope, J.; Chong, A.; Scott, A. C.; Dawson, M.; Wells, G. A. H. Feline spongiform encephalopathy. [Correspondence]. Veterinary Record 1991 128 22 532 UK

The diagnosis of 7 cases of naturally occurring scrapie-like encephalopathy in the domestic cat are reported. It is suggested that the disease in cats is called feline spongiform encephalopathy (FSE). The cases were diagnosed on histopathological examination of the brain. Pathologically modified host protein, PrP was also demonstrated in the brain of each case both by immunoblotting and by detection of fibrils.

* Wyatt, J. M.; Pearson, G. R.; Smerdon, T. N.; Gruffydd-Jones, T. J.; Wells, G. A. H.; Wilesmith, J. W. Naturally occurring scrapie-like spongiform encephalopathy in five domestic cats. Veterinary Record 1991 129 11 233-236

This paper describes the clinical and pathological findings in 5 cats with spongiform encephalopathies, including further observations on the original case. All the cats had a progressive, neurological disease involving locomotor disturbances, abnormal behaviour and, in most cases, altered sensory responses. Histopathological examination of the central nervous system revealed changes pathognomonic of the scrapie-like encephalopathies, including widespread vacuolation of neuronal perikarya and an astrocytic reaction.

* Peet, R. L.; Curran, J. M. Spongiform encephalopathy in an imported cheetah. Australian Veterinary Journal 1992 69 7 171

A 5.5-year-old cheetah at the Broome Zoo was observed to be ataxic and disorientated during December 1991. Blood samples showed a strong positive titre to toxoplasmosis. The animal was killed 4 weeks after the onset of clinical symptoms when it exhibited falling, locomotory weakness and distress. PM examination showed no visible lesions. Histopathology showed widespread axonal degeneration and demyelination of all tracts in the spinal cord. Severe spongiform change was visible in the grey matter of the neuroaxis, especially in the corpus striatum, midbrain and thalamic areas. On the basis of neuropathology, a diagnosis of spongiform encephalopathy was made and samples were forwarded to the reference laboratory in Weybridge, UK. The presence of fibrils was confirmed by electron microscopy. Meanwhile, a quarantine order was placed on the zoo and the previously buried carcasses were disinterred and incinerated. The cheetah was born at Marwell Zoo in England on 16 June 1986 and imported together with 2 littermates to Australia on 9 May 1989. Marwell Zoo practised a 'feeding in' of culled carcasses to other zoo animals, particularly felids and canids. The cheetah probably ingested the infective agent while still in England. This is the first diagnosis of spongiform encephalopathy in a cheetah and of spongiform encephalopathy in a zoo animal outside the UK.

* Willloughby, K.; Kelly, D. F.; Lyon, D. G.; Wells, G. A. H. Spongiform encephalopathy in a captive puma (Felis concolor). Veterinary Record 1992 131 19 431-434 UK

In 1991 a captive adult puma developed ataxia, a hypermetric gait and whole body tremor. Her diet consisted of chicken and rabbit carcasses and parts of cattle carcasses. She had no known access to sheep or goat meat. The signs progressed over a period of 6 weeks. Histopathological examination following euthanasia demonstrated spongiform encephalopathy, gliosis and mild non-suppurative meningoencephalitis. Immunostaining with a polyclonal antiserum revealed prion protein (PrP) associated with these changes in sections of cervical spinal cord and medulla. This is the first confirmed case of a scrapie-like spongiform encephalopathy described in a non-domestic cat in the United Kingdom.


* Bruce, M.; Chree, A.; McConnell, I.; Foster, J.; Pearson, G.; Fraser, H. Transmission of bovine spongiform encephalopathy and scrapie to mice: strain variation and the species barrier. Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences 1994 343 1306 405-411

Results from various transmission experiments are reviewed. Transmissions of bovine spongiform encephalopathy (BSE) from 7 unrelated cattle sources gave remarkably uniform disease characteristics in mice, differing from over 20 previous and contemporary transmissions of sheep and goat scrapie. Transmissions to mice of spongiform encephalopathy from 6 species (including sheep and goats) experimentally or naturally infected with BSE gave similar results to direct BSE transmissions from cattle. It is concluded that the BSE agent has retained its identity when passaged through a range of species and the 'donor' species has little specific influence on disease characteristics in mice, adding to evidence for an agent-specific informational molecule. On transmission of BSE or scrapie to mice the incubation periods are long compared with subsequent mouse-to-mouse passages (the 'species barrier'). Contributing factors include a low efficiency of infection on interspecies transmission, the apparent failure of intracerebrally injected 'foreign' inoculum to establish infection directly in mouse brain and the selection of variant strains of agent which replicate most readily in the new host species.

