D476.PDF

Rev. sci. tech. Off. int. Epiz., 2002, 21 (3), 505-512
Clinical variation in foot and mouth disease:
sheep and goats
R.P. Kitching & G.J. Hughes
National Centre for Foreign Animal Disease, 1015 Arlington Street, Winnipeg, Manitoba R3E 3M4, Canada
Summary
Foot and mouth disease (FMD) in adult sheep and goats is frequently mild or
unapparent, but can cause high mortality in young animals. The recent outbreak
of FMD in the United Kingdom has highlighted the importance of sheep in the
epidemiology of the disease, although there have been numerous examples in the
past where small ruminants have been responsible for the introduction of FMD
into previously disease-free countries. The difficulty in making a clinical
diagnosis should encourage the development of more rapid screening tests to
assist in future control programmes.
Keywords
Control – Diagnosis – Foot and mouth disease – Goats – Sheep.
Introduction
The outbreak of foot and mouth disease (FMD) that occurred
in the United Kingdom (UK) in 2001 has provided a good
example of how difficult it is to make a clinical diagnosis of the
disease in sheep (3). The outbreak predominantly affected the
sheep population, and the policy adopted by the UK
Government of slaughtering infected animals within 24 h of
suspicion of disease put intolerable pressure on field
veterinarians to make a clinical diagnosis on the evidence of
lesions indistinguishable from those produced by a variety of
other causes. Where samples were collected, over 50% of the
flocks slaughtered were not confirmed as positive for FMD
virus, viral antigen or genome by the laboratory.
The susceptibility of sheep and goats to FMD can vary with the
breed of animal and strain of virus. For example, the Hong
Kong topotype of serotype O FMD virus has only once been
isolated from a species other than the pig, and although never
specifically used to infect sheep or goats, the inability of this
strain to grow in experimentally inoculated cattle would
suggest that it would also not naturally infect small ruminant
hosts either (9). Conversely, there are strains of serotype O FMD
virus circulating in the Middle East where sheep and goats form
the majority of the susceptible population, which appear very
well adapted to small ruminants, and there are many examples
of FMD being carried into countries previously disease-free by
the movement of infected sheep and goats. In 1983, FMD
spread from Spain into Morocco with infected sheep. In 1989,
FMD was introduced to Tunisia by infected sheep, and was
originally misdiagnosed as bluetongue, because of the signs of
lameness; not until the disease had spread to cattle was it
recognised as FMD, by which time it had already been carried
into neighbouring countries. In 1994, FMD was transported by
illegally imported sheep from Turkey onto the Greek island of
Lesbos, from where it was taken onto the mainland; infection
was certainly present on Lesbos from May, but was not
positively diagnosed until August, which led to extensive
spread of the disease in eastern Greece. There are other
examples of sheep carrying virus from Turkey to Greece and
Bulgaria, in 1994 and 1993, respectively. Saudi Arabia banned
the importation of cattle from India in the early 1990s because
of the threat of rinderpest, but continued to import sheep and
goats. Nucleotide sequencing of isolates of serotypes O, A and
Asia 1 collected in Saudi Arabia during this period showed
them to be identical to those circulating previously in India
(Figs 1, 2 and 3). In 1994, an isolate later to be known as the
pan-Asian topotype was imported into Saudi Arabia by infected
livestock, probably from India; the disease then spread
throughout the Middle East, eventually causing the 1996
outbreaks in Bulgaria and Greece. Today this strain is still
present in the region, and has replaced all other strains of
serotype O. A close relative of this strain, but probably
imported from South-East Asia, caused the 2001 UK outbreak
(20).
Serotype O FMD virus has been recovered from over 90% of
the positive samples from sheep submitted to the World
Reference Laboratory for FMD, Pirbright, UK. Asia 1 serotype
© OIE - 2002
506
Rev. sci. tech. Off. int. Epiz., 21 (3)
A5/Allier/60
A22/IRQ/24/64
A22/IND/300/94
A/SAU/16/95
A/SAU/19/95
17.9%
A/SAU/24/95
A/SAU/35/94
A/TUR/3/95
18
16
14
12
10
8
6
4
2
0
Percentage nucleotide difference (nt 475-639 of VP1)
Fig. 1
Dendrogram showing the close genomic relationship between foot and mouth disease serotype A isolates from India and Saudi Arabia
(N.J. Knowles, personal communication)
has also been isolated from goat samples submitted from
Bangladesh and goats imported from this country were
responsible for an outbreak of Asia 1 in Kuwait. Isolation of
other serotypes is rare, but does not necessarily indicate that
infection of small ruminants with these serotypes does not
occur; for example, Kuwait reported isolating South African
Territories (SAT 2) virus from sheep during the incursion of
FMD into Saudi Arabia during 2000. However, even in East
Africa, where outbreaks due to serotypes O, A, C, SAT 1 and 2
are common, predominantly serotype O virus was identified in
clinically affected sheep and goats.
