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Foot and Mouth Fact Sheet

Synopsis of Foot and Mouth
Clinical Signs and Symptoms
Diagnosis and Treatment
Economic Consequences and Disease Eradication
Outbreaks
Sources and Related Articles

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Synopsis of Foot and Mouth

Foot-and-Mouth Disease (FMD) is a severe, highly contagious infectious disease of cloven-hoofed domestic and wild animals, such as cattle, pigs, sheep, goats, and water buffalo. A virus of the family Picornaviridae, genus Aphthovirus, is the causative agent; and, there are seven immunologically distinct serotypes: A, O, C, Asia 1, SAT (Southern African Territories) 1, SAT 2, and SAT 3. This disease spreads widely and rapidly and causes clinical consequences that vastly reduce the animal’s commercial value. For this reason, FMD is widely believed to be the most economically devastating livestock disease and, according to some experts, is the animal equivalent of smallpox. FMD is enzootic in parts of Asia, South America, the Middle East, and Africa. Outbreaks in these areas occur in sporadic zones under favorable conditions. North America, Australia, New Zealand, Chile, Central America, and parts of Europe are considered to be free of FMD.

Transmission occurs through a variety of mechanisms:
- Inhalation or ingestion (from infected source to susceptible animals)
- Direct contact with infected animals
- Mechanical fomites (e.g., vehicles, instruments, feed, etc.)
- Airborne (up to 60 km overland and 300 km by sea) in temperate zones under proper conditions (these include a high viral load, stable atmospheric conditions, and a susceptible population downwind)
- Virus is shed in saliva, feces, urine, milk, semen, and breath for up to four days before clinical signs appear in acutely infected animals

Sources of virus:

Incubating and clinically affected animals
Breath, saliva, feces, and urine; milk and semen (up to four days prior to clinical signs)
Meat and by-products in which pH has remained above 6.0
Carriers, especially cattle and water buffalo; convalescent animals and exposed vaccinates (virus persists in the oropharynx for up to 30 months in cattle or longer in buffalo, 9 months in sheep)
African Cape buffalo are the major maintenance host of SAT serotypes

Dose Required to initiate infection by different routes:

The table shows typical examples of the minimum number of infectious units (tissue culture infective dose; TCID₅₀) required to initiate experimental infection by a variety of routes. The exact doses required vary according to the strain of FMD used and the experimental protocol.

**Source:** AleffGroup, 2002. Pathogenesis of FMD. Available at http://aleffgroup.com/avisfmd/a010-fmd/mod0/0221-pathogenesis.html.
Species	Respiratory	Oral
Cattle	10 - 1000	3 million
Sheep	15 - 100	Not known
Pigs	~ 400	10⁵

Morbidity is high in a susceptible population (up to 100%); mortality is generally less than 1%.
In humans, FMD can cause pyrexia, anorexia, and vesicular lesions. There have been about 40 human cases of FMD reported worldwide.

Clinical Signs and Symptoms

Animals:

Susceptibility:
- High susceptibility - cloven-hoof mammals of the order Artiodactyla, including cattle, pigs, sheep, goats, buffalo, yaks, and wildlife
- Susceptible - antelope, elephants, and giraffes
- Susceptible under experimental conditions - rats, mice, hedgehogs, and armadillos
- Low susceptibility - camels, llamas, alpacas, and African Cape buffalo (major maintenance host for SAT serotypes)
Communicability:
- Sheep and goats are considered maintenance hosts since they have very mild symptoms.
- Pigs are considered amplifying hosts since they produce many times more virus particles in their respiratory secretions than other animals.
- Cattle are considered the indicators for this disease since they are generally the first species to show signs of illness.
For more information on clinical signs and symptoms in animals, click on one of the following links:
- Foot and Mouth Disease: Ageing of Lesions. (Defra, 2004)

Cloven-Hoofed Mammals:

