BSE: Science & research - Pathogenesis of BSE and infectivity studies
Pathogenesis refers to the study of the disease process, the sequence in which the tissues of the body become infected and the progression of clinical signs both in experimentally- and naturally-infected animals. Understanding the disease process provides information on when, and which, tissues in a BSE-infected animal may be infectious to other animals after disease onset. This is important both for animal and public health.
Research has been funded since the 1980s to investigate the following broad topics:
Pathogenesis and infectivity of tissues using mouse and cattle bioassays
Early MAFF-funded studies used bioassays of bovine tissues into mice to determine which tissues carried infectivity. A large number of tissues taken from cattle experimentally infected with BSE were studied, including those from the central nervous system (such as brain tissue), the non-central nervous system (such as skin, reproductive tissues, internal organs) and fluids (such as milk and blood). Evidence of infectivity was found in the central nervous system tissues and the lower small intestine (distal ileum).
Later research funded by Defra showed that cattle bioassays are significantly more sensitive than mouse bioassay. Tissues negative from the earlier mouse studies were tested using cattle bioassay experiments to ensure that tissues with lower levels of infectivity were not missed. These studies found that the distal ileum, brain stem (caudal medulla), cranial nerves (trigeminal ganglia) and spinal cord (including dorsal root) were infectious (1). This study was transferred to the Food Standards Agency and later results indicated that BSE infectivity could also be detected in the lingual tonsils (2).
Action taken
These studies have supplied data for various BSE risk assessments, to underpin BSE controls and to designate Specified Risk Materials (SRM). For example, the interim results of the pathogenesis studies were used to expand the definition of specified risk materials to include bovine intestines and tonsils.
Infectious dose
Defra has funded research (projects SE1918, SE1930) to examine the attack rates and incubation periods for BSE infection in cattle after the oral administration of different amounts of BSE. All doses in the first study (1–100 gram) resulted in individuals becoming infected with BSE. In a second study using lower doses, animals developed BSE after oral challenge with as little as 1 milligram of BSE-infected brain material (3). This work is still in progress (project SE1930).
Modelling work has also been undertaken using data from mouse bioassay experiments to investigate the question of how the risk of infection accumulates with cumulative low doses of BSE (project SE1841). The study showed that one large oral dose was more likely to cause disease than the same amount of material given in smaller, multiple doses. Also the incubation periods for disease are shorter and less variable if all the material is consumed in one dose (4).
Action taken
Results from dosing experiments reinforced the need for tight animal feed controls to prevent meat and bone meal being used in the feed industry.
References
1. Wells GA, Hawkins SA, Green RB, Austin AR, Dexter I, Spencer YI, Chaplin MJ, Stack MJ & Dawson M (1998) Vet. Rec. 142(5): 103-106.
2. Wells GA, Spiropoulos J, Hawkins SA & Ryder SJ (2005) Vet. Rec. 26;156(13): 401-407.
3. Wells GA, Konold T, Arnold ME, Austin AR, Hawkins SA, Stack M, Simmons MM, Lee YH, Gavier-Widén D, Dawson M & Wilesmith JW (2007) J. Gen. Virol. 88(Pt 4):1363-73.
4. Gravenor MB, Stallard N, Curnow R & McLean AR (2003) PNAS. 100 (19): 10960-10965.
Links to further information
Pagepublished: 18 March, 2008