Experimental H-type and L-type bovine spongiform encephalopathy in cattle: observation of two clinical syndromes and diagnostic challenges

Abstract

BackgroundThe 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.ResultsTwo 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.ConclusionsThe 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.

Polymorphisms in the Prion Protein Gene of cattle breeds from Brazil

“…This country imports meat and bone meal for feeding dairy cattle. Konold et al (2012) demonstrated that cattle exposed to meal containing the brain stem of animals infected with BSE develop the disease. Bovines from Turkey have a high frequency of the heterozygous 23-bp genotype and the 12-bp insertion genotype (Un et al 2008).…”

“…The development of classic BSE may be associated with the incorporation of meat and bone meal containing PrP Sc into the bovine diet (Konold et al 2012).…”

Protocol for further laboratory investigations into the distribution of infectivity of Atypical BSE

“…When discriminating the different forms of BSE, immunohistochemistry (IHC) in brain has been reported to allow discrimination of distinguishable immunolabelling patterns for C-BSE, L-BSE and H-BSE, especially when focusing on rostral areas of the brain, and cerebellum (Konold et al, 2012). Western blotting (WB) allows prompt identification of H-BSE cases according to the molecular mass of the unglycosylated PrP fraction and the detection of the protein by antibodies binding to N-terminal epitopes (e.g.…”

“…Intracerebral challenge studies with both Atypical BSE forms were also performed by Konold et al (2012), in which PrP Sc deposition was identified in muscle spindles and in the trigeminal ganglion following a limited study of potential peripheral distribution. This study is described in more detail in Section 2.2.…”

Bovine spongiform encephalopathy and food safety

“…Only one strain, classical BSE, was responsible for the BSE epidemic and the associated epidemic of vCJD 8 . The atypical H-type and L-type strains typically occur in cattle over eight years of age, and appear to arise spontaneously 9,10 .…”