Transmission
As is the case with other ruminants, sheep and goats are highly
susceptible to infection with FMD virus by the aerosol route,
with as little as 20 TCID50 (tissue culture infectious doses) being
sufficient for infection. Aerosol production by infected pigs can
be as high as log10 8.6 TCID50 per day, theoretically sufficient to
infect over 20 million sheep. Aerosol production by infected
sheep, however, is considerably less, and whereas there are
reports of airborne virus spreading from pigs over 250 km to
infect cattle (France to England in 1981) (5), aerosol
PAK/1/54
TAI/2/95
IND/26/95
IND/40/95
14.8%
IND/233/95
IND/43/95
SAU/39/94
SAU/40/94
IND/51/95
18
16
14
12
10
8
6
4
2
0
Percentage nucleotide difference (nt 475-636 of VP1)
Fig. 2
Dendrogram showing the close genomic relationship between foot and mouth disease serotype Asia 1 isolates from India and Saudi Arabia
(N.J. Knowles, personal communication)
© OIE - 2002
507
Rev. sci. tech. Off. int. Epiz., 21 (3)
O1/Kaufbeuren/66
O1/Manisa/69
O/IND/6/94
15.4%
O/IND/9/94
O/SAU/15/94
O/SAU/62/94
O/SAU/65/94
O/SAU/58/94
O/SAU/72/94
O/SAU/100/94
O/SAU/28/95
O/SAU/14/95
O/SAU/20/95
O/SAU/77/94
18
16
14
12
10
8
6
4
2
0
Percentage nucleotide difference (nt 475-639 of VP1)
Fig. 3
Dendrogram showing the close genomic relationship between foot and mouth disease serotype O isolates from India and Saudi Arabia
(N.J. Knowles, personal communication)
transmission from infected sheep is unlikely to occur over
distances greater than 100 metres (7, 26). Sheep are also less
likely to become infected by airborne virus than cattle because
of their lower respiratory volume. Sheep and goats are probably
most often infected by direct contact with infected animals. The
virus may infect sheep and goats through abrasions on the skin
or mucous membranes, through contaminated food, as well as
by the respiratory route. During the FMD outbreak that took
place in the UK in 2001, disease spread was reported to occur
frequently by mechanical carriage of virus between flocks by
humans or vehicles.
Sheep-to-sheep spread by contact appears to be restricted, to
the extent that the rate of transmission within an affected flock
is lower than that observed in infected pig or cattle herds. A
good example of this phenomenon is illustrated by the
outbreak of FMD that took place in Greece during 1994.
Serological investigations showed that in many of the affected
flocks not all individuals had sero-converted to the virus,
indicating that the virus had not disseminated sufficiently to
infect entire flocks. In some flocks affected towards the end of
the outbreak, only 20% of the sheep were sero-positive (21).
There was suspicion, but little firm evidence, that the 1993
outbreak of FMD in Italy had also failed to maintain itself in
affected sheep flocks. Similarly, evidence from the recent UK
epidemic shows considerable variation in the level of intra-flock
infection rates. On one farm visited, only 5% of 237 sheep that
were blood tested were sero-positive, and 3% were viruspositive, whereas 91% of the 75 cattle present were clinically
affected. On a second farm tested, 8% of 148 sheep were seropositive, 24% virus-positive, whilst 98 of 100 cattle showed
clinical signs (1). A recent study by Hughes (14) has provided
supportive evidence for the observed difference between the
dynamics of FMD transmission in sheep populations as
compared with cattle and pigs. The study showed that, using
the 1994 Greek outbreak strain, there was significant reduction
in the level of infection and estimated transmission rates over
time during serial passage through groups of sheep. These
results infer that some, possibly most, strains of FMD virus may
die out if they are restricted to sheep. Infection of cattle or pigs
may be sufficient to increase the level of circulating virus and
consequently the probability of transmission of infection to
© OIE - 2002
508
in-contact sheep, thereby re-establishing the disease. This
hypothesis requires further investigation using other strains of
FMD virus. The limited transmission that may occur within
closed sheep populations is also often masked by the lack of
clinical signs (see above).
