Open Access Highly Accessed Research article

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

Timm Konold1*, A Robin Sayers2, Amanda Sach3, Gemma E Bone1, Steven van Winden4, Gerald AH Wells1, Marion M Simmons1, Michael J Stack1, Angus Wear5 and Steve AC Hawkins1

Author Affiliations

1 Veterinary Laboratories Agency Weybridge, Host Pathology and Susceptibility Department, New Haw, Addlestone, KT15 3NB, UK

2 Veterinary Laboratories Agency Weybridge, Centre for Epidemiology and Risk Analysis, New Haw, Addlestone, KT15 3NB, UK

3 ADAS Drayton, Alcester Road, Stratford upon Avon, CV37 9RQ, UK

4 Royal Veterinary College, Department of Veterinary Clinical Sciences, North Mymms, Hatfield, AL9 7TA, UK

5 Veterinary Laboratories Agency Newcastle, Laboratory Services, Longbenton, Newcastle-upon-Tyne, NE12 9SE, UK

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BMC Veterinary Research 2010, 6:53  doi:10.1186/1746-6148-6-53

Published: 9 December 2010

Abstract

Background

Various clinical protocols have been developed to aid in the clinical diagnosis of classical bovine spongiform encephalopathy (BSE), which is confirmed by postmortem examinations based on vacuolation and accumulation of disease-associated prion protein (PrPd) in the brain. The present study investigated the occurrence and progression of sixty selected clinical signs and behaviour combinations in 513 experimentally exposed cattle subsequently categorised postmortem as confirmed or unconfirmed BSE cases. Appropriate undosed or saline inoculated controls were examined similarly and the data analysed to explore the possible occurrence of BSE-specific clinical expression in animals unconfirmed by postmortem examinations.

Results

Based on the display of selected behavioural, sensory and locomotor changes, 20 (67%) orally dosed and 17 (77%) intracerebrally inoculated pathologically confirmed BSE cases and 21 (13%) orally dosed and 18 (6%) intracerebrally inoculated but unconfirmed cases were considered clinical BSE suspects. None of 103 controls showed significant signs and were all negative on diagnostic postmortem examinations. Signs indicative of BSE suspects, particularly over-reactivity and ataxia, were more frequently displayed in confirmed cases with vacuolar changes in the brain. The display of several BSE-associated signs over time, including repeated startle responses and nervousness, was significantly more frequent in confirmed BSE cases compared to controls, but these two signs were also significantly more frequent in orally dosed cattle unconfirmed by postmortem examinations.

Conclusions

The findings confirm that in experimentally infected cattle clinical abnormalities indicative of BSE are accompanied by vacuolar changes and PrPd accumulation in the brainstem. The presence of more frequently expressed signs in cases with vacuolar changes is consistent with this pathology representing a more advanced stage of disease. That BSE-like signs or sign combinations occur in inoculated animals that were not confirmed as BSE cases by postmortem examinations requires further study to investigate the potential causal relationship with prion disease.