Foot-and-mouth disease

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Overview
Foot-and-mouth disease (FMD, Latin binomial Aphtae epizooticae), sometimes called hoof-and-mouth disease, is a highly contagious and sometimes fatal viral disease of cattle and pigs. It can also infect deer, goats, sheep, and other bovids with cloven hooves, as well as elephants, rats, and hedgehogs. 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.

Causes
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 April 1994. 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 characterized 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, the viral genetic material). 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 to 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 won't 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.

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 1.5 miles 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.

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. The major reason this outbreak was so serious was the time between infection being present at the first outbreak loci and the time that countermeasures were put into operation against the disease such as transport bans and detergent washing of both vehicles and personnel entering livestock areas.

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.

Economic issues
Outbreaks of foot-and-mouth disease have resulted in the slaughter of millions of animals, despite this being a frequently non-fatal disease. The destruction of animals is primarily to prevent the disease from spreading throughout herds intended for human consumption or producing milk. 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.

Foot-and-mouth disease infecting humans

 * Description
 * Suspected case in 2001
 * A case in 1966:
 * In the 1884 outbreak in Britain

New suspected cases
There is also currently a suspected case of FD under discovery in Solihull, where a temporary control zone has been set up by Defra as detailed below: