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Research in Veterinary Science 2002, 73, 195–199
doi:10.1016/S0034-5288(02)00105-4, available online at http://www.idealibrary.com on
REVIEW
Foot and mouth disease
GARETH DAVIES
Zinna, Kettlewell Hill, Woking, Surrey GU21 4JJ, UK
SUMMARY
Foot and mouth disease (FMD) affects cloven-footed animals. It is caused by seven species (‘‘types’’) of Foot and Mouth
virus (FMDV) in the genus aphthovirus, family Picornaviridae (ICTV 2000). FMDV is a single-stranded RNA virus, with
a protein coat consisting of four capsid proteins enumerated as VP1, VP2, VP3, and VP4 (Garland and Donaldson
1990). 2002 Elsevier Science Ltd. All rights reserved.
HOST SPECIES
CATTLE, sheep, goats, and pigs are the main domesticated species infected. The Water Buffalo (Bubalus
bubalis) can become infected and may also transmit
infection to other species. Camelids, experimentally
infected, contract the disease (Lubroth et al 1990) but
there is no evidence of transmission to other domestic
livestock and there seems to be some doubt as to
whether they play any role in the epidemiology of the
disease in domestic livestock (Fondevila et al 1995).
A wide range of wild cloven-footed animals contract
FMD including deer and pigs. During the 2001 epidemic
in the United Kingdom there was great concern that the
various species of deer now abundant in the country
might contract the disease and act as a persistent reservoir of infection. In the event, investigation of a number
of cases of apparent disease failed to reveal the presence
of FMD virus. The African Buffalo (Syncercus caffer)
appears to be particularly susceptible to infection and
may act as a reservoir host (see later).
Although FMD is known as a disease of clovenfooted animals it can occur naturally in other animals,
e.g., the hedgehog (Erinaceus spp.) (McCauley 1963),
and infection has been established experimentally in a
number of other species. However, it is doubtful whether these animals play any part in the epidemiology of
the disease (Snowdon 1968).
FMD is not considered zoonotic. Although clinical
cases have been proven in human, these are extremely
rare in relation to human exposure during outbreaks
(Sellers et al 1970).
DISTRIBUTION
The seven types of FMD virus are: A, O, C, South
African Territories (SAT) 1, 2, and 3 and Asia 1. Types
O, A, and C are the strains that have been identified in
Europe and South America whilst O, A, and Asia 1 are
common throughout Asia. SAT strains 1 and 2 are
found throughout Africa whilst SAT 3 is confined to
Southern Africa. The strains found in the Middle East
0034-5288/02/$ - see front matter
include A, O, Asia 1, and SAT 1. These serotypes are
so defined because they do not cross-protect.
FMD is endemic in much of Africa and Asia and
parts of South America. Meat exporting countries such
as Argentina and Uruguay have made great efforts to
eliminate infection and were successful until 2001.
North America, Australia, and New Zealand have either never encountered the disease or have been free
for many years. Europe is also free apart from periodic
incursions, mainly from the Middle East. The world
situation has been reviewed by Kitching (1998) but the
position is fluid and up-to-date accounts of the incidence of FMD can be found in Food and Agriculture
Organisation (EMPRES) and Office International des
Epizooties (OIE) bulletins.
The development of molecular techniques has enabled the characterisation of individual strains of virus
(Kitching 1992). The genetic relationship between
strains can be calculated from the percentage nucleotide differences and it is now possible to trace the
movement of individual strains across countries and
continents. Thus the Pan-Asia O strain was first identified in Northern India before spreading westward to
Bulgaria and Greece in 1996 and now to the United
Kingdom (Knowles et al 2001).
PATHOGENESIS
The replication of the infectious particles is extremely rapid after entry through the upper respiratory
tract or lung, with viraemia seeding infection into the
epithelium where secondary virus multiplication results
in vesicles and shedding from the udder in milk (Hyslop 1965, Sellars 1971). The incubation period, from
infection to clinical signs, may be as short as 2/3 days or
as long as 14 days (Garland and Donaldson 1990) and
infected animals may become infectious before showing clinical signs (Burrows 1968a). The virus is excreted
during viraemia for some days; thereafter as serum
antibody develops viraemia decreases, and the animal
ceases to be infectious as the lesions heal.
2002 Elsevier Science Ltd. All rights reserved.
196
G. Davies
The disease is characterised by vesicular lesions on
the coronary band of the hooves and in the mucosa of
the mouth including the tongue and palate. The vesicles typically contain clear or straw-coloured fluid before they burst and heal. There is a rise in body
temperature of some 3–4 C. The lesions in sheep are
often difficult to find and may be confused with other
conditions (Ayers et al 2001).
The disease varies considerably in its severity. It may
result in death or severe morbidity particularly in neonates but in areas where the infection is endemic the
disease may be mild and the few vesicles that appear
may heal without further damage.
fectants (Sellars 1968). Cleansing and disinfection,
whilst laborious, is effective in eradicating the agent
from infected premises.
Virus survival in carcases is a crucial factor in regulating the international trade in meat. Following
slaughter the virus is inactivated within 48 hours provided the pH drops to below 6.0. as normally occurs in
the skeletal muscles during the period of rigor mortis.
However, the virus may survive in lymph nodes and bone
marrow (Cottral et al 1969) and when tissues containing
FMDV are frozen the virus can survive for years.
THE CARRIER STATE
EPIDEMIOLOGY
Few descriptions of FMD epidemics have been
published with the exception of the 2001 UK epidemic
(Gibbens et al 2001) and the 1993 Italian epidemic
(Marangon et al 1994).
Several factors determine the epidemiology of the
disease and therefore the control measures. The factors
are:
• the incubation period,
• the infectious period and the quantity of virus particles expelled,
• the spread of virus by aerosol,
• the survival of virus in fomites,
• the persistence of the virus in carcases,
• the existence of carriers,
• the density of the host populations.
THE SPREAD OF THE VIRUS
Infected animals are only infectious for a matter of
days (Burrows 1968a,b) but during that period the
amount of virus expelled may vary enormously with the
species affected, the stage of the disease and the virus
strain. Pigs excrete considerably greater quantities of
virus than either cattle or sheep (Sellars and Parker
1969).
During the 1967 FMD epidemic in the UK, it was
discovered that airborne virus spread could infect animals some distance away. Survival of the virus in
aerosols depends on the relative humidity (Donaldson
1972, Donaldson et al 2001) and airborne spread is a
feature of the disease in moist temperate as opposed to
dry tropical climates. Computer models have been
developed to predict the extent of airborne spread
(Gloster et al 1982, Sorensen et al 2000).
VIRUS SURVIVAL
FMD virus can survive for long periods at neutral
pH, particularly at low temperatures. Faeces and other
organic matter may protect it and the virus can survive
in straw for up to 15 weeks (Cottral et al 1969). However, the virus is acid and alkali labile and acidic
preparations at a pH 6.5 or below are effective disin-
The carrier state in FMD is the subject of much
debate and it is no exaggeration to say that it has
achieved iconic status in the international regulations
governing trade because of the concern that some animals recovering from the disease may become carriers
and spread the disease to others. The extensive literature relating to the carrier state in FMD has been reviewed by Salt (1993), Thomson (1996), and Moonen
and Schrijver (2000).
A carrier animal is defined as one from which the virus
can be recovered 28 days or more after infection. The
carrier state in FMD is an inapparent infection in which
the intermittent isolation of the virus from the oropharynx is currently the sole means of detection, Carriers
have been recorded in cattle (Van Bekkum et al 1959),
African buffalo (Hedger and Condy 1985), sheep (Burrows 1968a,b), and goats but not in pigs. It occurs with all
serotypes and has been identified in both experimentally
and naturally infected animals (Van Bekkum et al 1959,
Hedger 1968). It is well established that a proportion of
animals infected by FMD virus eventually become
‘‘carriers’’ with equal facility irrespective of whether
they have been vaccinated, passively immunised or are
immunologically na€ive cattle (Sutmoller 1971).
The prevalence of carriers is high immediately after
infection but declines, as do the virus titres, with time
and most cattle clear the infection after 4–5 months
(Thomson 1996). The carrier period appears to vary
between species, being in excess of 12 months in cattle,
up to 9 months in sheep and goats and at least 5 years
in African Buffalo (Condy et al 1985).