The probability of transmission of FMD virus from infected
sheep is highest during the viraemic phase and peaks at or just
before the appearance of clinical signs. This period correlates
well with the period of virus excretion (4) which ends at the
point of sero-conversion (2). Levels of virus excretion are strainspecific (4).
Clinical signs
The incubation period in sheep following infection with FMD
virus is usually between three and eight days (19), but can be
as short as 24 h following experimental inoculation, or as long
as twelve days, depending on the susceptibility of the sheep, the
dose of virus and the route of infection. The duration of
viraemia is between one and five days. Hughes et al. (15) were
unable to detect viraemia in 8% of sheep that sero-converted in
a series of transmission experiments. Clinical signs appear up to
three days after the start of viraemia, approximately seven days
after exposure to contact infection – giving the period between
exposure to infection and the onset of viraemia as between
three and seven days (13, 15). Vesicular disease may fail to
develop in approximately 25% of infected sheep (12, 15), a
further 20% may develop only a single observable lesion. In
79 sheep infected with the 1994 Greek strain, lesions in those
animals that developed vesicular disease were visible for less
than three days (15).
Rev. sci. tech. Off. int. Epiz., 21 (3)
field situation, lameness due to other causes may already be
present and may conceal the presence of FMD. Vesicles may
develop in the interdigital cleft, on the heel bulbs and on the
coronary band, but they usually rupture rapidly (Fig. 5) and
their appearance may be hidden by the coexisting presence of
foot rot. Hair or wool may have to be deflected upwards to
render lesions on the coronary band visible, but, in sheep,
lesions can easily be confused with the coronitis seen with
bluetongue. Vesicles also form in the mouth, but they rupture
easily and are usually only seen as shallow erosions, most
commonly on the dental pad, adjacent to the incisors (Fig. 6),
but also on the tongue, hard palate, lips and gums. In one study,
of 57 sheep with foot lesions due to FMD, only 4 had mouth
lesions and only 2 of these had mouth lesions without foot
lesions (15). Vesicles may also be observed on the teats,
particularly of milking sheep and goats and rarely, on the vulva
Fig. 5
Coronary band lesions due to foot and mouth disease are
usually mild, and difficult to see
Lameness is usually the first indication of FMD in sheep and
goats (Fig. 4). An affected animal develops fever, is reluctant to
walk, and may separate itself from the rest of the flock. In the
Fig. 4
Lameness is usually the first sign of foot and mouth disease in
sheep
© OIE - 2002
Fig. 6
A ruptured vesicle on the dental pad of a sheep infected with
foot and mouth disease virus
Rev. sci. tech. Off. int. Epiz., 21 (3)
and prepuce. Affected rams are unwilling to work, and lactating
animals suffer a temporary loss of milk yield. Secondary
infections may cause mastitis and persistent lameness and the
compromised epithelium can predispose to rapid transmission
of other viral infections such as sheep and goat pox and peste
des petits ruminants. Uncomplicated infections with FMD virus
are usually followed by rapid recovery in the adult animal.
The clinical disease in young lambs and kids is characterised by
death without the appearance of vesicles, due to heart failure.
Affected flocks may lose up to 90% of the lamb crop, and the
image of large numbers of lambs falling down dead when
stressed, as may occur when a stranger walks into the flock, is
dramatic.
Pathology
Local replication of FMD virus occurs at the site of entry, in the
mucosa of the respiratory tract or at a skin or mucous
membrane abrasion. The virus then spreads throughout the
body favouring epithelial tissue in the adult and heart muscle in
the juvenile. Lytic changes in the cells of the stratum spinosum
and consequent oedema give rise to the characteristic vesicles
and accumulation of granulocytes, and in the developing
myocardium of young animals, to a lympho-histiocytic
myocarditis (6). Depending on the speed with which the virus
overwhelms the function of the heart, gross lesions may be
apparent on post mortem as diffuse grey spots or more
organised ‘tiger’ stripes, particularly in the left ventricle and
interventricular septum.
In adult animals, recovery from FMD uncomplicated by
secondary pathogens, is usually rapid, but the virus will persist
in the tonsillar tissue for up to nine weeks in sheep and for a
shorter period in goats.
