Overview of Foot-and-Mouth Disease
Foot-and-mouth disease (FMD) is a highly communicable viral disease caused by an Aphthovirus of the family Picornaviridae. There are 7 serotypes: A, O, C, Asia 1, and SAT (Southern African Territories) 1, 2, and 3. Further diversity is found in strains within each serotype. It primarily affects cloven-hooved animals of the order Artiodactyla. Livestock hosts include cattle, pigs, sheep, goats, and experimental infections in alpacas and llamas. FMD virus has also been reported in >70 species of wild artiodactyls, including bison, giraffes, Indian elephants, and several species of deer and antelope. The disease is characterized by fever and vesicles in the mouth and on the muzzle, teats, and feet and is spread through direct contact or aerosolized virus via respiratory secretions, milk, semen, and ingestion of feed from infected animals (meat, offal, milk). In a susceptible population, morbidity reaches 100% with rare fatalities except in young animals. FMD was once distributed worldwide but has been eradicated in some regions, including North America and Western Europe. In endemic countries, FMD places economic constraints on the international livestock trade and can be easily reintroduced into disease-free areas unless strict precautions are in place. Outbreaks can severely disrupt livestock production and require significant resources to control, as in the 2001 UK outbreak.
FMD is endemic in many countries of the Middle East, Africa, Asia, and in parts of South America. Where FMD still occurs, serotypes are not uniformly distributed. Six of the 7 serotypes have occurred in Africa (O, A, C, SAT-1, SAT-2, SAT-3), 4 in Asia (O, A, C, Asia-1), and 3 in South America (O, A, C). North and Central America, Australia, New Zealand, Greenland, Iceland, and Western Europe are free of FMD. In 2001, FMD was introduced into the UK, where it spread to Ireland, the Netherlands, and France. The highly virulent pan-Asiatic serotype O causing the outbreak was the same found throughout Asia.
The virus is transmitted via direct or indirect contact with infected secretions and excretions (including semen and milk), mechanical vectors (people, horses, dogs, cats, birds, vehicles), and air currents over land or water. The virus can enter the body via inhalation, ingestion, or through skin wounds and mucous membranes. Breeding is a possible route of transmission for the SAT viruses in African buffalo populations. An example scenario for introduction into a previously FMD-free area is for a susceptible population, such as pigs, given imported food derived from an infected animal (meat, offal, milk). Virus then spreads from pigs, which can expire up to 3,000 times more virus than cattle, to more susceptible cattle hosts via aerosol. Virus was reported to travel over water >250 km (155 miles) from Brittany, France, to the Isle of Wight, UK, in 1981, but it usually travels no more than 10 km (~6 miles) over land. FMD has high agroterrorism potential because of its infectivity, high transmissibility through wind and inanimate objects, and potential for large economic losses.
People can act as mechanical vectors of FMD by carrying virus on clothing or skin. FMD is not considered a public health problem, but there are reports of people who work in FMD vaccine laboratories who have developed antibodies to the virus. There are few reports of people with laboratory-confirmed cases of clinical illness between 1921 and 1969. The disease in people is usually short-lived and mild, with symptoms including vesicular lesions and influenza-like illness.
The primary site of infection and replication of FMD is in the mucosa of the pharynx. The virus may also enter through skin lesions or the GI tract. Once distributed throughout the lymphatic system, the virus replicates in the epithelium of the mouth, muzzle, teats, feet, and areas of damaged skin (eg, knees and hocks of pigs). Vesicles then develop at the organs and rupture within 48 hr. More than 50% of ruminants that recover from illness and those that are vaccinated and have been exposed to virus can carry virus particles in the pharyngeal region—up to 3.5 yr in cattle, 9 mo in sheep, and >5 yr in African buffalo.
FMD virus is environmentally resistant and inactivates outside the pH range 6–9 and desiccation and at temperatures >56°C (132.8°F). It is resistant to lipid solvents such as ether and chloroform, but sodium hydroxide (lye), sodium carbonate (soda ash), citric acid, and acetic acid (vinegar) are effective disinfectants. Iodophores, quaternary ammonium compounds, hypochlorite, and phenols are less effective disinfectants, especially in the presence of organic matter.
