Diagnostic reliability of clinical signs in cows with suspected bovine spongiform encephalopathy

Prion diseases are characterized by the prominent accumulation of the misfolded form of a normal cellular protein (PrPSc) in the central nervous system. The pathological features and biochemical properties of PrPSc in macaque monkeys infected with the bovine spongiform encephalopathy (BSE) prion have been found to be similar to those of human subjects with variant Creutzfeldt–Jakob disease (vCJD). Non-human primate models are thus ideally suited for performing valid diagnostic tests and determining the efficacy of potential therapeutic agents. In the current study, we developed a highly efficient method for in vitro amplification of cynomolgus macaque BSE PrPSc. This method involves amplifying PrPSc by protein misfolding cyclic amplification (PMCA) using mouse brain homogenate as a PrPC substrate in the presence of sulfated dextran compounds. This method is capable of amplifying very small amounts of PrPSc contained in the cerebrospinal fluid (CSF) and white blood cells (WBCs), as well as in the peripheral tissues of macaques that have been intracerebrally inoculated with the BSE prion. After clinical signs of the disease appeared in three macaques, we detected PrPSc in the CSF by serial PMCA, and the CSF levels of PrPSc tended to increase with disease progression. In addition, PrPSc was detectable in WBCs at the clinical phases of the disease in two of the three macaques. Thus, our highly sensitive, novel method may be useful for furthering the understanding of the tissue distribution of PrPSc in non-human primate models of CJD.

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Bovine Spongiform Encephalopathy and Public Health

Journal of the Hellenic Veterinary Medical Society ◽

10.12681/jhvms.15768 ◽

2018 ◽

Vol 49 (3) ◽

pp. 171

Author(s):

E. KALDRYMIDOU (Ε. ΚΑΛΔΡΥΜΙΔΟΥ) ◽

G. KANAKOUDIS (Γ. ΚΑΝΑΚΟΥΔΗΣ) ◽

K. KATSARAS (Κ. ΚΑΤΣΑΡΑΣ) ◽

Th. TSANGARIS (Θ. ΤΣΑΓΓΑΡΗΣ) ◽

N. PAPAIOANNOU (Ν. ΠAΠΑΪΩΑNNOΥ)

Keyword(s):

Public Health ◽

Central Nervous System ◽

Nervous System ◽

Bovine Spongiform Encephalopathy ◽

Clinical Signs ◽

The Body ◽

Spongiform Encephalopathy ◽

Structural Element ◽

Vacuolar Degeneration ◽

Spongiform Encephalopathies

Bovine Spongiform Encephalopathy (BSE) is a transmissible degenerative disease of the central nervous system. It belongs to a group of diseases which affect man and various kinds of animals and they have a similar histopathological appearance. The harmful agent of BSE and all the others spongiform encephalopathies have not been totally clarified. Today according to the predominant opinion this agent is consisted mainly or/and only of an abnormal protein, which is called prion. In various observations the harmful agent appears like proteinaceous cylinders which are consisted of aggregations or polymerized forms of the agent and it is called prion-protein (PrP). It has been proved that there are two isoforms of PrP. The first of them, called PrPc, is produced from many cells of man and animals and consists a cellular structural element. The second, called PrPs t, due to its specific properties, it is considered to be pathological and responsible for the spongiform encephalopathies. The replication of PrPsc seems to take place in the lysosomes of central nervous system cells, dendritic, and other reticular cells of the lymphatic organs through transformation of PrPc into PrPsc. It appears BSE caused by feeding meat and bone meals to cattle which were originated from scrapie infected sheep. Refering to the pathogenesis originating from experimental data it seems that initially the PrF* enters the body by food and afterwards is settled in various lymphoid organs where the first replication takes place. It is believed that BSE is transmitted through the nerves to the CNS, where it creates the characteristic lesions of vacuolar degeneration of the neurons and finally the spongiosis. Then the clinical signs are expressed. The nervous signs characterised by behavioural alterations of the animals and kinetic abnormalities. The diagnosis of the disease is made by the observation of the histopathological lesions, the detection of Scrapie Associated Fibrils-SAF by EM, the immunohistochemical detection of prpsc i n histological samples or by electrophoresis (Western blotting test). BSE was proved to be transmissible to other animals and there is a possibility that it could be done to man through the food chain. According to the above in these years, from the appearance of the disease until now, have been taken bans from Great Britain as well as from E.U. for the eradication of the disease and the protection of the public health. These instructions should be followed by the authorities and additionally the consumers ought to be informed for the possible danger of various animal products.

