Foot-and-Mouth Disease Hazard Specific Plan
2. Foot-and-Mouth Disease Overview
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Foot-and-mouth disease (FMD) is an acute, highly contagious viral infection of cloven-hoofed domestic animals and wildlife, easily transmitted by direct and indirect contact, as well as by aerosols. The disease is characterized by the formation of vesicles (fluid-filled blisters) and erosions in the mouth and nostrils, on the teats, and on the skin between and above the hoofs. The disease has significantly compromised development of livestock industries in infected countries and has also resulted in widespread international trade restrictions against animals and products originating in such countries. Canada has been FMD-free (without vaccination) since 1952. An outbreak of FMD in Canada would be a national disaster. FMD must also be considered a potential agent for agricultural terrorism.
FMD virus is a member of the Picornaviridae family of RNA viruses, which are small, non-enveloped viruses. There are seven immunologically distinct serotypes of FMD virus; namely, serotypes (also just called types) A, O, C, Southern African Territories (SAT) 1, SAT2, SAT3, and Asia 1. Within these serotypes, there can be a wide spectrum of antigenic diversity. Serotype A was divided into 32 subtypes (e.g. A22) and serotype O into 11 subtypes (e.g. O1), but this system is now considered obsolete, as there are more subtypes. Some taxonomists used genotypes for divisions within serotypes. Strains exist within subtypes within which individual isolates are identified during outbreaks. More recently, FMD virus taxonomists have been referring to topotypes, which are based on both genetic similarity and geographic lineages. It is important to appreciate that no, or very minor, cross protection exists between different serotypes. Vaccine cross protection within serotypes is limited, particularly within the serotypes A and SAT, as well as, to some degree, serotype O. Serotype Asia 1 is apparently the only serotype where vaccine matching may not be difficult.
2.2 Susceptible Species
FMD has a wide host range in both domestic and wild cloven-hoofed animals, including cattle, swine, sheep, goats, water buffalo, bison, antelope, deer, and elk. FMD was reported in mule-deer depopulated in California in 1924-1925. It also appeared in Zebu cattle in 1924 and 1925 in Texas. Indian elephants, but apparently not African elephants, are also susceptible, but seemingly do not play a role in FMD epidemiology. Llamas and alpacas have a high natural resistance to infection. Some will develop mild clinical signs following direct contact with infected cattle, but will not transmit FMD to other camelids under field conditions. The Bactrian camel (two-humped camel) is susceptible to FMD and develops severe lesions, while the dromedary camel (one-humped camel) is apparently resistant to infection. Horses are not cloven hoofed and are therefore resistant.
Wildlife experimental studies have been limited in the serotype and strain used. Early studies in 1974 on wildlife demonstrated the susceptibility of white-tailed deer, along with red, fallow, and roe deer. Further work was conducted in the 2000s at Plum Island Animal Disease Center (Greenport, N.Y.) for bison, elk, pronghorn, and mule deer, using type O1 Manisa. This work confirmed the possibility that these species could be infected, but suggested that elk are not efficient transmitters of FMD virus. Work on feral swine, using FMD virus A24 in 2009, showed susceptibility (Cruzeiro et al., 2009), but the role of feral swine in FMD epidemics is unknown. Feral swine or wild boars have been associated with recent FMD transmission in outbreaks in Israel, Turkey, and Bulgaria. However, wildlife experimental studies have been limited in the serotype and strain used. The epidemiology of the FMD viruses (type SAT) in the African buffalo is relatively well understood, as is FMD ecology (types O and A) in antelope in Central Asia. South American susceptible wildlife (rodents and deer) is experimentally susceptible, but its role in nature has not been studied.
Experimentally, other species, including mice, rats, guinea pigs, rabbits, embryonating chicken eggs, and chickens, may be infected, but this often requires artificial transmission of the virus, and infection of these species has not been implicated in significant spread of FMD.
