• If you are having problems logging in please use the Contact Us in the lower right hand corner of the forum page for assistance.

BSE: THE EFFECT OF ORAL EXPOSURE DOSE ATTACK RATE INCUBATION

flounder

Well-known member
Bovine spongiform encephalopathy: the effect of oral exposure dose on attack
rate and incubation period in cattle
G. A. H. Wells1, T. Konold1, M. E. Arnold1, A. R. Austin1,, S. A. C.
Hawkins1, M. Stack1, M. M. Simmons1, Y. H. Lee2, D. Gavier-Widén3, M.
Dawson1, and J. W. Wilesmith1,

1 Veterinary Laboratories Agency, Woodham Lane, New Haw, Addlestone, Surrey
KT15 3NB, UK
2 National Veterinary Research and Quarantine Service, Anyang, Republic of
Korea
3 National Veterinary Institute (SVA), SE-75189 Uppsala, Sweden


Correspondence
G. A. H. Wells
[email protected]

The dose–response of cattle exposed to the bovine spongiform encephalopathy
(BSE) agent is an important component of modelling exposure risks for
animals and humans and thereby, the modulation of surveillance and control
strategies for BSE. In two experiments calves were dosed orally with a range
of amounts of a pool of brainstems from BSE-affected cattle. Infectivity in
the pool was determined by end-point titration in mice. Recipient cattle
were monitored for clinical disease and, from the incidence of
pathologically confirmed cases and their incubation periods (IPs), the
attack rate and IP distribution according to dose were estimated. The dose
at which 50 % of cattle would be clinically affected was estimated at 0.20 g
brain material used in the experiment, with 95 % confidence intervals of
0.04–1.00 g. The IP was highly variable across all dose groups and followed
a log-normal distribution, with decreasing mean as dose increased. There was
no evidence of a threshold dose at which the probability of infection became
vanishingly small, with 1/15 (7 %) of animals affected at the lowest dose (1
mg).

Present address: Oak Farm, Harpsden Bottom, Henley-on-Thames, Oxon RG9 4HY,
UK.

Present address: NSPAC, Defra, Whittington Road, Worcester WR5 2SU, UK.

Present address: Defra, 1a Page Street, London SWIP 4PQ, UK, and Department
of Infectious and Tropical Diseases, London School of Hygiene and Tropical
Medicine, University of London, Keppel Street, London WC1E 7HT, UK.



http://vir.sgmjournals.org/cgi/content/abstract/88/4/1363


BSE INQUIRY
Volume 2: Science
3. The nature and cause of BSE
Dose
Dose-related experiments (including the attack rate experiment)
Summary


Transmission of BSE and scrapie to sheep and goats by intracerebral and oral
routes
3.165 Initiated in June 1988 at the NPU, this experiment set out to compare
transmission of both BSE and scrapie to two breeds of sheep, one
susceptible, the other resistant to scrapie infection, and to goats which
are rarely susceptible to natural scrapie. Its aim was to determine,
firstly, if BSE behaved differently from scrapie in these animals and,
secondly, if BSE transmission was influenced by the route of challenge.

3.166 Sheep of both breeds and goats were inoculated either intracerebrally
with 0.05 g of infected BSE brain material, or orally with 0.5 g of infected
material. The size of the intracerebral inoculations was based on that used
for standard scrapie transmissions and was effectively limited by the volume
of material that could be introduced into the brain. 6 Amounts used for oral
administration were limited by the physical quantity of bovine material
available, and so, in order to inoculate several animals, it was necessary
to use a smaller quantity of inoculum (0.5 g) than if the available material
had been administered to one animal.

3.167 BSE was found to transmit to both scrapie-resistant and susceptible
sheep breeds as well as to goats following intracerebral inoculation. This
result was significant in that it showed that BSE transmitted to animals
which were not susceptible to scrapie infection. BSE was also found to
transmit orally to these animals, showing that the amount of infectivity
contained in 0.5 g of brain material was sufficient to cause disease. The
results also showed that the two inoculation routes were similarly efficient
in transmitting disease, when it had been commonly accepted that the
intracerebral route was much more efficient than the oral route.

3.168 Results of positive oral transmission to scrapie-susceptible sheep
were known to scientists conducting the experiment by November 1990, 7
although it was not clear if the sheep had succumbed to infection with
natural scrapie or BSE. This was more than a year before the start of the
attack rate experiment. Oral transmission of BSE to negative-line sheep was
not recorded until October 1991. 8

3.169 It is not clear when MAFF officials became aware of the oral
transmission of BSE to sheep, let alone the amount of material that was
sufficient to cause disease. Results were supplied periodically by the NPU
to the CVL in the form of a data sheet which contained updates of all NPU
experiments. It is not clear who received these reports, though it appears
that they were distributed prior to the NPU/CVL R&D meetings. 9 The quantity
of material administered orally to the animals was not recorded on these
data sheets, so those not familiar with the design of the experiment would
not necessarily have appreciated the significance of the oral transmission.
Interim results of this experiment were published in the Veterinary Record
in 1993. 10

3.170 These results showed that a small amount of infectious material
administered orally was sufficient to cause BSE, even across a species
barrier. This information could have usefully guided decisions made on the
design of the attack rate experiment in cattle.







tss
 
Top