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Sheep-Passaged Bovine Spongiform Encephalopathy Agent Exhibits Altered Pathobiological Properties in Bovine-PrP Transgenic Mice

Journal of Virology ◽

10.1128/jvi.01356-06 ◽

2006 ◽

Vol 81 (2) ◽

pp. 835-843 ◽

Cited By ~ 52

Author(s):

Juan Carlos Espinosa ◽

Olivier Andréoletti ◽

Joaquín Castilla ◽

María Eugenia Herva ◽

Mónica Morales ◽

...

Keyword(s):

Bovine Spongiform Encephalopathy ◽

Clinical Signs ◽

Health Concern ◽

Mouse Bioassay ◽

Spongiform Encephalopathy ◽

Species Barrier ◽

Subsequent Passage ◽

Sheep Scrapie ◽

Cattle And Sheep ◽

Transmission Barrier

ABSTRACT Sheep can be experimentally infected with bovine spongiform encephalopathy (BSE), and the ensuing disease is similar to scrapie in terms of pathogenesis and clinical signs. BSE infection in sheep is an animal and human health concern. In this study, the transmission in BoPrP-Tg110 mice of prions from BSE-infected sheep was examined and compared to the transmission of original cattle BSE in cattle and sheep scrapie prions. Our results indicate no transmission barrier for sheep BSE prions to infect BoPrP-Tg110 mice, but the course of the disease is accelerated compared to the effects of the original BSE isolate. The shortened incubation period of sheep BSE in the model was conserved in subsequent passage in BoPrP-Tg110 mice, indicating that it is not related to infectious titer differences. Biochemical signature, lesion profile, and PrPSc deposition pattern of both cattle and sheep BSE were similar. In contrast, all three sheep scrapie isolates tested showed an evident transmission barrier and further adaptation in subsequent passage. Taken together, those data indicate that BSE agent can be altered by crossing a species barrier, raising concerns about the virulence of this new prion towards other species, including humans. The BoPrP-Tg110 mouse bioassay should be considered as a valuable tool for discriminating scrapie and BSE in sheep.

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Relationship between clinical signs and postmortem test status in cattle experimentally infected with the bovine spongiform encephalopathy agent

BMC Veterinary Research ◽

10.1186/1746-6148-6-53 ◽

2010 ◽

Vol 6 (1) ◽

pp. 53 ◽

Cited By ~ 9

Author(s):

Timm Konold ◽

A Robin Sayers ◽

Amanda Sach ◽

Gemma E Bone ◽

Steven van Winden ◽

...

Keyword(s):

Bovine Spongiform Encephalopathy ◽

Clinical Signs ◽

Spongiform Encephalopathy ◽

Bovine Spongiform Encephalopathy Agent

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Changes in Retinal Function and Morphology Are Early Clinical Signs of Disease in Cattle with Bovine Spongiform Encephalopathy

PLoS ONE ◽

10.1371/journal.pone.0119431 ◽

2015 ◽

Vol 10 (3) ◽

pp. e0119431 ◽

Cited By ~ 11

Author(s):

M. Heather West Greenlee ◽

Jodi D. Smith ◽

Ekundayo M. Platt ◽

Jessica R. Juarez ◽

Leo L. Timms ◽

...

Keyword(s):

Bovine Spongiform Encephalopathy ◽

Clinical Signs ◽

Retinal Function ◽

Spongiform Encephalopathy

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Prions in the peripheral nerves of bovine spongiform encephalopathy-affected cattle

Journal of General Virology ◽

10.1099/vir.0.82779-0 ◽

2007 ◽

Vol 88 (6) ◽

pp. 1850-1858 ◽

Cited By ~ 39

Author(s):

Kentaro Masujin ◽

Danny Matthews ◽

Gerald A. H. Wells ◽

Shirou Mohri ◽

Takashi Yokoyama

Keyword(s):

Nervous System ◽

Bovine Spongiform Encephalopathy ◽

Dorsal Root Ganglia ◽

Dorsal Root ◽

Prion Diseases ◽

Stellate Ganglion ◽

Clinical Signs ◽

Spongiform Encephalopathy ◽

Blotting Technique ◽

The Central Nervous System

With the use of increasingly sensitive methods for detection of the abnormal isoform of prion protein (PrPSc) and infectivity in prion diseases, it has recently been shown that parts of the peripheral nervous system (PNS) of bovine spongiform encephalopathy (BSE)-affected cattle may become infected. It has been reported that prions spread to the central nervous system (CNS) via the PNS in sheep scrapie, but the pathogenesis of BSE in cattle is less well understood. To determine whether parts of the PNS other than those implicated directly in the hypothetical pathogenetic spread of agent from the intestine to the CNS become involved before or after the CNS is affected, PrPSc distribution was investigated by a highly sensitive Western blotting technique in dorsal root ganglia, stellate ganglion, phrenic, radial and sciatic nerves, adrenal gland and CNS of cattle that were inoculated orally with BSE-affected brain and culled sequentially. In experimentally BSE-affected cattle, PrPSc was first detected in the CNS and dorsal root ganglia; subsequently, PrPSc accumulation was detected in the peripheral nerve trunks. PrPSc was also detected in the adrenal glands of cattle that showed clinical signs. No PrPSc was detected in the PNS of BSE-negative cattle. This study shows that, with respect to dorsal root ganglia, a paravertebral sympathetic ganglion and the somatic nerves examined, PrPSc is detected in the PNS during the disease course at the same time as, or after, it accumulates in the CNS.

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Meningoencephalitis Tuberculosa in a Holstein Cow

Veterinary Pathology ◽

10.1354/vp.42-6-856 ◽

2005 ◽

Vol 42 (6) ◽

pp. 856-858 ◽

Cited By ~ 5

Author(s):

E. Oruç

Keyword(s):

Bovine Spongiform Encephalopathy ◽

Plasma Cells ◽

Clinical Signs ◽

Giant Cells ◽

Spongiform Encephalopathy ◽

Multinucleated Giant Cells ◽

Holstein Cow ◽

Acid Fast Bacilli ◽

The Brain

The gross and histopathologic lesions of meningoencephalitis tuberculosa in a 4-year-old Holstein cow showing clinical signs compatible with bovine spongiform encephalopathy are described in this report. Grossly, numerous gray to yellow, firm and caseous nodules were seen on the ventral surfaces of the brain and in the lateral and fourth ventricles. Histopathologically, foci of caseation and dystrophic mineralization were surrounded by multinucleated giant cells, epitheloid macrophages, plasma cells, lymphocytes and fibrous proliferation. Ziehl-Neelsen stains of the lesions revealed masses of slender acid-fast bacilli in the necrotic centers of lesions and within surrounding giant cells.

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RT-QuIC detection of pathological prion protein in subclinical goats following experimental oral transmission of L-type BSE

BMC Research Notes ◽

10.1186/s13104-021-05859-3 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Alessandra Favole ◽

Maria Mazza ◽

Antonio D’Angelo ◽

Guerino Lombardi ◽

Claudia Palmitessa ◽

...

Keyword(s):

Bovine Spongiform Encephalopathy ◽

Prion Protein ◽

Current Knowledge ◽

Clinical Signs ◽

Small Ruminants ◽

Transmissible Spongiform Encephalopathies ◽

Spongiform Encephalopathy ◽

Surveillance Systems ◽

Oral Transmission

Abstract Objective The spread of bovine spongiform encephalopathy (BSE) agent to small ruminants is still a major issue in the surveillance of transmissible spongiform encephalopathies (TSEs). L-type bovine spongiform encephalopathy (L-BSE) is an atypical form of BSE with an unknown zoonotic potential that is transmissible to cattle and small ruminants. Our current knowledge of bovine atypical prion strains in sheep and goat relies only on experimental transmission studies by intracranial inoculation. To assess oral susceptibility of goats to L-BSE, we orally inoculated five goats with cattle L-BSE brain homogenates and investigated pathogenic prion protein (PrPsc) distribution by an ultrasensitive in vitro conversion assay known as Real-Time Quaking Induced Conversion (RT-QuIC). Results Despite a prolonged observation period of 80 months, all these animals and the uninfected controls did not develop clinical signs referable to TSEs and tested negative by standard diagnostics. Otherwise, RT-QuIC analysis showed seeding activity in five out of five examined brain samples. PrPsc accumulation was also detected in spinal cord and lymphoreticular system. These results indicate that caprine species are susceptible to L-BSE by oral transmission and that ultrasensitive prion tests deserve consideration to improve the potential of current surveillance systems against otherwise undetectable forms of animal prion infections.

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