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Two mouse-adapted scrapie agents of different sheep origin were compared. The titre, reached in the brains of mice in the terminal stage of scrapie, is of the same order for both agents. There is a threefold difference between the incubation periods of the two agents in some mouse strains, of which C57 is one, and in this strain incubation of the 22A agent, given as a large dose by a peripheral route, occupies almost the whole life-span.The most fundamental difference between the agents concerns the reversal of the ranking of incubation periods, typically in the VM and C57 mouse strams: incubation of ME7 in VM takes almost twice as long as in C57, whereas most sub-lines of 22A take half as long in VM as in C57. The implications of this type of host-genotype, agent-strain interaction are discussed in terms of the possible nature of agent differences, the possibility of latent infection and the consequences for scrapie eradication programmes.

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