FMD is shed into milk in dairy cows before clinical signs develop, so there is opportunity for virus to spread farm to farm and from cow to calf via raw milk. FMD may survive pasteurization depending on the method (high temperature short time, ultra high temperature, laboratory pasteurization); the lipid component of milk protects virus during heating. FMD virus survives up to 20 wk on hay or straw bedding, in dry fecal matter for up to 14 days in summer, in a fecal slurry for up to 6 mo in winter, in urine for 39 days, and in soil for 3 (summer) to 28 (winter) days.
The incubation period of FMD is variable and depends on the host, environment, route of exposure, and virus strain. After infection with FMD virus, the average incubation period for sheep and goats is 3–8 days, ≥2 days for pigs, and 2–14 days in cattle. The incubation period can be as short as 18 hr for host-adapted strains in pigs, especially under intense direct contact.
Clinical signs in cattle include pyrexia of ~104° F, followed by vesicular development on the tongue, hard palate, dental pad, lips, gums, muzzle, coronary band, interdigital cleft, and teats in lactating cows. Acutely affected individuals may salivate profusely, stamp their feet, and prefer to lie down. Ruptured oral vesicles can coalesce and form erosions but heal rapidly, roughly 11 days after vesicle formation. Feet vesicles take longer to heal and are susceptible to bacterial infection leading to chronic lameness. Secondary bacterial mastitis is common due to infected teat vesicles and resistance to milking. After vesicular disease develops, cattle quickly lose condition and milk yield, which can persist chronically.
Infected pigs show mild lameness and blanching around the coronary band and may develop a fever of up to 107°F. Affected pigs become lethargic, huddle among other pigs, and have little interest in feed. Vesicles develop on the coronary band, heel of the foot including accessory digits, snout, mandible, and tongue. Additional vesicles may form on the hocks and knees of pigs housed on rough surfaces. Depending on the severity of vesicles, the horn of the foot may completely slough off and cause chronic lameness in recovered pigs. Young pigs <14 wk old may die without clinical signs of illness because of viral damage to the developing myocardium.
Lameness is usually the first clinical sign of FMD infection in sheep and goats. This is followed by fever and vesicular development on the interdigital cleft, heel bulbs, coronary band, and mouth. Vesicles may also form on the teats of lactating animals and rarely on the vulva and prepuce. Secondary infections result in reduced milk yield, chronic lameness, and predisposition to other viral infections, including sheep/goat pox (see Sheeppox and Goatpox) and peste des petits ruminants (see Peste des Petits Ruminants). Similarly to young pigs, infection in immature sheep and goats results in death without clinical signs due to heart failure.
Experimentally infected camelids are commonly reported to have mild clinical illness, if at all, but can have severe infections resulting in salivation and mouth lesions and sloughing of the footpad and skin of the tarsal and carpal joints. Water buffalo can have mouth and foot lesions, which heal faster and are less severe than those in cattle. FMD infections in wildlife resemble clinical illness in their domestic counterparts, but more severe lesions such as sloughing of antlers or toe horn are reported.
In cattle and pigs, the clinical signs of FMD are indistinguishable from those of vesicular stomatitis (see Vesicular Stomatitis), and in pigs from those of swine vesicular disease (see Swine Vesicular Disease) and vesicular exanthema (see Vesicular Exanthema of Swine). Therefore, laboratory confirmation is essential for diagnosis of FMD and should be performed in specialized laboratories that meet OIE requirements for Containment Group 4 pathogens. Countries lacking access to a national or regional laboratory meeting these guidelines should send specimens to an OIE FMD reference laboratory. The tissue of choice for sampling is vesicular epithelium or fluid. At least 1 g of epithelium should be placed in a transport medium of phosphate-buffered saline (PBS) or equal parts glycerol and phosphate buffer with pH 7.2–7.6. Samples should be kept refrigerated or transported on ice. If vesicles are not present, oropharyngeal fluid can be collected via probang cup or pharyngeal swabbing for virus isolation or reverse transcription PCR (RT-PCR). Serum (blood) samples may also be tested by these means (OIE Terrestrial Manual 2012). Repeated sampling may be necessary to identify a carrier, because virus presence may be low and fluctuate.
