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Table of Contents:
Taxonomy Information
  1. Species:
    1. Foot-and-mouth disease virus (Website 1):
      1. Common Name: Aftosa, Aphthous Fever
      2. GenBank Taxonomy No.: 12100
      3. Description: Foot-and-mouth disease virus (FMDV) is the prototype member of the Aphthovirus genus of the family Picornaviridae. Picornaviridae are nonenveloped viruses with single-stranded RNA genome of positive polarity. In addition, they are highly labile and rapidly lose infectivity at pH values of less than 7.0(Knipe et al., 2001). The virus exists in the form of seven different serotypes: A, O, C, Asia1, and South African Territories 1 (SAT1), SAT2, and SAT3, but a large number of subtypes have evolved within each serotype. Based upon the pioneering poliovirus genotyping studies of Rico-Hesse, FMDVs have been divided into genotypes based on comparisons of VP1 sequence data. For example, in a comprehensive study of FMD type O viruses they could be grouped into eight topotypes based on nucleotide differences of up to 15%. Similar studies are in progress for type A, C and Asia 1(Mason et al., 2003). Foot and Mouth Disease is endemic in parts of Asia, Africa, the Middle East and South America(Website 2). Outbreaks have occurred in every livestock-containing region of the world with the exception of New Zealand, and the disease is currently enzootic in all countries except Australia and North America. The disease affects domestic cloven-hoofed animals, including cattle, swine, sheep, and goats, as well as more than 70 species of wild animals, including deer. The recent outbreaks of foot-and-mouth disease (FMD) in a number of FMD-free countries, in particular Taiwan in 1997 and the United Kingdom in 2001, have significantly increased public awareness of this highly infectious disease of cloven-hoofed livestock. Furthermore, world concern following the terrorist attacks in the United States has raised the possibility that terrorist organizations or rogue states might target the $100 billion/year U.S. livestock industry by employing the etiologic agent of FMD. Although FMD does not result in high mortality in adult animals, the disease has debilitating effects, including weight loss, decrease in milk production, and loss of draught power, resulting in a loss in productivity for a considerable amount of time. Mortality, however, can be high in young animals, where the virus can affect the heart. In addition, cattle, sheep, and goats can become carriers, and cattle can harbor the virus for up to 2 to 3 years. FMD is one of the most highly contagious diseases of animals or humans, and FMDV rapidly replicates and spreads within the infected animal, among in-contact susceptible animals, and by aerosol(Grubman et al., 2004).
      4. Variant(s):
Lifecycle Information
  1. Foot-and-mouth disease virus lifecycle
    1. Stage Information:
      1. virion(Grubman et al., 2004):
        • Size: The FMD virion has a diameter of about 25 nm.
        • Shape: By electron microscopy, the FMD virion appears to be a round particle with a smooth surface. FMDV is distinguished from other picornaviruses by the lack of a surface canyon, or pit, which has been shown to be the receptor binding site for the entero-and cardioviruses. Another feature of the virion is the presence of a channel at the fivefold axis which permits the entry of small molecules, such as CsCl, into the capsid, resulting in FMDV having the highest buoyant density of the picornaviruses.
        • Description: FMDV, like other members of the Picornaviridae, has a relatively short infectious cycle in cultured cells. Depending on the multiplicity of infection, newly formed infectious virions begin to appear at between 4 and 6 hours after infection. The virus is cytocidal, and infected cells exhibit morphological alterations, commonly called cytopathic effects, which include cell rounding and alteration and redistribution of internal cellular membranes. The virus also causes biochemical alterations, including inhibition of host translation and transcription(Grubman et al., 2004).
    2. Picture(s):
      • Foot and Mouth disease virion



        Description: Aphthovirus: Molecular surface of Foot and Mouth Disease Virus, radially depth cued, as solved by X-ray crystallography(Website 135).
Genome Summary
  1. Genome of Foot-and-mouth disease virus
    1. Description: The virion is a 140S particle(Grubman et al., 2004). The genome of FMDV, which is over 8000 bases in length, is covalently bound at its 5-terminus to a 2324 amino acid residue genome-linked protein, 3B. In the mature virus, the genome is encapsidated in an icosahedral structure composed of 60 copies of four proteins (1A, 1B, 1C, and 1D). The genome contains a single long open reading frame (ORF), that has two alternative initiation sites, and the encoded polyprotein can be processed into over a dozen well-described mature polypeptides as well as a variety of partial cleavage intermediates. Most of the proteolytic events that produce these mature products are mediated by three viral proteinases, Lpro, 2A, and 3Cpro. The precise nature of the cleavage mechanisms utilized by 2A and the maturation cleavage of capsid protein 1AB into 1A and 1B remains unclear(Mason et al., 2003).
  2. Genome of Foot-and-mouth disease virus A
    1. Foot-and-mouth disease virus A(Website 106)
      1. GenBank Accession Number: NC_011450
      2. Size: 8161 bp(Website 106).
      3. Gene Count: The genome contains a single long open reading frame (ORF), that has two alternative initiation sites, and the encoded polyprotein can be processed into over a dozen well-described mature polypeptides as well as a variety of partial cleavage intermediates(Mason et al., 2003).
      4. Description: TEXT.
      5. Picture(s):
  3. Genome of Foot-and-mouth disease virus SAT 1
    1. Foot-and-mouth disease virus SAT 1(Website 108)
      1. GenBank Accession Number: NC_011451
      2. Size: 8173 bp(Website 108).
      3. Gene Count: The genome contains a single long open reading frame (ORF), that has two alternative initiation sites, and the encoded polyprotein can be processed into over a dozen well-described mature polypeptides as well as a variety of partial cleavage intermediates(Mason et al., 2003).
      4. Description: TEXT.
      5. Picture(s):
  4. Genome of Foot-and-mouth disease virus SAT 2
    1. Foot-and-mouth disease virus SAT 2(Website 110)
      1. GenBank Accession Number: NC_003992
      2. Size: 8203 bp(Website 110).
      3. Gene Count: The genome contains a single long open reading frame (ORF), that has two alternative initiation sites, and the encoded polyprotein can be processed into over a dozen well-described mature polypeptides as well as a variety of partial cleavage intermediates(Mason et al., 2003).
      4. Description: TEXT.
      5. Picture(s):
  5. Genome of Foot-and-mouth disease virus SAT 3
    1. Foot-and-mouth disease virus SAT 3(Website 112)
      1. GenBank Accession Number: NC_011452
      2. Size: 8170 bp(Website 112).
      3. Gene Count: The genome contains a single long open reading frame (ORF), that has two alternative initiation sites, and the encoded polyprotein can be processed into over a dozen well-described mature polypeptides as well as a variety of partial cleavage intermediates(Mason et al., 2003).
      4. Description: TEXT.
      5. Picture(s):
  6. Genome of Foot-and-mouth disease virus Asia 1
    1. Foot-and-mouth disease virus Asia 1(Website 114)
      1. GenBank Accession Number: NC_004915
      2. Size: 8167 bp(Website 100).
      3. Gene Count: The genome contains a single long open reading frame (ORF), that has two alternative initiation sites, and the encoded polyprotein can be processed into over a dozen well-described mature polypeptides as well as a variety of partial cleavage intermediates(Mason et al., 2003).
      4. Description: TEXT.
      5. Picture(s):
  7. Genome of Foot-and-mouth disease virus O
    1. Foot-and-mouth disease virus O(Website 116)
      1. GenBank Accession Number: NC_004004
      2. Size: 8134 bp(Website 116).
      3. Gene Count: The genome contains a single long open reading frame (ORF), that has two alternative initiation sites, and the encoded polyprotein can be processed into over a dozen well-described mature polypeptides as well as a variety of partial cleavage intermediates(Mason et al., 2003).
      4. Description: TEXT.
      5. Picture(s):
  8. Genome of Foot-and-mouth disease virus C
    1. Foot-and-mouth disease virus C(Website 118)
      1. GenBank Accession Number: NC_002554
      2. Size: 8115 bp(Website 118).
      3. Gene Count: The genome contains a single long open reading frame (ORF), that has two alternative initiation sites, and the encoded polyprotein can be processed into over a dozen well-described mature polypeptides as well as a variety of partial cleavage intermediates(Mason et al., 2003).
      4. Description: TEXT.
      5. Picture(s):
Biosafety Information
  1. General biosafety information
    1. Level: Due to the highly contagious nature and economic importance of FMD for many countries, the laboratory diagnosis and serotype identification of the virus should be done in a virus-secure laboratory. Countries lacking access to such a specialised national or regional laboratory should send specimens to the OIE/FAO World Reference Laboratory (WRL) for FMD(Website 132).
Culturing Information
  1. Primary culture (Website 132):
    1. Description: In animals with a history of vesicular disease, the detection of FMD virus in samples of vesicular fluid, epithelial tissue, milk, or blood is sufficient to establish a diagnosis. Diagnosis may also be established by the isolation of FMD virus from the blood, heart or other organs of fatal cases. Suspensions of field samples suspected to contain FMD virus once clarified are inoculated into cell cultures or unweaned mice. The cell cultures should be examined for cytopathic effect (CPE) for 48 hours. If no CPE is detected, the cells should be frozen and thawed, used to inoculate fresh cultures and examined for CPE for another 48 hours(Website 132).
    2. Medium: Primary culture of calf thyroid cells have been shown to be as sensitive for virus detection as intradermal inoculation in cattle, although primary pig, calf or lamb kidney cells can be used. But cryopreservation of the primary cells, after only one passage, result in less susceptibility and established cell lines such as IBR S2 or BHK 21 exhibit considerable inconsistency. In case of a vesicular condition in pigs, IBR-S2 cell line, susceptible to the SVD virus, permit the isolation of this virus, which grows only on porcine cells. IBR-S2 cells also prove to be useful to isolate porcinophilic strains of FMD virus(Remond et al., 2002).
    3. Upper Temperature: survival times at 37 degrees and 56 degrees celcius are 10 days and less than 30 minutes, respectively(Musser et al., 2004).
    4. Lower Temperature: The FMD virus is fairly stable at low temperatures, surviving for one year at 4 degrees celcius(Musser et al., 2004).
    5. Upper pH: 9.0(Musser et al., 2004).
    6. Lower pH: 6.0(Musser et al., 2004).
    7. Note: For laboratory diagnosis, the tissue of choice is epithelium. Ideally, at least 1 g of epithelial tissue should be collected from an unruptured or recently ruptured vesicle. Epithelial samples should be placed in a transport medium composed of equal amounts of glycerol and 0.04 M phosphate buffer pH 7.2-7.6, preferably with added antibiotics (penicillin [1000 international units (IU)], neomycin sulphate [100 IU], polymyxin B sulphate [50 IU], mycostatin [100 IU]). If 0.04 M phosphate buffer is not available, tissue culture medium or phosphate buffered saline (PBS) can be used instead, but it is important that the final pH of the glycerol/buffer mixture be in the range pH 7.2-7.6. Samples should be kept refrigerated or on ice until received by the laboratory. Where epithelial tissue is not available from ruminant animals, for example in advanced or convalescent cases, or where infection is suspected in the absence of clinical signs, samples of OP fluid can be collected by means of a probang (sputum) cup (or in pigs by swabbing the throat)(Website 132).
Epidemiology Information:
  1. Outbreak Locations:
    1. General: More than 50 of the 162 Member Countries of the Office International des Epizooties (OIE), the World Organisation for Animal Health, have obtained recognition from the OIE for freedom from foot and mouth disease (FMD) without vaccination. The virus continues to circulate in two-thirds of the remaining countries, thus dividing the globe into two zones. This has significant effects on international trade patterns in susceptible animals and animal products. Consequently, countries that do not have FMD-free status continue to suffer a severe handicap in terms of access to international markets. This situation was highlighted by the sudden and largely unexpected resurgence of FMD in Europe, South America and Asia at the beginning of the 21st Century. This endemic situation with respect to FMD in many parts of the world is a constant threat to countries that have acquired FMD-free status at considerable cost and effort. The threat has been exacerbated over the last decade by accelerated trade and movements of people due to globalization. At the same time, developed countries have either decreased or discontinued vaccination. The dangerous cocktail of globalization and non-immunised animals exploded in 2001, first in South America and then in the United Kingdom and other countries of the European Union(Vallat et al., 2003). In 1997 an FMD outbreak was reported in Taiwan, a country that had been free of the disease for 68 years. This devastating outbreak resulted in the slaughter of more than 4 million pigs, almost 38% of the entire pig population, at a cost of approximately U.S $6 billion and reminded the international animal health community of the severe economic consequences that a FMD outbreak could have for a previously disease-free country. Starting in late 1999 and 2000, a series of FMD outbreaks occurred in a number of countries in East Asia. This was followed by an outbreak in South Africa and culminated in the destructive outbreak in the United Kingdom, which then spread to the European continent. These outbreaks reemphasized the extreme virulence of the FMDV in a variety of animal species, the vulnerability of FMD-free countries as well as countries where FMD is enzootic to new viral strains, the efforts of globalization on increasing the risks of disease incursion, and hence the need for countries to more closely monitor for the presence of exotic disease(Grubman et al., 2004).
    2. Europe and Central Asia: In the past, the disease has ravaged European livestock, but has been gradually brought under control, at great cost, by preventive vaccination programmes, supplemented by the destruction of infected herds in most of the countries of continental Europe and, in the United Kingdom (UK) and Nordic countries, by destruction of infected herds alone. After careful evaluation of the two possible options for preventing the re-occurrence of the disease in Europe to either continue or discontinue mass vaccination the European Union decided to prohibit all vaccination after 1991. FMD remained and is still endemic in the Middle East, including Asian Turkey (Anatolia), and despite efforts of the Governments of Turkey and Europe, Anatolia appears to be a permanent source of sporadic outbreaks in the Balkans and a threat to Europe. In recent years, FMD was reported mainly in the Balkans. Despite these occasional incursions of FMD into south-east Europe, in all cases, the control measures were efficient and the disease never spread to such an extent as to become endemic. A major outbreak, which affected 2,030 farms occurred in the UK between February and September 2001. This was the first major epidemic of FMD in Europe since preventive vaccination had been abandoned in continental Europe in 1991. The disease also spread to Ireland, France and the Netherlands although the number of outbreaks was limited in these countries(Leforban et al., 2003).
    3. South America: Since the signing in 1987 of the Hemispheric Plan for the Eradication of Foot-and-Mouth Disease by the countries of South America, clinical cases of foot and mouth disease have decreased significantly throughout the continent. During the early 1990s, national laboratories diagnosed an average of 766 cases per year in South America. By the late 1990s, this continent-wide average had fallen to 130. By the end of the 1990s, the international community recognized Argentina, Chile, Guyana, and Uruguay as free of FMD without vaccination. In 1999, clinical signs of FMD were absent in 60% of all cattle on the continent. These cattle represented 41% of all herds in South America and extended over 60% of the geographical area of the continent. However, in the spring of 2001, FMD re-appeared in certain countries of the Southern Cone. This wide-spread re-occurrence of the disease in Argentina, Uruguay and the State of the Rio Grande do Sul in Brazil called into question whether countries in South America can achieve and maintain FMD-free status, with or without vaccination(Melo et al., 2003).
