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

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.

No abnormal prion protein detected in the milk of cattle infected with the bovine spongiform encephalopathy agent.

Milk specimens were collected from lactating cows that had previously been challenged with bovine spongiform encephalopathy (BSE)-infected brain at 4-6 months of age. One group of 10 animals received a single oral dose of 100 g, a second group received 1 g and the third was made up of unexposed controls. The cows were inseminated artificially, and calved at approximately 2 years of age and annually thereafter. Milking was done within the first week following calving and at 10-weekly intervals during the lactation period. Specimens were centrifuged to obtain a fraction enriched for somatic cells and these fractions were analysed for disease-associated, abnormal prion protein (PrP(BSE)) by using a modified commercial BSE ELISA and a different confirmatory assay. No abnormal prion protein has so far been identified in the cell fraction of milk from cattle incubating BSE by using these methods at their limits of detection.