Immunohistochemical study of PrPSc distribution in neural and extraneural tissues of two cats with feline spongiform encephalopathy
Monika M Hilbe , Guido G Soldati , Kati K Zlinszky , Sabina S Wunderlin and Felix F Ehrensperger
BMC Veterinary Research 2009, 5:11doi:10.1186/1746-6148-5-11
Published: 31 March 2009
Abstract (provisional) Background Two domestic shorthair cats presenting with progressive hind-limb ataxia and increased aggressiveness were necropsied and a post mortem diagnosis of Feline Spongiform Encephalopathy (FSE) was made. A wide spectrum of tissue samples was collected and evaluated histologically and immunohistologically for the presence of PrPSc. Result Histopathological examination revealed a diffuse vacuolation of the grey matter neuropil with the following areas being most severely affected: corpus geniculatum medialis, thalamus, gyrus dentatus of the hippocampus, corpus striatum, and deep layers of the cerebral and cerebellar cortex as well as in the brain stem. In addition, a diffuse glial reaction involving astrocytes and microglia and intraneuronal vacuolation in a few neurons in the brain stem was present. Heavy PrPSc immunostaining was detected in brain, retina, optic nerve, pars nervosa of the pituitary gland, trigeminal ganglia and small amounts in the myenteric plexus of the small intestine (duodenum, jejunum) and slightly in the medulla of the adrenal gland.
Conclusions The PrPSc distribution within the brain was consistent with that described in other FSE-affected cats. The pattern of abnormal PrP in the retina corresponded to that found in a captive cheetah with FSE, in sheep with scrapie and was similar to nvCJD in humans.
In cattle orally infected with BSE immunostaining in the follicles of the distal ileum was observed only after the onset of clinical disease at 36, 38 and 40 months after exposure . Neurons in the enteric nervous system were positive in only one animal from each of the groups killed 38 and 40 months after exposure, but even then the staining was sparse and confined to the myenteric plexus. In contrast none of the follicles in the distal ileum showed evidence of immunostaining for PrPSc and only a few animals showed sparse staining in the myenteric plexus in naturally affected cattle with BSE. The mesenteric lymph nodes were negative 6 months after exposure in the experimental animals. Some authors concluded that the restricted distribution of the BSE agent in the lymphoreticular system of cattle contrasts with the distribution of the scrapie agent in sheep which, in most cases, spreads rapidly after the initial early involvement of the system . The restricted distribution of BSE appears to be also true for FSE. Mice inoculated intraperitoneally or intracerebrally with brain material from cats with FSE had progressive neurological signs similar to those seen in mice affected with scrapie or BSE. Moreover some authors postulate, that the distribution of vacuolar degeneration was identical to that seen in mice terminally infected with primary sources of BSE and the lesion profile in mice 12 inoculated with FSE resembles that observed in BSE, rather than scrapie. It was postulated, therefore, that BSE and FSE probably arose from a common source . The source of infection at least in one cat presented here could have been canned food contaminated with nervous tissue of BSE infected cattle before the ban.
Conclusions In conclusion, the two FSE cases described here had essentially the same histological lesions and PrPSc distribution in the brain and the peripheral tissues as reported in earlier FSE cases. In addition we were able to demonstrate PrPSc accumulation in the retina, the neurohypophysis, trigeminal ganglion and in the adrenal medulla, but not in lymphatic tissues nor in the bone marrow. The kidneys showed random immunohistochemical staining in the mesangial glomerular tufts. This was seen in the kidneys of one FSE as well as in the control cats. Even though in experimentally infected Syrian hamsters and in scrapie infected sheep a possible prionuria and infectivity of urine is postulated, our findings confirm previously reported observations in the kidney of FSE cases, showing that immunohistochemical labelling of glomerular structures has to be regarded as unspecific. In summary, the distribution of PrPSc in FSE is similar to BSE but different from classical scrapie. In analogy, horizontal PrPSc transmission in FSE appears to be unlikely.
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FELINE SPONGIFORM ENCEPHALOPATHY: FIRST CONFIRMED CASE REPORTED IN PORTUGAL
J.F. Silva1, J.J. Correia, 1 J. Ribeiro2, S. Carmo2 and L.Orge31 Faculdade de Medicina Veterinária (UTL), Lisbon, Portugal 2 Clínica Veterinária Ani+, Queluz, Portugal 3 Laboratório Nacional de Investigação Veterinária, Unidade de BSE, Lisbon, PortugalFeline spongiform encephalopathy (FSE), affecting domestic and captive feline species, is a prion disease considered to be related to bovine spongiform encephalopathy (BSE). Here we report the first case diagnosed in Portugal, highlighting the neuroapthological findings. In 2004 a 9-year old intact female Siamese cat was referred with chronic progressive behavioural changes, polydipsia, gait abnormalities and episodes of hypersalivation. Clinical signs progressed to tetraparesis and dementia and euthanasia was performed. At necropsy, brain and spinal cord had no significative changes. Tissue samples from brain, cerebellum, brainstem and spinal cord were collected for histopathology and immunohistochemistry for detection of PrPres. Histology revealed neuropil and neuronal perikarion vacuolation in several areas of the central nervous system together with gliosis and cell rarefaction at the granular layer of the cerebellum. Immunohistochemical detection of PrPres showed a strong and widespread PrPres accumulation as granular and linear deposits as well as associated with some neurons. These findings are supportive of FSE. To the authors knowledge this is the first confirmed case of FSE reported in Portugal.
