Volume 2: Science
4. The link between BSE and vCJD
The effect of route of infection on disease phenotype

4.25 The different animal and human TSEs are known to vary in their clinical presentation and histopathological patterns. For example, behavioural signs herald the onset of disease in scrapie, BSE and sporadic CJD, ¹ whereas kuru and iatrogenic CJD (from contaminated growth hormone injections) present as cerebellar syndromes with prominent ataxia. ² Iatrogenic CJD due to intracerebral or intraocular transplants manifests as classical CJD with progressive dementia. ³ Familial CJD and Gerstmann-Sträussler-Scheinker (GSS) syndrome show a wide range of phenotypes characteristic of the specific prion mutation and, in some cases, depending on a polymorphic variation at the PrP gene locus. ⁴ These observations are consistent with the concept that disease pattern can be dependent on host susceptibility factors such as genotype and on the strain of agent. However, it is also conceivable that, given the mechanism of prion disorders whereby neurodegeneration is caused by the aggregation of PrP^Sc followed by cell death, the pattern of nerve cells targeted in the brain may also depend on the route of infection.

4.26 Indeed, the incubation period and clinical symptoms of iatrogenic CJD have been found to differ depending on the mode of infection. ⁵ When the infectious agent is introduced into or near the brain, incubation is significantly shorter than when the agent is introduced peripherally. Disease has been shown to develop within around 20 months when the infective agent is introduced either by surgical instrumentation or tissue transplantation. In contrast, infection through injection of contaminated human growth hormone yields disease after an average of 13 years. ⁶ As mentioned above, clinical symptoms also differ: intracerebral inoculation produces a demential clinical syndrome similar to sporadic CJD, whereas peripheral inoculation and grafts of dura mater result in a syndrome similar to kuru.

4.27 Variant CJD has recently (1999) been found to differ from sporadic, familial and iatrogenic CJD in that the lymphoreticular system in patients with vCJD contains high levels of PrP^Sc. ⁷ This finding may reflect a route of infection through the alimentary canal, rather than spontaneous PrP mutation in somatic cells as postulated in sporadic CJD, germ line mutation as in familial CJD, or parenteral inoculation as in iatrogenic CJD.

4.28 Uncertainty remains on the question of how BSE might have been transmitted to humans to cause vCJD. Oral exposure to the BSE agent through infected meat products seems more likely than, for example, infection through parenteral medicines containing contaminated bovine material, because of the high level of infectivity invariably found in the LRS. Research aimed at correlating clinical findings with the route of inoculation in experimental systems may allow the route of infection in cases of vCJD to be inferred, and could lead to practical strategies for disease prevention.