Bovine spongiform encephalopathy (BSE) is a fatal neurodegenerative disease that belongs to transmissible spongiform encephalopathy (TSE). Since the first case was identified in the UK in 1986, BSE spread to other countries including Japan. Its incidence peaked in 1992 in the UK and from 2001 to 2006 in many other countries, but a feed ban aimed at eliminating the recycling of the BSE agent and other control measures aimed at preventing food and feed contamination with the agent were highly effective at reducing the spread of BSE. In 2004, two types of atypical BSE, H-type BSE (H-BSE) and L-type BSE (L-BSE), which differ from classical BSE (C-BSE), were found in France and Italy. Atypical BSE, which is assumed to occur spontaneously, has also been detected among cattle in other countries including Japan. The BSE agent including atypical BSE agent is a unique food-safety hazard with different chemical and biological properties from the microbial pathogens and toxic chemicals that contaminate food. In this review, we summarize the reported findings on the tissue distribution of BSE prions in infected cattle and other aspects of BSE, as well as the control measures against the disease employed in Japan. Topics that require further studies are discussed based on the summarized findings from the perspective of food safety. Key word: BSE, atypical, vCJD, control measure, origin tified in the UK in 1986 1). The UK epidemic was attributed to the exposure to an infectious agent in 1981-1982 in association with a dramatic reduction in the use of organic solvents in the manufacture of meat and bone meal (MBM) 2). The annual number of BSE cases reported in the UK increased

Since 2004, a novel bovine spongiform encephalopathy (BSE), distinct from the conventional 'classical BSE' (C-BSE), has been reported as an atypical BSE. Atypical BSE is detected mostly in aged cattle, and it is suggested that atypical BSE may occur spontaneously. Relaxation of the relevant countermeasures such as feed ban, which prevents the use of bovine meat-and-bone meal as feed, has been discussed in recent years owing to the decrease in C-BSE cases. If atypical BSE occurs spontaneously without exposure to an agent called abnormal prion protein (PrP Sc ), complete removal of these measures will be difficult. In this study, we verified the possibility that L-BSE, which is a subtype of atypical BSE, occurs spontaneously. We first hypothesized that L-BSE occurs only through the process of infection via oral exposure. If the hypothesis was true, the infection of L-BSE would be mostly limited to calves under 1 year of age due to their high susceptibility, and the feed ban would effectively reduce the number of infected calves by birth cohort. Thus, we created a mathematical model to estimate the number of infected calves by birth cohort and compared the effectiveness of the feed ban on C-BSE and L-BSE. The number of tested animals and detected cases in nine European countries were used for this analysis. Our results showed that the estimated number of infected calves in the birth cohort indicated that feed ban was less effective on L-BSE. This result supports the alternative hypothesis that at least a part of the L-BSE can occur without infection via oral exposure. Our results suggest that the complete abolition of countermeasures, such as feed ban, should be discussed carefully. As for the occurrence mechanism, although there remains uncertainty to reach conclusions, it is reasonable to assume that L-BSE can occur spontaneously at present.