Foot-and-mouth disease (FMD) or hoof-and-mouth disease (Aphtae epizooticae) is a highly contagious and sometimes fatal viral disease of cloven-hoofed animals, including domestic animals such as cattle, water buffalo, sheep, goats and pigs, as well as antelope, bison and other wild bovids, and deer.

In addition, hedgehogs and elephants are susceptible to the disease. The llama and alpaca may develop mild symptoms but are resistant to the disease and will not pass it on to others of the same species. In laboratory experiments, mice, rats and chicken have been successfully infected by artificial means, but it is not believed that they would contract the disease under natural conditions. Just as humans may spread the disease by carrying the germs on their clothes and body, animals that are not susceptible to the disease may still aid in spreading it. This was the case in Canada in 1952 when an outbreak flared up again after dogs had carried off bones from dead animals. Wolves are thought to play a similar role in the former Soviet Union.

Humans are very rarely affected. Foot-and-mouth disease virus (FMDV) is the prototypic member of the Aphthovirus genus in the Picornaviridae family. This picornavirus is the etiological agent of the acute systemic vesicular disease that affects cattle and other animals worldwide. It is a highly variable and transmissible virus.

The cause of FMD was first shown to be viral in 1897 by Friedrich Loeffler. He passed the blood of an infected animal through a fine porcelain filter and found that the fluid that was collected could still cause the disease in healthy animals.

FMD occurs throughout much of the world, and whilst some countries have been free of FMD for some time, its wide host range and rapid spread represent cause for international concern. After World War II, the disease was widely distributed throughout the world. In 1996, endemic areas included Asia, Africa, and parts of South America; as of August 2007, Chile is disease free, and Uruguay and Argentina have not had an outbreak since 2001. North America, Australia and Japan have been free of FMD for many years. New Zealand has never had a case of foot and mouth disease. Most European countries have been recognized as disease free, and countries belonging to the European Union have stopped FMD vaccination.

However, in 2001, a serious outbreak of FMD in Britain resulted in the slaughter of many animals, the postponing of the general election for a month, and the cancellation of many sporting events and leisure activities such as the Isle of Man TT. Due to strict government policies on sale of livestock, disinfection of all persons leaving and entering farms and the cancellation of large events likely to be attended by farmers, a potentially economically disastrous epizootic was avoided in the Republic of Ireland, with just one case recorded in Proleek, Co. Louth. In August 2007, FMD was found at two farms in Surrey, England. All livestock were culled and a quarantine erected over the area. There have since been two other suspected outbreaks, although these seem now not to be related to FMD.

There are seven FMD serotypes: O, A, C, SAT-1, SAT-2, SAT-3, and Asia-1. These serotypes show some regionality, and the O serotype is most common.

Symptoms

The average incubation period of the Foot and Mouth virus varies but is generally around 3-8 days. The disease is characterised by high fever that declines rapidly after two or three days; blisters inside the mouth that lead to excessive secretion of stringy or foamy saliva and to drooling; and blisters on the feet that may rupture and cause lameness. Adult animals may suffer weight loss from which they do not recover for several months as well as swelling in the testicles of mature males, and in cows, milk production can decline significantly. Though most animals eventually recover from FMD, the disease can lead to myocarditis (inflammation of the heart muscle) and death, especially in newborn animals. Some infected animals remain asymptomatic, but they nonetheless carry FMD and can transmit it to others.

Infection with foot-and-mouth disease tends to occur locally - that is, the virus is passed on to susceptible animals through direct contact with infected animals or with contaminated pens or vehicles used to transport livestock. The clothes and skin of animal handlers such as farmers, standing water, and uncooked food scraps and feed supplements containing infected animal products can harbor the virus as well. Cows can also catch FMD from the semen of infected bulls. Control measures include quarantine and destruction of infected livestock, and export bans for meat and other animal products to countries not infected with the disease.

Foot-and-mouth disease is caused by FMDV, an Aphthovirus of the viral family Picornaviridae. The members of this family are small (25-30 nm), nonenveloped icosahedral viruses that contain single-stranded RNA (ribonucleic acid). When such a virus comes in contact with a host cell, it binds to a receptor site and triggers a folding-in of the cell membrane. Once the virus is inside the host cell, its protein coat dissolves. New viral RNA and components of the protein coat are then synthesized in large quantities and assembled to form new viruses. After assembly, the host cell lyses (bursts) and releases the new viruses.

