Download Studies on the transmission of natural scrapie in an infected flock

SE1845 Final report – Executive Summary
Scrapie is a fatal disease that affects the brain of sheep and goats. This disease has been
endemic in the National sheep flocks for over 250 years and is become known as classical
scrapie. The disease is similar to that of BSE (Bovine Spongiform Encephalopathy – Mad
Cows Disease) which affects cattle and CWD (Chronic Wasting Disease) that affects deer.
These types of diseases are known as transmissible spongiform encephalopathies (TSEs)
and are believed to be caused by prion protein (PrP). Prion protein is found naturally in the
cells of the body but something causes the natural prion protein (PrPc) to change into a
disease specific prion protein (PrPd) which then destroys the brain cells causing the host to
loose coordination and other bodily functions finally leading to death.
Currently, the most widely accepted hypothesis on the origin of the BSE epidemic in the UK is
that it was caused by cattle consuming TSE (possibly scrapie) affected meat-and-bone meal
(MBM) which was added to cattle and other animal feed as a source of protein prior to1996.
Although there is no evidence that scrapie can be transmitted to humans studies show that
BSE can cause a similar brain disease in humans’, vCJD (variant Creutzfeldt - Jakob
disease).
Following the BSE outbreak there has been a greater need to protect the consumer from all
types of TSEs and the eradication of BSE and scrapie in the UK has been at the forefront of
Government policy for the last 10 years.
The government’s policy for the eradication of classical scrapie has been based on research
carried out in the1998 on the genetic make-up of the sheep prion protein and the variations in
amino acids along the gene and how these can affect the sheep’s chances of getting the
disease. Variations in three areas of the PrP gene (136, 154 and 171) seem to be
responsible for the degree of risk of an individual sheep developing clinical classical scrapie.
Sheep carrying the VRQ (valine at 136, arginine at 154 and glutamine at 171) and ARQ
(alanine at 136) alleles are susceptible to scrapie, although to varying degrees, whereas
sheep homozygous for the ARR allele are believed to be highly resistant.
The control of natural ovine TSEs has recently been focused on the use of selective breeding
to reduce the incidence of the natural disease by decreasing the frequency of high–risk alleles
in the sheep population. The National Scrapie Plan (NSP) was introduced in 2004 as a means
of eradicating Scrapie from the national flocks www.defra.gov.uk/nsp. In addition, selective
culling and/or depopulation of complete flocks that are infected with scrapie have been
introduced in all European Union (EU) member states (Annex VII of EC Regulation
999/2001).
This study investigated the transmission of natural scrapie to scrapie-free sheep when
introduced to a farm environment housing a flock of scrapie-affected sheep.
The farm that provided the source of infection for this study has held a flock of sheep of
varying genotypes, for the past 10 years. This flock was developed by the purchase of
siblings or offspring from scrapie-affected ewes in national flocks, and maintained by the
Veterinary Laboratories Agency (VLA) as a breeding flock to encourage a high incidence of
scrapie.
The scrapie-free lambs used in this study derived from ewes originally imported from New
Zealand; free of scrapie. Lambs homozygous for the VRQ PrP genotype (most susceptible for
scrapie) and lambs homozygous for the ARQ PrP genotype (also susceptible to scrapie) were
used in this study.
In this study lambs were exposed to areas of the farm routinely used by the scrapie-affected
flock e.g. lambing environment, dirty lambing pens (used by the scrapie-affected ewes) and
pasture. Some lambs were given direct contact with scrapie-affected ewes and their lambs.
To study the transmission of scrapie at lambing time, believed to be a highly infectious
environment, pregnant ewes were introduced into the lambing pens to lamb alongside the
scrapie–affected ewes. A group of five lambs, born in the lambing shed alongside the scrapieaffected ewes were retained in the dirty lambing pens, after the removal of the scrapie
affected ewes to pasture, for 6 weeks before removal to barrier accommodation (lambing and
lambing pens for 6 weeks). Another group of pregnant ewes were brought into the dirty
lambing pens, after the removal of the scrapie-affected ewes, where they lambed and were
housed for 6 weeks before removal to barrier accommodation (to study transmission of
scrapie from infected lambing pens). To find out if length of time in which the lamb is exposed
to the infection effects the rate of transmission a group of five lambs and their dams, until
weaning at 12 weeks, were maintained in the flock alongside the scrapie-affected sheep for
12 months before removing to barrier accommodation (exposure to lambing, lambing pens
and pasture with direct contact).
A number of scrapie-free lambs were born on a clean farm and transported to the infected
farm at two days old with their dams, direct to pasture. Some were put to graze directly with
the scrapie-affected ewes and lambs whilst others were put on pasture previously grazed by
scrapie-affected sheep but had no direct contact with the sheep. Groups of ~5 lambs were
removed from pasture at 6 weeks, 12 weeks and 52 weeks to barrier accommodation.
To further study the effect duration of exposure has on the rate of transmission, lambs born to
scrapie-affected ewes in the same year were removed at 6 weeks, 12 weeks and 52 weeks to
barrier accommodation. Lambs of the most susceptible genotype (VRQ/VRQ), that remain in
the scrapie-affected flock for the duration of their lives, normally become affected by scrapie
~20 months of age. These groups acted as positive controls.
A group of five lambs were taken from the clean farm and transported directly to the barrier
accommodation to act as negative controls.
All lambs of the VRQ/VRQ genotype that had exposure to the lambing environment became
infected with scrapie as did those that went to pasture with direct contact with the scrapieaffected sheep. Some of the lambs of the same genotype, exposed to pasture only with no
direct contact with scrapie-affected sheep also became infected with scrapie. This
demonstrates that the scrapie infection is present in the lambing environment and remains on
pasture after the scrapie-affected sheep have been removed and can be transmitted to clean
sheep exposed to these areas of the farm.
In this study only a few lambs of the ARQ/ARQ genotype became infected with scrapie
although some of the ones that were exposed to pasture, in direct contact with the scrapieaffected ewes and lambs, became infected. Scrapie disease in sheep of this genotype seems
to be unpredictable as some sheep of this genotype can survive on the infected farm for
several years whilst others contract scrapie and die within two years. It is thought some other
factors could play an important part in the unpredictability of the transmission of scrapie
disease in sheep of this genotype.
There was some evidence that the duration of exposure did affect the rate of transmission
although this could not be measured successfully in this study due to the small numbers of
animals used.