    4. Middle East and North Africa: Only one country in the Middle East (Cyprus) is presently included in the OIE list of foot and mouth disease-free countries. The region is regarded as that most affected by FMD in the world. FMD has been recorded in all countries in the Middle East on numerous occasions between 1960 and 2000, serotype O being the most prevalent. In the past, exotic FMD viruses were the cause of panzootics, which spread to many areas of the region, even extending to the frontier of Europe. A remarkable example was the rapid dissemination of serotype SAT 1 virus, which occurred initially in Bahrain in December 1961. The virus spread north-westwards to reach Iraq, Jordan, Israel, and Syria by April 1962, continuing to Iran and Turkey. In September 1962, this serotype crossed the Bosporus to enter Europe for the first time, and in November, caused an outbreak further west, near the border between Turkey and Greece. Historically, epidemics mainly affected cattle and spread from east to the west in the Middle East. The slow spread of FMD from Tunisia in 1989 to Morocco in 1991 exemplifies the difficulty in controlling the disease since unregulated movements of herds of small ruminants may play an important role in spreading infection. The situation in the Middle East and North Africa constitutes a threat to other regions of the world, especially Europe(Aidaros et al., 2003).
    5. East Asia: Japan regained the status of freedom from foot and mouth disease without vaccination in September 2000 and the Republic of Korea likewise obtained this status in September 20001. However, new outbreaks of FMD caused by the Pan-Asian topotype have occurred in pigs in the Republic of Korea since May 20002. Taipei China has not experienced an outbreak of FMD since February 20001 and the country is currently implementing and eradication programme. These countries had been free from FMD for many decades when in 1997, the FMD virus once again invaded the region, particularly in 2000; this resulted in widespread occurrence of the disease. The types of FMDV were investigated by genome analysis, and in each case the virus concerned was found to be a member of the pan-Asian O lineage(Sakamoto et al., 2003).
    6. South-East Asia: Of the ten countries in South-East Asia, FMD is endemic is seven (Cambodia, Laos, Malaysia, Myanmar, the Philippines, Thailand, and Vietnam) and three are free of the disease (Brunei, Indonesia and Singapore). Part of the Philippines is also recognized internationally as being free of FMD. From 1996 to 2001, serotype O viruses caused outbreaks in all seven of the endemically infected countries. On the mainland, three different type O lineages have been recorded, namely: the South-East Asian topotype, the pig-adapted or Cathay topotype and the pan-Asian topotype. Prior to 1999, one group of SEA topotype viruses occurred in the eastern part of the region and another group in the western part. However, in 1999, the pan-Asian lineage was introduced to the region and has become widespread. The Cathay topotype was reported from Vietnam in 1997 and is the only FMD virus currently endemic I the Philippines. Type Asia 1 has never been reported from the Philippines but was reported from all countries on the mainland except Vietnam between 1996 and 2001. Type A virus has not been reported east of the Mekong River in the past six years and seems to be mainly confined to Thailand with occasional spillover into Malaysia. The distribution and movement of FMD in the region is a reflection of the trade-driven movement of livestock(Gleeson et al., 2003).
    7. Sub-Saharan Africa: Six of the seven serotypes of FMDV (i.e. all but Asia 1) are prevalent in Africa although there are marked regional differences in distribution. Three of these serotypes are unique in Africa -- the three SAT serotypes. Serotype C may also now be confined to Africa because it has not been reported elsewhere recently. In southern Africa at least, the SAT serotypes have an intimate and probably ancient association with African buffalo (Syncerus caffer) that is instrumental in their maintenance. Within each of the six prevalent serotypes, with the possible exception of C, there are a number of different lineages with more or less defined distributions (topotypes) that in some cases are sufficiently immunologically different from one another to require specific vaccines to ensure efficient control. This immunological diversity in prevalent serotypes and topotypes, in addition to the uncontrolled animal movement in most parts of the continent, render FMD difficult to control in present circumstances. This fact, together with poorly developed intercontinental trade in animals and animal products has resulted in the control of FMD being afforded a low priority in most parts of the continent, although the northern and southern regions of the continent are an exception. As a consequence, eradication of FMD from Africa as a whole is not a prospect within the foreseeable future(Vosloo et al., 2002A).
  2. Transmission Information:
    1. From: Artiodactyla , To: Humans (Sutmoller et al., 2003)
      Mechanism: The circumstances in which it does occur in humans are not well defined, though all reported cases have had close contact with infected animals. There is one report from 1834 of three veterinarians acquiring the disease from deliberately drinking raw milk from infected cows. There is no report of infection from pasteurized milk, and the Food Standards Agency considers that foot and mouth disease has no implications for the human food chain(Prempeh et al., 2001). People in contact with infected animals are exposed to enormous amounts of virus. Using large-volume air samplers, Sellers found that in a period of 30 minutes 10 million IU could be collected from the air of a stable housing infected pigs(Sutmoller et al., 2003). Sampling of human subjects, who had been in contact with diseased animals, showed that virus could be recovered from the nose, throat, and saliva of these people immediately after leaving the room. Nasal swabs of such persons usually contain 100-1000 IU, but some may contain as many as 10,000 IU(Sutmoller et al., 2003).
    2. From: Humans , To: (Musser et al., 2004). (Sutmoller et al., 2003)
      Mechanism: Nonsusceptible animals, such as horses, foxes, rats, birds, and humans, are a means of mechanical spread of the virus(Musser et al., 2004). 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(Kitching et al., 2002B). People who work with infected animals or materials will carry FMD virus on their hair and skin and on clothes. If contaminating virus is not removed by showering and change of clothes there is a high probability that a susceptible animal will receive sufficient virus to become infected by fomites, aerosol or handling. In the 1967-68 epidemic in UK, veterinarians were incriminated in 6 of 51 outbreaks and in 4 other cases non-veterinary personnel were involved. Sellers reported that, under exceptional circumstances, FMD virus carried in the nose and throat could be transmitted from man to animals. Shortly after begin in contact with infected animals, these researchers discarded clothes, showered and moved to a different compound and succeeded, in transmitting and infecting one steer by examining the animals and at the same time sneezing, snorting, coughing and breathing a the muzzles of the animals. The exposure of each animal to this treatment lasted 30s for each person. However, in practice, such intimate contacts between people and susceptible cloven-hoofed animals is unlikely(Sutmoller et al., 2003).
    3. From: Artiodactyla , To: Cattle (Kitching et al., 2002C)
      Mechanism: Susceptible cattle coming into contact with an infected animal, whether sheep, goat, pig or wildlife species may be infected by the respiratory rout or through an abrasion on the skin or mucous membranes(Kitching et al., 2002C). Infection of cattle generally occurs via the respiratory route by aerosolized virus. Infection can also occur through abrasions on the skin or mucous membranes, but is very inefficient, requiring almost 10,000 times more virus. Virus is excreted into the milk of dairy cattle as well as in semen, urine and feces, and calves can become infected by inhaling milk droplets(Grubman et al., 2004). In 1981, cattle on the Isle of Wight in the United Kingdom were infected by windborne aerosol virus produced by infected pigs in Brittany, France and the virus was carried over 250 km across the English channel(Kitching et al., 2002C).
    4. From: Cattle , To: Artiodactyla (Kitching et al., 2002C)
      Mechanism: The transmission of FMD virus within an unvaccinated herd is usually rapid, as was seen during the recent outbreak in the UK win which over 90% of a group could be showing clinical signs by the time the disease was first identified. Even within a vaccinated herd, the aerosol production of virus from a single infected animal can overcome the immunity of others in the herd resulting in a further increase in the level of challenge and the appearance of clinical disease(Kitching et al., 2002C). In all parts of the world with the exception of sub-Saharan Africa, FMD in free-ranging or captive wildlife appears to be an extension of the disease in lifestock. This has been documented for free-ranging moose, Alces alces, as well as in fallow, roe and red deer in Europe. In the former Soviet Union, FMD was described in free-ranging reindeer Rangifer tarandus and saiga Saiga tatarica, while in India severe clinical signs and mortality were reported in the blackbuck Antilope cervicapra. High ranging mortality also occurred in free-ranging mountain gazelles in Israel during epidemics in cattle. Similarly, outbreaks of FMD in zoological gardens in Paris, Zurich, and Buenos Aires coincided with outbreaks in FMD in domestic animals(Thomson et al., 2003). Infected cattle also aerosolize large amounts of virus, which can infect other cattle in addition to other species(Grubman et al., 2004). Infected cattle also produce up to log10 5.1 TCID50 of aerosol virus per day, and a large dairy herd could infect neighboring herds with their combined output of virus(Grubman et al., 2004). Cattle with FMD are usually the greatest producers of FMD virus of all species. It can be estimated that one infected cow, in addition to exhaled air, contaminates the environment with some 10 billion or more IU during the first week of disease with excretions (faeces, urine, milk), salivation, sloughed-off blister epithelium and vesicular fluid. The total amount of virus excreted by pigs and sheep is, in general, much smaller than cattle(Sutmoller et al., 2003).
    5. From: Artiodactyla , To: Pigs (Kitching et al., 2002D)
      Mechanism: Pigs usually become infected with the virus by eating FMDV-contaminated products, by direct contact with another infected animal, or by being placed in a heavily contaminated environment, for example a pen, an abattoir lairage or a transport lorry that has previously housed or transported infected animals. Pigs are considerably less susceptible to aerosol infection than ruminants, and recent studies using several virus strains indicated that a pig may require up to 6,000 50% tissue culture infective doses TCID50, possibly as much as 600 times more than the exposure to aerosol virus required by a bovine or an ovine, to cause infection. While this figure may vary with individual pigs and potentially could be different for certain FMDV strains, it was consistent with many field and experimental observations which described situations in which pigs were not infected when physically separated from infected animals. Once infection is established within a pig herd, transmission by direct contact between infected and susceptible animals can be very rapid, and many routes of viral entry bay be involved, i.e. aerosol, oral, mucosal, and through damaged epithelium which may play an important role under intensive conditions or other conditions (transportation and at abattoirs) where aggression among pigs may be increased(Kitching et al., 2002D). In the United States, feral pig populations are very large and widespread. Foot and mouth disease in feral pigs has been the subject of considerable research and modeling. For example, Australian scientists have estimated that FMD will spread among feral pigs at a rate of 2.8 km per day when pigs are at a fairly low population density (1 to 2/km2)(Leighton et al., 2002).
    6. From: Pigs , To: Artiodactyla (Kitching et al., 2002D)
      Mechanism: Pigs infected with FMDV do produce more aerosol virus than ruminants, and the same studies showed that the aerosol production from infected pigs infected with different stains also differed considerably. Maximum excretion of aerosol virus coincides with development of clinical disease and lesions on the snout, tongue and feet, and declines over the following 3 to 5 days as the antibody response develops(Kitching et al., 2002D). In 1981, cattle on the Isle of Wight in the United Kingdom were infected by windborne aerosol virus produced by infected pigs in Brittan, France and the virus was carried over 250 km across the English Channel(Kitching et al., 2002C).
    7. From: Artiodactyla , To: Sheep and Goats (Grubman et al., 2004)
      Mechanism: Sheep are highly susceptible to virus infection via aerosol and can excrete airborne virus; however during outbreaks they are most like infected by contact with other animals(Grubman et al., 2004). As is the case with other ruminants, sheep and goats are highly susceptible to infection with FMD virus by the aerosol route. Aerosol production by pigs can be as high as log10 8.6 TCID50 per day, theoretically sufficient to infect over 20 million sheep. But sheep are 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(Kitching et al., 2002B).
    8. From: Sheep and Goats , To: Artiodactyla (Kitching et al., 2002B)
      Mechanism: Aerosol production by infected sheep is considerably less. Aerosol transmission from infected sheep is unlikely to occur over distances greater than 100 meters. 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. 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 virus-positive, whereas 91% of the 75 cattle present were clinically affected(Kitching et al., 2002B). 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, which ends at the point of sero-conversion. Levels of virus excretion are strain specific(Kitching et al., 2002B). Because it is very difficult to make a clinical diagnosis of FMD in sheep, the disease can be spread to other livestock prior to detection(Grubman et al., 2004). A recent study by Hughes 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 though 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 and pigs may be sufficient to increase the level of circulating virus and consequently the probability of transmission of infection to in-contact sheep, thereby re-establishing the disease. This hypothesis requires further investigation using other strains of FMD virus(Kitching et al., 2002B).
    9. From: African Buffalo , To: African Buffalo (Vosloo et al., 2002A)
      Mechanism: Most infections are believed to occur as a result of childhood epidemics within buffalo breeding herds when large numbers of juveniles (about 10% of each breeding herd) are recruited annually into the susceptible populations. They can become infected on the waning of maternally-derived immunity obtained from colostrum(Vosloo et al., 2002A). Infection of individual animals within the breeding herds of buffalo usually occurs when maternal immunity starts to wane at 2-4 months of age. Calves are not necessarily infected by their dams, and it is presumed that SAT viruses spread mainly during minor epidemics among animals in breeding herds, with carriers ensuring that the viruses survive interepidemic periods. Transmission of SAT type viruses between individual buffaloes appears to occur by two processes: (1) contact transmission between acutely infected and susceptible individuals, which is likely to account for most infections, and (2) occasional transmission between carrier buffaloes and susceptible individuals. However, the mechanism whereby carrier transmission occurs between buffaloes is obscure. A possibility, for which the evidence is still obscure, is sexual transmission(Thomson et al., 2003).
    10. From: African Buffalo , To: Cattle (Bastos et al., 2003)
      Mechanism: Transmission of SAT-type virus from persistently infected African buffalo to cattle under experimental and natural conditions has been unequivocally demonstrated(Bastos et al., 2003). Buffalo calves lose their maternal antibodies at 2-6 months of age and thereafter show seroconversion for one or more of the three types of SAT virus. Apparently during that period they acquire the infection from their dams. It has been quite difficult to show that the infection can pass from buffalo to domestic livestock species, but studies of Thomson in 1992 indicated that young buffalo in the acute stage of infection are likely to be the most infectious animals in the herd. Those contagious calves are responsible for maintaining FMD virus in the herd and the spread of FMD to other wildlife or domestic livestock species(Sutmoller et al., 2002). Buffalo bulls in the field have been observed by farmers to mount domestic cows on occasion and it is possible that sexual activity may be a way in which SAT-type viruses are transmitted form African buffaloes to cattle(Thomson et al., 2003).
    11. From: African Buffalo , To: Impala (Thomson et al., 2003)
      Mechanism: African buffaloes in the KNP in south Africa have been shown to be the usual source of infection for impala on the basis of sequencing studies(Thomson et al., 2003). Other susceptible species, principally impala, probably become exposed while infection is circulating among buffalo calves, possibly around permanent water points, where animals congregate(Thomson et al., 2003).
    12. From: Hedgehog , To: Artiodactyla (Thomson et al., 2003)
      Mechanism: There is evidence suggesting transmission in both directions between cattle and European hedgehogs Erinaceus europaeus, and for latent infections of hibernating hedgehogs. However, these reports should be viewed with caution, because there is not evidence that hedgehogs have participated in the propagation of FMD viruses in Europe or Africa in recent times(Thomson et al., 2003). During and outbreak in Norfolk in 1946 nine hedgehogs were found dying from FMD over an 11-week period. It was thought that there had been hedgehog to hedgehog transmission and that they had contributed to local spread of the disease. The authors considered that the outbreak could have originated in the hedgehogs as they had access to kitchen scraps containing imported meat products(Simpson et al., 2002).