AS implied in the Inset 25 we must not _ASSUME_ that transmission of BSE to other species will invariably present pathology typical of a scrapie-like disease.
2005 DEFRA Department for Environment, Food & Rural Affairs
Area 307, London, SW1P 4PQ Telephone: 0207 904 6000 Direct line: 0207 904 6287 E-mail: h.mcdonagh.defra.gsi.gov.uk
Mr T S Singeltary P.O. Box 42 Bacliff Texas USA 77518
21 November 2001
Dear Mr Singeltary
TSE IN HOUNDS
Thank you for e-mail regarding the hounds survey. I am sorry for the long delay in responding.
As you note, the hound survey remains unpublished. However the Spongiform Encephalopathy Advisory Committee (SEAC), the UK Government’s independent Advisory Committee on all aspects related to BSE-like disease, gave the hound study detailed consideration at their meeting in January 1994. As a summary of this meeting published in the BSE inquiry noted, the Committee were clearly concerned about the work that had been carried out, concluding that there had clearly been problems with it, particularly the control on the histology, and that it was more or less inconclusive. However was agreed that there should be a re-evaluation of the pathological material in the study.
Later, at their meeting in June 95, The Committee re-evaluated the hound study to see if any useful results could be gained from it. The Chairman concluded that there were varying opinions within the Committee on further work. It did not suggest any further transmission studies and thought that the lack of clinical data was a major weakness.
Overall, it is clear that SEAC had major concerns about the survey as conducted. As a result it is likely that the authors felt that it would not stand up to r~eer review and hence it was never published. As noted above, and in the detailed minutes of the SEAC meeting in June 95, SEAC considered whether additional work should be performed to examine dogs for evidence of TSE infection. Although the Committee had mixed views about the merits of conducting further work, the Chairman noted that when the Southwood Committee made their recommendation to complete an assessment of possible spongiform disease in dogs, no TSEs had been identified in other species and hence dogs were perceived as a high risk population and worthy of study. However subsequent to the original recommendation, made in 1990, a number of other species had been identified with TSE ( e.g. cats) so a study in hounds was less
critical. For more details see-
As this study remains unpublished, my understanding is that the ownership of the data essentially remains with the original researchers. Thus unfortunately, I am unable to help with your request to supply information on the hound survey directly. My only suggestion is that you contact one of the researchers originally involved in the project, such as Gerald Wells. He can be contacted at the following address.
Dr Gerald Wells, Veterinary Laboratories Agency, New Haw, Addlestone, Surrey, KT 15 3NB, UK
You may also wish to be aware that since November 1994 all suspected cases of spongiform encephalopathy in animals and poultry were made notifiable. Hence since that date there has been a requirement for vets to report any suspect SE in dogs for further investigation. To date there has never been positive identification of a TSE in a dog.
I hope this is helpful
Yours sincerely 4
HUGH MCDONAGH BSE CORRESPONDENCE SECTION
CONCEPT NOT FOR FURTHER STUDY OF MATERIAL OBTAINED IN A SURVEY OF HOUNDS FOR EVIDENCE OF A SCRAPIE-LIKE SPONGIFORM ENCEPHALOPATHY (SE)
b) Fibrillar material closely similar to SAF, found in BSE/Scrapie, was observed in 19 (4.3%) cases, all of which were hounds > 7 years of age. 14/19 of these suspected SAF results correlated with cases in the unresolveable histopathological category.
The following proposals address the hypothesis that the hound survey observations represent a PrP related or scrapie-like disease of dogs in which the pathological response, and possible the spread of infectivity, is neuroanatomically localized. By inference this could also mean that the disorder is clinically silent and non-progressive.
PET FOODS MAD CATS AND MAD DOGS BSE/TSEs
worse still, there is serious risk the media could get to hear of such a meeting…
Crushed heads (which inevitably involve brain and spinal cord material) are used to a limited extent but will also form one of the constituent raw materials of meat and bone meal, which is used extensively in pet food manufacturer…
2. The Parliamentary Secretary said that he was concerned about the possibility that countries in which BSE had not yet been detected could be exporting raw meat materials (in particular crushed heads) contaminated with the disease to the UK for use in petfood manufacture…
YOU explained that imported crushed heads were extensively used in the petfood industry…
In particular I do not believe one can say that the levels of the scrapie agent in pet food are so low that domestic animals are not exposed…
HOWEVER, why ignore the old science and transmission studies to date ???