Incubation: 2-14 days
Clinical signs and symptoms:
- Pyrexia (up to 106°F for 1 to 2 days prior to onset of other clinical signs)
- Anorexia
- Lameness
- Agalactia in milking animals
- Vesicles in oral cavity (mucosal surfaces, including tongue, dental pad, gums, and lips)
- Vesicles on feet (bulbs of heel, interdigital cleft, and coronary bands)
- Vesicles may also appear on the muzzle, nares, and teats
- Painful lesions can produce drooling, bruxism, foot stamping, and lip smacking
- Ruptured vesicles (occurs within hours to 2 days) discharge either clear or cloudy fluid and leave raw, eroded areas surrounding by ragged fragments of loose tissue
- Recover generally occurs within 8 to 15 days
Complications:
- Tongue erosions, further increasing anorexia
- Superinfection of lesions, particularly on feet
- Hoof deformation or sloughing of hoof horn
- Mastitis with permanent impairment of milk production
- Myocarditis
- Abortion
- Permanent weight loss, loss of heat control ("panters") due to pituitary effects
Ageing of lesions in cattle:
- Day 1: Blanching of epithelium followed by formation of fluid-filled vesicles
- Day 2: Freshly ruptured vesicles characterized by raw, bright-red exposed dermis, a clear edge to the lesion and no deposition of fibrin
- Day 3: Lesions start to lose their sharp demarcation and bright-red color. Deposition of fibrin starts to occur
- Day 4: Considerable fibrin deposition has occurred and regrowth of epithelium is evident at the periphery of the lesion
- Day 7: Extensive scar tissue formation and healing has occurred. Some fibrin deposition is usually still present
Case-fatality rate:
- Greater than 60% in young animals of all susceptible species, primarily due to myocardial effects
- Less than 1% in adult animals

Sheep and Goats:

Incubation: 2-14 days
Clinical signs and symptoms:
- Pyrexia (up to 106°F for 1 to 2 days prior to onset of other clinical signs)
- Anorexia
- Lameness
- Agalactia in milking animals
- Vesicles (mucosal surfaces, including tongue, dental pad, gums, and lips) are less pronounce than in other species and are most visible in the dental pad.
- Vesicles on feet (bulbs of heel, interdigital cleft, and coronary bands) may go unrecognized.
- Painful lesions can produce drooling, bruxism, foot stamping, and lip smacking
- Rupture of vesicles occurs within hours to 2 days, leaving erosions
- Recover generally occurs within 8 to 15 days

Pigs:

Incubation: 2-14 days
Clinical signs and symptoms:
- Pyrexia (up to 106°F for 1 to 2 days prior to onset of other clinical signs)
- Anorexia
- Lameness
- Vesicles most commonly seen on rostrum of snout and around nares, but can also appear on the tongue, dental pad, gums, cheek, hard and soft palate, lips, muzzle, coronary bands, teats, udder, corium of dewclaws, and interdigital spaces.
- Painful lesions can produce drooling, bruxism, foot stamping, and lip smacking
- Rupture of vesicles occurs within hours to 2 days, leaving erosions
- Erosive lesions can be seen in areas of surface contact, such as the hocks and tarsal areas.
- Recover generally occurs within 8 to 15 days

Humans:

In humans, FMD can cause pyrexia, anorexia, and vesicular lesions. There have been about 40 human cases of FMD reported worldwide.

Diagnosis and Treatment

Diagnostic Samples:

Samples for diagnostic purposes for animals include the following:
- Epithelium
  - 1 gram epithelium with intact vesicles or recently ruptured vesicles in transport media (1:1 glycerol, 0.04 M phosphate buffer, pH 7.2-7.4, with antibiotics, 1,000 IU penicillin); samples should be refrigerated, not frozen, until arrival at laboratory
- Oropharyngeal fluid
  - Collected by probang cup (speculum) or swab in transport media (0.08 M phosphate buffer with 0.01% bovine albumin, 0.0002% phenol red, and antibiotics, 1,000 IU penicillin, and a final pH of 7.2; samples should be frozen to -40°C immediately and transported on solid carbon dioxide or liquid nitrogen until arrival at laboratory
Samples should be packaged and shipped according to national and international hazardous material shipping requirements, and laboratories should be notified when specimens are being submitted.