    13. From: Cattle , To: Deer (Thomson et al., 2003)
      Mechanism: It might be considered that they could act as ideal hosts for the virus and that they might well acts as excellent reservoirs of infection. In the 1924 outbreak in California, over 20,000 deer were shot in order to control the spread of disease and over 2,000 had active or healed lesions. Yet in Europe, deer do not appear to act as disseminators of virus. In the UK during periodic outbreaks of FMD over the past fifty years, there has never been any suggestion that deer have directly involved. In an area such as the New Forest in the south of England, which is over 1000 square miles in extend, cattle and pigs share the forest grazings with at least four species of deer. Despite outbreaks in the farm livestock, no deer has ever been seen to be infected clinically. Many years ago, many deer were culled during an outbreak so that they could be examined by veterinary experts none were found with lesions(McDiarmid et al., 1975). Roe deer Capreolus capreolus, fallow deer Dama dama, sika deer Cervus Nippon, red deer Cervus elaphus and muntjac Muntiacus muntjac excreted FMD virus following experimental infection in approximately the same quantities as sheep and cattle. It has furthermore been shown that infection between deer and domestic livestock may occur in either direction(Thomson et al., 2003). White-tailed deer were shown to be susceptible to infection with FMD virus type O. The disease was transmitted by contact from deer to other deer, from deer to cattle, and from cattle to deer. White-tailed deer were clearly susceptible to infection from this strain of FMD virus both by intranasal inoculation and by contact exposure(McVicar et al., 1974).
    14. From: Deer , To: Artiodactyla (Thomson et al., 2003)
      Mechanism: Most deer, including white-tailed deer and mule deer like those found in North America, were assigned a high hazard category because of demonstration of FMDV transmission. At least one white-tailed deer remained a carrier of FMDV for 11 weeks after infection. Exotic deer, including red, sika, and fallow, have been gaining popularity for use on deer farms or game ranches. Such deer have been found to both acquire and transmit FMDV under natural conditions. There is no information on transmission from other cervids such as moose and elk. Accordingly, those cervids were placed in a moderate category(USDA et al., 1994). The opinion that FMD infected deer constitutes a low risk because sick animals hide and probably die, is not valid. Like cattle or sheep, susceptible deer are very infectious prior to the development of the lesions while they still actively move and graze. Also deer with sub-clinical or minor lesions will still roam around(Sutmoller et al., 2003). Roe deer Capreolus capreolus, fallow deer Dama dama, sika deer Cervus Nippon, red deer Cervus elaphus and muntjac Muntiacus muntjac excreted FMD virus following experimental infection in approximately the same quantities as sheep and cattle. It has furthermore been shown that infection between deer and domestic livestock may occur in either direction(Thomson et al., 2003).
    15. From: Artiodactyla , To: Llama. (Lubroth et al., 1990)
      Mechanism: Foot-and-mouth disease virus was shown to be transmitted from either cattle to llamas, llamas to swine or llamas to llamas(Lubroth et al., 1990). In a large experimental study where llamas were exposed to FMD infected pigs and cattle, the llamas were poorly susceptible to FMD and the few infected llamas only had virus in their pharyngeal mucosa for a short time. Moreover, recovered animals did not transmit virus to other susceptible species. Clearly, to become infected llamas need exceptional infection pressure. The lack of sero-conversion, when exposed to normal outbreak situations, indicates that llamas do not play a role in FMD epidemics(Sutmoller et al., 2003).
    16. From: Artiodactyla , To: Rodents. (Thomson et al., 2003)
      Mechanism: Capybaras (Hydrochaeris hydrochaeris) are susceptible to FMD and they may play a role in the epidemiology of FMD in cattle in South America(Thomson et al., 2003). The capybara, a large rodent that lives in groups in close contact with grazing livestock, has been shown to develop clinical disease. Capybaras were exposed to FMDV type O by the intramuscular route and virus was isolated from most of the organs collected from four animals slaughtered 24-48 hours post-inoculation. The remaining capybaras developed vesicular lesions on their feet between 72 and 96 hours post-infection and virus was shed in feces until at least 10 days post-infection. The susceptibility to capybaras to this strain of FMDV by intramuscular inoculation does not necessarily mean that they constitute an actual reservoir and the epidemiological significance of FMD in the species is unknown. Most likely cattle are the primary host and capybaras a dead-end host(Sutmoller et al., 2003).
    17. From: Rodents. , To: Artiodactyla (Sutmoller et al., 2003)
      Mechanism: Rats, mice and birds might transmit the disease mechanically. FMDV has been found in rat feces and urine and in bird droppings. The maximum titer found in rat feces was 1000 ID50 per g. Sellers states that the feces from 160 rats would be required to attain sufficient virus to infect cattle by ingestion. However, the chance of infection will also depend on the numbers of animals contacting the infectious source, raising the likelihood of a transmission occurring with sources containing low viral loads. It has also been suggested that contamination of dust by rat feces or urine may lead to infection by inhalation. In this instance only a few IU would be required. It must be emphasized that the role of vermin such as rats is insignificant under conditions of extensive cattle management as occur in South America. Vermin might spread FMD from infected premises, particularly when cleaning and decontaminating have eliminated normally available feed sources(Sutmoller et al., 2003).
    18. From: Invertebrates. , To: Artiodactyla (USDA et al., 1994)
      Mechanism: Although the role of flies and ticks in the epizootiology of FMD is not usually large, it has been demonstrated that ticks and some species of biting flies can transmit the virus through bite. Tick, flies, and biting flies were categorized as high hazards, based either on transmission capability or long carrier status (whether mechanically or biologically). Houseflies can carry FMDV both externally and internally; whether they can transmit the virus is unknown. It is unlikely that the virus multiplies in the cells of invertebrates. However, experimental transovarial infection of a portion of a population of Dermacentor ticks has been reported(USDA et al., 1994).
  3. Environmental Reservoir:
    1. Artiodactyla(Sutmoller et al., 2003):
      1. Description: Currently, carrier animals are defined as those from which live virus can be isolated at 28 days, or later, after infection. The role of carrier animals in the spread of virus in the filed is still controversial. The mechanisms for the establishment and maintenance of the carrier state are not well understood, since persistence can occur in animals exposed to virus after either acute disease or vaccination. It does appear that the immune status of the animal probably controls the level of virus replication. Alexanderson and colleagues have proposed two mechanisms for the development of persistence in the pharynx. One suggests that FMDV can infect immune system cells, such as macrophages, or other immunologically privileged sites, leading to evasion of the immune response. The second mechanism proposes that the virus exploits the host response to provide favorable intracellular conditions for long-term persistence, possibly by utilizing cytokine signalling(Grubman et al., 2004).
    2. cattle(Sutmoller et al., 2003):
      1. Description: In the late 50s and early 60s it was shown that in countries with endemic FMD, virus could be isolated from the mucous and cell debris form oropharyngeal mucosa in as much as half of the cattle population. However, dependent on the virus strain, type of cattle and local circumstances figures may vary and individual cattle will show differences in duration and level of virus excretion. The long-term persistence of FMDV in the pharyngeal area of cattle is measured in years rather than in months(Sutmoller et al., 2003). More than 50% of cattle have recovered from infection with FMD virus and vaccinated cattle that have had contact with live virus become carriers. The FMD virus persists particularly in the basal epithelial cells of the pharynx and dorsal soft palate, and can be recovered from some animals for over three years, although the carrier state does not usually extend beyond a year(Kitching et al., 2002C).
      2. Survival: The FMD virus is pH sensitive, with an optimal pH between 7.2 and 7.6, and is inactivated at a pH less than 6.0 and greater than 9.0. The FMD virus is fairly stable at low temperatures, surviving for 1 year at 4 degrees C, but can survive for progressively shorter times as temperature increases. For instance, survival times at 37 degrees and 56 degrees C are 10 days and less than 30 minutes, respectively. However, the virus is not inactivated during pasteurization at 72 degrees C for 15 seconds. Milk from naturally infected cows must be heated to 100 degrees C for greater than 20 minutes for virus inactivation. The virus can be persistent in the environment and survives in the soil for 3 days in the summer and 28 days in the winter. In dry fecal material, the virus survives for 14 days in the summer, whereas it can survive for 6 months in manure slurry in winter conditions. The virus survives for up to 39 days in urine. To inactivate the FMD virus in slurry, the slurry must be heated to 67C for 3 minutes(Musser et al., 2004). Unlike those of other picornoviruses, the FMDV capsid is dissociated at pHs of below 6.5 into 12S pentameric subunits. The reason for this instability is thought to be a cluster of His residues at the interface between BP2 and VP3, which become protonated at low pH, weakening the capsid through electrostatic repulsion. This low-pH-induced instability of FMDV leads to difference in the mechanism of its uncoating upon infection of cells compared to that for other picornaviruses and also probably plays a role in the targeting of the virus to specific tissues and organs in susceptible hosts(Grubman et al., 2004). Preserved by refrigeration and freezing and progressively inactivated by temperatures above 50C. Inactivated by sodium hydroxide (2%), sodium carbonate (4%), and citric acid (0.2%). Resistant to iodophores, quaternary ammonium compounds, hypochlorite and phenol, especially in the presence of organic matter. Survives in lymph nodes and bone marrow at neutral pH, but destroyed in muscle when pH is less than 6.0 i.e. after rigor mortis. Can persist in contaminated fodder and the environment for up to 1 month, depending on the temperature and pH conditions(Website 121). When compared with viruses such as the smallpox virus, FMD virus is relatively fragile, but under the cool, moist, and often cloudy conditions (low ultraviolet light concentration) of winter and spring in the UK, it survives for several days and often longer(Gibbs et al., 2003).
    3. sheep and goats(Sutmoller et al., 2003):
      1. Description: Sheep and goats less frequently become a carrier and for shorter periods of than cattle often lasting for only 1-5 months. However, in some animals the carrier state may last up to 12 months. Unequivocal evidence of transmission form carrier sheep or goats has neither been demonstrated under experimental conditions or in the field(Sutmoller et al., 2003). A recent study by Hughes 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(Kitching et al., 2002B).
    4. Cervidae(Sutmoller et al., 2003):
      1. Description: FMDV was seldom recovered from the pharynx from red and roe deer beyond 14 days post-exposure. Fallow deer carried the virus for a minimum of 5 weeks. Two months after exposure 6 from the 12 deer were still positive. White tailed deer in the USA carried FMD virus regularly up to 5 weeks after exposure, but one deer had virus in the OP fluid as long as 11 weeks post-exposure(Sutmoller et al., 2003). Exotic deer, including red, sika, and fallow, have been gaining popularity for use on deer farms or game ranches. Such deer have been found to both acquire and transmit FMDV under natural conditions. There is no information from other cervids such as moose and elk(USDA et al., 1994). All of the deer tested 4 weeks after exposure had virus in the OPF and therefore could be classified as carriers. Generalization is not possible with such a small experimental group but he presence of virus in the OPF of one animal 11 weeks after exposure makes the existence of relatively long term carriers a distinct possibility(McVicar et al., 1974).
    5. African Buffalo(Sutmoller et al., 2003):
      1. Description: Individual animals may maintain the infection for periods of at least 5 years, but in most buffalo the rates peak in the 1-3 year age-group. Individual buffalo may be persistently infected with more than one type of FMDV in the pharyngeal region(Sutmoller et al., 2003). African buffalo are efficient maintenance hosts of the SAT type viruses, with individual animals maintaining the virus for up to 5 years, and isolated herds for up to 24 years although persistence in individual buffaloes is probably not lifelong(Vosloo et al., 2002A).
    6. Animal-origin product, fomites or vehicles(USDA et al., 1994):
      1. Description: Many animal-origin products and other fomites or vehicles can serve as possible modes of FMDV transmission. A total of 76 products (15 nonfood and 61 food) and 21 fomites were identified by the USDA in this publication(USDA et al., 1994). Diseased animals excrete the virus in tremendous quantities. The most common way of dissemination is by infected live animal and contaminated animal products. Indirect transmission can be made by people, vehicles, equipment, hay or bedding contaminated with feces or urine of diseased animals. Over the years, illegal activities, have often been attributed to introductions of FFMD into non-infected countries, such as the importation of infected meat and feeding to pigs of non-heat treated swill(Sutmoller et al., 2003). The virus has a remarkable capacity for remaining viable in carcasses, in animal byproducts, in water, in such materials as straw and bedding, even in pastures. In 1994, USDA examined the source of all primary FMD outbreaks worldwide from 1870 through 1993. The study found that of the 558 outbreaks with a reported source, contaminated meat, meat products or garbage caused 66 percent of the outbreaks. For the latter 25 years under the study, the sources of most of the 69 primary FMD outbreaks were livestock importations, animal vaccines (including both contaminated vaccines and escapes of virus from vaccine production facilities), and contaminated meat, meat products or garbage(Federal et al., 2001). Primary infections in FMD free countries have frequently involved pigs, often on swill feeding holdings. Swill from ships and aircrafts forms a special risk in this respect. Therefore, swill feeding practices are not compatible with a FMD free status unless the swill is processed in officially validated plants that are well-controlled by the government(Sutmoller et al., 2003).
    7. Biologics(USDA et al., 1994):
      1. Description: The primary role of biologics in the transmission of FMDV has been through the use of improperly inactivated FMD vaccine. Outbreaks have occurred primarily in Europe due to the use of formalin-inactivated vaccines. In the early 1900's other biologics were found to be contaminated with FMDV. It is less likely that problems with inactivation or contamination of vaccines could occur today given the techniques now used by most manufacturers(USDA et al., 1994). During the past 20 years on at least at two occasions FMDV escaped from technically well-equipped high-containment laboratories causing outbreaks outside the facilities. Therefore, regular international inspection of FMD laboratories and vaccine production plants is needed. Inspection must be carried out on the status of facilities and equipment, on logistics, and on the execution of the internal control on bio-containment and biosafety. This is particularly important for such laboratories in countries with a FMD free status(Sutmoller et al., 2003).
    8. Semen(USDA et al., 1994):
      1. Description: FMDV was found in semen as early as 12 hours after inoculation of bulls and as long as 42 days after contact exposure. In addition, heifers artificially inseminated with infected semen have developed FMD. In swine, FMDV has not been transmitted through artificial insemination even though semen from infected swine contains FMDV. Consequently, although further transmissibility studies in swine may be warranted, porcine semen was categorized as a low hazard(USDA et al., 1994).
    9. Hides(USDA et al., 1994):
      1. Description: FMDV remained infective in hides preserved by 4 conventional methods for varying lengths of time, all over 14 days. The authors of the study noted that these experimentally observed time periods should not be considered maximum survival times. Further, imported hides were suspected of causing the 1914 outbreak in the United States, in which at least 22 states and the District of Columbia were affected. Untanned hides and skins are currently allowed into the United States if they are hard dried, pickled in a solution of salt containing mineral acid or treated with lime in such a manner and for such a period as to have become dehaired. No studies were found in which the effect of such processing on FMDV was examined(USDA et al., 1994).
    10. Other Animals(USDA et al., 1994):
      1. Description: Ninety-nine animals were identified as possible sources of FMDV Of those, 31 were characterized as high, 50 as moderate, and 18 as low. A complete listing of all 99 animals can be found in this publication(USDA et al., 1994).
  4. Intentional Releases:
    1. Intentional Release Information(Gibbs et al., 2003):
      1. Description: While there is no evidence to suggest that the recent epidemic of foot-and-mouth disease (FMD) in the UK and its subsequent spread to continental Europe were caused by bioterrorism, the extent of the epidemic shows that FMD could be a very powerful weapon for a bioterrorist wishing to cause widespread disease in livestock and economic disruption for the targeted country. A report by the National Academies has highlighted the vulnerability of the nations food supply. FMD was identified as the most important animal disease that the US must be prepared for. The potential use of FMD to physically cripple livestock and to economically cripple a country has been recognized for many years. Few know that in the 1970s the Irish Republican Army threatened to release FMD virus in the UK; in the 1980s Australia had to respond to an extortionist who similarly threatened to use FMD virus. Not surprisingly, there are unsubstantiated reports that al Qaeda has also studied the malevolent use of the virus(Gibbs et al., 2003).
      2. Emergency Contact: Due to FMDs highly infectious nature, any detection of the disease in the United States would warrant immediate activation of APHIS Emergency Operations Center. If FMD is found in the United States, the U.S. Department of Agricultures (USDA) Animal and Plant Health Inspection Service (APHIS) officials stationed in the Center would help to coordinate local, State, and Federal response and eradication efforts, coordinate inter-agency planning, and implement national communication and information-sharing strategies. APHIS has already established a toll-free telephone number that concerned citizens and cooperators can call to obtain information on FMD and APHIS response efforts. 1-800-6-1-9327(Website 120).
      3. Delivery Mechanism: Ways by which the virus or infectious RNA may escape or be carried out from laboratories include: Personnel, Air Effluent and other waste Equipment(Website 122). Compared to bio-terror, agro-terror is appallingly easy. Animal diseases of greatest concern are those that, by nature, are very infectious and spread rapidly through herds and flocks. FMD, for instance, is the most contagious disease known to exist, spreading from animal to animal with incredible rapidity and in a more efficient manner than even the most contagious of human diseases. Bringing FMDV into a naive area is surprisingly simple, and once introduced, it will spread quite readily, without any requirement for weaponization to facilitate spread(Brown et al., 2003). Were FMD to occur through bioterrorism, it is probable that terrorists would trigger several outbreaks in different parts of the country, possibly caused by several serotypes of the virus. Multiple routes of transmission demand complex disease control responses and disruption of society(Gibbs et al., 2003).
      4. Containment: FMD is one of the most contagious diseases known and manipulating the virus in the laboratory without adequate precautions is a hazard. The escape of a single infectious unit of FMDV from a laboratory could potentially cause an outbreak. The main sources of virus or infectious RNA (in increasing risk of hazard) are: infected tissue cultures, infected baby mice, guinea pigs, rabbits etc., physical and chemical processing of large quantities of virus outside closed vessels (e.g., concentration, purification, inactivation, etc.), infected pigs, cattle, sheep, goats and other susceptible animals. Ways by which the virus or infectious RNA may escape or be carried out from laboratories include: Personnel, Air Effluent and other waste Equipment. Therefore all laboratories manipulating FMD virus must work under high containment conditions. The safety precautions must preclude any escape of virus and special attention must be given to: the prevention of illegal entry into the restricted area, the presence of changing and showering facilities, the responsible behaviour of personnel within and when they leave the laboratory, application of rules for primary containment, the use of inactivated virus where possible, the maintenance of negative air pressure where virus is manipulated and decontamination of exhaust air, the decontamination of effluent, the disposal of carcasses in a safe manner, the decontamination of equipment and materials before removal from the restricted area. To achieve this containment a variety of technical installations and a comprehensive set of disease security regulations are required under the supervision of a Disease Security Officer(Website 122). The evidence that the virus can be transmitted by aerosol alerted workers for the need to operate under negative pressure, particularly when large amounts of the agent are involved. Circulating air should be filtered appropriately(Brown et al., 2001B). U.S. research and diagnostic work with live foot-and-mouth disease virus is permitted only in an island-based laboratory(USDA et al., 1994). The proven strategy for controlling an FMD outbreak includes several key actions: Quarantine and stop movement of animals and products. Disinfect vehicles and personnel. Slaughter infected and contact animals. Destroy infected carcasses. Assess the need for strategic vaccination of animals and implement this action as appropriate(Federal et al., 2001).
Diagnostic Tests Information
  1. Immunoassay Test:
    1. ELISA :
      1. Time to Perform: 1-hour-to-1-day
      2. Description: At the OIE/FAO WRL for FMD, the preferred procedure for the detection of FMD viral antigen and identification of viral serotype is the ELISA. This is an indirect sandwich test in which different rows in multi-well plates are coated with rabbit antisera to each of the seven serotypes of FMD virus(Website 132).
    2. Complement Fixation (Vangrysperre et al., 1996):
      1. Time to Perform: 1-hour-to-1-day
      2. Description: The ELISA is preferable to the complement fixation (CF) test because it is more sensitive and specific, and it is not affected by pro- or anti-complementary factors. If ELISA reagents are not available, however, the CF test may be performed. Antisera to each of the seven types of FMD virus are diluted in veronal buffer diluent (VBD) in 1.5-fold dilution steps from an initial 1/16 dilution to leave 25 l of successive antiserum dilutions in U-shaped wells across a microtitre plate or appropriate volumes in test tubes. To these are added 50 l of 3 units of complement, followed by 25 l of test sample suspension(s). The test system is incubated at 37C for 1 hour prior to the addition of 25 l of 1.4% standardised sheep red blood cells (SRBC) in VBD sensitised with 5 units of rabbit anti-SRBC. The reagents are incubated at 37C for a further 30 minutes and the plates are subsequently centrifuged and read. Appropriate controls for the test suspension(s), antisera, cells and complement are included. CF titres are expressed as the reciprocal of the serum dilution producing 50% haemolysis. A CF titre greater than or equal to 36 is considered to be a positive reaction. Titre values of 24 should be confirmed by retesting an antigen that has been amplified through tissue culture passage(Website 132).
    3. Virus Neutralization (Website 132):
      1. Time to Perform: 2-to-7-days
      2. Description: FMD virus infection can be diagnosed by the detection of a specific antibody response. The tests generally used are virus neutralisation (VN) and ELISA. VN test is serotype specific, requires cell culture facilities and takes 2 to 3 days to provide results. The ELISA is a blocking- or competitive-based assay that uses serotype-specific polyclonal or monoclonal antibodies. It is therefore serotype specific, sensitive and quantitative, and has the advantage that it is quicker to perform, is less variable, and is not dependent on tissue culture systems. Low titre false-positive reactions can be expected in a small proportion of the sera in either test. An approach combining screening by ELISA and confirming the positives by the VN test minimises the occurrence of false-positive results. The quantitative VN microtest for FMD antibody is performed with IB-RS-2, BHK-21, lamb or pig kidney cells in flat-bottomed tissue-culture grade microtitre plates. Stock virus is grown in cell monolayers and stored at -20C after the addition of 50% glycerol. (Virus has been found to be stable under these conditions for at least 1 year.) The sera are inactivated at 56C for 30 minutes before testing. The control standard serum is 21-day convalescent serum (usually pig). A suitable medium is Eagles complete medium/LYH (Hanks balanced salt solution with yeast lactalbumin hydrolysate) with antibiotics(Website 132).
      3. False Positive: Low titre false-positive reactions can be expected in a small proportion of the sera in either test(Website 132).
    4. Liquid-phase blocking ELISA (Vangrysperre et al., 1996):
      1. Time to Perform: 1-hour-to-1-day
      2. Description: FMD virus infection can be diagnosed by the detection of a specific antibody response. The tests generally used are virus neutralisation (VN) and ELISA. VN test is serotype specific, requires cell culture facilities and takes 2 to 3 days to provide results. The ELISA is a blocking- or competitive-based assay that uses serotype-specific polyclonal or monoclonal antibodies. It is therefore serotype specific, sensitive and quantitative, and has the advantage that it is quicker to perform, is less variable, and is not dependent on tissue culture systems. Low titre false-positive reactions can be expected in a small proportion of the sera in either test. Antigens are prepared from selected strains of FMD virus grown on monolayers of BHK-21 cells. The unpurified supernatants are used and pretitrated according to the VN protocol but without serum. The final dilution chosen is that which, after addition of an equal volume of diluent (see below), gives an absorbance on the upper part of the linear region of the titration curve (optical density approximately 1.5). PBS containing 0.05% Tween 20 and phenol red indicator is used as a diluent (PBST). Guinea-pig antisera prepared by inoculating guinea-pigs with 146S antigen of one of the seven serotypes and preblocked with NBS is used as the detecting antibody. Predetermined optimal concentrations are prepared in PBS containing 0.05% Tween 20, and 5% dried, nonfat skimmed milk (PBSTM). Rabbit (or sheep) anti-guinea-pig immunoglobulin conjugated to horseradish peroxidase and preblocked with NBS is used at a predetermined optimum concentration in PBSTM. Test sera are diluted in PBST(Website 132).
      3. False Positive: Low titre false-positive reactions can be expected in a small proportion of the sera in either VN or ELISA(Website 132).
      4. Antigen:
        • 146S
    5. Nonstructural Protein Antibody Test (Website 132):
      1. Time to Perform: unknown
      2. Description: Antibody to VIAA is conventionally detected by AGID. The test is based on immunoprecipitation lines formed in the agar between the FMD antigen (concentrated cell-culture fluids rich in FMD virus RNA-dependent RNA polymerase or 3D) located in a centre well, and hexagonally arranged adjacent wells containing standard positive sera or unknown test sera. Precipitation lines forming between the test sera and the control antigen well that show identity with the lines of precipitation formed by the reference sera, confirm the specificity of the reactions. Antibody to expressed, recombinant FMD virus NS proteins can be measured by ELISA or immunoblotting. No single test format has yet been conclusively demonstrated to be optimal. A MAb trapping (MAT) ELISA for detecting antibody to 3ABC and blocking ELISAs for detecting antibody to 3AB or 3ABC have been shown to be sensitive, specific and reliable in a number of laboratories. The simultaneous detection of antibody to several NS proteins in a single test by ELISA or by enzyme-linked immuno-electrotransfer blot (EITB), a type of Western blot, (8) is useful for confirmation of animals positive for antibody to 3AB or 3ABC. There are currently no internationally recognized standards for antibody to FMD virus NS proteins(Website 132). Although it is recognized that measuring antibody to the RNA polymerase or 3D protein alone cannot differentiate infection from vaccination, this antigen is still useful as an indicator of previous exposure to FMD antigen which is not serotype specific. The leader protease (L protein) is the less immunogenic NS protein and therefore cannot be recommended. NS proteins 2C, 3AB and 3ABC have the potential to discriminate infected from vaccinated or naive. Out of them, 3ABC is the most immunogenic and has been extensively studied. To avoid non-specific reactions against antigen from host cell expression system, which can co-purify with the recombinant products, mapping of continuous immunodominant site was undertaken with overlapping peptides from 2C and 3ABC. One synthetic peptide was selected in 3B protein to set up a peptide based ELISA with promising specificity(Remond et al., 2002).
  2. Nucleic Acid Detection Test:
Infected Hosts Information
  1. Humans
    1. Taxonomy Information:
      1. Species:
        1. Homo sapiens (Website 123):
          • Common Name: Homo sapiens
          • GenBank Taxonomy No.: 9606
          • Description: Foot and mouth disease is a zoonosis, but it crosses the species barrier with difficulty and with little effect. Given the high incidence of the disease in animals, both in the past and in recent outbreaks worldwide, its occurrence in man is rare so experience of the human infection is limited. The last human case reported in Britain occurred in 1966. The type of virus most often isolated in humans is type O followed by type C and rarely A. The incubation period in humans is 2-6 days(Prempeh et al., 2001).
    2. Infection Process:
      1. Infectious Dose: Sampling of human subjects, who had been in contact with diseased animals, showed that virus could be recovered from the nose, throat, and saliva of these people, immediately after leaving the room. Nasal swabs of such persons usually contain 100-1000 IU, but some may contain as many as 10,000 IU(Sutmoller et al., 2003),
      2. Description: The route of transmission of FMDV from animals to man is unclear, although the virus has been detected in the upper respiratory tract of exposed individuals who did not contract infection(Prempeh et al., 2001),
    3. Disease Information:
      1. Foot and mouth disease :
        1. Incubation: The incubation period in humans is 2-6 days(Prempeh et al., 2001),
        2. Prognosis:
            Symptoms have been mild and self-limiting. Patients have usually recovered about a week after the last blister formation(Prempeh et al., 2001),
        3. Diagnosis Summary: Criteria for establishing a diagnosis of FMD in man are the isolation of the virus from the patient and or identification of specific antibodies after infection. Laboratory tests for diagnosis of human FMD are the same as for animals(Bauer et al., 1997),
        4. Symptom Information :
          • Description: Symptoms have been mild and self-limiting, mainly uncomfortable tingling blisters on the hands, but also fever, sore throat, and blisters on the feet and in the mouth, including the tongue(Prempeh et al., 2001). Proven cases of FMD have occurred in several countries in Europe, Africa and South America(Bauer et al., 1997). Human infection with FMDV has been described but only a few cases have been confirmed virologically by the isolation of virus and detection of a specific immune response(Brown et al., 2001A).
          • Symptom -- Vesicles (Bauer et al., 1997):
            • Description: Vesicles develop on the hands, mostly on the fingers, occasionally on the feet and in the region of the mouth, especially on the tongue and palate. A tingling, burning sensation of the fingers and palms precedes the development of vesicles between fingers at the lateral sites of the hand and the volar surfaces of terminal phalanges. Similar sensations are felt in the feet if they are involved. Sometimes the only blisters occur in the oral cavity. Here the greatest discomfort arises. The pain involved in eating, drinking and talking is intense. Excessive salivation adds to the distress. The aphthae may be as small as a pin head or as large as 2 cm in diameter. In this area the spinose layer of the epidermis experiences a colliquative necrosis. Initially the blisterfluid is clear and yellowish but soon becomes inspissated. Blisters dry up within two or three days with skin being sloughed, sowing the red basal layer of the epidermis. Secondary blisters may appear up to five days after the primary ones have developed(Bauer et al., 1997).
          • Symptom -- Fever :
            • Description: The onset is characterized by mild headache, malaise with fever that reaches as high as 39.5 degrees celcius(Bauer et al., 1997).
    4. Prevention:
      1. Biosecurity(Website 117)
        • Description: Travelers can make sure they do not bring in prohibited food items and other products, such as soiled footwear and soiled clothing items, that could present a risk of transmitting FMD and other diseases. Travelers should ensure that luggage, packages, and mail are free of any prohibited meats, dairy products, and other at-risk materials before they are shipped to the United States. Travelers should also shower and shampoo prior to and again after returning to the United States from an FMD-affected country. Launder and/or dry clean clothes before your return to the United States if possible. If you visited a farm or had any contact with livestock on your trip, you should avoid all contact with livestock, zoo animals, or wildlife for 5 days after your return to the United States(Website 124),
    5. Model System:
      1. Rodent(Sobrino et al., 2001)
        1. Model Host: .
          Rodent(Sobrino et al., 2001),
        2. Model Pathogens:
        3. Description: The intraperitoneal inoculation of FMDV produces death in suckling mice, and this has been extensively exploited to titrate virus infectivity. Likewise, FMDV can be adapted, by serial passages, to produce clinical symptoms in guinea-pigs, an animal model that has been used mostly for immunological analysis(Sobrino et al., 2001),
  2. Cattle
    1. Taxonomy Information:
      1. Species:
        1. Bos taurus (Website 125):
          • Common Name: Bos taurus
          • GenBank Taxonomy No.: 9913
          • Description: FMD in the highly productive beef and dairy breeds of Europe, North America and Australia is characterized by severe clinical signs. Index cases on farms exposed to low level aerosol virus may develop only mild or even subclinical infection, but as the virus replicates in the first infected animal and is produced in large quantities, so the remaining animals in the herd appear with multiple vesicles in the mouth and on the feet and udder. The disease is considerably less obvious in the breeds of cattle indigenous to Africa and Asia, where FMD is mostly endemic. However, FMD is also economically important in these regions, further reducing an already low milk yield, causing the death of young calves, and interfering with the function of adult cattle to pull a plough or cart(Kitching et al., 2002C).
    2. Infection Process:
      1. Infectious Dose: Cattle injected in the tongue epithelium with only 1IU may become infected, while a higher dose of 10-100 IU is required for aerosol exposure(Sutmoller et al., 2003), Cattle are very susceptible by the respiratory route, requiring as little as 20 TCID50 of virus to establish infection, but may require 10,000 times more to become infected by the oral route(Kitching et al., 2002C),
      2. Description: The FMD virus replicates at the site of entry, either in the mucosa and lymphoid tissue of the upper respiratory tract or in the dermal and subdermal tissue of a skin abrasion. The virus enters the blood circulation as free virus or associated with mononuclear cells and is distributed around the body to glandular tissue and predilection sites in the stratum spinosum, where secondary replication takes occurs(Kitching et al., 2002C), A number of studies have suggested that the lung or pharyngeal areas are the sites of initial virus replication with rapid dissemination of the virus to oral and pedal epithelial areas, possibly mediated by cells of monocyte/macrophage origin. In cattle experimentally infected via aerosol, it was found, by in situ hybridization, that within the first 24 hours, virus was present in respiratory bronchiolar epithelium, subepithelium, and interstitial areas of the lung. By 72 hours, signal was detected in epithelial cells of the tongue, soft palate, feet, tonsils, and tracheobronchial lymph nodes. Other studies, however, have suggested that the pharynx, not the lungs, may be the initial site of replication in infected cattle. The conflicting observations about the region of the respiratory tract that is initially infected in cattle exposed to aerosols may be the result of a number of variables, including aerosol particle size, strain of virus, or how the aerosol was generated(Grubman et al., 2004),
    3. Disease Information:
      1. Foot and mouth disease :
        1. Incubation: Between 2-14 days depending on the infecting dose, the strain of the virus, and the susceptibility of the individual host(Kitching et al., 2002C),
        2. Prognosis:
            Healing of the mouth lesions is usually rapid; the erosions fill with fibrin and by day 11 after vesicle formation, they appear as areas of pink fibrous tissue, without normal tongue papillae. Healing of the ruptured vesicles on the feet is more protracted and the lesions are susceptible to secondary bacterial infection, sometimes resulting in under-run sole and chronic lameness. Yearling cattle may fail to fully recover their production potential, due to damage to glandular tissue such as thyroid and some have been referred to as hairy panters because of changes to their coat and what appears to be impaired respiratory function, although the pathological changes are not well documented(Kitching et al., 2002C),
        3. Diagnosis Summary: Initial diagnosis is usually made on the basis of clinical signs, with or without a history of contact between the herd and an infected animal, or report of FMD in the vicinity. In a fully susceptible herd, the clinical signs are frequently severe and pathognomonic. However, in endemic regions in cattle that have partial natural or vaccinal immunity, clinical signs may be mild and may be missed(Kitching et al., 2002C), SVD, vesicular stomatitis, and vesicular exanthema of swine cause vesicular lesions in swine and cattle that cannot be distinguished from those caused by FMD(Grubman et al., 2004), Currently FMD is confirmed by antigen capture enzyme-linked immunosorbent assay (ELISA) and virus isolation. While ELISA can be obtained in three to four hours after the sample is received by the laboratory, a negative result must be confirmed by inoculation of the sample into sensitive cultures followed by confirmation of the virus serotype by ELISA. These assays can take up to four days, a time frame incompatible with the need to rapidly detect disease and initiate an appropriate disease control strategy(Grubman et al., 2004), RT-PCR methods have been used to rapidly detect and type FMDV and to detect virus infection in asymptomatic animals. However, this assay is often not superior in sensitivity to ELISA and virus isolation and, in addition, is labor-intensive. Most recently, real-time RT-PCR methods have been examined by a number of groups with the aim of developing portable on-site diagnosis. The assay is specific and as sensitive as virus isolation, and viral RNA could be detected in oral and nasal samples from experimentally infected animals 24 to 96 hours before the onset of clinical signs. In addition, the assay is rapid, results can be obtained in about 2 hours and the cycler is portable. The next steps required for assessing and validating this assay are optimization of conditions with all possible field samples (blood, milk, tissue) and testing under field conditions(Grubman et al., 2004), In 1966 Cowan and Graves identified a highly immunogenic FMDV NS antigen, called the virus infection-associated antigen (VIAA), which reacted with sera from convalescent animals but not with sera from vaccinated animals. However, in later studies, investigators found that sera from multiply vaccinated animals, and even from some animals, which had received a single vaccination, had antibodies to VIAA. The major reason that antibodies against an NS protein are present in sera from vaccinated animals is that FMD vaccines are not purified and, depending upon the manufacturer, contain various amounts of contaminating NS proteins. Nevertheless, VIAA, which was subsequently identified as the viral RNA polymerase is currently used in an agar-gel immunodiffusion test to differentiate infected from vaccinated animals. To improve the reliability of this diagnostic assay, investigators have targeted other NS proteins as potential diagnostic reagents. They recommend the use of NS proteins 3AB, 2C, 3C, and 2B, or their respective peptides, as antigens in an ELISA-based assay. ELISA-based assays with various NS proteins produced by recombinant baculovirus, in E. coli, or with synthetically produced peptides to NS proteins have been developed. Currently, these assays are being validated(Grubman et al., 2004), A minimum of 2 cm squared of epithelium from a ruptured vesicle in a 50/50 mixture of glycerine and 0.04 molar buffered phosphate (pH 7.4-7.6) should be sent to a laboratory designated for handling live FMD virus and equipped with the necessary reagents for typing a positive sample. Whole and clotted blood samples and probang samples may also be sent(Kitching et al., 2002C), Antibodies to FMD virus can be detected in the milk of cattle that have recovered from FMD, using either the liquid phase blocking enzyme-linked immunosorbent assay (ELISA) (LPBE) or a specific isotype assay (SIA) for vovine immunoglobulin G1 (IG1). However, whereas the LPPBE would not detect antibodies derived as a consequence of vaccination, the SIA was able to identify 95 percent of cattle vaccinated up to 12 months previously, in the study reported. There was also a strong correlation between serum antibody titres and milk antibody titres, to the extent that individual and herd immunity levels against FMD could be assessed using the SIA on individual or bulk tank milk samples, respectively(Kitching et al., 2002C),
        4. Symptom Information (Kitching et al., 2002C):
          • Description: Foot and mouth disease in cattle is usually clinically obvious in the unvaccinated herds of countries in which the disease occurs only occasionally. However, in vaccinated herds and in some breeds indigenous to areas in which FMD is endemic, the disease may circulate undetected(Kitching et al., 2002C). FMD in cattle is usually clinically obvious in the unvaccinated herds of countries in which the disease occurs only occasionally. However, in vaccinated herds and in some breeds indigenous to areas in which FMD is endemic, the disease may circulate undetected(Kitching et al., 2002C).
          • Symptom -- vesicles (Kitching et al., 2002C):
            • Description: Vesicles develop on the tongue, hard palate, dental pad, lips, gums, muzzle, coronary band and interdigital space. Vesicles may also be seen on the teats, particularly of lactating cows. Stamp feet as they try to relieve pressure. They prefer to lie down and resist attempts to raise them. Lactating cattle with teat lesions are difficult to milk and ruptured vesicles frequently become infected, predisposing to secondary mastitis. Vesicles in mouth rupture rapidly, usually within 24 hours, leaving a shallow erosion surrounded by shreds of epithelium. Vesicles on the feet may remain intact for two or three days before rupturing. Severe form with some vaccinated cattle: the tongue swells and protrudes from the mouth and the majority of the tongue epithelium is shed(Kitching et al., 2002C).
            • Picture(s):
          • Symptom -- Myocarditis (Kitching et al., 2002C):
            • Description: Young calves may die before the appearance of vesicle because of the predilection of the virus to invade and destroy cells of the developing heart(Kitching et al., 2002C). Although mortality rates in mature cattle with FMD are usually low, they can be quite high in calves. Death in calves is due to acute myocarditis. Myocardial lesions are referred to as tiger heart(Musser et al., 2004).
            • Picture(s):
              • Clinical Signs - mycardial necrosis (Website 138)



                Description: In very young animals, myocardial necrosis can occur, appearing as pale streaks in the ventricular wall(Website 138).
          • Symptom -- Salivation (Kitching et al., 2002C):
            • Description: Acutely infected cattle salivate profusely and develop nasal discharge, at first mucoid, then mucopurulent(Kitching et al., 2002C). The quintessential clinical sign in infected cattle is excessive drooling, which typically occurs after vesicle and ulcer formation. Cattle sometimes display smacking of their lips(Musser et al., 2004).
            • Picture(s):
          • Symptom -- Fever (Musser et al., 2004):
            • Description: In cattle infected with FMD virus, a febrile response, with rectal temperatures ranging from 39.5 degrees to 41 degrees celcius is usually detectable prior to vesicle formation and continues for 3 to 4 days afterward(Musser et al., 2004).
          • Symptom -- Decreased Production (Musser et al., 2004):
            • Description: With viremia and vesicle development, lethargy and anorexia or poor food intake typically develop. Vesicles and erosions can occur on the teats, and mastitis may develop secondarily. Milk production and feed consumption may decrease gradually or precipitously depending on the virulence of the serotype and the strain of the virus(Musser et al., 2004).
        5. Treatment Information:
          • Quarantine, local eradication, revaccination (Smith et al., 2002): Where FMD is endemic, quarantine, local eradication, virus typing and revaccination of contact and at-risk cattle with the appropriate virus subtype should be considered. Good nursing care and administration of systemic antimicrobial drugs to limit secondary bacterial pneumonia and mastitis are recommended. Soft feeds such as chopped green grass are much more palatable than hay to sore-mouthed animals(Smith et al., 2002).
    4. Prevention:
      1. Stamping Out(Sutmoller et al., 2003)
        • Description: Stamping-out consists of the killing and disposal of all susceptible livestock on the infected farms and their immediate contact farms that most likely infected followed by a thorough disinfection, cleaning, disinfection procedure of the premises, the first disinfection begin to prevent the production of virus aerosols during the cleaning. In traditionally FMD free countries, stamping-out is the first option to eradicate the disease. As a first line of defense it is often quite successful, at least if the disease has not yet spread too widely and if the density of the livestock in the area is relatively low. Also, during the first days of an outbreak the proper vaccine may not be available. The choice of the stamping-out option should also depend on the possibility of tracing dangerous contacts, political will and available resources(Sutmoller et al., 2003), In countries free of the disease, a policy of slaughter of all infected and in-contact susceptible animals is usually employed(Kitching et al., 2002C), The slaughter of infected or at-risk herds should be the primary means for controlling diseases such as FMD as long as they are detected at an early stage(Leforban et al., 2002),
        • Efficacy:
          • Rate: This stamping out policy is standard and is recognized by the Office International des Epizooties (OIE) as the most appropriate way to break the chain of virus transmission and thus control and eradicate the disease in industrialized countries(Gibbs et al., 2003).
          • Duration: Control of the disease in FMD-free countries include an exclusion and slaughter policy. However, stamping out of infected and contact animals alone may not be sufficient to eradicate the virus promptly and vaccination is now considered an acceptable alternative or adjunct(Clavijo et al., 2004). Cattle have been infected by entry into decontaminated premises, up to four months after culling, cleaning and disinfection had occurred: 12 occurrences of this were reported in the winter of 1967-1968 in the UK. The mechanisms of such infection are unclear, but apparently the virus was able to survive that length of time in the environment or in some unknown other host(Sutmoller et al., 2003).
        • Complication: Heavy equipment used in these operations is difficult to decontaminate and might be a source of infection or contamination of roads when being driven to another job or back home Disposal of cadavers also presents a risk since virus in lesions, excrements and excretions is not rapidly destroyed after death and might be disseminated by transport of cadavers, by pyres, at burial sites or digester plants. Transport systems for carcasses are not bio-secure, neither is the handling of the carcasses at the rendering plants. The highest risk comes probably from the involvement of large numbers of contractors not trained in disease containment(Sutmoller et al., 2003), After the 2001 outbreak in the UK, public reaction, questioned the need for large-scale slaughter of susceptible animals, particularly the slaughter of vaccinated animals that were healthy(Grubman et al., 2004),
      1. Circle Culling(Sutmoller et al., 2003)
        • Description: So-called circle culling and culling of contiguous farms has been applied in the UK and in the Netherlands as an extension of usual stamping-out procedures. The aim of the circle is to eliminate incubating infections that may have spread from the outbreak farm(s) and create a fire break around the outbreak. The diameter of the circle was based on the analysis of spread of FMD during the outbreak using computer models. However, the calculated distance of spread must include spread due largely to the culling process itself as an additional transmission mechanism(Sutmoller et al., 2003), In countries free of the disease, a policy of slaughter of all infected and in-contact susceptible animals is usually employed(Kitching et al., 2002C), The slaughter of infected or at-risk herds should be the primary means for controlling diseases such as FMD as long as they are detected at an early stage(Leforban et al., 2002),
        • Efficacy:
          • Rate: Although ring culling reduces the need for surveillance, it creates potentially much higher numbers of cadavers, some of which might be infected(Sutmoller et al., 2003).
          • Duration:
        • Complication: Most culled farms within the circle are not infected and do not represent a risk of further spread of the disease and, therefore, are culled unnecessarily. The operation itself has a high-risk of disseminating FMDV over short and long distances.A long drawn-out campaign is very disruptive for the rural society as a whole, including sectors like tourism. The rural community may fear the control measures more than the disease, and live under this fear for several months after the last case. The consequent application of circle and of contiguous culls pose a threat to zoological collections and valuable (rare) breeding stock. Massive killing and destruction of livestock usually is not done with adequate respect for animal welfare and bio-ethical principles. The small risk represented by hobby farms and smallholdings is not taken into account. An enormous serological surveillance exercise is often required to detect residual infection since new cases could easily re-start the epidemic at its tail end, particularly if movement controls are prematurely lifted. Finally, many culls represent a human tragedy and traumatic experience not only for farmers and their families but for many veterinarians as well. The risk-avoidance behavior of farmers leads to social isolation and breakdown of the socialeconomic and trading patterns of rural communities(Sutmoller et al., 2003),
      1. Vaccination
        • Description: In endemic or epi-endemic regions, strategic or general vaccination is required with vaccine containing the FMD subtypes that are active in the area. This could be carried out with the more classical aqueous vaccine or with oil-adjuvant vaccine(Sutmoller et al., 2003), The current FMD vaccine is an inactivated whole-virus preparation that is formulated with adjuvant prior to use in the field. A number of countries have established vaccine banks, which contain concentrated antigen stored in the gaseous phase of liquid nitrogen. Banks contain antigen against a number of virus serotypes and provide member countries with an almost immediate source of vaccine(Grubman et al., 2004), Vaccination would be used to control an outbreak in an endemic area. Vaccination may also be used to surround a focal outbreak of a disease to prevent the virus from spreading and the vaccinated animals may be subsequently slaughtered to reduce the delay in re-establishing trading status. A buffer zone containing vaccinated animals may be used to separate an area within a country in which FMD is endemic from an FMD-free area, from which exports of cattle and cattle products are sourced(Kitching et al., 2002C), Aqueous vaccines must be applied twice yearly. In general, current oil-adjuvant vaccines protect cattle of different breeds more effectively. Cattle up to 2 years should be vaccinated twice yearly. Thereafter, a yearly vaccination will maintain their immune status(Sutmoller et al., 2003),
        • Efficacy:
          • Rate: Normally, when a number of animals are vaccinated, some animals fail to develop immunity. Should these animals become infected and develop clinical FMD, they can excrete large amounts of virus, which may overcome the vaccinal immunity of the other animals in the group(Kahn et al., 2002).