Diagnosis
Clinical diagnosis of FMD in sheep and goats is difficult because
of the usually transient appearance of lesions and their
similarity to those caused by other common diseases of small
ruminants. Laboratory confirmation of a diagnosis of FMD is
therefore essential. Samples of vesicle epithelium, if available, or
heart muscle from a dead lamb or kid, should be collected into
50% phosphate/glycerol, buffered to pH 7.4-7.6, and
submitted together with whole and clotted blood to a
laboratory equipped to handle the diagnosis and with the
necessary disease-secure facilities. This will either be a
designated government laboratory or the regional FMD
reference laboratory. Alternatively, samples can be sent to the
World Reference Laboratory for FMD at Pirbright in the UK,
following the necessary procedures (23). In the laboratory, the
tissue samples will be prepared as a 10% suspension for antigen
509
detection enzyme-linked immunosorbent assay (ELISA) (23)
or used directly in a polymerase chain reaction (PCR) (24) to
serotype the virus. Sensitive tissue cultures, such as primary
bovine thyroid or lamb kidney cells, will also be inoculated
with the tissue suspension and/or the whole blood and serum,
to grow the virus for further characterisation, and to amplify
the antigen if insufficient quantities were present in the original
sample to provide an initial diagnosis by ELISA. The antigenic
characteristics of the strain will be compared with existing
vaccine strains in order to identify a suitable vaccine if one is
required, or to confirm the use of one that is already helping to
control the outbreak (17). A segment of the viral genome (part
of the 1D gene) can also be sequenced and compared in the
reference laboratory database to determine the relationship of
the virus to other viruses circulating in the region, which may
give an indication of its origin (18).
Due to the difficulty in detecting clinical FMD in sheep and
goats, the disease may be present in the flock for a considerable
time prior to discovery and samples may be collected from
recovering animals. These animals will no longer have live virus
in their tissues, except possibly in the pharynx, but antibodies
to FMD virus will be detectable using either the liquid phase
blocking ELISA (23), the solid phase competition ELISA (22)
or the virus neutralisation test (23). However, if vaccine has
been used in the flock, these tests will not distinguish between
antibodies resulting from infection and those resulting from
vaccination. Animals that have been infected with replicating
virus develop antibodies to the non-structural proteins of FMD
virus, and these may be detected using the 3ABC ELISA or
enzyme-linked immuno-electrotransfer blot (EITB), although
neither test has been fully validated for use in small ruminants
(23). Alternatively, the presence of infection within the flock
can be investigated by collecting samples using a probang
sampling cup which recovers mucous and superficial epithelial
cells from the pharynx, the site of virus persistence (16). The
probang sample is then tested for the presence of FMD virus as
for tissue and blood samples.
A pen-side diagnostic test would have been particularly
valuable during the recent UK outbreak to assist field
veterinarians in their clinical diagnosis. One, similar to a test
which had been developed for rinderpest diagnosis, was in the
process of validation and was used with some success towards
the end of the outbreak (11, 25). The test relies on FMD viral
antigen being recognised by a monoclonal antibody (Mab)
attached to a coloured latex bead. The antigen/Mab/bead
complex is trapped by a fixed band of additional anti-FMD
virus monoclonal antibody as it migrates along a
chromatographic strip, creating an easily identifiable coloured
line over the fixed band of Mab as the latex beads concentrate.
The result can be read in 10 minutes. However, the test requires
the amount of antigen usually found in the epithelium of a
ruptured vesicle, but would not be sufficiently sensitive to
detect antigen in a blood sample; in many cases of FMD in
sheep, there may not be sufficient epithelium available for the
© OIE - 2002
510
test to be used. Adaptations of the PCR could also provide a
more rapid diagnosis, either to detect viral genome in nasal
swabs before the development of clinical disease, or for use in
portable machines taken to suspect premises (8).
Rev. sci. tech. Off. int. Epiz., 21 (3)
can also give the impression that the vaccination programme
has been successful, when in reality the virus is circulating
freely. The ability of the particular strain to maintain itself in the
small ruminant population becomes critical in these situations,
but, as discussed above, has so far received little attention.
Once the sample is received by a competent diagnostic
laboratory, and assuming the sample was properly collected
and stored during transport, the available tests are extremely
sensitive and specific, and for positive samples, the result can
usually be available in a few hours. However, before the
laboratory can report that no virus was detected, the sample
must be passaged on tissue culture and then blind-passaged a
further one or two times, each passage requiring 48 hours.