* Collinge, J.; Palmer, M. S.; Sidle, K. C. L.; Hill, A. F.; Gowland, I.; Meads, J.; Asante, E.; Bradley, R.; Doey, L. J.; Lantos, P. L. Unaltered susceptibility to BSE in transgenic mice expressing human prion protein. Nature (London) 1995 378 6559 779-783

Two lines of transgenic mice expressing human PrP at the levels of 50 (Tg110) and 200% (Tg152) were challenged intracerebrally with Creutzfeldt-Jacob disease (CJD) inocula from a human case and with a second passage of a single isolate of human prions from a CJD case and the species type of PrP<sup(Sc)> was determined by immunodot blot. Incubation periods to CJD prions were 484<+->40 days and 287<+->12 days in Tg110 and Tg152 mice, respectively. The same type of mice were further inoculated with bovine spongiform encephalopathy (BSE) inocula. Incubation periods were not significantly different between the transgenic mice and the non-transgenic controls. It is suggested that the failure of human PrP to shorten incubation times indicates an absence of pathological bovine PrP<sup(Sc)>/human PrP<sup(C)> interactions. No human PrP<sup(Sc)> was detected by immunodot blot in the brains of the mice. A further experiment, the results of which are still awaited, was carried out by inoculating BSE into mice expressing only human PrP. The mice remained well at 264 days after inoculation.

* Wyatt, J. M.; Pearson, G. R.; Gruffydd-Jones, T. J.

304. Collinge, J.; Palmer, M. S.; Sidle, K. C. L.; Hill, A. F.; Gowland, I.; Meads, J.; Asante, E.; Bradley, R.; Doey, L. J.; Lantos, P. L. Unaltered susceptibility to BSE in transgenic mice expressing human prion protein. Nature (London) 1995 378 6559 779-783

Two lines of transgenic mice expressing human PrP at the levels of 50 (Tg110) and 200% (Tg152) were challenged intracerebrally with Creutzfeldt-Jacob disease (CJD) inocula from a human case and with a second passage of a single isolate of human prions from a CJD case and the species type of PrP<sup(Sc)> was determined by immunodot blot. Incubation periods to CJD prions were 484<+->40 days and 287<+->12 days in Tg110 and Tg152 mice, respectively. The same type of mice were further inoculated with bovine spongiform encephalopathy (BSE) inocula. Incubation periods were not significantly different between the transgenic mice and the non-transgenic controls. It is suggested that the failure of human PrP to shorten incubation times indicates an absence of pathological bovine PrP<sup(Sc)>/human PrP<sup(C)> interactions. No human PrP<sup(Sc)> was detected by immunodot blot in the brains of the mice. A further experiment, the results of which are still awaited, was carried out by inoculating BSE into mice expressing only human PrP. The mice remained well at 264 days after inoculation.

spongiform encephalopathy.

* Merz, P. A.; Somerville, R. A.; Wisniewski, H. M.; Manuelidis, L.; Manuelidis, E. E. Scrapie-associated fibrils in Creutzfeldt-Jakob disease. Nature, UK 1983 306 5942 474-476

Scrapie associated fibrils (SAF) that have been described in the brain of scrapie affected mice and hamsters (VB 51, abst 5599) were found in the brain of a human case of Creutzfeldt-Jakob disease (CJD) and the brain a case of the familial Gerstmann-Straussler syndrome, which may be a variant of CJD; SAF were not present in three control brains. SAF were also found in the brains of clinically affected guinea pigs, hamsters and mice in which CJD tissue was passaged, and also the spleens of scrapie affected mice and a CJD affected hamster. Their presence in spleen as well as brain tissue. indicates that this may represent the infective agent and not be a pathological response to the disease.

* Narang, H. K. Scrapie-associated tubulofilamentous particles in scrapie hamsters. Intervirology 1992 34 2 105-111

Examination of thin sections from the cerebral cortex of scrapie-infected hamster brains detected characteristic circular 26-30 nm diameter tubulofilamentous particles, identical to those previously described in both experimentally induced scrapie in mice and hamsters and natural scrapie of sheep, bovine spongiform encephalopathy and human Creutzfeldt-Jakob disease and mice and chimpanzees infected with Creutzfeldt-Jakob disease. Longitudinal forms of tubulofilamentous particles were also observed in dendrites and myelinated axons. Both transverse and longitudinally cut particles were readily distinguished from microtubules and synaptic vesicles, thus there appears to be no relationship between tubulofilamentous particles, and microtubules or synaptic vesicles.