Foot-and-mouth disease infecting humans

Humans can be infected with foot-and-mouth disease through contact with infected animals, but this is extremely rare. Some cases were caused by laboratory accidents. Because the virus that causes FMD is sensitive to stomach acid, it cannot spread to humans via consumption of infected meat, except in the mouth before the meat is swallowed. In the UK, the last confirmed human case occurred in 1966, and only a few other cases have been recorded in countries of continental Europe, Africa, and South America. Symptoms of FMD in humans include malaise, fever, vomiting, red ulcerative lesions (surface-eroding damaged spots) of the oral tissues, and sometimes vesicular lesions (small blisters) of the skin. According to a newspaper report Foot and Mouth disease killed two children in England in 1884, suspectedly due to infected milk.

There is another viral disease with similar symptoms, commonly referred to as "hand, foot and mouth disease", that occurs more frequently in humans, especially in young children; the cause, Coxsackie A virus, is different from FMDV. Both are members of the Picornaviridae family, but while FMDV belongs to the Aphthovirus genus, Coxsackie viruses belong to the Enteroviruses.

Because FMD rarely infects humans but spreads rapidly among animals, it is a much greater threat to the agriculture industry than to human health. Farmers around the world can lose huge amounts of money during a foot-and-mouth epizootic, when large numbers of animals are destroyed and revenues from milk and meat production go down.

Virus replication

Soon after infection, the single stranded positive RNA that constitutes the viral genome is efficiently translated using a cap-independent mechanism driven by the internal ribosome entry site element (IRES). This process occurs concomitantly with the inhibition of cellular protein synthesis, caused by the expression of viral proteases. Processing of the viral polyprotein is achieved cotranslationally by viral encoded proteases, giving rise to the different mature viral proteins. Viral RNA as well as viral proteins interact with different components of the host cell, acting as key determinants of viral pathogenesis. In depth knowledge of the molecular basis of the viral cycle is needed to control viral pathogenesis and disease spreading.

Vaccination

Seven main types of Foot and Mouth Virus are believed to exist. Like other viruses, the FMD virus continually evolves and mutates, thus one of the difficulties in vaccinating against FMD is the huge variation between and even within serotypes. There is no cross-protection between serotypes (meaning that a vaccine for one serotype will not protect against any others) and in addition, two strains within a given serotype may have nucleotide sequences that differ by as much as 30% for a given gene. This means that FMD vaccines must be highly specific to the strain involved. Vaccination only provides temporary immunity that lasts from months to years.

Currently, the World Organisation for Animal Health recognizes countries to be in one of three disease states with regards to FMD: FMD present with or without vaccination, FMD-free with vaccination, and FMD-free without vaccination. Countries that are designated FMD-free without vaccination have the greatest access to export markets, and therefore many developed nations, including Canada, the United States, and the UK, work hard to maintain their current FMD-free without vaccination status.

There are several reasons cited for restricting export from countries using FMD vaccines. The most important is probably that routine blood tests, relying on antibodies, cannot distinguish between an infected and a vaccinated animal. This would severely hamper screening of animals used in export products, risking a spread of FMD to importing countries. A widespread preventive vaccination would also conceal the existence of the virus in a country. From there, it could potentially spread to countries without vaccine programs. Lastly, an animal that is infected shortly after being vaccinated can harbour and spread FMD without showing symptoms itself, hindering containment and culling of sick animals as a remedy.

Many early vaccines used dead samples of FMD virus to inoculate animals. However, those early vaccines sometimes caused real outbreaks. In the 1970s, scientists discovered that a vaccine could be made using only a single key protein from the virus. The task was to produce such quantities of the protein that could be used in the vaccination. On June 18, 1981, the U.S. government announced the creation of a vaccine targeted against FMD; this was the world's first genetically engineered vaccine.

The North American FMD Vaccine Bank is housed at the United States Department of Agriculture's (USDA) Foreign Animal Disease Diagnostic Laboratory (FADDL) at Plum Island Animal Disease Center. The Center, located off the coast of Long Island, NY, is the only place in the United States where scientists can conduct research and diagnostic work on highly contagious animal diseases such as FMD. Because of this limitation US companies working on FMD usually use facilities in other countries where such diseases are endemic.

Outbreaks

US, 1914

The US has had 9 FMD outbreaks since 1870. The most devastating outbreak happened in 1914. It originated from Michigan but it was its entry into the stockyards in Chicago that turned it into an epizootic. 3500 livestock herds were infected across the US, totaling over 170000 cattle, sheep and swine. The eradication came at a cost of 4.5 million 1914 USD dollars. A 1924 outbreak in California resulted not only in the slaughter of 109000 farm animals, but also 22000 deer. The US saw its latest FMD outbreak in Montebello, California in 1929. This outbreak originated in hogs that had eaten infected meat scraps from a tourist steamship that had stocked meat in Argentina. 3600 animals were slaughtered and the disease was contained in as little as one month.