Laboratory diagnosis is usually performed via antigen capture–ELISA or serotyping ELISA. This is the preferred method for countries with endemic FMD for viral antigen detection and serotyping (OIE Terrestrial Manual 2012). Concurrent virus isolation may be performed, preferably in primary bovine thyroid cell culture. Detecting nucleic acids via RT combined with real-time PCR is more sensitive and rapid than conventional methods and may be more useful when samples contain low concentrations of virus. ELISA is preferred over complement fixation tests because of its increased sensitivity and specificity, but complement fixation may be performed if ELISA reagents are not available. Commercially available lateral flow devices have not yet been validated by the OIE.
Serologic tests for FMD are used to certify animals for import/export (ie, trade), confirm suspected cases of FMD, test efficacy of vaccination, and provide evidence for absence of infection. Testing cut-offs may be set at different levels for herd-based surveillance versus certifying freedom of infection for trade purposes. The choice of serologic test depends on the vaccination status of the animals. Serologic tests for antibodies to the viral structural (capsid) proteins cannot be used in vaccinated animals, because FMD vaccines induce antibodies to these proteins. Detection of antibodies to nonstructural proteins, which are expressed only during virus replication, can be used to determine past or present infection with any of the 7 serotypes, whether or not the animal has been vaccinated. However, they are less sensitive and may result in false-negatives in cases with limited virus replication such as vaccinated animals that become infected, because the vaccine suppresses viral replication (OIE Terrestrial Manual 2012).
The OIE classifies countries and regions as FMD-free without vaccination, FMD-free with vaccination, suspended FMD-free status with or without vaccination, and unrecognized (World Organization for Animal Health, 2013). The current global status of FMD distribution shows geographic areas of viral “hotspots” where FMD prevalence indices are highest over long periods of time. They are commonly located in poor countries where veterinary services and resources are inadequate to control or eradicate FMD. Combined use of trade and movement restrictions of animals and animal products has not completely prevented introductions of FMD into FMD-free areas. These viral incursions into countries or regions where FMD is not enzootic are usually controlled by slaughter of all infected and susceptible animals, strict restriction of animal and vehicle movement around infected premises, proper carcass disposal, and environmental disinfection, without the use of vaccines. Inactivated virus vaccines are limited in their use, because they protect for only 4–6 mo against the specific serotype(s) contained in the vaccine and protect animals from clinical illness but not viral persistence in the pharyngeal region; therefore, they can induce a carrier state. Additionally, it is difficult to distinguish infected animals from vaccinated animals unless purified killed vaccines are used. Therefore, vaccination is used more in enzootic countries to protect producing animals, particularly high-yielding dairy cattle, from clinical illness because slaughter of all at-risk individuals may be economically unfeasible and can cause food shortages.
Rapid disease reporting is essential to control an FMD outbreak in nonendemic countries. Veterinarians who encounter any vesicular disease in the USA should immediately inform their state or federal veterinary authorities. After an outbreak, tracing is done through epidemiologic inquiries to help identify the source of disease introduction. In countries where mass slaughter is not possible, strict quarantining and movement restriction should be enforced. However, quarantine may not be long enough to prevent carrier animal movement after an outbreak. When mass euthanasia is performed, infected carcasses must be disposed of via incineration, burial, or rendering on or close to the infected premises. Scavengers and rodents should be prevented or killed to prevent mechanical dissemination of virus. Buildings should be cleaned with a mild acid or alkali disinfectant and fumigation, and people that have come into contact with virus may be asked to decontaminate their clothing and avoid contact with susceptible animals for a period of time.
In some regions, FMD persistence in wildlife populations, such as the wild African buffalo, can make FMD eradication unrealistic. Control measures, such as fencing of wildlife reserves to prevent contact with domestic livestock, have helped limit the spread of virus in certain areas. A twice-yearly vaccination buffer zone in livestock proximal to endemic wildlife reserves may additionally help decrease outbreak occurrence.
There is no specific treatment for FMD, but supportive care may be allowed in countries where FMD is endemic.