* Prusiner, S. B.; Cochran, S. P.; Alpers, M. P. Transmission of scrapie in hamsters. Journal of Infectious Diseases 1985 152 5 971-978

Hamsters developed scrapie 100-160 days after eating either scrapie-infected hamsters or infected brain. The clinical signs and neuropathology of scrapie transmitted by cannibalism were identical to those observed after intracerebral or intraperitoneal inoculation of the agent. Oral transmission of scrapie appears to be extremely inefficient. Cannibalism requires a dose of the scrapie agent about 10<sup(9)> times greater than that needed to produce the disease by intracerebral injection for comparable periods of incubation. These results provide evidence for oral transmission of scrapie and may explain the spread of kuru by cannibalism. The inefficiency of oral infection with scrapie might also have implications for understanding the sporadic occurrence and worldwide distribution of Creutzfeldt-Jakob disease.

* Fraser, H.; Bruce, M. E.; Chree, A.; McConnell, I.; Wells, G. A. H. Transmission of bovine spongiform encephalopathy and scrapie to mice. Journal of General Virology 1992 73 8 1891-1897

Transmission from 4 cases of bovine spongiform encephalopathy (BSE) to mice resulted in neurological disease in 100% of recipient animals, after incubation periods of between 265 and 700 days after injection. The results from the 4 cases were very similar to one another. There were major differences in the incubation period between the 4 inbred strains of mice tested, and even between strains of the same Sinc genotype, and the incubation periods of Sinc heterozygote mice were much longer than those for any of the inbred strains. Transmission from a case of natural scrapie differed in two important respects: there were no differences in the incubation period between mouse strains of the same Sinc genotype, and that of the heterozygotes was between those of the Sinc homozygotic parental strains. The distribution of vacuolar degeneration in the brains of mice infected with scrapie also differed from those infected with the BSE isolates. Transmission was also achieved from formol-fixed BSE brain. The results show that the same strain of agent caused disease in the BSE cases, and that the relationship of BSE to scrapie in sheep is unclear.

* Jeffrey, M.; Scott, J. R.; Williams, A.; Fraser, H. Ultrastructural features of spongiform encephalopathy transmitted to mice from three species of bovidae. Acta Neuropathologica 1992 84 5 559-569

The ultrastructural neuropathology of mice experimentally inoculated with brain tissue of nyala (Tragelaphus angasi; subfamily Bovinae), or kudu (Tragelaphus strepsiceros; subfamily Bovinae) affected with spongiform encephalopathy was compared with that of mice inoculated with brain tissue from cows (Bos taurus; subfamily Bovinae) with bovine spongiform encephalopathy (BSE). As fresh brain tissue was not available for nyala or kudu, formalin-fixed tissues were used for transmission from these species. The effect of formalin fixation was compared with that of fresh brain in mice inoculated with fixed and unfixed brain tissue from cows with BSE. The nature and distribution of the pathological changes were similar irrespective of the source of inoculum or whether the inoculum was from fresh or fixed tissue. Vacuolation caused by loss of organelles and swelling was present in dendrites and axon terminals. Vacuoles were also seen as double-membrane-bound and single-membrane-bound structures within myelinated fibres, axon terminals and dendrites. Vacuoles are considered to have more than one morphogenesis but the structure of vacuoles in this study was nevertheless similar to previous descriptions of spongiform change in naturally occurring and experimental scrapie, Creutzfeldt-Jakob disease, Gerstmann-Straussler-Scheinker syndrome and kuru. Other features of the ultrastructural pathology of the transmissible spongiform encephalopathies including dysytrophic neurites and scrapie-associated particles of tubulovesicular bodies were also found. Neuronal autophagy was a conspicuous finding. It is suggested that excess prion protein (PrP) accumulation, or accumulation of the scrapie-associated protease-resistant isoform of PrP, may lead to localised sequestration and phagocytosis of neuronal cytoplasm and to neuronal loss.

* Butler, D. A.; Scott, M. R. D.; Bockman, J. M.; Borchelt, D. R.; Taraboulos, A.; Hsiao, K. K.; Kingsbury, D. T.; Prusiner, S. B. Scrapie-infected murine neuroblastoma cells produce protease-resistant prion proteins. Journal of Virology 1988 62 5 1558-1564

There is evidence that prions contain protease-resistant sialoglycoproteins, designated PrP<sup(Sc)>, encoded by a cellular gene. The prion protein (PrP) gene also encodes a normal cellular protein designated PrP<sup(C)>. Clonal cell lines were established which support the replication of mouse scrapie or Creutzfeldt-Jakob disease prions. Mouse neuroblastoma N2a cells were exposed to mouse scrapie prions and cloned. After limited proteinase K digestion, three PrP-immunoreactive proteins with apparent molecular masses of 20-30 kilodaltons were detected in extracts of scrapie-infected N2a cells by Western (immuno-) blotting. The identity of these PrP<sup(Sc)> molecules was confirmed using monospecific antiserum raised against a synthetic peptide corresponding to a portion of the prion protein. Those clones synthesizing PrP<sup(Sc)> molecules possessed scrapie prion infectivity as measured by bioassay; clones without PrP<sup(Sc)> showed no infectivity. Detection of PrP<sup(Sc)> molecules in scrapie-infected N2a cells supports the contention that PrP<sup(Sc)> is a component of the infectious scrapie particle.