          • Duration: The duration of immunity following a single dose of high-potency vaccine in a previously naive animal is usually less than a few months against homologous challenge, and shorter for heterologous challenge. A booster dose given 3 to 4 wk after the initial dose will prolong the immunity for up to 6 mo, but this can be dependent on the level of exposure of the vaccinated animals to live virus challenge(Kahn et al., 2002).
        • Contraindicator: Freedom from disease, as established through stamping out, allowed exports to open in 3 months, compared with 12 months when vaccine was used. While the Netherlands used emergency vaccination to control the epidemic, it subsequently culled all vaccinated animals to allow its markets to open early. With the knowledge that vaccination could significantly delay resumption of the UK export market, the question of whether or not to vaccinate created considerable controversy during the (2001) epidemic(Gibbs et al., 2003),
        • Complication: High-containment facilities are required for the production of vaccine. Vaccinated animals develop antibody responses against the contaminating proteins, in addition to the viral structural proteins, making it difficult to reliably distinguish vaccinated from infected or convalescent animals with currently approved diagnostic tests. Most Virus preparations are concentrated cell culture supernatants from FMDV-infected cells and, depending on the manufacturer, contain various amounts of contaminating viral NS proteins. The vaccine does not induce rapid protection against challenge by direct inoculation or direct contact. Vaccinated animals can become long-term carriers following contact with FMDV(Grubman et al., 2004), Interference in response to vaccination by young animals with high levels of maternally derived antibody. Only when it is below a LPBE titer of 1:45 will the calf respond to vaccination. The problem of the approximately one month time gap between susceptibility to infection and vaccination can only be managed by keeping the calves isolated from any source of FMD virus during that period(Kitching et al., 2002C), A misconception is that vaccination causes the carrier status. This is impossible since FMD vaccine is an inactivated, safe vaccine. A vaccinated animal must be exposed to a large quantity of FMDV in order to become a carrier, for instance when vaccinated cattle come in contact with large numbers of diseased pigs. Because vaccination suppresses the amount of FMDV that is released into the environment (low morbidity!) it is very unlikely that vaccinated animals will become carriers. It is also unlikely that vaccinated animals become carriers through infection by FMDV transmitted by fomites or people and brought from infected farms. It is thus very unlikely that new carriers will be induced in vaccinated herds. Carriers among vaccinated cattle have not caused FMD outbreaks among susceptible non-vaccinated livestock populations nor have they hampered FMD eradication efforts(Sutmoller et al., 2003),
      1. Ring Vaccination
        • Description: It has been demonstrated that early FMD vaccination of herds or flocks round the infected premise creates a cordon of protective animals that can stop effectively the diffusion of the disease. The size of the ring required depends on the rapidity of action of the vaccine and the anticipated rapidity of potential spread of infection from the IP, and location of high-risk farms, which might amplify infection for onward spread. For example, to get ahead of the disease with a vaccine would require 45 days to stimulate immunity and create an area in which farms/animals are protected before the anticipated first contact with virus. The higher the anticipated aerosol transmission, the larger the area that would be required to ensure an adequately immunised ring. Therefore, ring vaccinations should be performed without delay and should include all susceptible species. Preferably, the vaccination should be carried out from the outside of the ring towards the center of the outbreak. Simultaneously, to protect the most endangered farms as soon as possible, vaccination should proceed from the center towards the outside. In the immediate vicinity of the outbreak farm, the large (cattle) holdings should be vaccinated first because potentially, those are the largest aerosol collectors(Sutmoller et al., 2003),
        • Efficacy:
          • Rate: Outbreaks in the vaccinated zone or ring will usually cease within 10 days of effective herd immunity being reached, and frequently cease well before this(Sutmoller et al., 2003).
          • Duration:
        • Complication: This control option is heavily penalized by present OIE regulations because of the 1224 months waiting period to regain the status of freedom from FMD, depending on whether or not stamping-out was applied(Sutmoller et al., 2003),
      1. Ring Vaccination followed by Slaughter
        • Description: Fear of carriers among vaccinated animals has led to suppressive vaccination. In that approach, vaccination is used to control the outbreak(s), but all vaccinated animals have to be killed before FMD free status can be regained. It was used in The Netherlands in the main outbreak area to control the recent outbreak(Sutmoller et al., 2003),
        • Efficacy:
          • Rate: Four to six days after vaccination all vaccinated animals will have sufficient protection to prevent dissemination of virus. The vaccinated animals can be killed over a more extended period, depending on incinerator capacity(Sutmoller et al., 2003).
          • Duration:
        • Complication: Suppressive vaccination creates several of the problems mentioned for circle culling, with the exception of the risk of dissemination of the virus. This risk is much reduced, because 46 days after vaccination all vaccinated animals will have sufficient protection to prevent dissemination of virus. The vaccinated animals can be killed over a more extended period, depending on incinerator capacity. It is interesting to note that, although vaccinated pigs do not become carriers they still must be slaughtered as well!(Sutmoller et al., 2003),
      1. Fencing(Sutmoller et al., 2002)
        • Description: The establishment of wildlife conservancies has created a problem with regard to FMD because the Office International des Epizooties (OIE) presently considers any territory on which buffalo infected with FMD viruses occur as infected. Zones recognized as free of FMD by the OIE need to be separated from infected zones by a defined surveillance zone of at least 10km deep (International Health Code, 1992). According to the OIE recommendations this means that landowners acquiring even one infected buffalo cause their land to be in an infected zone and, by implication, their neighbors to be in a surveillance zone. However, in May 1997 it was accepted by the OIE that infected and free zones may be separated by a barrier instead of a surveillance zone. It appears that modified low-maintenance buffalo control fence complemented with buffer zones or vaccination zones may be a cost-effective solution to the containment of FMD in wildlife zones(Sutmoller et al., 2002), The floods of 2000 in southern Africa damaged the Kruger National Park game fence extensively, and there were several accounts of buffalo that had escaped from the park. The VPI gene, which codes for the major antigenic determinant of the FMD virus, was used to determine phylogenetic relationships between virus isolates obtained from the outbreaks and those previously obtained from buffalo in the KNP. These results demonstrate that buffalo were most probably the source of the outbreaks, indicating that disease control using fencing as well as vaccination is extremely important to ensure that FMD does not become established in domestic livestock(Vosloo et al., 2002B),
        • Contraindicator: The construction of a game fence along international borders if there are no wildlife areas in the neighboring countries would serve no purpose as far as FMD control is concerned(Sutmoller et al., 2002), In principle, wildlife fences should not be constructed only between wildlife zones and the farming areas. They should not run through the middle of any wildlife zones, but between them and any commercial farms or communal lands. Also from a FMD control point of view there is no need to fence through communal lands or along international borders(Sutmoller et al., 2002),
        • Complication: Fences are supposed to prevent close contact between infected animals and noninfected animals from the same species or from different species. However, other transmission mechanisms, such as intermediate hosts, must be accounted for(Sutmoller et al., 2002), The use of fencing has been severely criticised by conservationists, because the fences sometimes have blocked migration routes and access of wildlife to water, resulting in ecological disturbances and wildlife mortality. The necessity for fencing is increasingly questioned -- the argument being that vaccination alone should be sufficient to protect livestock from infection(Thomson et al., 2003),
  3. Pigs
    1. Taxonomy Information:
      1. Species:
        1. Suidae (Website 126):
          • Common Name: Suidae
          • GenBank Taxonomy No.: 9821
          • Description: Domestic pigs play an important role in the epizootiology of FMD as initiators and amplifiers. They can acts as initiators of FMD by the consumption of infected garbage. Pigs serve as amplifiers of the virus because they can excrete aerosols that contain up to 3,000 times more virus than produced by an equal number of cattle or sheep. One characteristic that distinguishes pigs from cattle and sheep is that they appear to harbor the virus only during clinical stages of the disease and therefore do not act as carriers(USDA et al., 1994).
    2. Infection Process:
      1. Infectious Dose: Pigs are considerably less susceptible to aerosol infection than ruminants, and recent studies using several virus strains indicated that a pig may require up to 6,000 50% tissue culture infective dose TCID50, possibly as much as 600 times more than the aerosol virus required by a bovine or an ovine to cause infection. The infectious dose for a pig by the oral route is approximately log10 TCID50, although this value may be lower if abrasions are present in and around the mouth(Kitching et al., 2002D),
      2. Description: Initial replication of the virus occurs at the site through which the virus gains entry, followed by rapid dissemination to most of the epithelial sites within the animal. Interestingly, virus can be found at sites where clinical lesions either were not present or do not form. While pigs excrete large amounts of aerosolized virus, recent evidence suggests that much more viral replication takes place in the nasal mucosa than in the lungs(Grubman et al., 2004),
    3. Disease Information:
      1. Foot and mouth disease :
        1. Incubation: The Cathay topotype of serotype O, including the Taiwan 1997 outbreak strain, is adapted to and highly virulent in pigs. For these strains, clinical signs can be observed within 18h in pigs after being placed in a heavily contaminated pen. For other strains, the incubation period may be as short as 24 hours for pigs kept in intense direct contact. More frequently, the incubation period is two or more days depending on the type of exposure(Kitching et al., 2002D),
        2. Prognosis:
            The vesicles usually rupture within 24 hours to 48 hours also depending on the trauma to which they are exposed. Depending on the severity of the lesions, the horn of the digits may be sloughed after development of the vesicles. Adult pigs will recover if the damage to their feet is not totally debilitating, although they may suffer chronic lameness. Fattening pigs will require longer to reach their slaughter weight. Young pigs up to 14 weeks of age, but particularly those less than 8 weeks of age, may die without developing any clinical signs of FMD, due to heart failure, characterized by acute or hyper-acute myocarditis. Unlike ruminants that have recovered from FMD infections, pigs do not become carriers. Mezencio found evidence of the FMDV genome in sera collected from recovered pigs, but no live virus, and there is no epidemiological support for the persistence of live virus in recovered pigs. Studies at the Institute for Animal Health in Pirbright have consistently found no evidence of viral ribonucleic acid (RNA) persisting in the blood of infected pigs, even using highly sensitive real-time reverse transcriptase polymerase chain reaction(Kitching et al., 2002D),
        3. Diagnosis Summary: The diagnosis of FMD in pigs is based initially on the appearance of clinical signs. However, these can be confused with those caused by vesicular stomatitis, swine vesicular disease virus, or, in the past, vesicular exanthema virus. The laboratory diagnostic tests for FMD in pigs are the same as those used for sheep and cattle, with the additional requirement to also include SVDV reagents on the antigen detection enzyme-linked immunosorbent assay (ELISA). Some strains of FMDV, particularly the Cathay top type, will not easily grow on cells of bovine or ovine origin, as used for routine isolation of FMDV in many laboratories, and for this reason, suspensions of epithelium from a suspect clinical lesion from pigs should also be put onto pig cells, such as IB-RS-2, other susceptible pig kidney cell lines, or primarily pig kidney cells(Kitching et al., 2002D),
        4. Symptom Information :
          • Description: In intensely reared pigs, the introduction of FMD results in severe clinical disease and vesicular lesions in adult and fattening animals, and high mortality in piglets(Kitching et al., 2002D).
          • Symptom -- vesicles (Kitching et al., 2002D):
            • Description: Vesicles develop on the coronary band and heel of the foot (including the accessory digits), on the snout, lower jaw and tongue. Lesions on the coronary band are the most consistent findings in pigs while lesions at other sites may be found less regularly. Vesicles on the tongue of pigs are most often found far back on the tongue or as tiny vesicles-erosions near the tip of the tongue. Pigs housed on rough concrete floors may show additional lesions on their hocks and elbows or other areas of previously damaged skin, and lactating sows frequently develop vesicles on the udder(Kitching et al., 2002D).
            • Picture(s):
              • Clinical Signs - foot lesions (Kitching et al., 2002D)



                Description: Foot and mouth disease in a pig showing lesions at day 2 after first appearance of clinical signs(Kitching et al., 2002D).
              • Clinical Signs - advanced foot lesions (Kitching et al., 2002D)



                Description: Foot and mouth disease in a pig showing loss of epithelium at day 4 after first appearance of clinical signs(Kitching et al., 2002D).
              • Clinical Signs - advanced foot lesions with loss of horn (Kitching et al., 2002D)



                Description: Foot and mouth disease in a pig showing loss of horn from digit(Kitching et al., 2002D).
              • Clinical Signs - unruptured vesicle on nose (Website 139)



                Description: Large unruptured vesicle on nose [from: http://www.thepigsite.com/FeaturedArticle/Default.asp?AREA=FeaturedArticle&Display=305](Website 139).
              • Clinical Signs - ruptured vesicle on nose (Website 139)



                Description: Ruptured vesicle on nose(Website 139).
          • Symptom -- Fever (Kitching et al., 2002D):
            • Description: May develop a fever up to 42 degrees C, but most often this is in the range of 39 degrees to 40 degrees C. Temperature increase in FMD-infected pigs may sometimes be inconsistent, short-lived or close to the normal variation seen and severely affected pigs may even have a drop in temperature to below the normal range. Local signs of inflammation such as heat and pain when touching and applying finger pressure on areas of the feet may often be detected by careful clinical examination before any increase in body temperature is apparent(Kitching et al., 2002D).
          • Symptom -- Lethargy (Kitching et al., 2002D):
            • Description: Affected pigs become lethargic and remain huddled together and take reduced or little interest in food(Kitching et al., 2002D).
        5. Treatment Information:
          • Slaughter (Kitching et al., 2002D): In countries usually free of FMD, control of FMD in pigs is generally achieved by the slaughter of all clinically affected and in-contact susceptible animals, together with movement restrictions and disinfection(Kitching et al., 2002D).
            • Complication: The speed with which FMD spread in Taipei China, when the disease entered in 1997 made it impossible to control by slaughter alone, and vaccination was introduced(Kitching et al., 2002D).
    4. Prevention:
      1. Stamping out(Kitching et al., 2002D)
        • Description: In countries usually free of FMD, control of FMD in pigs is generally achieved by the slaughter of all clinically affected and in-contact susceptible animals, together with movement restrictions and disinfection(Kitching et al., 2002D),
        • Efficacy:
          • Rate: The speed with which FMD spread in Taipei China, when the disease entered in 1997 made it impossible to control by slaughter alone, and vaccination was introduced(Kitching et al., 2002D).
          • Duration:
        • Complication: Heavy equipment used in these operations is difficult to decontaminate and might be a source of infection or contamination of roads when being driven to another job or back home Disposal of cadavers also presents a risk since virus in lesions, excrements and excretions is not rapidly destroyed after death and might be disseminated by transport of cadavers, by pyres, at burial sites or digester plants. Transport systems for carcasses are not bio-secure, neither is the handling of the carcasses at the rendering plants. The highest risk comes probably from the involvement of large numbers of contractors not trained in disease containment(Sutmoller et al., 2003), After the 2001 outbreak in the UK, public reaction, questioned the need for large-scale slaughter of susceptible animals, particularly the slaughter of vaccinated animals that were healthy(Grubman et al., 2004),
      1. Vaccination(Kitching et al., 2002D)
        • Description: Given the rapid generation time of pigs, it is usually considered uneconomic or impractical to attempt to maintain immunity in a national pig herd, and in vaccinating countries, usually only cattle and sometimes the sheep, are vaccinated. FMD vaccines for use in pigs must have an oil adjuvant, as the aluminium hydroxide saponin adjuvant used for cattle and sheep vaccines is not effective in stimulating good protection against FMD in pigs, although the same adjuvant appears to work well in certain other virus vaccines in pigs(Kitching et al., 2002D),
        • Efficacy:
          • Rate: Protection can be provided to naive pigs by day 4 post-vaccination using high potency vaccines with some of the newer oil adjuvants now available(Kitching et al., 2002D).