2.3 Global Distribution
The FMD virus is unevenly distributed throughout the world, reflecting factors such as livestock density and species mix, patterns of husbandry, animal movement and trade, wildlife reservoirs, and incentives and capacities for disease control. The virus exists as multiple serotypes and subtypes with absent or incomplete cross-immunity, likely differences in species predilections and modes of persistence and transmission, and with distributions that are partly based on historical and chance events. The situation is dynamic and affected by viral evolution, waxing and waning host immunity, and changing ecosystems and trading patterns. Despite the propensity and opportunities for the spread of the FMD virus into new regions, comparisons of VP1 gene sequences of viruses (structural protein VP1 of FMD virus is the most frequently studied protein due to its significant roles in virus attachment, protective immunity, and serotype specificity) submitted over many years show a tendency for similar viruses to recur in the same parts of the world. This presumably reflects some degree of either ecological isolation or adaptation. On this basis, the global pool of FMD viruses can be subdivided into seven "regional pools" in which genetically and antigenically distinctive virus strains tend to occur within a defined region. Table 1 provides the seven regional pools that are referred to in this document and what they represent.
|Pool No.||Region Represented|
|Pool 1||Asia east [O, A, Asia 1]|
|Pool 2||Asia south [O, A, Asia 1]|
|Pool 3||Eurasia [O, A, Asia 1]|
|Pool 4||Africa east [A, O SAT1,2,3]|
|Pool 5||Africa west [O, A SAT1,2 ]|
|Pool 6||Africa south [SAT1,2,3]|
|Pool 7||America south [O,A]|
Virus circulation and evolution within these regional virus pools result in changing priorities for appropriately adapted vaccines. Periodically, viruses spread between pools and to free regions.
New methodologies in molecular biology have allowed for the defining of different topotypes of FMD virus. This has permitted the tracing of outbreaks from one region to another, as well as better vaccine matching.
In 2009, the Food and Agriculture Organization (FAO) of the United Nations launched the Progressive Control Pathway for Foot-and-Mouth Disease (PCP-FMD) to assist and facilitate the efforts of countries where FMD is still endemic to progressively reduce the impact of FMD and the load of the FMD virus. The FAO adopted the PCP-FMD as a working tool in the design of FMD country control programs (and some regional programs) and as of May 2011, the World Organisation for Animal Health (OIE) has officially endorsed national FMD programs. The PCP-FMD is a set of FMD control activity stages that, if implemented, will enable countries to progressively increase the level of FMD control with OIE endorsement of their program.
In North America, FMD was last reported in 1929 (U.S.), 1952 (Canada), and 1954 (Mexico). The EU adopted a non-vaccination policy in January 1992, when the disease was considered under control, though sporadic outbreaks did occur in Europe and Asia in 1993, 1994, 1996, and 2000 (and in Russia and Turkey in 1995). Within the past 10 years, acute outbreaks in previously FMD-free countries – including Japan (2000, 2010), South Korea (2000, 2002, 2010-2011), North Korea (2007, 2011), South Africa (2000, 2006, 2007, 2011), Argentina (2001, 2006), Russia (2006, 2007, 2010), Bulgaria (2010-2011), and the UK (2001, 2007) – and FMD's extension to Europe have reinforced the need for permanent FMD awareness. This is due to the continuing FMD threat through illegal imports, the global movements of animals and animal products, and possibly even increased international travel, as people and any contaminated surface may passively transmit the virus.
The OIE website provides a list-of-FMD-free countries, and those countries recognized by the Canadian Food Inspection Agency (CFIA) as FMD-free are listed on the CFIA's website.
FMD is highly contagious. It can spread over great distances through direct contact between infected and susceptible animals, and through indirect contact with contaminated animal products (meat, raw milk, and hides), feed, bedding, and inanimate objects (fomites). Large amounts of virus will be present in tissues, excretions, and secretions (including milk, blood, semen, urine and feces) shortly before the onset of clinical signs in cattle and pigs, and one or two days before the appearance of clinical signs in sheep. Mechanical transfer of infected meat or bones by dogs, foxes, or birds is possible. In Canada's 1952 outbreak, a second nidus of infection in April was attributed to contaminated meat bones that were held in a freezer but later carried off by dogs.
Humans can carry the virus on hands, under fingernails, on clothes, on footwear, on agricultural equipment and machinery, and on any other surface that may have become contaminated with virus. The virus may be introduced from fomites through the skin or mucous membranes of susceptible animals by brushes or surgical instruments, or orally by ingestion of contaminated feed. Mechanical transmission by insects has never been shown experimentally. Birds have to be heavily contaminated to transmit FMD as mechanical vectors. In rare circumstances, birds may be considered mechanical vectors whose droppings can remain infective for 26 hours and whose feathers can remain infective for 91 hours. The risk of transmission of FMD by birds during an outbreak must be considered low, but it cannot be completely ruled out.