United Kingdom, 1967

In October 1967, a farmer in Shropshire reported a lame sow, which was later diagnosed with FMD. The source was believed to be remains of legally-imported infected lamb from Argentina and Chile. The virus spread and in total, 442,000 animals were slaughtered and the outbreak had an estimated cost of £370 million.

Taiwan, 1997

Taiwan had previous outbreaks of FMD in 1913-14 and 1924-29 but had since been spared epidemics , and considered itself free of FMD as late as in the 1990s. On the 19th of March 1997, a swine sow at a farm in Hsinchu prefecture, Taiwan was diagnosed with a strain of FMD which only infects swine. Mortality was high, nearing 100% in the infected flock. The cause of the outbreak was not determined, but the farm was near a port city known for its pig-smuggling industry and illegal slaughterhouses. Smuggled swine or contaminated meat are thus likely sources of the disease.

The disease spread fast among swine herds in Taiwan, with 200-300 new farms being infected daily. Causes for this include the high swine density in the area with up to 6,500 hogs per square mile, feeding of pigs with untreated garbage and farm's proximity to slaughterhouses. Other systemic issues like lack of laboratory facilities, slow response and initial lack of a vaccination program contributed. It is also alleged that farmers intentionally introduced FMD to their flocks, because the payment offered to farmers for culled swine was at a time higher than the market value of the swine.

A complicating factor is the endemic spread of Swine vesicular disease (SVD) in Taiwan. The symptoms are indistinguishabe from FMD, which may have led to previous mis-diagnosing of FMD as SVD. Laboratory analysis was seldomly used for diagnosis and FMD may thus have gone unnoticed for some time in Taiwan.

The swine depopulation was a massive undertaking, with the military contributing substantial manpower. At peak capacity, 200,000 hogs per day were disposed of, mainly by electrocution. Carcasses was disposed of by burning and burial, but burning was avoided in water resource protection area. In April industrial incinerators were running around the clock to dispose of the carcasses.

Initially, 40,000 combined vaccines for the strains O1, A24 and Asia were available and administered to zoo animals and valuable breeding hogs. At the end of March, half a million new doses of vaccines for O1 and Asia1 were made available. On the 3rd of May, 13 million doses of O1 vaccine arrived, and both the March and May shipments were distributed free of charge. There was a danger of vaccination crews spreading the disease; therefore, trained farmers were allowed to administer the vaccine under veterinary supervision.

Taiwan had previously been the major exporter of pork to Japan and among the top 15 pork producers in the world in 1996. During the outbreak, over 3.8 million swine was destroyed at a cost of $6.9 billion USD. The Taiwanese pig industry was devastated as a result and the export market in ruins. In 2007, Taiwan was considered free of FMD, but were still conducting a vaccination program, which restricts the export of meat from Taiwan.

United Kingdom, 2001

The outbreak of foot-and-mouth disease in the United Kingdom in the spring and summer of 2001 was caused by the "Type O pan Asia" strain of the disease. This episode saw more than 2,000 cases of the disease in farms throughout the British countryside. Around seven million sheep and cattle were killed in an eventually successful attempt to halt the disease. The county of Cumbria was the worst affected area of the country, with 843 cases. By the time the disease was halted by October 2001, the crisis was estimated to have cost Britain £8bn ($16bn) in costs to the agricultural and agricultural support industries and to the outdoor industry. What made this outbreak so serious was the amount of time between infection being present at the first outbreak loci, and the time when countermeasures were put into operation against the disease, such as transport bans and detergent washing of both vehicles and personnel entering livestock areas. The outbreak was probably caused by infected pigs which had been fed garbage that had not been properly heat-sterilized. It is further believed that the garbage contained remains of infected meat which had been illegally imported to Britain.

China, 2005

In April 2005, an Asia-I strain of FMD appeared in the eastern provinces of Shandong and Jiangsu. During April and May, it spread to suburban Beijing, the northern province of Hebei and northwestern autonomous region Xinjiang Uyghur. On the 13th of May, China reported the FMD outbreak to the World Health Organization and the OIE. This was the first time China has publicly admitted to having FMD. China is still reporting FMD outbreaks. In 2007, Reports filed with the OIE documented new or ongoing outbreaks in the provinces of Gansu, Qinghai and Xinjiang. This included reports of domestic yak showing signs of infection.

