FRI BRIEFINGS Bovine Spongiform Encephalopathy An Updated Scientific Literature Review M. Ellin Doyle Food Research Institute University of Wisconsin–Madison Madison WI 53706 Contents Summary34B ......................................................................................................................................2 Bovine Spongiform Encephalopathy .........................................................................................4 BSE surveillance and detection..............................................................................................4 BSE in the UK........................................................................................................................4 BSE in Canada and the United States.....................................................................................5 BSE in other countries............................................................................................................5 BSE prions and pathogenesis .................................................................................................5 BSE in sheep ..........................................................................................................................6 BSE in other animals..............................................................................................................6 Other Spongiform Encephalopathies in Animals .....................................................................7 Scrapie....................................................................................................................................7 Chronic Wasting Disease (CWD) ..........................................................................................9 Transmissible Mink Encephalopathy (TME) .......................................................................10 Feline Spongiform Encephalopathy (FSE)...........................................................................11 Spongiform Encephalopathies in Humans ..............................................................................11 Creutzfeldt-Jakob Disease (CJD) ........................................................................................11 Sporadic CJD .......................................................................................................................12 Variant Creutzfeldt-Jakob Disease (vCJD) ..........................................................................12 Kuru .....................................................................................................................................13 Prions as Causative Agents of TSEs ........................................................................................14 Prion strains and structure....................................................................................................14 Normal functions of prions ..................................................................................................15 Altered forms as causes of disease .......................................................................................16 Stability of prions.................................................................................................................17 Routes of infection ...............................................................................................................17 Other causes proposed for BSE ..........................................................................................18 Eradication and Control of TSEs .............................................................................................19 Strategies to reduce or control incidence of TSEs in animals...............................................19 Strategies to minimize or eliminate human exposure...........................................................21 Treatment of TSEs ....................................................................................................................23 Diagnostics .................................................................................................................................24 Reviews and general methodology.......................................................................................24 Determination of disease in animal/human tissues...............................................................24 Determination of nervous tissue or abnormal prions in food................................................26 Determination of ruminant and other animal protein in feed................................................27 Acknowledgments .....................................................................................................................27 References ..................................................................................................................................27 Appendix — FRI Briefing, September 2002: Bovine Spongiform Encephalopathy............ following page 40 Prepared by M. Ellin Doyle, Ph.D., [email protected] November 2004 http://fri.wisc.edu/docs/pdf/BSE04update.pdf Food Research Institute, University of Wisconsin–Madison 2 FRI BRIEFINGS: Bovine Spongiform Encephalopathy Summary Although the number of cases of BSE has decreased dramatically since peak inci- dence in 1992, this disease is still of concern as cases continue to be diagnosed in Europe and Japan and two cases have been reported in North America. Recent reports from France, Italy, and Japan presented evidence that more than one strain of BSE exists in cattle. Of particular interest in the UK are the animals born after the 1996 ban on animal protein in animal feed — the so-called BARB (Born After the Real Ban) cohort. According to the latest statistics from the UK there are 70 such cases, including 4 born in 1999. Another concern in the UK is the possibility that BSE was transmitted to sheep by contaminated feed and the potential for spread of BSE among sheep similar to scrapie transmission. Unlike BSE-infected cattle that have infective prions confined to the nervous system, disease-associated prions have been detected in a variety of tissues in sheep with scrapie or BSE. Most recently, experiments demonstrated that infectious prions are present at low but consistent levels in muscles of some scrapie-infected sheep. Relative prion concentrations indicate that infectivity is about 5000-fold lower in muscles than in brain tissue but these prions were detectable in muscles several months before clinical signs of scrapie appeared. In North America, chronic wasting disease in farmed and wild deer and elk has been reported from 12 states and two Canadian provinces. Recent experimental data demonstrated that CWD infectivity from decomposed carcasses of deer with CWD and from fecal matter or other material excreted from deer with CWD persists in the environment for over two years. This material has caused CWD in deer newly introduced to infective paddocks. However, cattle grazing in areas inhabited by CWD-infected deer do not acquire this disease. Investigations of 12 TSE cases in persons known to have consumed deer meat concluded that none were related to CWD. Conversion of the human prion protein by CWD-associated prions has been observed in vitro but it appears that CWD is not easily transmissible to humans or cattle. Variant CJD cases continue to be diagnosed in the UK but the rate of increase in cases is not increasing, leading some experts to revise downward predictions of the future extent of the epidemic. However, all of the vCJD cases tested to date have one specific form of the prion protein. It has been observed in sheep that animals with less susceptible prion genotypes can eventually develop scrapie but the incubation period is longer. Whether this will be the case for vCJD is not known. Screening of 12,674 appendectomy samples in the UK revealed that 3 contained vCJD prions. This suggests that 237/1,000,000 persons may have a subclinical infection and reinforces recommendations to prevent iatrogenic transmission of vCJD. Prepared by M. Ellin Doyle, Ph.D. November 2004 Food Research Institute © University of Wisconsin–Madison http://fri.wisc.edu/docs/pdf/BSE04update.pdf FRI BRIEFINGS: Bovine Spongiform Encephalopathy 3 In early 2004, some published research provided evidence that human vCJD may be transmitted by blood transfusions. Comparison of data on blood donors and recipients and on cases of vCJD in the UK revealed that 48 individuals received a blood transfusion from a person who later developed vCJD. One person developed symptoms of vCJD 6.5 years after a transfusion of red blood cells at 68 years of age (significantly older than the usual vCJD cases). It is possible that both the donor and recipient contracted vCJD by eating contaminated beef but the researchers estimate that the probability of this is about 1/15,000 to 1/30,000. Brain homogenates from monkeys that had been infected with BSE were used to infect other monkeys either orally or by intravenous injection. Survival times were 14 to 26 months shorter for animals infected intravenously, and much higher concentrations of prions were present in spleen and tonsils of these animals. This demonstrates that the intravenous route is a highly efficient means of transmission. Topical application of TME prions to the tongue following a superficial wound also resulted in a high incidence of disease and a short incubation period in hamsters. This suggests that animals, including livestock and humans, with tongue abrasions may have an increased susceptibility to TSEs