Although the carrier state in FMD is well documented, the evidence for carrier animals transmitting
infection to others is uncertain. When oro-pharngeal
fluid containing residual virus is injected into cattle or
pigs infection results (Van Bekkum 1973). However, a
large number of experiments have failed to demonstrate transmission from carrier animals (usually cattle)
to susceptible in-contact animals.
The field evidence for transmission from carriers is
equivocal and relates, in the main, to the carrier state in
African buffalo infected with SAT strains of virus.
Thomson (1996) states that ‘‘to date there are no unequivocal reports of transmission of FMD from persistently infected domestic livestock to susceptible
animals other than the circumstantial data available
from historical accounts and the events associated with
Foot and mouth disease
SAT 2 outbreaks in cattle in Zimbabwe between 1983
and 1991’’.
In summary there is no reliable contemporary field
data on which to base a quantitative assessment of the
risk posed by carrier animal. The experimental data
indicates that, if transmission of infection from carriers
occurs, it does so at very low frequencies or under a
particular set of, as yet unidentified, circumstances.
CONTROL
There are two approaches to controlling or eradicating FMD: slaughter and vaccination. Slaughter may be
used on its own, as in the UK, or in some combination
with vaccination as in the Continental countries during
the post war period. Most countries, and particularly
those where incursions of FMD are a constant threat,
vaccinate without resorting to slaughter. All control
programmes must include strict controls on the movement of animals.
DIAGNOSIS
Control programmes that include an element of
slaughter depend on prompt diagnosis.
The symptoms of FMD in cattle and pigs are usually
discernable during clinical examination and, for the
greater part, the identification of FMD infected herds
relies on clinical judgements. These may be confirmed
by laboratory tests and confirmatory tests are essential
when the disease makes its first appearance in a
country or zone. Clinical diagnosis in sheep can be less
certain (Ayers et al 2001) and for this species laboratory confirmation is desirable if not essential.
Erosive lesions in the buccal cavity are characteristic
of other diseases such as mucosal disease and rinderpest, whilst foot lesions in sheep may be caused by foot
rot. However salivation, lameness in all four feet, and a
sharp rise in temperature are characteristics of FMD
and should always be a cause for suspicion.
During the recent epidemic in the UK, where the
initial spread was amongst the sheep population, laboratory tests were widely used either to confirm clinical
diagnoses or to establish disease freedom. Laboratory
facilities were established to handle a volume of
100,000 tests for antibody a week.
Tests were used either to detect virus antigen or
serum antibody as described in the OIE Manual of
Standards. Virus in tissue samples was identified using
an antigen detection ELISA. Negative samples were
further examined in tissue culture. Serum samples were
tested for antibody using a liquid phase blocking ELISA (Ferris and Dawson 1988) or, in the later stages by
a solid phase blocking ELISA, positive samples being
further tested by the virus neutralisation test.
VACCINATION
Vaccines are widely employed to control FMD. The
nature of the immune response and the prospects for
197
improve vaccines have been reviewed by Doel (1996).
The vaccines currently available are inactivated and
contain whole virus in a semi-purified state. The immunological component of the virus appears to be the
VP1 polypeptide and protection can be conferred with
this peptide alone (Bittle et al 1982). Vaccines may
include one or several of the serotypes but the strain
used should match the field strains that are causing the
disease. Most vaccines contain aluminium hydroxide as
an adjuvant but oil based vaccines are also used in pigs.
A high level of immunity can be induced by potent
vaccines within a few days in both cattle and pigs (Salt
et al 1998, Doel et al 1994) but the interval between
vaccination and protection may be some 14 days with
the usual commercial vaccines.
The current generation of FMD vaccines protect
animals for periods up to 12 months (Cox and Barnett
2000) but the immunity conferred is not absolute and
FMD wild virus may multiply to a greater or lesser extent in a vaccinated animal. Vaccine programme failures
may be attributable to overwhelming challenge as in
large intensive units (Donaldson and Kitching 1989) or
to inadequate population cover that leaves sufficient
unvaccinated and therefore susceptible animals for the
virus to maintain itself and continue circulating.