United Kingdom, 2007

An outbreak of foot-and-mouth disease in the United Kingdom was confirmed by the Department for Environment, Food and Rural Affairs, on 3 August 2007, on farmland located in Normandy, Surrey. All livestock in the vicinity were culled on 4 August. A nationwide ban on the movement of cattle and pigs was imposed, with a 3 km (1.9 mile) protection zone placed around the outbreak sites and the nearby virus research and vaccine production establishments, together with a 10 km (6.2 mile) increased surveillance zone.

On 4 August, the strain of the virus was identified as an "01 BFS67-like" virus, one linked to vaccines and not normally found in animals, and isolated in the 1967 outbreak. The same strain was used at the nearby Institute for Animal Health and Merial Animal Health Ltd at Pirbright, 2½ miles (4 km) away which is an American/French owned research facility, and was identified as a possible source of infection.

On 12 September, a new outbreak of the disease was confirmed in Egham, Surrey, 19km (12 miles) away from the original outbreak, with a second case being confirmed on a nearby farm on 14 September.

On 19 September 2007, there was a suspected case of FMD in Solihull, where a temporary control zone has been set up by Defra.

Economic and ethical issues

Outbreaks of foot-and-mouth disease have resulted in the slaughter of millions of animals, despite this being a frequently non-fatal disease for adult animals (2-5% mortality), though young animals can have a high mortality. The Taiwan outbreak that only affected pigs also showed a high mortality for adults. The destruction of animals is primarily to halt further spread, as growth and milk production may be permanently affected, even in animals that have recovered. Due to international efforts to eradicate the disease, infection would also lead to trade bans being imposed on affected countries. Critics of current policies to cull infected herds argue that the financial imperative needs to be balanced against the killing of many animals, especially when a significant proportion of infected animals, most notably those producing milk, would recover from infection and live normal lives, albeit with reduced milk production. On the ethical side, one must also consider that FMD is a painful disease for the affected animals. The vesicles/blisters are painful in themselves, and restrict both eating and movement. Through ruptured blisters, the animal is at risk from secondary bacterial infections and, in some cases, permanent invalidisation.

Warning notice

This notice is posted where FMD is suspected and a temporary control zone has been set up by Defra:

Failure to comply with this Declaration may be an offence under section 72 or 73 of the Animal Health Act 1981. Note – The declaration of a Temporary Control Zone takes precedence over the previously declared Restricted Zone measures for its duration. A map is attached for ease of reference. Annex 1 The Zone comprises that part of England contained within a circle with a radius of 3 kilometres centred on grid reference SP 1752681268. The grid reference is a British National Grid Reference. Annex 2 1. No person shall move any susceptible animal into or out of the Zone except where the movement is – (a) through the Zone without stopping under a licence authorising movement within the Restricted Zone, granted before the creation of the Zone; or (b) necessary to complete a journey started under a licence authorising movement within the Restricted Zone, granted before the creation of the Zone. 2. No person shall move any susceptible animal from or to premises in the Zone (without leaving the Zone) except to complete a journey started before the creation of the Zone, under the authority of a licence authorising movement within the Restricted Zone granted before the creation of the Zone. 3. The keeper of a susceptible animal in the Zone shall take all such steps as are necessary to prevent it from straying from the premises on which it is kept.

References

See also

• Hand, foot and mouth disease (HFMD)
• Swine vesicular disease (SVD)
• Animal viruses

External links

• 2007 Outbreak Foot and Mouth Disease Timeline
• News updates on the 2007 UK Foot-and-mouth disease outbreak
• Foot-and-mouth disease in man
• Foot and Mouth Livestock Symptoms Guide and Images
• Levy, Jay A., Heinz Fraenkel-Conrat, and Robert A. Owens. "Picornaviridae." Chap. 2, section 2.2 in Virology. Englewood Cliffs, NJ: Prentice Hall, 1994. -
• A Manufactured Plague: The History Of Foot-and-mouth Disease In Britain (2004, ISBN 1-84407-080-8) by Abigail Wood, a veterinary researcher at the University of Manchester.
• The Lab-On-Site Project has more information in Foot and Mouth Disease Virus
• Intervet International has a site devoted to FMD detailing information about Control, Vaccination, Legal Issues, and Preparation
• Current status of Foot and Mouth worldwide at International des Epizooties
• Animal viruses
• Armstrong R, Davie J, Hedger RS (1967). "Foot-and-mouth disease in man". Br Med J 4 (5578): 529–30.
• In the 1884 outbreak in Britain