Pigs are important amplifiers of the virus (e.g. on average, one pig may excrete as much virus as 60 to 3,000 cattle, depending on the virus strain). Large concentrations of pigs can generate virus aerosols (plumes) that can move over considerable distances, if environmental conditions are suitable. Airborne survival is favoured by cooler weather and a relative humidity of 60% or higher. As cattle – and to some extent, sheep and other ruminants – are most susceptible to airborne FMD infection, compared with pigs that are relatively resistant to infection by that route, airborne spread is usually from pigs to cattle downwind. The 1981 isolation of FMD virus on the Isle of Wight was attributed to airborne spread over the English Channel. The Institute for Animal Health in Pirbright, UK, reports that under ideal conditions, the virus can travel 60 km downwind (based on findings during the 1967 outbreaks on the Cheshire Plains, UK) on land during an outbreak, and up to almost 280 km over water (the Isle of Wight outbreak). Prior to this work by the Institute for Animal Health, it was generally accepted that the maximum aerosol spread over land was 10 km. Although airborne or plume spread can be dramatic, virus plumes are usually not important in the long-distance spread of the disease, unless special, yet poorly understood, conditions occur. However, airborne spread may be significant within a 10- to 20-km radius.
Under normal conditions, airborne transmission from cattle and sheep is unlikely to occur over distances in excess of 3 km. Simulation studies in Australia demonstrated that the domestic threat of wind-borne spread is low. Similarly, Western Canada does not generally have the periods of high relative humidity believed to promote aerosol spread over large areas.
Initial introduction of infection in pigs is primarily by ingestion of contaminated feedstuff, although infection can occur via inhalation in highly contaminated pens or by close contact with infected animals. Cattle are more susceptible to infection by inhalation of aerosols, but can also be infected by direct or indirect contact transmission. Sheep are considered a maintenance host, exhibiting few clinical signs despite being infected and shedding virus. The role of sheep in disease spread was particularly dramatic during the 2001 UK FMD outbreak.
2.4.1 Incubation Period
With natural routes of transmission and high doses of exposure, the incubation period in cattle can be as short as 2-3 days, but with very low doses it can be up to 10-14 days. While spread is occurring within a herd or flock, the typical incubation period is 2-6 days. The incubation period for between-farm spread is more likely 2-14 days. In pigs, clinical signs can be seen within 24 hours, following exposure in highly contaminated pens or direct contact with infected animals. More frequently, clinical signs are seen after two days or more, and the incubation period can be up to nine and even 14 days.
In sheep, the incubation period is usually 3-8 days, but it can be as short as 24 hours following experimental inoculation, or as long as 12-14 days, depending on the susceptibility of the animal, the dose of virus, and the route of infection.
For regulatory purposes, the OIE's Terrestrial Animal Health Code 2011 cites a standard incubation period of 14 days. The EU Directive 2003/85/EC cites 21 days for incubation in sheep and goats, prior to the onset of clinical signs. (This is mainly due to the low expression of clinical signs in these species.)
2.4.2 Persistence in the Environment and Animal Origin Products
The FMD virus is small and non-enveloped (i.e. not covered by a lipid envelope derived from the infected cell). FMD virus is labile in acid and alkaline conditions.
The virus has the following general properties:
- The virus is most stable at pH 7.4-7.6 but will survive for an extended time at pH 6.7-9.5, if the temperature is reduced to 4°C or lower. Outside a pH of 6-10, inactivation is relatively rapid, and below pH 5.0 or above pH 11.0, inactivation is very rapid.
- The virus replicates best at 37 degrees in an infected cell or animal, but outside the living cell, virus stability is best at much reduced temperatures (i.e. at freezing or at 4°C). And it is known that the virus starts to fall apart at temperatures above 30°C-33°C, and that instability increases dramatically at temperatures of 50°C and above. However, the presence of organic material can protect the virus to some degree. For example, while pasteurization can inactivate most foot-and-mouth disease virus (FMDV) in milk, infectious virus may survive in the lipid or cell fraction, even after pasteurization. Similarly, full inactivation in meat products requires at least 70°C for 30 minutes, or more, or a process consistent with canning food.
- Raising the temperature reduces the survival time of any virus present. At temperatures below the freezing point, the virus is stable almost indefinitely. Although there is some variation between strains in resistance to temperature and/or pH stress, exposure to 70°C for 30 minutes is sufficient to destroy most strains.