* Barlow, R. M.; Middleton, D. J. Dietary transmission of bovine spongiform encephalopathy to mice. Veterinary Record 1990 126 5 111-112

Groups of weanling female (57B1 and CRH) mice were fed minced brain tissue collected from 4 advanced clinical cases of bovine spongiform encephalopathy (BSE). The brain tissue was fed at night when the mice were also given pooled cerebrospinal fluid diluted in water to replace normal drinking water. Commercial rodent nuts containing only vegetable protein were fed during the day; control mice received only the nuts. The onset of neurological signs was insidious and progressed to paresis with remissions in 4 to 6 weeks. The first 5 cases in C57B1 mice were killed 15-18 months after the start of feeding at which time no neurological disease was evident in the CRH mice. Histological examination of the brains of the clinically affected mice revealed vacuolation of neurones and neuropil in the medulla and midbrain together with prion protein aggregates in the neuropil. These features, considered to be diagnostic of subacute transmissible spongiform encephalopathy, were absent from control mice killed at the same time. Mice fed various other tissue pools from the 4 cases of BSE will be kept for their lifespan and should allow an assessment to be made of the relative infectivity of the various tissues.


* Kamin, M.; Patten, B. M. Creutzfeldt-Jakob disease. Possible transmission to humans by consumption of wild animal brains. American Journal of Medicine 1984 76 1 142-145

Although the natural mode of spread of the agent responsible for Creutzfeldt-Jakob disease is not known, several reports suggest transmission through eating contaminated food or brain. Four patients with Creutzfeldt-Jakob disease are described, who had a history of eating the brains of wild goat or squirrel. Those patients indicate the possible acquisition of Creutzfeldt-Jakob disease by ingestion of the agent from a presumptive reservoir in the central nervous system of wild animals.

* Wood, J. L. N.; Done, S. H. Natural scrapie in goats: neuropathology. Veterinary Record 1992 131 5 93-96 UK

The brains of the 20 goats affected with natural scrapie received at the Central Veterinary Laboratory, Weybridge, UK since 1975 were examined microscopically. Lesions of a spongiform encephalopathy were found in the brainstem, cerebellum, diencephalon, corpus striatum, and also in the neopallium or cerebral cortex. The lesions in the neopallium have not previously been reported in natural scrapie in goats. Deposits of amyloid were present in the thalamus in 3 of the 20 goats.

* Perrin, G. G.; Perrin, G. J.; Benoit, C. Detection of scrapie-associated fibrils in scrapie in goats. Veterinary Record 1991 129 19 432 France

Three goats, 2 4-year-old sisters and the 3-year-old progeny of one of them were examined for wasting, fine head tremor and over-excitability triggered by noise. They all came from a flock in which scrapie had previously been suspected, but never confirmed. The animals were killed and brain samples cultured for Listeria were negative. Histopathology showed the presence of spongiform encephalopathy patterns as single and multiple vacuolisation of neuronal cytoplasm in the medulla. Electron microscopy revealed clusters of scrapie-associated fibrils.

* Dawson, M.; Wells, G. A. H.; Parker, B. N. J.; Scott, A. C. Primary parenteral transmission of bovine spongiform encephalopathy to the pig. [Correspondence]. Veterinary Record 1990 127 13 338

Ten, weaned one- to two-week old piglets from a specific pathogen free breeding herd were inoculated under halothane anaesthesia by simultaneous injections intracerebrally (0.5 ml) intravenously (1 to 2 ml) and intraperitoneally (8 to 9 ml) with an inoculum consisting of 10% saline suspension of pooled homogenised brainstem from 4 natural bovine spongiform encephalopathy cases. Control piglets were similarly inoculated with saline. After 69 weeks one challenged pig showed mild aggressive behaviour towards the animal attendants. Intermittent inappetence and depression were also noted. Within one week the behavioural changes included aimless biting activity and there was mild symmetrical ataxia. The ataxia progressed and 5 weeks after onset of signs the gait ataxia was generalised with hypermetria and wide-based stance. At this time the pig was killed. Histopathological examination of the brain revealed spongiosis of grey matter neuropil with greatest intensity in the medial geniculate body, superior colliculus and corpus striatum. There was sparse vacuolation of neuronal perikarya in the dorsal nucleus of the vagina nerve and widespread astrocytic reaction. Characteristic fibrils associated with transmissible spongiform encephalopathies were detected by electron microscopy.