Differential Diagnosis:

In animals:
- Diseases that are clinically indistinguishable: vesicular stomatitis, swine vesicular disease, and vesicular exanthema of swine
- Other conditions to consider in differential diagnosis:
  - Rinderpest
  - Infectious bovine rhinotracheitis
  - Bluetongue
  - Bovine herpes mammillitis
  - Bovine popular stomatitis
  - Malignant catarrhal fever
  - Peste des petits ruminants
  - Bovine viral diarrhea
  - Bovine mucosal disease
  - Foreign bodies or trauma

Clinical Diagnosis:

FMD should be considered whenever salivation and lameness occur simultaneously and a vesicular lesion is seen or suspected. Fever often precedes other clinical signs; therefore, febrile animals should be carefully examined. Early diagnostic lesion may be found before the animals start to salivate, have a nasal discharge, or become lame. To avoid missing a diagnosis, examine the mouth of a lame animal and the feet of any animal with signs or lesions involving the mouth or nostrils. Typically, FMD spreads rapidly and there is a high clinical attack rate; however, this cannot be counted upon, for a relatively avirulent strain could appear, or more resistant animals (sheep) could be affected.

Laboratory Tests:

ELISA is prescribed by the World Organization for Animal Health for trade purposes.
Virus isolation (for diagnostic purposes):
- Cells such as bovine thyroid, swine, bovine, or ovine kidney cells, as well as suckling mice can be used for isolation
- Requires time
- Requires high level of biosecurity
Antigen detection methods:
- Antigen-capture ELISA
  - Uses monoclonal antibodies or serotype-specific serum
  - More specific and sensitive
  - Not affected by pro- and anti-complement factors
- Complement fixation and virus neutralization
  - Largely replaced by antigen-capture ELISA
  - Depends on tissue cultures and is, therefore, more prone to variability
Antibody detection methods:
- ELISA
  - Can be employed as a serotype-specific serologic test
  - Faster and less variable
  - Requires less restrictive biocontainment facilities
  - Performed on milk in surveillance situations
  - Nonserotype-specific tests for antibodies to nonstructural proteins are available for herd screening; however, they have lowered sensitivity and lack standardization.
- Virus neutralization
  - Can be employed as a serotype-specific serologic test
  - Results can take 2 to 3 days
  - False-positives (low titers) can occur in severely diseased animals
Other diagnostic methods:
- Reverse transcriptase polymerase chain reaction (RT-PCR)
  - A portable "pen side" RT-PCR test has been evaluated in a limited number of trials with favorable results (100% specificity and sensitivity equal to or exceeding virus isolation standard)
  - Advantage: Detection prior to clinical onset
- In-situ hybridization
Click here for more in depth information on diagnostic testing and vaccines for FMD published by OIE in the Manual of Diagnostic Tests and Vaccines for Terrestrial Animals, Part 2, Section 2.1, Chapter 2.1.1.

Treatment:

In animals:
- There is no specific treatment for animals affected with FMD.
- Vaccines:
  - Immunity to one serotype does not confer immunity to other serotypes, and vaccines must be tailored to the local strain.

Economic Consequences and Disease Eradication

Economic Consequences:

Loss of livestock
Costs associated with eradication efforts
International trade embargoes
Increased costs to consumers

Disease Prevention and Control:

