BACKGROUND:The majority of atypical bovine spongiform encephalopathy (BSE) cases so far identified worldwide have been detected by active surveillance. Consequently the volume and quality of material available for detailed characterisation is very limiting. Here we report on a small transmission study of both atypical forms, H- and L-type BSE, in cattle to provide tissue for test evaluation and research, and to generate clinical, molecular and pathological data in a standardised way to enable more robust comparison of the two variants with particular reference to those aspects most relevant to case ascertainment and confirmatory diagnosis within existing regulated surveillance programmes.RESULTS:Two groups of four cattle, intracerebrally inoculated with L-type or H-type BSE, all presented with a nervous disease form with some similarities to classical BSE, which progressed to a more dull form in one animal from each group. Difficulty rising was a consistent feature of both disease forms and not seen in two BSE-free, non-inoculated cattle that served as controls. The pathology and molecular characteristics were distinct from classical BSE, and broadly consistent with published data, but with some variation in the pathological characteristics. Both atypical BSE types were readily detectable as BSE by current confirmatory methods using the medulla brain region at the obex, but making a clear diagnostic distinction between the forms was not consistently straightforward in this brain region. Cerebellum proved a more reliable sample for discrimination when using immunohistochemistry.CONCLUSIONS:The prominent feature of difficulty rising in atypical BSE cases may explain the detection of naturally occurring cases in emergency slaughter cattle and fallen stock. Current confirmatory diagnostic methods are effective for the detection of such atypical cases, but consistently and correctly identifying the variant forms may require modifications to the sampling regimes and methods that are currently in use.

Background The function of the autonomic nervous system can be assessed by determining heart rate variability (HRV), which is impaired in some brainstem diseases in humans. Transmissible spongiform encephalopathies (TSEs) in sheep are diseases characterised by accumulation of disease-associated prion protein in the brainstem, including nuclei of the parasympathetic nervous system. This study was undertaken to assess whether analysis of HRV can be used as an aid in the diagnosis of TSEs in clinically affected, naturally or experimentally infected sheep. Findings When HRV indices were compared between 41 clinical TSE cases (18 sheep infected with scrapie and 23 sheep infected with bovine spongiform encephalopathy), 11 control sheep and six sheep reported as scrapie suspects or dosed with BSE brain homogenate, which were not confirmed as TSE cases by postmortem tests, no significant differences were found between the groups. Median heart rate was significantly different but only when sheep were grouped by gender: it was higher in female TSE cases than in control sheep and higher in female than castrated male ovine classical BSE cases. Conclusions HRV analysis was not useful as a diagnostic aid for TSEs of sheep.

Background Heart rate variability (HRV) analysis is a method to assess the function of the autonomic nervous system. Brainstem nuclei that influence HRV are affected by vacuolar changes and accumulation of disease-associated prion protein (PrP d ) in bovine spongiform encephalopathy (BSE) resulting in clinical signs suggestive of an increased parasympathetic tone. It was hypothesised that BSE in cattle causes changes in the autonomic nervous system; this was tested by comparing HRV indices derived from 1048 electrocardiograms, which were recorded from 51 naturally or experimentally infected cattle with BSE confirmed by postmortem tests, 321 clinical suspect cases or cattle inoculated with potentially infectious tissue without disease confirmation and 78 BSE-free control cattle. Findings Statistically significant differences were found for low or high frequency power, their normalised values and ratio when the last recording prior to cull or repeated recordings were compared but only between male and female cattle of the three groups and not between groups of the same gender, even though BSE cases of each gender appeared to be more nervous during the recording. The same findings were made for heart rate, deviation from the mean RR interval and vasovagal tonus index when repeated recordings were compared. BSE cases with severe vacuolar changes in the parasympathetic nucleus of the vagus nerve had a significantly lower low:high frequency power ratio but not a lower heart rate than BSE cases with mild vacuolation, whereas severity of vacuolar changes in the solitary tract nucleus or intensity of PrP d accumulation in both nuclei did not appear to have any affect on either index. Abnormalities in the electrocardiogram were detected in 3% of the recordings irrespective of the BSE status; sinus arrhythmia was present in 93% of the remaining recordings. Conclusions HRV analysis was not useful to distinguish BSE-positive from BSE-negative cattle grouped by gender, and HRV indices appeared to be mainly influenced by gender. There is agreement with earlier studies that vacuolar changes in the brainstem may be associated with an increased parasympathetic tone in BSE and that abnormalities in an electrocardiogram can be detected in cattle without evidence of heart disease.

BACKGROUND:As there is limited information about the clinical signs of BSE and scrapie in goats, studies were conducted to describe the clinical progression of scrapie and BSE in goats and to evaluate a short clinical protocol for its use in detecting scrapie-affected goats in two herds with previously confirmed scrapie cases. Clinical assessments were carried out in five goats intracerebrally infected with the BSE agent as well as five reported scrapie suspects and 346 goats subject to cull from the two herds, 24 of which were retained for further monitoring. The brain and selected lymphoid tissue were examined by postmortem tests for disease confirmation.RESULTS:The sensitivity and specificity of the short clinical protocol in detecting a scrapie case in the scrapie-affected herds was 3.9% and 99.6%, respectively, based on the presence of tremor, positive scratch test, extensive hair loss, ataxia and absent menace response. All BSE- and scrapie-affected goats displayed abnormalities in sensation (over-reactivity to external stimuli, startle responses, pruritus, absent menace response) and movement (ataxia, tremor, postural deficits) at an advanced clinical stage but the first detectable sign associated with scrapie or BSE could vary between animals. Signs of pruritus were not always present despite similar prion protein genotypes. Clinical signs of scrapie were also displayed by two scrapie cases that presented with detectable disease-associated prion protein only in lymphoid tissues.CONCLUSIONS:BSE and scrapie may present as pruritic and non-pruritic forms in goats. Signs assessed for the clinical diagnosis of scrapie or BSE in goats should include postural and gait abnormalities, pruritus and visual impairment. However, many scrapie cases will be missed if detection is solely based on the display of clinical signs. PrPd accumulation in the brain appeared to be related to the severity of clinical disease but not to the display of individual neurological signs.

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.

Gemma Bone, a youth delegate with the UK Youth Climate Coalition reports on the Copenhagen climate summit, and asks why it failed to produce a fair, ambitious and binding global deal.

Scrapie in sheep can present with a range of clinical and pathological features. The variation in the pathological phenotype has been attributed mainly to differences in the breed and the prion protein genotype of affected sheep as well as the strain of agent producing the infection. The influence of these factors on the clinical phenotype has not been studied extensively. This study was conducted to investigate factors that may affect the clinical presentation.A detailed clinical assessment was performed on 162 confirmed classical scrapie field cases in Great Britain. Fourteen healthy, scrapie-free sheep were assessed by the same clinical methods to provide a baseline of normal behaviour Eight prion protein genotypes were affected and the majority displayed pruritic behaviour (97%) and loss of body condition (76%). Cud soiling, temperament change, pruritus, poor body condition, frequent nibbling and increased rubbing were positively or negatively associated with the genotypes ARQ/ARQ ARQ/VRQ or VRQ/VRQ. Breed and flock were highly correlated with genotype due to the selection of cases. A significant association was found between the presence of tremors, temperament change, loss of body condition, abnormal gait, teeth grinding, pruritus and other clinical variables.This study confirms the variability of clinical signs in scrapie although almost all sheep displayed signs of pruritus. The clinical presentation may be influenced by the genotype (and possibly breed, flock or predominant strain).

Background: The variability in the clinical or pathological presentation of transmissible spongiform encephalopathies (TSEs) in sheep, such as scrapie and bovine spongiform encephalopathy (BSE), has been attributed to prion protein genotype, strain, breed, clinical duration, dose, route and type of inoculum and the age at infection. The study aimed to describe the clinical signs in sheep infected with the BSE agent throughout its clinical course to determine whether the clinical signs were as variable as described for classical scrapie in sheep. The clinical signs were compared to BSE-negative sheep to assess if disease-specific clinical markers exist.Results: Forty-seven (34%) of 139 sheep, which comprised 123 challenged sheep and 16 undosed controls, were positive for BSE. Affected sheep belonged to five different breeds and three different genotypes (ARQ/ARQ, VRQ/VRQ and AHQ/AHQ). None of the controls or BSE exposed sheep with ARR alleles were positive. Pruritus was present in 41 (87%) BSE positive sheep; the remaining six were judged to be pre-clinically infected. Testing of the response to scratching along the dorsum of a sheep proved to be a good indicator of clinical disease with a test sensitivity of 85% and specificity of 98% and usually coincided with weight loss. Clinical signs that were displayed significantly earlier in BSE positive cases compared to negative cases were behavioural changes, pruritic behaviour, a positive scratch test, alopecia, skin lesions, teeth grinding, tremor, ataxia, loss of weight and loss of body condition. The frequency and severity of each specific clinical sign usually increased with the progression of disease over a period of 16-20 weeks.Conclusion: Our results suggest that BSE in sheep presents with relatively uniform clinical signs, with pruritus of increased severity and abnormalities in behaviour or movement as the disease progressed. Based on the studied sheep, these clinical features appear to be independent of breed, affected genotype, dose, route of inoculation and whether BSE was passed into sheep from cattle or from other sheep, suggesting that the clinical phenotype of BSE is influenced by the TSE strain more than by other factors. The clinical phenotype of BSE in the genotypes and breed studied was indistinguishable from that described for classical scrapie cases.

Background Atypical scrapie is a recently recognised form of transmissible spongiform encephalopathy of sheep that differs from classical scrapie in its neuropathological and biochemical features. Most cases are detected in apparently healthy sheep and information on the clinical presentation is limited. Case presentation This report describes the clinical findings in two sheep notified as scrapie suspects and confirmed as atypical scrapie cases by immunohistochemistry and Western immunoblotting. Although both sheep displayed signs suggestive of a cerebellar dysfunction there was considerable variation in the individual clinical signs, which were similar to classical scrapie. Conclusion Any sheep presenting with neurological gait deficits should be assessed more closely for other behavioural, neurological and physical signs associated with scrapie and their presence should lead to the suspicion of scrapie.