* Guiroy, D. C.; Williams, E. S.; Yanagihara, R.; Gajdusek, D. C. Topographic distribution of scrapie amyloid-immunoreactive plaques in chronic wasting disease in captive mule deer (Odocoileus hemionus hemionus). Acta Neuropathologica 1991 81 5 475-478

Chronic wasting disease (CWD), a progressive neurological disorder of captive mule deer, black-tailed deer, hybrids of mule deer and white-tailed deer and Rocky Mountain elk, is characterized by widespread spongiform change of the neuropil, intracytoplasmic vacuolation in neuronal perikarya and astrocytic hypertrophy and hyperplasia. The topographic distribution of amyloid plaques reactive to antibodies prepared against scrapie amyloid in CWD-affected captive mule deer is described. Scrapie amyloid-immunoreactive plaques were found in the cerebral gray and white matter, in deep subcortical nuclei, in isolation or in clusters in areas of vacuolation, and perivascularly, in subpial and subependymal regions. In the cerebellum, immunoreactive amyloid plaques were observed in the molecular, pyramidal and granular layers. Scrapie amyloid-immunoreactive deposits were also seen in neuronal perikarya. Furthermore, amyloid plaques in CWD-affected captive mule deer were alcianophilic at 0.3 M magnesium chloride indicating the presence of weakly to moderately sulphated glycosaminoglycans. These results confirm that CWD in captive mule deer belongs to the subacute virus spongiform encephalopathies.

* Williams, E. S.; Young, S. Neuropathology of chronic wasting disease of mule deer (Odocoileus hemionus) and elk (Cervus elaphus nelsoni). Veterinary Pathology 1993 30 1 36-45 USA\Wyoming

The pathology of the central nervous system of 9 mule deer and 6 elk with chronic wasting disease, a spongiform encephalopathy of mule deer and elk, was studied by light microscopy. Lesions were similar in both species and were characterized by spongiform transformation of gray matter, intracytoplasmic vacuolation of neurons, neuronal degeneration and loss, astrocytic hypertrophy and hyperplasia, occurrence of amyloid plaques, and absence of inflammatory response. Distribution and severity of lesions were evaluated at 57 locations; there were only minor differences between deer and elk. Consistent, severe lesions occurred in olfactory tubercule and cortex, hypothalamus, and the parasympathetic vagal nucleus of deer, and sections examined from these regions would be sufficient to establish a diagnosis of chronic wasting disease. Lesions were milder in these locations in elk but were sufficiently apparent to be diagnostic. Other differences included increased severity of lesions in some thalamic nuclei in elk in contrast to deer, the occurrence of amyloid plaques detected by haematoxylin and eosin and histochemical stains in deer in contrast to elk, and the presence of milk white matter lesions in elk but not in deer. Lesions of chronic wasting disease were qualitatively comparable to those of scrapie, bovine spongiform encephalopathy, transmissible mink encephalopathy, and the human spongiform encephalopathies. Topographical distribution and lesion severity of chronic wasting disease were most similar to those of scrapie and bovine spongiform encephalopathy. Duration of clinical disease did not affect lesion distribution or severity in either species.

* Guiroy, D. C.; Williams, E. S.; Liberski, P. P.; Wakayama, I.; Gajdusek, D. C. Ultrastructural neuropathology of chronic wasting disease in captive mule deer. Acta Neuropathologica 1993 85 4 437-444 USA

Chronic wasting disease (CWD), a progressive uniformly fatal neurological disorder, is characterized neuropathologically by intraneuronal vacuolation, spongiform change of the neuropil and astrocytic hyperplasia and hypertrophy. Ultrastructural neuropathological findings consist of extensive vacuolation in neuronal processes, within myelin sheaths, formed by splitting at the major dense lines or within axons; dystrophic neurites (dendrites, axonal preterminals and myelinated axons containing degenerating mitochondria and pleomorphic, electron-dense inclusion bodies); prominent astrocytic gliosis; amyloid plaques; and giant neuronal autophagic vacuoles. Other findings include activated macrophages and occasional spheroidal structures containing densely packed fibrillar material of unknown origin, abundant structures suggestive of degenerating microtubules entrapped in filamentous masses, vacuoles and myelin figures. Similar findings have been previously observed in scrapie-infected hamsters and Creutzfeldt-Jakob disease (CJD)-infected mice, bovine spongiform encephalopathy, and CJD indicating that CWD in captive mule deer (Odocoileus hemionus hemionus) belongs to the subacute spongiform encephalopathies (transmissible brain amyloidoses)

* Guiroy, D. C.; Williams, E. S.; Song, K. J.; Yanagihara, R.; Gajdusek, D. C. Fibrils in brains of Rocky Mountain elk with chronic wasting disease contain scrapie amyloid. Acta Neuropathologica 1993 86 1 77-80 USA