          • Duration: Usually, vaccination is delayed until 10 to 12 weeks of age and repeated 2 weeks later, which may provide sufficient immunity until slaughter weight is reached. Sows should be vaccinated at least twice yearly during pregnancy(Kitching et al., 2002C).
        • Complication: The immune response to FMD vaccine in young pigs is poor, and protection is best provided by vaccination of the pregnant sow so that immunity can be passed on in the colostrum of the sow. However, in the presence of maternally derived immunity, an effective immune response from vaccination cannot be initiated before 8 weeks of age. In the presence of clinical disease within a pig herd, vaccination is unlikely to provide sufficient protection, and even using vaccines of high potency (50 percent protective dose), vaccinated pigs in contact with clinically affected pigs commonly develop clinical signs. This is not evidence of poor vaccine quality, but of the extremely high excretion level of FMDV in pigs and of the virulence of some strains of FMDV in pigs(Kitching et al., 2002D),
  4. Sheep and Goats
    1. Taxonomy Information:
      1. Species:
        1. Ovis aries (Website 127):
          • Common Name: Ovis aries
          • GenBank Taxonomy No.: 9940
        2. Capra hircus (Website 133):
          • Common Name: Capra hircus
          • GenBank Taxonomy No.: 9925
          • Description: 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 has also been isolated from goat samples submitted from Bangladesh and goats imported from this country were also responsible for an outbreak of Asia 1 in Kuwait. Isolation of other serotypes is rare, but does not necessarily indicate that the infection of small ruminants with this serotypes does not occur; for example Kuwait reported isolating 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 type O virus was identified in clinically affected sheep and goats(Kitching et al., 2002B).
    2. Infection Process:
      1. Infectious Dose: As is the case with other ruminant, sheep and goats are highly susceptible to infection with FMD virus by the aerosol route, with as little as 20 TCID50 being sufficient for infection. Aerosol production by infected pigs can be as high as log 10 8.6 TCID50 per day, theoretically sufficient to infect over 20 million sheep(Kitching et al., 2002B),
      2. Description: Local replication of FMD virus occurs at the site of entry, in the mucosa of the respiratory tract or at the skin or mucosa membrane abrasion. The virus then spreads throughout the body favoring epithelial tissue in the adult and heart muscle in the juvenile(Kitching et al., 2002B),
    3. Disease Information:
      1. Foot-and-mouth disease(i.e., Foot-and-mouth disease) :
        1. Incubation: The incubation period in sheep following infection with FMD virus is usually between three and eight days, but can be as short as 24 hours following experimental inoculation, or as long as 12 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. Clinical signs appear up to 3 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(Kitching et al., 2002B),
        2. Prognosis:
            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(Kitching et al., 2002B),
        3. Diagnosis Summary: In general the clinical signs of FMD in sheep were mild and easily confused with those of other conditions, such as foot rot. The term silent spreaders eloquently describes the situation, and it is not surprising that the presence of infection in a flock was often revealed only when cattle in contact showed clinical signs as an indicator host(Gibbs et al., 2003), Collection of vesicle epithelium or heart muscle from a dead lamb or kid, should be collected into 50 percent phosphate glycerol, buffered to pH 7.4 to 7.6, and submitted with whole and clotted blood. The tissue samples will be prepared as a 10 percent suspension for antigen detection ELISA or used directly in a PCR 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. 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, the solid phase competition ELISA, or the virus neutralization test. If vaccine has been used on 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-structured proteins of FMD virus, and these may be detected using the 3ABC ELISA or enzyme-linked immuno-electrotransfer blot, although neither test has been fully validated for use in small ruminants. 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. The probang sample is then tested for the presence of FMD virus as for tissue and blood samples(Kitching et al., 2002B),
        4. Symptom Information :
          • Description: Foot and mouth disease 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 of where small ruminants have been responsible for the introduction of FMD into previously disease-free countries(Kitching et al., 2002B). There are strains of serotype O FMD virus circulating in the Middle East where sheep and goats from the majority of the susceptible population, which appear very well adapted to small ruminants, and there are many examples of FMD begin 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. In 1994, FMD was transported by illegally imported sheep from Turkey onto the Greek island of Lesbos. 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. The recent outbreak in the United Kingdom predominantly affected the sheep population(Kitching et al., 2002B).
          • Symptom -- Vesicles (Kitching et al., 2002B):
            • Description: Vesicular disease may fail to develop in approximately 25 percent of infected sheep, a further 20 percent 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 3 days. Vesicles may develop in the interdigital cleft, on the heel bulbs and on the coronary band, but they usually rupture rapidly and their appearance may be hidden by the coexisting presence of foot rot. 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, but also on the tongue, hard palate, lips and gums. Vesicles may also be observed on the teats, particularly of milking sheep and goats and rarely, on the vulva and prepuce(Kitching et al., 2002B).
            • Picture(s):
          • Symptom -- Lameness (Kitching et al., 2002B):
            • Description: Lameness is usually the first indication of FMD in sheep and goats. An affected animal develops a fever, is reluctant to walk, and may separate itself from the rest of the flock(Kitching et al., 2002B).
            • Picture(s):
          • Symptom -- myocarditis (Kitching et al., 2002B):
            • Description: 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 percent of the lamb crop(Kitching et al., 2002B).
          • Symptom -- decreased production (Kitching et al., 2002B):
            • Description: Affected rams are unwilling to work, and lactating animals suffer a temporary loss of milk yield(Kitching et al., 2002B).
        5. Treatment Information:
          • Slaughter (Kitching et al., 2002B): TEXT.
            • Complication: The difficulties encountered in identifying clinical disease (in the recent UK experience) resulted in large numbers of healthy animals being slaughtered, while other infected flocks went unrecognised, allowing the virus to spread(Kitching et al., 2002B).
    4. Prevention:
      1. Slaughter
        • Description: 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 an in-contact animals or vaccination. In countries previously free from FMD, an initial attempt is usually made to eradicate the disease by slaughter(Kitching et al., 2002B),
      1. Vaccination
        • Description: 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(Kitching et al., 2002B),
        • Efficacy:
          • Rate: The often silent nature of the disease in adult sheep can give the impression that the vaccination programme has been successful, when in reality the virus is circulating freely(Kitching et al., 2002B).
          • Duration: 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(Kitching et al., 2002B). Classical aqueous vaccines and oil-adjuvant FMD vaccines protect sheep very well. In general, oil vaccines induce a longer lasting immunity(Sutmoller et al., 2003).
        • Complication: 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(Kitching et al., 2002B),
  5. African Buffalo
    1. Taxonomy Information:
      1. Species:
        1. Syncerus caffer (Website 128):
          • Common Name: Syncerus caffer
          • GenBank Taxonomy No.: 9970
          • Description: It is becoming increasingly apparent that some wild-life, Africa Buffalo particularly, as is the case for sheep and goats among domestic animals, frequently suffer infection that is not apparent. They may nonetheless excrete FMD virus while in the acute stage of the infection(Thomson et al., 2003).
    2. Infection Process:
      1. Infectious Dose: There are no reports of the dose of FMD virus required to infect wildlife(Thomson et al., 2003),
      2. Description: ,
    3. Disease Information:
      1. Foot and mouth disease :
        1. Prognosis:
        2. Diagnosis Summary: The diagnosis of FMD in wildlife is more complicated than in domestic stock because the variation in severity of presenting signs is greater than in domestic animals. Persistent infections of ruminants may be identified by collection of specimens in a probang cup. This material is then inoculated into sensitive cell cultures that enable any viable virus present to replicate and cause cytopathic effects. Because the test may fail to detect virus in some animals -- the virus appears intermittently and in varying quantities -- it cannot be relied upon to detect all persistently infected individuals. Therefore, where persistent infection is suspected, as many animals as possible should be sampled. Animals that produce negative results should be resampled at least twice at weekly intervals. Sera should be collected from as many suspect animals as possible. Virus neutralization and liquid-phase blocking ELISA are commonly used for all species. Serological tests that detect antibodies to the non-structural proteins of FMD viruses, such as the 3ABC ELISA, are particularly useful in wildlife because they are not vaccinated and therefore positive results are indicative of infection with one of the apthovirus serotypes(Thomson et al., 2003),
        3. Symptom Information :
          • Description: Most infections in African buffaloes caused by SAT type viruses are thought to be subclinical because few of the over 47,000 buffalo examined after being culled in the Kruger National Park, where FMD is endemic, had clinical signs or lesions suggestive of FMD. Absence of clinical FMD or signs of healed lesions in buffalo in Botswana, Zimbabwe and Uganda has also been reported. It is clear that while some, possibly most infections of buffalo with SAT viruses do not cause disease, in some circumstances at least, typical FMD may result. However, disease has not been reliably recorded in free-living buffalo(Thomson et al., 2003). Most buffalo in the Kruger National Park are infected with all three SAT types by the age of two years(Vosloo et al., 2002B). In parts of sub-Saharan Africa, African buffaloes serve as maintenance hosts for the SAT types of FMDV(Thomson et al., 2003).
          • Symptom -- Vesicles (Thomson et al., 2003):
            • Description: Typical mouth lesions of FMD developed in what appeared to be a natural outbreak caused by a SAT 1 virus. Six were found to have lesions in the mouth. These occurred on the tongue, insides of the cheeks and, in one case, on the hard palate. Some lesions were large (70 x 30 mm), foul smelling and the affected epithelium was brittle and came off in granules. Within a week, ulcers and erosions formed with rounded epithelial edges and a clear pink floor. Foot lesions did not occur in any of the animals. This account accords with an earlier observation, also made in the Kruger National Park among a group of 8 buffalo captured and kept in pens. Lesions in the mouth were confined to the dental pad, palate, dorsum of the tongue and lips. On the feet, lesions were found on the coronary band and in the interdigital cleft(Thomson et al., 2003).
            • Picture(s):
          • Symptom -- myocarditis (Thomson et al., 2003):
            • Description: Young animals of any species may die acutely of myocarditis, which appears grossly as whitened streak-like areas of the myocardium(Thomson et al., 2003).
    4. Prevention:
      1. Fencing
        • Description: The establishment of wildlife conservancies has created a problem with regard to FMD because the Office International des Epizooties (OIE) presently considers any territory on which buffalo infected with FMD viruses occur as infected. Zones recognized as free of FMD by the OIE need to be separated from infected zones by a defined surveillance zone of at least 10km deep (International Health Code, 1992). According to the OIE recommendations this means that landowners acquiring even one infected buffalo cause their land to be in an infected zone and, by implication, their neighbors to be in a surveillance zone. However, in May 1997 it was accepted by the OIE that infected and free zones may be separated by a barrier instead of a surveillance zone. It appears that modified low-maintenance buffalo control fence complemented with buffer zones or vaccination zones may be a cost-effective solution to the containment of FMD in wildlife zones(Sutmoller et al., 2002), The floods of 2000 in southern Africa damaged the Kruger National Park game fence extensively, and there were several accounts of buffalo that had escaped from the park. The VPI gene, which codes for the major antigenic determinant of the FMD virus, was used to determine phylogenetic relationships between virus isolates obtained from the outbreaks and those previously obtained from buffalo in the KNP. These results demonstrate that buffalo were most probably the source of the outbreaks, indicating that disease control using fencing as well as vaccination is extremely important to ensure that FMD does not become established in domestic livestock(Vosloo et al., 2002B),
        • Contraindicator: The construction of a game fence along international borders if there are no wildlife areas in the neighboring countries would serve no purpose as far as FMD control is concerned(Sutmoller et al., 2002), In principle, wildlife fences should not be constructed only between wildlife zones and the farming areas. They should not run through the middle of any wildlife zones, but between them and any commercial farms or communal lands. Also from a FMD control point of view there is no need to fence through communal lands or along international borders(Sutmoller et al., 2002),
        • Complication: Fences are supposed to prevent close contact between infected animals and noninfected animals from the same species or from different species. However, other transmission mechanisms, such as intermediate hosts, must be accounted for(Sutmoller et al., 2002), The use of fencing has been severely criticised by conservationists, because the fences sometimes have blocked migration routes and access of wildlife to water, resulting in ecological disturbances and wildlife mortality. The necessity for fencing is increasingly questioned -- the argument being that vaccination alone should be sufficient to protect livestock from infection(Thomson et al., 2003),
  6. Impala
    1. Taxonomy Information:
      1. Species:
        1. Aepyceros melampus (Website 129):
          • Common Name: Aepyceros melampus
          • GenBank Taxonomy No.: 9897
          • Description: Some impala may develop severe, although usually non-fatal FMD, while others remain clinically normal(Thomson et al., 2003).
    2. Infection Process:
      1. Infectious Dose: There are no reports of the dose of FMD virus required to infect wildlife. However, aerosols containing as little as one cell culture infective dose established infection in impala(Thomson et al., 2003),
      2. Description: TEXT,
    3. Disease Information:
      1. Foot and mouth disease :
        1. Prognosis:
            Some impala may develop severe, although usually non-fatal FMD, while others remain clinically normal(Thomson et al., 2003),
        2. Diagnosis Summary: The diagnosis of FMD in wildlife is more complicated than in domestic stock because the variation in severity of presenting signs is greater than in domestic animals. Persistent infections of ruminants may be identified by collection of specimens in a probang cup. This material is then inoculated into sensitive cell cultures that enable any viable virus present to replicated and cause cytopathic effects. Because the test may fail to detect virus in some animals -- the virus appears intermittently and in varying quantities -- it cannot be relied upon to detect all persistently infected individuals. Therefore, where persistent infection is suspected, as many animals as possible should be sampled. Animals that produce negative results should be resampled at least twice at weekly intervals. Sera should be collected from as many suspect animals as possible. Virus neutralization and liquid-phase blocking ELISA are commonly used for all species. Serological tests that detect antibodies to the non-structural proteins of FMD viruses, such as the 3ABC ELISA, are particularly useful in wildlife because they are not vaccinated and therefore positive results are indicative of infection with one of the apthovirus serotypes(Thomson et al., 2003),
        3. Symptom Information :
          • Description: Some impala may develop severe, although usually non-fatal FMD, while others remain clinically normal(Thomson et al., 2003). The only locality in which overt FMD has been reported regularly in wildlife over the last 60 years is the Kruger National Park in South Africa, where there have been 31 recorded outbreaks in impala since 1938, and 23 since routine surveillance was introduced in the mid 1960s. Eight (26 percent) were caused by SAT1, 15 (48 percent) by SAT2, three (10 percent) by SAT3, and five (16 percent) were untyped(Thomson et al., 2003).
          • Symptom -- vesicles (Thomson et al., 2003):
            • Description: In impala, as in small domestic ruminants, mouth lesions are usually most severe on the dental pad, but may occur elsewhere, especially on the tongue. Foot lesions begin as coronitis, sometimes vesiculating around the entire coronet. Vesicles at any site rupture early in the course of the disease, so that the blisters are often eroded by the time that an animals is examined(Thomson et al., 2003).