Vaccines can be employed prophylactically to protect a population against future challenge, or in emergency, to deal with a current epidemic.
Prophylactic vaccination on a national scale is usually confined to cattle and such programmes successfully eliminated FMD from Continental post-war
Europe. It is widely assumed that for vaccine to be used
on a national scale, 80% cover of the population is
sufficient, which is a broad generalisation derived from
experience in human populations. The structure of
domesticated animal populations in herds and flocks,
and their variable density in intensive units or range
conditions, are important factors. Preliminary investigations by Keeling and others suggest that livestock
populations can be protected against major epidemics
of FMD if 50% or more of the susceptible animals are
vaccinated.
Vaccination in the face of an epidemic is a contentious issue. A recent epidemic in Uruguay was eliminated by vaccination without recourse to slaughter
(Sutmoller 2002) but it is more usual for vaccination to
supplement the slaughter of infected and in-contact
herds. The disadvantage of vaccination is said to be the
inevitable delay before the animals are protected but
with high potency vaccines the delay is only of the
order of 4–5 days (Salt et al 1998).
The advantage of vaccination is that it does not require large numbers of operatives and little in the way
of equipment whereas slaughter requires large teams to
diagnose, slaughter, disinfect premises, and bury or
burn carcases. Immediate destruction of animals on
farms where clinical cases have occurred is vital
(Howard and Donnelly 2000).
The general reluctance to vaccinate in the face of an
epidemic is due to international adherence to OIE and
other standards governing trade in animals and animal
products. As matters stand at the moment a country
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G. Davies
can be granted FMD free status and resume exports 3
months after the last outbreak if control is by slaughter.
If animals are vaccinated the interval is 12 months
(OIE Animal Health Code).
The rationale for this difference appears to be that
clinical signs of infection would be masked in vaccinated populations and that traditional serological tests
would not distinguish vaccinates from animals that
have encountered live infection. There is also the risk
that vaccinates, which have encountered infection and
become carriers, may later become infectious and
spread disease. As discussed above this latter claim
rests on flimsy foundations but the problem of distinguishing vaccinates from infected stock by serological
testing is one that is the subject of extensive research.
Responses to vaccination may be differentiated from
natural infection either by employing ‘‘marker’’ vaccines that give rise to a distinctive serological response
because of gene deletions, or by devising tests that
distinguish responses to vaccine from those to field virus. There are as yet no FMD marker vaccines but a
great deal of progress has been made in devising tests
to distinguish vaccinates from infected animals and
these rely on the fact that modern FMD vaccines
contain few non-structural proteins (NSPs). This area
of research has been reviewed by Mackay (1998) and
the conclusions are that whilst the tests are adequate
for distinguishing naturally infected herds from vaccinated herds, the sensitivity for detecting individual
animal is not high enough to allow the tests to be used
to identify and remove individual animals in a postvaccination surveillance programme.
FOOT AND MOUTH DISEASE IN
INTERNATIONAL TRADE
Foot and mouth disease is an OIE list A disease
(OIE Animal Health Code). This list is reserved for
transmissible diseases that are considered to be of
socio-economic importance within countries and that
are of significance in international trade. There is little
hard evidence to support the claim that FMD is of
considerable economic importance as the few published cost-benefit studies do not set down actual
morbidity and mortality rates in infected stock. This is
understandable as in developed countries the disease
is eradicated before it can cause damage. The losses
are the cost of the slaughter and other control measures (Davies 1993, Perry et al 1999). Nevertheless the
disease and its control are of the greatest importance
in the formulation of international animal health
strategies and the authorities have, over the years,
adopted a zero risk approach in drafting regulations
for international trade. The United Kingdom epidemic
has highlighted the deficiencies of such an approach in
the face of the epidemiological risks posed by increasing volumes of global travel and the integration
of widely diverse societies and economies. It is to be
hoped that the epidemic will stimulate a fresh approach to the problem of FMD; one that recognises
that perfect risk free solutions are not always possible
and that progress can only be made by devising risk
reduction measures that are consonant with the reality
of world trade.
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