Recently, scrapie amyloid-immunoreactive plaques have been detected in brain tissues of chronic wasting disease (CWD) affected captive mule deer. Rocky Mountain elk and hybrids of captive mule deer and white-tailed deer. Abnormal fibrils were isolated from brain tissues of Rocky Mountain elk using negative-stain electron microscopy. These fibrils resemble those found in scrapie-infected hamster brain. Protein bands with relative molecular masses of 26 to 30 kilodaltons were shown to be immunoreactive to antibodies raised against scrapie amyloid by Western immunoblotting. Immuno-dot blot showed similar reactivity. These results support the clinical and pathological diagnosis of the disease and provide further evidence that CWD belongs to the subacute spongiform encephalopathies

* Kingsbury, D. T. Genetics of response to slow virus (prion) infection. Annual Review of Genetics 1990 24 115-132

This paper reviews the genetic control of neurodegenerative diseases that affect animals (scrapie, bovine spongiform encephalopathy, transmissible mink encephalopathy and chronic wasting disease of deer and elk) and humans. Studies on the influence of the host's genetic background on the susceptibility and incubation time of these diseases are discussed with data, not only on domestic animals and humans, but also on mice, including transgenics. Consideration is also given to work on recombinant DNA and restriction fragment length polymorphism studies on the host gene for prion protein (Prn-P), and to properties (host range, thermal stability, variability in lesions and strain differences) of the disease agents. It concludes that the host plays a significant role in determining the pattern of infection and incubation time for these diseases. Incubation time appears to be a stable property of the agent-host combination, and is not a stable property of the agent strain alone. Studies on gene transfer in transgenic mice strongly suggest that scrapie and the human diseases are probably all genetic diseases, and that the transmissible factor is host encoded. The host gene for prion protein is responsible for (1) the variation in the host response to the infecting material, (2) the incubation time, (3) the pathology of the brain and the deposition of amyloid, and (4) the host range of the resulting transmissible agent. In addition to Prn-p, another gene, Pid-1, may be involved in the control of incubation time, but its identity is obscure.

* Kirkwood, J. K.; Wells, G. A. H.; Wilesmith, J. W.; Cunningham, A. A.; Jackson, S. I. Spongiform encephalopathy in an Arabian (Oryx leucoryx) and a greater kudu (Tragelaphus strepsiceros). Veterinary Record 1990 127 17 418-420 UK

Clinical, pathological and epidemiological details of scrapie-like encephalopathies are described in an Arabian oryx and a greater kudu in a zoo in London, UK. Clinical signs included ataxia and loss of condition with a short, progressive clinical course (22 and three days, respectively). Histopathological examination of the brains revealed spongiform encephalopathy characteristic of that observed in scrapie and bovine spongiform encephalopathy (BSE). It seems probable that these cases have a common aetiology with BSE. Scrapie-like spongiform encephalopathies have now been described in five species of exotic artiodactyls in Britain indicating a, hitherto inapparent, wider range of ruminant species as natural hosts for these diseases.

* Kirkwood, J. K.; Wells, G. A. H.; Cunningham, A. A.; Jackson, S. I.; Scott, A. C.; Dawson, M.; Wilesmith, J. W. Scrapie-like encephalopathy in a greater kudu (Tragelaphus strepsiceros) which had not been fed ruminant-derived protein. Veterinary Record 1992 130 17 365-367

* Kirkwood, J. K.; Wells, G. A. H.; Cunningham, A. A.; Jackson, S. I.; Scott, A. C.; Dawson, M.; Wilesmith, J. W. Scrapie-like encephalopathy in a greater kudu (Tragelaphus strepsiceros) which had not been fed ruminant-derived protein. Veterinary Record 1992 130 17 365-367

A 19-month-old greater kudu (Tragelaphus strepsiceros), whose dam had died 15 months earlier with spongiform encephalopathy, required euthanasia after developing severe ataxia and depression with an apparently sudden onset. No macroscopic abnormalities were detected on PM examination but a scrapie-like spongiform encephalomyelopathy was apparent on histopathological examination of brain and segments of spinal cord. Negative stain electron microscopy of proteinase K-treated detergent extracts of tissue from the brain stem revealed the presence of scrapie associated fibrils, and a 25 to 28 kDa band comparable with that identified as abnormal PrP (prion protein) from the brains of domestic cattle with spongiform encephalopathy was detected using rabbit antiserum raised against mouse PrP. The animal was born 9 months after the statutory ban on the inclusion of ruminant-derived protein in ruminant feeds and, as no other possible sources of the disease were apparent, it appears likely that the infection was acquired from the dam.

