Pathogenesis of mouse scrapie: Effect of route of inoculation on infectivity titres and dose-response curves

Abstract

The relative efficiencies of different routes of inoculation were determined by the comparison of operational estimates of infectivity titre in standard scrapie inocula. The variation in titre between routes was up to 4 −log 10LD 50 units. The intracerebral route was the most efficient, followed by the intravenous, intraperitoneal and subcutaneous routes. The relationship between the dose of agent and length of incubation period was studied for these routes of inoculation. When the dose of agent was corrected for the efficiency of infection by each route, similar dose-response relationships were found for all 3 peripheral routes of inoculation, suggesting that the mode of pathogenesis may be similar in each case. The dose-response relationships for intracerebrally injected scrapie were similar to those obtained with peripheral routes at low effective doses, but differed at higher doses. The concentration of agent in brain in the clinical stage of scrapie was always the same irrespective of the dose of agent and route of inoculation that had been used to infect mice. This finding indicates that clinical scrapie develops when a certain threshold concentration of agent is achieved in brain. It is concluded that the main differences in the pathogenesis of scrapie following different routes of inoculation occur in the early agent-host interactions which determine the efficiency of infection.