Immediate notification of state and federal health officials
According to APHIS, your participation if vital in the U.S. efforts against FMD. Both the early recognition of disease signs and the prompt notification of veterinary officials will help set in motion an effective State and Federal eradication program and is essential if eradication is to be carried out successfully. Your warning may prevent FMD from becoming established in the U.S., or, if it does spread, reduce the time and money needed to wipe it out.
Click on one of the following links for more detailed information on USDA restrictions on products from countries with FMD: 1 (APHIS, Protecting America from FMD) or 2 (APHIS, Restrictions on import of animals and by-products).
Prevention:
- Protect FMD-free areas by animal movement control and surveillance.
- Quarantine infected animals and place import restrictions on feed, animal products, and livestock from areas without FMD-free status.
- Give routine vaccinations in enzoonotic regions to reduce production impact of the disease.
Outbreak Control:
- Outbreaks can be controlled by one or a combination of two methods: Stamping out (slaughter of all animals) and routine vaccination of host animals.
  - Stamping-out procedures:
    - Quarantine of the premises
    - Slaughter of affected, recovered, and exposed animals
    - Trace-back to the source of infection and other potential exposures
    - Movement restriction around the affected premises
    - Disinfection of premises and all infected materials with sodium hydroxide, sodium carbonate, or citric acid
    - Destruction of carcasses, manure, and animal products in the area, usually by incineration
    - 21-day movement and restocking restrictions of the premises
  - Vaccination in conjunction with slaughter procedures:
    - Ring vaccination, possibly within the infected premises, can be employed to control the spread of the disease. This method was used in the Netherlands during the FMD outbreak in 2001.
    - In areas densely populated with livestock and with particular regards to pigs, ring vaccination poses a valuable tool to deal economically with an outbreak that is recognized early. In areas sparsely populated with livestock, stamping out or "ring culling" is the economically optimal method for dealing with an outbreak.
  - Routine vaccination procedures:
    - Conventional vaccines are typically inactivated virus with an adjuvant. Immunity lasts four to six months after two initial vaccinations one month apart, depending on the antigenic relationship between the vaccine and the outbreak strains.
    - Protection is conferred a minimum of four days after vaccination in cattle and 21 days in pigs. Protection is considered to be the prevention of clinical signs and, therefore, the associated viral shedding.
    - The currently employed vaccine approach has the potential to produce carrier status in recipient animals. Research is currently under way to produce a marked vaccine using newer molecular techniques.
    - Many countries have an antigen banking arrangement, where FMD antigens are stored on liquid nitrogen, ready to be manufactured into vaccine in an emergency.
    - If vaccines are used in a previously FMD-free area, recovery of disease-free status occurs after 12 months of no reported cases without slaughter of vaccinated animals. Recovery of status can be attained after three months of no reported cases if the vaccinated animals are slaughtered along with affected and contact animals.
Viability:
- The virus survives in lymph nodes and bone marrow at a neutral pH, but is destroyed in muscle when in pH less than 6.0 (i.e., after rigor mortis)
- Resistance to physical and chemical action:
  - Temperature: Preserved by refrigeration and freezing and progressively inactivated by temperatures above 50°C
  - pH: Optimal range is between 6.0 and 9.0 and is inactivated by pH less than 6.0 or greater than 9.0
  - Disinfectants: Resistant to iodophores, quaternary ammonium compounds, hypoclorite, and phenols, especially in the presence of organic matter and is inactivated by sodium hydroxide (2%), sodium carbonate (4%), and citric acid (0.2%)
- The virus can remain viable on a variety of materials for variable lengths of time, depending on environmental conditions (survival decreases with increasing heat and decreasing humidity)
  - Fecal material: Up to 100 days (liquid slurry)
  - Hay: Up to 105 days
  - Bran: Up to 140 days
  - Wool: Less than 21 days, average 18 days
  - Snow-covered soil: More than 185 days
- Meat and by-products in which the pH remains above 6 can serve as a source of viable virus.
- Animals that have recovered or have been vaccinated can serve as carriers (animals with virus persistence in the pharyngeal region more than 28 days post infection are considered to be carriers).
  - Cattle: Up to 3.5 years
  - Sheep: Up to 9 months
  - African Cape buffalo: Lifelong (herd setting)
  - Pigs: Do not become carriers
Click on one of the following links for more information on lessons learned: 1 (National Audit Office, Department for Environment, Food and Rural Affairs, 2005), 2 (Department of Health, UK, 2001), and 3 (GAO, 2002).
Public health issues:
- FMD is not considered a public health threat, although humans can contract the disease. FMD virus can cause pyrexia, anorexia, and vesicular lesions in humans. Most reported cases in humans have been in laboratory workers and in people having close contact with affected animals.
- FMD should not be confused with hand, foot, and mouth disease, which does affect humans.

FMD and Bioterrorism:

Defined as a category A disease by the OIE
- Category A diseases are highly communicable diseases which have the potential for serious and rapid spread, irrespective of national borders, which are of serious socioeconomic or public health consequences and which are of major importance in the international trade of livestock and products.
Bioweapon potential:
- High rate of morbidity in multiple species
- Highly communicable and spreads rapidly once introduced into nonimmune herds
- Can lead to dramatic economic losses
  - Up to $14 billion (9.5%) of U.S. farm income would be lost in the event of an outbreak similar to the 2001 epidemic in the UK, according to recent economic models.
  - The most affected sectors would be the cattle, milk, sheep, and swine markets and would mostly affect export markets and consumer demand.