* Kirkwood, J. K.; Cunningham, A. A.; Wells, G. A. H.; Wilesmith, J. W.; Barnett, J. E. F. Spongiform encephalopathy in a herd of greater kudu (Tragelaphus strepsiceros): epidemiological observations. Veterinary Record 1993 133 15 360-364 UK

A small herd of greater kudu, derived from 3 individuals, has been maintained at the Zoological Society of London since 1970. Spongiform encephalopathy has been diagnosed in 5 out of 8 of the animals born in this herd since 1987. With the possible exception of the first confirmed case, none of these is thought to have been exposed to feeds containing ruminant-derived protein. The pattern of incidence suggests that greater kudu are very susceptible to the disease and that natural lateral transmission may have occurred among them.

* Kirkwood, J. K.; Cunningham, A. A.; Austin, A. R.; Wells, G. A. H.; Sainsbury, A. W. Spongiform encephalopathy in a greater kudu (Tragelaphus strepsiceros) introduced into an affected group. Veterinary Record 1994 134 7 167-168 UK

A 39-month-old female greater kudu, which had been transferred to Regent's Park Zoo 27 months earlier, was destroyed in November 1992 after showing progressive neurological signs consistent with spongiform encephalopathy for 8 weeks. Spongiform encephalopathy was confirmed histologically. The kudu which had been born at Marwell Zoological Park, UK where no cases of the disease have been detected in the kudu herd, had apparently not eaten feeds containing ruminant-derived protein although her dam had been exposed to such feeds. The kudu had had contact with 2 other kudu at Regent's park in which the disease had been diagnosed; one had died 4 months after the kudu had been introduced and the second was found to have the condition when examined post mortem in February 1992. The possible modes of transmission are discussed.

* Cunningham, A. A.; Wells, G. A. H.; Scott, A. C.; Kirkwood, J. K.; Barnett, J. E. F. Transmissible spongiform encephalopathy in greater kudu (Tragelaphus strepsiceros). Veterinary Record 1993 132 3 68 UK

Three further cases of spongiform encephalopathy in greater kudu at the Zoological Society of London none of which was thought to have access to feed containing ruminant-derived protein are reported. The first case was male, born in May 1988 which developed rapidly progressive neurological signs when 37 months old. It was humanely slaughtered and spongiform encephalopathy was diagnosed on histopathological examination of the brain. The other 2 cases both males and born in October 1988 and August 1990 were slaughtered when 36 and 18 months old, respectively, because only one male can be kept in a kudu herd. Both were clinically normal at the time of slaughter and histological examination of the brains revealed sparse neuronal vacuolation with a bilaterally symmetrical and strictly localised distribution in the medulla oblongata. Sections of medulla immunostained with antiserum to PrP detected the protein principally in association with vacuolation, thus immunostaining was discrete in the subclinical cases and widespread in the clinical case. These cases provide further evidence that transmission of spongiform encephalopathy may have occurred in greater kudu.

* A 19-month-old greater kudu (Tragelaphus strepsiceros), whose dam had died 15 months earlier with spongiform encephalopathy, required euthanasia after developing severe ataxia and depression with an apparently sudden onset. No macroscopic abnormalities were detected on PM examination but a scrapie-like spongiform encephalomyelopathy was apparent on histopathological examination of brain and segments of spinal cord. Negative stain electron microscopy of proteinase K-treated detergent extracts of tissue from the brain stem revealed the presence of scrapie associated fibrils, and a 25 to 28 kDa band comparable with that identified as abnormal PrP (prion protein) from the brains of domestic cattle with spongiform encephalopathy was detected using rabbit antiserum raised against mouse PrP. The animal was born 9 months after the statutory ban on the inclusion of ruminant-derived protein in ruminant feeds and, as no other possible sources of the disease were apparent, it appears likely that the infection was acquired from the dam.

* Poidinger, M.; Kirkwood, J.; Almond, W. Sequence analysis of the PrP protein from two species of antelope susceptible to transmissible spongiform encephalopathy. Archives of Virology 1993 131 1/2 193-199 UK

The sequence of the coding regions of the PrP genes of the Arabian oryx and greater kudu were compared with the related sheep and bovine PrP gene sequences. The oryx gene sequence was very closely related to that of the sheep, encoding just one amino acid difference. The greater kudu gene sequence was more closely related to the bovine, encoding 4 amino acid differences. The effect that the gene sequences have on the transmission of spongiform encephalopathy to these antelope species is discussed.


* Baker, H. F.; Ridley, R. M.; Wells, G. A. H. Experimental transmission of BSE and scrapie to the common

marmoset. Veterinary Record 1993 132 16 403-406

Two young male common marmosets (Callithrix jacchus) were injected intracerebrally and intraperitoneally with a crude brain homogenate prepared from a cow with bovine spongiform encephalopathy (BSE). Two other marmosets were similarly injected with brain homogenate from a sheep with natural scrapie. The two animals injected with scrapie material developed neurological signs 38 and 42 months after injection and the 2 animals injected with BSE material developed neurological signs after 46 and 47 months. PM examination of the brains revealed spongiform encephalopathy especially in the basal nuclei and diencephalon of all the animals and, in addition, involvement of the cerebral cortex of the marmosets injected with scrapie material. The experiment extends the host range of experimental BSE to include a primate species.