            • Picture(s):
          • Symptom -- lameness (Thomson et al., 2003):
            • Description: In the acute stages animals may develop piloerection, probably due to fever, and locomotor signs relating to foot lesions. These vary from mild walking on eggs, with arched back and head held low, to severe carrying leg lameness. Other signs include licking or shaking of the feet, shifting weight from one leg to the other, holding one hoof off the ground, lagging behind the herd, and lying down with reluctance to rise. Discontinuity of the skin hoof junction results in a break or fault in the hoof-wall as the hoof grows, which is useful in estimating the time since the acute phase of the disease(Thomson et al., 2003).
          • Symptom -- myocarditis (Thomson et al., 2003):
            • Description: Young animals of any species may die acutely of myocarditis, which appears grossly as whitened streak-like areas of the myocardium(Thomson et al., 2003).
    4. Prevention:
      1. Fencing
        • Description: In south-eastern Zimbabwe, double fence lines with a defoliated zone about 10 metres wide between two lines were used to form the perimeters of commercial wildlife conservancies. The idea is that direct transmission across the fence lines would be precluded by prevention of direct contact between animals on either side of the fence. In the initial design, one of the fence lines was at least 1.8 m in height to prevent antelope from jumping over the fence(Sutmoller et al., 2002),
        • Contraindicator: The construction of a game fence along international borders if there are no wildlife areas in the neighboring countries would serve no purpose as far as FMD control is concerned(Sutmoller et al., 2002), In principle, wildlife fences should not be constructed only between wildlife zones and the farming areas. They should not run through the middle of any wildlife zones, but between them and any commercial farms or communal lands. Also from a FMD control point of view there is no need to fence through communal lands or along international borders(Sutmoller et al., 2002),
        • Complication: Fences are supposed to prevent close contact between infected animals and noninfected animals from the same species or from different species. However, other transmission mechanisms, such as intermediate hosts, must be accounted for(Sutmoller et al., 2002), The use of fencing has been severely criticised by conservationists, because the fences sometimes have blocked migration routes and access of wildlife to water, resulting in ecological disturbances and wildlife mortality. The necessity for fencing is increasingly questioned -- the argument being that vaccination (of livestock) alone should be sufficient to protect livestock from infection (from wildlife)(Thomson et al., 2003),
  7. Llama
    1. Taxonomy Information:
      1. Species:
        1. Lama glama (Website 134):
          • Common Name: Lama glama
          • GenBank Taxonomy No.: 9844
          • Description: The role of the South American camelids in FMD epizootiology is not completely known. The Pan American Health Organization regional health booklet does not list FMD as a disease of auquenids in any of the countries where these species are found. Outbreaks of FMD South American camelids have rarely been reported. In one case, alpacas, showing minor clinical disease, were associated with a field outbreak in a Puno (Peru) cattle population from which FMDV A24 virus was isolated. The authors concluded that these species could play a role as carriers of FMDV and potentially transmit the virus when in contact with susceptible animals(Lubroth et al., 1990).
    2. Disease Information:
      1. Foot and mouth disease :
        1. Prognosis:
            The inability in this study to isolate FMDV beyond the first week postinoculation or postcontact with FMDV-infected animal or premises is of paramount importance. This finding contrasts with what has been documented in other species. By 11 dpi, no evidence of any tongue trauma could be identified. Flaps of cornified epithelium attached only at the center of the footpad on the palmer and plantar aspects of the extremities were observed by 14 dpi(Lubroth et al., 1990),
        2. Diagnosis Summary: Serologic tests used in this study to detect FMDV antibodies in livestock and wild ruminants were equally capable of identifying the llamas that had had clinical evidence of FMD. Llamas that had a significant VN antibody titer early in the disease process were also positive with the VIAA immunodiffusion assay days later. Those llamas that were positive for VIAA also had antibodies against FMDV A24 by the VN test. The 2 llamas that did not have clinical disease were seronegative by the VN and VIAA tests(Lubroth et al., 1990), The diagnosis of FMD in wildlife is more complicated than in domestic stock because the variation in severity of presenting signs is greater than in domestic animals. Persistent infections of ruminants may be identified by collection of specimens in a probang cup. This material is then inoculated into sensitive cell cultures that enable any viable virus present to replicated and cause cytopathic effects. Because the test may fail to detect virus in some animals -- the virus appears intermittently and in varying quantities -- it cannot be relied upon to detect all persistently infected individuals. Therefore, where persistent infection is suspected, as many animals as possible should be sampled. Animals that produce negative results should be resampled at least twice at weekly intervals. Sera should be collected from as many suspect animals as possible. Virus neutralization and liquid-phase blocking ELISA are commonly used for all species. Serological tests that detect antibodies to the non-structural proteins of FMD viruses, such as the 3ABC ELISA, are particularly useful in wildlife because they are not vaccinated and therefore positive results are indicative of infection with one of the apthovirus serotypes(Thomson et al., 2003),
        3. Symptom Information :
          • Description: As members of the mammalian order Artiodactyla, it is not surprising that the South American camelids are susceptible to FMD. However, the multifarious FMD signs and lesions seen in these llamas were of interest -- ranging from a generalized infection, in which oral and lingual mucosa and feet were affected with severe lameness, to confirmed exposed asymptomatic contact llamas from which virus could be isolated only from OP samples without any serologic evidence of virus encounter. Three llamas developed generalized clinical disease with mild pyrexia, 2 after intra dermolingual inoculation, and 1 after exposure to a calf infected with FMDV serotype A24. Another contact llama developed vesicular lesion s on all 4 extremities but no oral lesions. Two contact llamas, in separate study groups, did not seroconvert or develop clinical signs of FMDV infection(Lubroth et al., 1990).
          • Symptom -- vesicles (Lubroth et al., 1990):
            • Description: In Group 1, at 24 hours postinoculation was characterized by sloughing of epithelium at the inoculation sites. By 48 hours, flaps of epithelium from ruptured vesicles covered the entire rostral portion of the tongue. The underlying lingual stroma was intensely hemorrhagic, contrary to what is commonly seen in bovine FMD. At 2-5 dpi, a stringy, frothy oral discharge was evident around the commisures of the mouth and from which FMDV A24 was readily isolated. The interdigial glands became turgid and conspicuous at 5-6 dpi, primarily on the hind feet. Vesicular fluid was observed seeping from the distal portion of one of the interdigital glands. Lameness was moderate. In group II, interspecies transmission was also achieved in the llama after contact exposure with an inoculated bovine. Transmission of the FMD was first suspected by seeing epithelial fissuring and blanching of the entire dorsal surface of the tongue in the juvenile contact llama at 4 dpc. Even though gingivae, lips and the hard palate were also involved and the temperature elevation was noted, this llama maintained adequate food and water intake and continued to interact normally with other llama in the room, the caretakers, and the author. Although lameness was not noted, evidence of foot involvement was seen after 14 dpc as a separation of the thick plantar and palmar cornified footpad epithelium from more proximal structures. As with the llama in Group I, this ruptured footpad vesicle was more apparent at the level of the abaxial hairline, medial and lateral. No coronary band lesions were seen(Lubroth et al., 1990).
          • Symptom -- myocarditis (Thomson et al., 2003):
            • Description: Young animals of any species may die acutely of myocarditis, which appears grossly as whitened streak-like areas of the myocardium(Thomson et al., 2003).
  8. Deer
    1. Taxonomy Information:
      1. Species:
        1. Cervidae (Website 130):
          • Common Name: Cervidae
          • GenBank Taxonomy No.: 9850
          • Description: Clinical signs were severe in roe and muntjac, less so in sika, and usually subclinical in fallow and red(Simpson et al., 2002). White-tailed deer (Odocoileus virginianus) were shown to be susceptible to infection with FMD virus type O. The clinical syndrome was intermediate in severity between that seen with cattle and that in sheep and goats similarly exposed(McVicar et al., 1974).
    2. Infection Process:
      1. Infectious Dose: There are no reports of the dose of FMD virus required to infect wildlife(Thomson et al., 2003),
      2. Description: TEXT,
    3. Disease Information:
      1. Foot and mouth disease :
        1. Prognosis:
            All of the deer tested 4 weeks after (experimental) exposure had virus in the OPF and therefore could be classified as carriers. Generalization is not possible with such a small experimental group but the presence of the virus in the OPF of one animal 11 weeks after exposure makes the existence of relatively long term carriers a distinct possibility(McVicar et al., 1974),
        2. Diagnosis Summary: The diagnosis of FMD in wildlife is more complicated than in domestic stock because the variation in severity of presenting signs is greater than in domestic animals. Persistent infections of ruminants may be identified by collection of specimens in a probang cup. This material is then inoculated into sensitive cell cultures that enable any viable virus present to replicated and cause cytopathic effects. Because the test may fail to detect virus in some animals -- the virus appears intermittently and in varying quantities -- it cannot be relied upon to detect all persistently infected individuals. Therefore, where persistent infection is suspected, as many animals as possible should be sampled. Animals that produce negative results should be resampled at least twice at weekly intervals. Sera should be collected from as many suspect animals as possible. Virus neutralization and liquid-phase blocking ELISA are commonly used for all species. Serological tests that detect antibodies to the non-structural proteins of FMD viruses, such as the 3ABC ELISA, are particularly useful in wildlife because they are not vaccinated and therefore positive results are indicative of infection with one of the apthovirus serotypes(Thomson et al., 2003),
        3. Symptom Information :
          • Description: The oral lesions closely resembled those seen in sheep and goats. Foot lesions were quite uniform in appearance and different from those that we have seen in either cattle, sheep or goats. They were characterized by involvement of the leathery pad, which covers the bulb of the heel. Initially the skin around the edge of the heel pad blanched. Separations and oozing of vesicular fluid soon followed, giving a characteristic wet appearance to the heel. At this time, gentle traction allowed the entire distal end of the heel pad to be peeled back to expose the reddened and extremely sensitive deeper tissue. The heel pad shriveled as healing of the deep layers progressed and eventually an area of gray-white scar tissue covered the bulb of the heel(McVicar et al., 1974).
          • Symptom -- vesicles (Thomson et al., 2003):
          • Symptom -- myocarditis (Thomson et al., 2003):
            • Description: Young animals of any species may die acutely of myocarditis, which appears grossly as whitened streak-like areas of the myocardium(Thomson et al., 2003).
        4. Treatment Information:
          • Slaughter (McVicar et al., 1974): Control of an extensive epizootic of foot-and-mouth disease in California between 1924 and 1926 was complicated by the extension of the infection into the deer herd of the Stanislaus National Forest. The disease was first diagnosed in the deer herd in July 1924 and by September 1925 22,000 deer had been slaughtered(McVicar et al., 1974).
    4. Prevention:
      1. Slaughter
        • Description: Control of an extensive epizootic of foot-and-mouth disease in California between 1924 and 1926 was complicated by the extension of the infection into the deer herd of the Stanislaus National Forest. The disease was first diagnosed in the deer herd in July 1924 and by September 1925 22,000 deer had been slaughtered(McVicar et al., 1974),
  9. Hedgehog
    1. Taxonomy Information:
      1. Species:
        1. Erinaceus europaeus (Website 131):
          • Common Name: Erinaceus europaeus
          • GenBank Taxonomy No.: 9365
          • Description: During an outbreak in Norfolk in 1946 nine hedgehogs were found dying from FMD over an 11-week period(Simpson et al., 2002).
    2. Infection Process:
      1. Infectious Dose: There are no reports of the dose of FMD virus required to infect wildlife(Thomson et al., 2003),
      2. Description: TEXT,
    3. Disease Information:
      1. Foot and mouth disease :
        1. Prognosis:
            During an outbreak in Norfolk in 1946 nine hedgehogs were found dying from FMD over an 11-week period(Simpson et al., 2002),
        2. Symptom Information :
          • Description: Hedgehogs had vesicular lesions to the foot pad, snout, lips, tongue and pernium(Simpson et al., 2002). There is evidence suggesting transmission in both directions between cattle and European hedgehogs, and for latent infection of hibernating hedgehogs. However, these reports should be viewed with caution, because there is no evidence that hedgehogs have participated in the propagation of FMD viruses in Europe or Africa in recent times(Thomson et al., 2003). During an outbreak in Norfolk in 1946 nine hedgehogs were found to be dying of FMD over an 11-week period(McVicar et al., 1974).
          • Symptom -- vesicles (Thomson et al., 2003):
            • Description: Hedgehogs had vesicular lesions to the foot pad, snout, lips, tongue and pernium(McVicar et al., 1974).
          • Symptom -- myocarditis (Thomson et al., 2003):
            • Description: Young animals of any species may die acutely of myocarditis, which appears grossly as whitened streak-like areas of the myocardium(Thomson et al., 2003).
Phinet: Pathogen-Host Interaction Network
Not available for this pathogen.
Lab Animal Pathobiology & Management

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References:
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Vangrysperre et al., 1996: Vangrysperre W, De Clercq K. Rapid and sensitive polymerase chain reaction based detection and typing of foot-and-mouth disease virus in clinical samples and cell culture isolates, combined with a simultaneous differentiation with other genomically and or symptomatically related viruses. Advances in Veterinary Science and Comparative Medicine. 1996; 141(2); 331-344. [PubMed: 8634024].
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Vosloo et al., 2002B: Vosloo W, Boshoff K, Dwarka R, Bastos, Armanda. The possible role that buffalo played in the recent outbreaks of foot-and-mouth disease in South Africa. Ann. NY Acad. Sci.. 2002; 969(text); 187-190. [PubMed: 12381589].
Website 100: Foot-and-mouth disease virus O5India
Website 106: Foot-and-mouth disease virus A, complete genome
Website 107: Foot-and-mouth disease virus A, complete genome graphic
Website 108: Foot-and-mouth disease virus SAT 1, complete genome
Website 109: Foot-and-mouth disease virus SAT 1, complete genome graphic
Website 110: Foot-and-mouth disease virus SAT 2, complete genome
Website 111: Foot-and-mouth disease virus SAT 2, complete genome graphic
Website 1119: Foot-and-mouth disease virus C, complete genome
Website 112: Foot-and-mouth disease virus SAT 3, complete genome
Website 113: Foot-and-mouth disease virus SAT 3, complete genome graphic
Website 114: Foot-and-mouth disease virus Asia 1, complete genome
Website 115: Foot-and-mouth disease virus Asia 1, complete genome graphic
Website 116: Foot-and-mouth disease virus O, complete genome
Website 117: Foot-and-mouth disease virus O, complete genome graphic
Website 118: Foot-and-mouth disease virus C, complete genome
Website 120: Emergency Response: Foot-and-Mouth Disease and Other Foreign Animal Diseases
Website 121: Foot and Mouth Disease
Website 122: Security Standards for FMD Laboratories
Website 123: Homo sapiens
Website 124: Protecting America From Foot-and-Mouth Disease and Other Highly Contagious Livestock Diseases
Website 125: Bos taurus
Website 126: Suidae
Website 127: Ovis aries
Website 128: Syncerus caffer
Website 129: Aepyceros melampus
Website 130: Cervidae
Website 131: Erinaceus europaeus
Website 132: Manual of standards Diagnostic Tests and Vaccines 2000: FOOT AND MOUTH DISEASE
Website 133: Capra hircus
Website 134: Lama glama
Website 135: Molecular surface of Foot and Mouth Disease Virus
Website 138: myocardial necrosis
Website 139: the pig site
 
Data Provenance and Curators:
PathInfo: Meg Conlon
HazARD: (for the section of Lab Animal Pathobiology & Management)
PHIDIAS: Yongqun "Oliver" He

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