Thus a week may elapse after receipt of a sample and before a
final report is issued from the laboratory. This can and
frequently does cause some frustration with the field staff, as
quarantine and movement restrictions would probably have
been kept in place until a result was available. However, there
are many examples where preliminary negative results have
been issued and restrictions prematurely removed, and then the
final result has been reported positive.
Attempts to vaccinate the national sheep population are usually
hindered by the numbers involved, the cost of vaccination, and
the resources required to administer the vaccine. The initial
intention to include sheep and goats in the vaccination
campaign throughout Turkey was recognised as unrealistic.
Vaccination was therefore targeted at all susceptible stock in
European Turkey (Thrace) and only certain areas of Anatolia.
Similarly, Morocco concentrated on vaccinating sheep and
goats on the border with Algeria, together with strategic
vaccination around affected areas during the last outbreak of
FMD in the country. Uruguay vaccinated only the cattle
population during the final stages of the successful FMD
eradication programme undertaken in the early 1990s, and left
the approximately 20 million sheep unvaccinated during this
period.
Control
Conclusion
The control of FMD in sheep and goats follows the same
principles as would apply to the disease in other susceptible
farm livestock, i.e. movement restrictions, disinfection and
either slaughter of affected and in-contact animals or
vaccination. In countries previously free from FMD, an initial
attempt is usually made to eradicate the disease by slaughter.
However, most countries will retain the option to vaccinate and
thus maintain membership of a vaccine bank which can
provide vaccine at short notice. In countries that have endemic
FMD, sheep may be included in regular vaccination campaigns,
although they are rarely vaccinated more than once a year.
Sheep and goats are usually given half or a third of the cattle
vaccine dose, and either oil or aluminium hydroxide/saponin
adjuvants can be used. The duration of immunity against
disease will depend on the severity of challenge with live virus
in the field, the antigenic relationship between the vaccine
strain and the field virus and the potency of the vaccine used.
The often silent nature of the disease in adult sheep and goats
The recent UK experience has demonstrated the importance of
sheep in the epidemiology of FMD caused by certain strains of
virus. The difficulties encountered in identifying clinical disease
resulted in large numbers of healthy animals being slaughtered,
while other infected flocks went unrecognised, allowing the
virus to spread. While some would argue that the policy
adopted was effective and the overkill justified (10), a more
traditional approach of methodical tracing and laboratory
testing may have been equally effective, less expensive and
morally more defensible. Both sides of the argument would
however probably agree on the need for more rapid and reliable
on-farm diagnosis, and a better understanding of the natural
history of FMD in small ruminants.
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Rev. sci. tech. Off. int. Epiz., 21 (3)
Variation des signes cliniques de la fièvre aphteuse chez les ovins
et les caprins
R.P. Kitching et G.J. Hughes
Résumé
Alors que les manifestations de la fièvre aphteuse sont souvent peu ou non
apparentes chez les ovins et caprins adultes, cette maladie peut provoquer une
forte mortalité parmi les jeunes sujets. L’épizootie de fièvre aphteuse qu’a
récemment connue le Royaume-Uni a souligné l’importance du mouton dans
l’épidémiologie de la maladie, même si la responsabilité des petits ruminants
dans l’introduction de la fièvre aphteuse en pays indemnes avait été maintes fois
établie par le passé. Les difficultés que rencontre le diagnostic clinique devraient
inciter à mettre au point des épreuves de dépistage plus rapides, qui
deviendraient de précieux auxiliaires dans les futurs programmes de prophylaxie.
Mots-clés
Caprins – Diagnostic – Fièvre aphteuse – Ovins – Prophylaxie.
■
Variación de las manifestaciones clínicas de la fiebre aftosa:
ovinos y caprinos
R.P. Kitching & G.J. Hughes
Resumen
Aunque en los ovinos y caprinos adultos suela revestir carácter benigno o
subclínico, la fiebre aftosa puede provocar una elevada mortalidad entre
animales jóvenes. El reciente brote en el Reino Unido puso de relieve la
importante intervención de las ovejas en la epidemiología de la fiebre aftosa,
aunque antes ya se habían producido muchos episodios en que pequeños
rumiantes introdujeron la fiebre aftosa en países hasta entonces indemnes. Las
dificultades inherentes al diagnóstico clínico deben servir de aliciente para crear
pruebas de detección más rápidas y ponerlas al servicio de futuros programas de
control.
Palabras clave
Caprinos – Control – Diagnóstico – Fiebre aftosa – Ovinos.
■
© OIE - 2002
512
Rev. sci. tech. Off. int. Epiz., 21 (3)
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