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Diagnosis of Experimental H-Type and L-Type BSE in Cattle

15 April 2012

Researchers in the UK have reported on their observation of two clinical syndromes and the diagnostic challenges presented by these two atypical forms of bovine spongiform encephalopathy (BSE). Difficulty rising was a consistent feature of both disease forms and they recommended modification of the usual diagnostic method in order to distinguish between typical and atypical forms of the disease.

The majority of atypical BSE cases so far identified worldwide have been detected by active surveillance, according to Timm Konold and colleagues with the Animal Health and Veterinary Laboratories Agency (AHVLA) at Weybridge in the UK, adding that consequently, the volume and quality of material available for detailed characterisation is very limiting.

In their paper published in BMC Veterinary Research, they 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.

In the introduction to the paper, Konold and co-authors explain that previously, experimental inoculation of cattle with agents found in transmissible spongiform encephalopathies (TSEs) of other species, such as scrapie or chronic wasting disease, have produced a neurological disease but in each case, the disease was different phenotypically from BSE. The introduction of active surveillance in various countries has resulted in the detection of other, putatively sporadic, forms of BSE in cattle which were characterised by different neuropathological or molecular features (L-type and H–type BSE), mainly affecting cattle eight years of age or older. Both forms of atypical BSE have subsequently been identified in the United Kingdom (UK).

To date, none of these ‘atypical’ BSE cases diagnosed in various countries in cattle have been reported as clinical suspects, suggesting that the diseases are different from classical BSE.

The AHVLA researchers used two groups of four cattle, intracerebrally inoculated with L–type or H–type BSE, all od which 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.

The researchers concluded that 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.

Specifically, Konold and colleagues report that when Western immunoblotting is used for diagnostic or confirmatory purposes, H–type BSE can readily be identified by its characteristic profile even when the signal is strong. In contrast, the characteristics of L–type BSE appear to be more subtle and their results suggest that when the signal is too intense, it is not readily differentiated by visual examination from a classical BSE profile.

The AHVLA group added that this observation has led to the routine dilution of samples from any positive BSE case that is subjected to Western immunoblotting under UK surveillance in order to maximise the opportunity for initial identification of this form of atypical BSE and to allow such samples to be subjected to further investigation for full characterisation.

Reference

Konold T., G.E. Bone, D. Clifford, M.J. Chaplin, S. Cawthraw, M.J. Stack and M.M. Simmons. 2012. Experimental H-type and L-type bovine spongiform encephalopathy in cattle: observation of two clinical syndromes and diagnostic challenges. BMC Veterinary Research, 8:22. doi:10.1186/1746-6148-8-22

Further Reading

- You can view the full report (as a provisional PDF) by clicking here.


April 2012

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