Species Born Onset/Died
Ocelot May 1987
Ocelot Jul 1980 Oct 1995
Puma 1986 May 1991
Puma 1980 May 1995
Puma 1978 May 1995
Lion Nov 1986 Dec 1998
Tiger 1981 Dec 1995
Tiger Feb 1983 Oct 1998
Ankole 1987 May 1995
Ankole 1986 Feb 1991
Bison 1989/90 Oct 1996
Maff data on 15 May 99
Feline Spongiform Encephalopathy (FSE) FSE was first identified in the UK in 1990. Most cases have been reported in the UK, where the epidemic has been consistent with that of the BSE epidemic. Some other countries (e.g. Norway, Liechtenstein and France) have also reported cases.Most cases have been reported in domestic cats but there have also been cases in captive exotic cats (e.g. Cheetah, Lion, Asian leopard cat, Ocelot, Puma and Tiger). The disease is characterised by progressive nervous signs, including ataxia, hyper-reactivity and behavioural changes and is fatal.The chemical and biological properties of the infectious agent are identical to those of the BSE and vCJD agents. These findings support the hypothesis that the FSE epidemic resulted from the consumption of food contaminated with the BSE agent.The FSE epidemic has declined as a result of tight controls on the disposal of specified risk material and other animal by-products.References: Leggett, M.M. et al.(1990) A spongiform encephalopathy in a cat. Veterinary Record. 127. 586-588Synge, B.A. et al. (1991) Spongiform encephalopathy in a Scottish cat. Veterinary Record. 129. 320Wyatt, J. M. et al. (1991) Naturally occurring scrapie-like spongiform encephalopathy in five domestic cats. Veterinary Record. 129. 233.Gruffydd-Jones, T. J.et al.. (1991) Feline spongiform encephalopathy. J. Small Animal Practice. 33. 471-476.Pearson, G. R. et al. (1992) Feline spongiform encephalopathy: fibril and PrP studies. Veterinary Record. 131. 307-310.Willoughby, K. et al. (1992) Spongiform encephalopathy in a captive puma (Felis concolor). Veterinary Record. 131. 431-434.Fraser, H. et al. (1994) Transmission of feline spongiform encephalopathy to mice. Veterinary Record 134. 449.Bratberg, B. et al. (1995) Feline spongiform encephalopathy in a cat in Norway. Veterinary Record 136. 444Baron, T. et al. (1997) Spongiform encephalopathy in an imported cheetah in France. Veterinary Record 141. 270-271Zanusso, G et al. (1998) Simultaneous occurrence of spongiform encephalopathy in a man and his cat in Italy. Lancet, V352, N9134, OCT 3, Pp 1116-1117.Ryder, S.J. et al. (2001) Inconsistent detection of PrP in extraneural tissues of cats with feline spongiform encephalopathy. Veterinary Record 146. 437-441Kelly, D.F. et al. (2005) Neuropathological findings in cats with clinically suspect but histologically unconfirmed feline spongiform encephalopathy. Veterinary Record 156. 472-477.TSEs in Exotic Ruminants TSEs have been detected in exotic ruminants in UK zoos since 1986. These include antelopes (Eland, Gemsbok, Arabian and Scimitar oryx, Nyala and Kudu), Ankole cattle and Bison. With hindsight the 1986 case in a Nyala was diagnosed before the first case of BSE was identified. The TSE cases in exotic ruminants had a younger onset age and a shorter clinical duration compared to that in cattle with BSE. All the cases appear to be linked to the BSE epidemic via the consumption of feed contaminated with the BSE agent. The epidemic has declined as a result of tight controls on feeding mammalian meat and bone meal to susceptible animals, particularly from August 1996.References: Jeffrey, M. and Wells, G.A.H, (1988) Spongiform encephalopathy in a nyala (Tragelaphus angasi). Vet.Path. 25. 398-399Kirkwood, J.K. et al (1990) Spongiform encephalopathy in an Arabian oryx (Oryx leucoryx) and a Greater kudu (Tragelaphus strepsiceros) Veterinary Record 127. 418-429.Kirkwood, J.K. (1993) Spongiform encephalopathy in a herd of Greater kudu (Tragelaphus strepsiceros): epidemiological observations. Veterinary Record 133. 360-364Kirkwood, J. K. and Cunningham, A.A. (1994) Epidemiological observations on spongiform encephalopathies in captive wild animals in the British Isles. Veterinary Record. 135. 296-303.Food and Agriculture Organisation (1998) Manual on Bovine Spongiform Encephalopathy.
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