Outbreaks

Animal outbreaks

History of FMD:
- The first recorded account of FMD occurred in Italy in 1514.
- England experienced a major outbreak in 1883 (estimated cost - $5,000,000)
- Germany experience an outbreak in 1890 (estimated 400,000 cattle, 230,000 sheep and goats, and 150,000 swine were infected)
- The U.S. experienced none outbreaks between 1870 and 1929. The largest outbreak occurred in October 1914, over 3,500 livestock herds in 22 different states and the District of Columbia were infected before the outbreak ended in September 1915 and cost the government $4.5 million for eradication. The other major outbreak occurred in 1924 and took 20 months to contain. Both the 1924 and 1929 outbreaks in California involved hogs that were fed raw garbage containing meat from countries with FMD.
- Click here for a detailed description of the FMD outbreak in the UK.
2001: Europe and the United Kingdom (France, Ireland, England, Netherlands)
- The outbreak originate in the United Kingdom (spreading to France and the Netherlands) and was attributed to feeding swine swill contaminated with a virus that originated in India (Pan Asian O strain).
- The outbreak was controlled by the "stamping out" method (i.e., slaughter of affected and in-contact animals).
- The epidemic costs an estimated 2.7 billion British pounds (excluding tourism and associated revenue) and led to the slaughter of about 4 million animals on 2,000 farms.
- For more information on this outbreak, click on one of the following links: 1 (Defra, 2001)
- The epidemic costs an estimated 2.7 billion British pounds (excluding tourism and associated revenue) and led to the slaughter of about 4 million animals on 2,000 farms.

Source: Defra, 2001. Animal Health and Welfare: Comparisons with 1967 - Infected premises by county 2001 outbreak. Available at http://nabc.ksu.edu/assets/uploads/FMD_map_big.jpg

Recent outbreaks:

2005:
- Botswana
- Brazil
- Columbia
- Congo
- Hong Kong
- Mongolia
- Myanmar
- Russia
- Zambia
2004:
- Israel
- Nigeria
- Peru
- South Africa
2003:
- Hong Kong
- Zimbabwe
- Argentina
- Bolivia
- Paraquay
- United Arab Emirates
- Venezuela
- Syria
- Botswana
- Libya
- Malawi
- South Africa
2002:
- Argentina
- Zambia
- Korea
- Kuwait
- Mongolia
- Palestine
- Paraquay
- Syria
- Brazil
- Venezuela
- Mozambique
- Swaziland
- Botswana
- Zimbabwe
2001:
- England
- Ireland
- France
- Netherlands
- Eritrea
- Israel
- Malawi
- Mali
- Uganda
- Brazil
- Kazakhstan
- Korea
- Kuwait
- Kyrgyzstan
- Malaysia
- Mongolia
- Qatar
- Saudi Arabia
- South Africa
- China
- Turkey
- Uruguay
- Argentina
- Azerbaijan
- Greece
- Namibia
- Swaziland
2000:
- Bhutan
- Egypt
- Tajikistan
- Zambia
- Brazil
- Columbia
- Georgia
- Japan
- Kazakhstan
- Korea
- Malaysia
- Mauritania
- Mongolia
- Russia
- South Africa
- China
- Uruguay
- Argentina
- Peru
- Greece
- Malawi
- Namibia
- Swaziland
- Zimbabwe
- Kuwait
- Saudi Arabia
Click on the following hyperlink for more detailed information on these outbreaks and for archived information for years prior to 2000 located at the Office des Epizooties Website: ftp://ftp.oie.int/infos_san_archives/eng/.
The International Committee, composed of Delegates of the OIE Member Countries, issued the following change in FMD status as of May 24, 2005: Resolves: That the Director General publish the following list of Member Countries recognized as FMD free countries where vaccination is not practiced, according to the provisions of Chapter 2.2.10. of the Terrestrial Code (1):
- Albania
- Australia
- Austria
- Belgium
- Bosnia and Herzegovina
- Bulgaria
- Canada
- Chile
- Costa Rica
- Croatia
- Cuba
- Cyprus
- Czech Rep.
- Denmark
- El Salvador
- Estonia
- Finland
- Former Yug. Rep. of Macedonia
- France
- Germany
- Greece
- Guatemala
- Guyana
- Honduras
- Hungary
- Iceland
- Indonesia
- Ireland
- Italy
- Japan
- Korea (Rep. of)
- Latvia
- Lithuania
- Luxembourg
- Madagascar
- Malta
- Mauritius
- Mexico
- Netherlands
- New Caledonia
- New Zealand
- Nicaragua
- Norway
- Panama
- Poland
- Portugal
- Romania
- Singapore
- Slovakia
- Slovenia
- Spain
- Sweden
- Switzerland
- Ukraine
- United Kingdom
- United States of America
- Vanuatu
Source: Office des Epizooties, November 2, 2005. Official Animal Health Status: Foot-and-Mouth Disease. Available at http://www.oie.int/eng/info/en_fmd.htm.