* Merz, P. A.; Rohwer, R. G.; Kascsak, R.; Wisniewski, H. M.; Somerville, R. A.; Gibbs, C. J., Jr.; Gajdusek, D. C. Infection-specific particle from the unconventional slow virus diseases. Science, USA 1984 225 4660 437-440

Scrapie-associated fibrils (SAF) are reported in the brain of scrapie-infected squirrel monkeys, human cases of Creutzfeldt-Jakob disease (CJD), and a kuru-infected squirrel monkey. These fibrils were not found in a series of control brains from man and animals with central nervous system disorders resulting in histological and ultrastructural features or disease symptoms similar to those of scrapie, kuru and Creutzfeld-Jakob disease. SAF were expected but not found in one case of naturally occurring scrapie in sheep, two cases of kuru and one case of CJD in squirrel monkeys; possible reasons for this are mentioned. The distinguishing features of SAF, amyloid fibrils and paired helical filaments are described. It is suggested that SAF are a specific marker for slow virus diseases and may be the aetiological agent.


* Marsh, R. F.; Bessen, R. A.; Lehmann, S.; Hartsough, G. R. Epidemiological and experimental studies on a new incident of transmissible mink encephalopathy. Journal of General Virology 1991 72 3 589-594 USA

Epidemiological investigation of a new incident of transmissible mink encephalopathy (TME) in Stetsonville, Wisconsin, USA, in 1985 showed that the mink rancher had never fed sheep products to his mink but did feed them large amounts of products from fallen or sick dairy cattle. To investigate the possibility that this occurrence of TME may have resulted from exposure to infected cattle, two Holstein bull calves were injected intracerebrally with mink brain from the Stetsonville ranch. Each bull developed a fatal spongiform encephalopathy 18 and 19 months after inoculation, respectively, and both bovine brains passaged back into mink were highly pathogenic by either intracerebral or oral inoculation. These results suggest the presence of a previously unrecognized scrapie-like infection in cattle in the United States.


* Schoon, H. A.; Brunckhorst, D.; Pohlenz, J. Spongiform encephalopathy in an ostrich (Struthio camelus). A case report. Spongiforme Enzephalopathie beim Rothalsstrauss (Struthio camelus). Ein kasuistischer Beitrag. Tierarztliche Praxis 1991 19 3 263-265 Germany

Clinical signs and PM examinations including histopathology of an adult female ostrich destroyed because of central nervous and locomotion disorders are described. A male ostrich had died with similar symptoms earlier but PM examination was not done in that case. In this case systemic arteriosclerotic lesions were combined with adiposis and signs of spongiform encephalopathy, localized in the brain stem and the medulla oblongata. Aetiology remained unknown. Differential diagnosis is discussed and the disease compared to the similar findings in mammals with BSE/scrapie.

Listserve item form Germany
6.18.96

There is proof of TSE infections with German ostriches in zoos, fed with ordinary poultry feed and meat from cattle slaughtered as emergency cases respectively.


Spongiform encephalopathies in captive wild animals in the British Isles

Kirkwood JK; Cunningham AA 
Veterinary Science Group, Institute of Zoology, London. 
Vet Rec, 135: 13, 1994 Sep 24, 296-303 
Since 1986, scrapie-like spongiform encephalopathy has been diagnosed in 19 captive wild animals of eight species at or from eight zoological collections in the British Isles. The affected animals have comprised members of the family Bovidae: one nyala (Tragelaphus angasi), four eland (Taurotragus oryx), and six greater kudu (Tragelaphus strepsiceros), one gemsbok (Oryx gazella), one Arabian oryx (Oryx leucoryx), and one scimitar-horned oryx (Oryx dammah), and members of the family Felidae: four cheetah (Acinonyx jubatus) and one puma (Felis concolor). In addition, three cases of a spongiform encephalopathy of unknown aetiology have been reported in ostriches (Struthio camellus) from two zoos in north west Germany. Three features suggest that some of these cases may have been caused by the agent of bovine spongiform encephalopathy (BSE). First, they have been temporally and geographically coincident with the BSE epidemic. Secondly, in all the ungulates for which details are available, it is possible that either the affected animal itself, or the herd into which it was born or moved, had been exposed to proprietary feeds containing ruminant-derived protein or other potentially contaminated material, and all the carnivores had been fed parts of cattle carcases judged unfit for human consumption. Thirdly, the pathological results of inoculating mice with a homogenate of fixed brain tissue from the nyala and from one greater kudu were similar to the results of inoculating mice with BSE brain tissue.