Sources and Related Articles

Sources:

OIE, April 22, 2002. Animal Disease Data: Foot-and-Mouth Disease. Available at http://www.oie.int/eng/maladies/fiches/a_A010.htm.
CIDRAP, 2004. Foot-and-Mouth Disease. Available at http://www.cidrap.umn.edu/cidrap/content/biosecurity/ag-biosec/anim-disease/foot-mouth.html.
House, J., 1998. Foot-and-Mouth Disease. Published in the 1998 Edition of the Foreign Animal Diseases "The Gray Book." Available at http://www.vet.uga.edu/vpp/gray_book/FAD/FMD.htm.
Southwest Missouri State University. Agricultural History Series: Foot and Mouth Disease. Available at http://ag.smsu.edu/footm1.htm.
USDA, APHIS, January 2002. Foot-and-Mouth Disease. Available at http://www.aphis.usda.gov/lpa/pubs/fsheet_faq_notice/fs_ahfmd.pdf.

Anonymous, April 24, 2001. Foot and Mouth Disease: Measures to Minimize Risk to Public Health from Slaughter and Disposal of Animals - Further Guidance. Published by the Department of Health. Available at http://www.dh.gov.uk/assetRoot/04/01/95/53/04019553.pdf.
Anonymous, January 2002. Protecting America from Foot-and-Mouth Disease and Other Highly Contagious Livestock Diseases. Published by APHIS Veterinary Services. Available at http://www.aphis.usda.gov/lpa/pubs/fsheet_faq_notice/fs_ahfmdpre.pdf.
Anonymous,2005. Foot-and-Mouth Disease (FMD): More Detailed Information on USDA Restrictions on Products from Countries with Foot-and-Mouth Disease. Published by APHIS. Available at http://www.aphis.usda.gov/lpa/issues/issues_archive/fmd/restrpro.html.
Anonymous, July 22, 2005. Foot and Mouth Disease. Published by the Office des Epizooties in the Manual of Diagnostic Tests and Vaccines for Terrestrial Animals, Part 2, Section 2.1., Chapter 2.1.1. Available at http://www.oie.int/eng/normes/mmanual/A_00024.htm.
Bourn, J., January 20, 2005. Foot and Mouth Disease: Applying the Lessons. National Audit Office, Press Office. London. Available at http://www.nao.org.uk/publications/nao_reports/04-05/0405184.pdf.
Donaldson, A. and J. Ryder (Defra in collaboration with Veterinary Exotic Diseases Division and the State Veterinary Service), 2004. Foot and Mouth Disease: Aging of Lesions. Defra Publications, Department of Environment, Food, and Rural Affairs, Noble House, London. Available at http://www.defra.gov.uk/animalh/diseases/fmd/pdf/ageing-lesions.pdf.
Dower, M., February 25, 2002. Northumberland Food and Mouth Inquiry. Published by the Northumberland County Council. Available at http://www.northumberland.gov.uk/vg/fmd_maps/fmdreport2002.pdf.
Dyckman, L. and A. Mittal, July 2002. Foot and Mouth Disease: To Protect U.S. Livestock, USDA Must Remain Vigilant and Resolve Outstanding Issues, GAO-02-808. U.S. General Accounting Office, Washington D.C. Available at http://www.gao.gov/new.items/d02808.pdf.

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