- The virus appears in all physiological fluids, and therefore all secretions and excretions, for up to four days prior to clinical signs, but this varies with strain. FMDV is distributed throughout the body. Survival of the virus post-mortem depends on the stage of disease at the time of slaughter. The pH changes associated with rigor mortis are normally sufficient to inactivate FMD virus in beef within 24 to 72 hours after slaughter. Freezing suspends the formation of acid, in which case the virus can survive for weeks or months, especially in lymph nodes, blood clots, bone marrow, and viscera.
- Sunlight has little or no direct effect on infectivity; any loss is mainly due to secondary drying and temperature.
- Veterinary Laboratories Agency (VLA) Weybridge provides rough guidelines for virus survival times:
- 50 days in water (only if the temperature is low and the pH is around neutral);
- 74 days on pasture at 8°C-18°C and high relative humidity;
- 26 to 200 days in soil, sacking or straw, depending on climate;
- 35 days on cardboard, wood, or metal that is contaminated with blood;
- 23 and 56 days in milk and semen, respectively;
- 56 days in sausages;
- 20 to 60 days in cheeses made from milk that was not heat-treated;
- 14 to 45 days in milk and butter, if preserved under cold conditions;
- two years in dried skim milk powder;
- up to two weeks on wool (longer if stored at 4°C for seven weeks);
- 21 days on hides;
- 14 days in dry manure (eight days in moist manure);
- 24 weeks in fecal slurries in severe winter conditions;
- at least a month in frozen semen (may survive longer);
- in semen up to four days before clinical signs, and old studies report up to 42 days;
- 34 to 42 days at 12°C-22°C in liquid manure;
- 21 days in wash water from pens;
- 39 days in urine; and
- embryos with intact Zona Pellucida and washed to International Embryo Transfer Society (IETS) standards are free of virus.
FMDV survives almost indefinitely at freezing temperatures. Semen and embryos (unless treated according to the IETS protocol) can retain the FMDV. Destruction of most strains occurs with heating to 70°C for 30 minutes (the OIE's Terrestrial Animal Health Code 2011, section 8.5.34).
2.4.3 Persistent Carriers
A reservoir is defined as an animal in which a disease organism that is pathogenic for some other species lives and multiplies without damaging its host. Currently, no known reservoir for FMD exists, although the African buffalo may carry FMDV for long periods of time and with no or minor clinical disease. An animal is considered a FMD carrier if the virus can be isolated more than 28 days after infection. Ruminants may become carriers, with the virus persisting in the pharyngeal region for up to five years in African buffalo, three years in cattle, nine months in sheep and four months in goats. This carrier state exists in spite of circulating antibodies of natural or vaccine origin. It is estimated that the majority (over 50%) of cattle may become carriers, regardless of their vaccination status. Pigs do not develop a carrier state.
Field experience has shown that some carriers have the ability to cause new outbreaks (e.g. SAT2 FMDV in African buffalo to cattle in Africa), but experiments (with animals other than African buffalo) have been unable to reproduce virus transmission from these carriers to susceptible animals by natural routes. This absence of transmission may be due to carriers shedding much less virus than acutely infected viremic animals, as well as the possibility that the virus that is shed is inaccessible (e.g. wrapped in mucus or partly inactivated by antibodies). There is no known wildlife carrier in North America. The potential presence of live FMDV in vaccinated ruminants, however, has a critical influence on international trade and the debate over vaccine use.
Infection could potentially persist indefinitely in susceptible wild animals. We are only aware of the African buffalo that may be infected with two or three serotypes simultaneously, and virus has been recovered from one animal after more than five years and a herd after almost 30 years. Persistence depends on the population dynamics of the species concerned, including population size, distribution, movement, breeding season, and the introduction of new and susceptible members.
Vaccinated cattle that became infected soon after they were vaccinated did not develop clinical disease. They transmitted the virus to in-contact cattle at seven days, but not at 30 days after infection. FMDV has been isolated from cattle in Zimbabwe 2-3 years after they were vaccinated in the face of a FMD outbreak.
2.4.4 Modes of Introduction and Transmission
A study of 24 FMD outbreaks (McLaws et al., 2007) over the period from 1992 to 2003 found that most (20) involved 150 herds or fewer. Four of the outbreaks were much larger, involving over 2,000 herds in each of the following countries: Argentina (in the year 2000), Uruguay (2001), the UK (2001); and Taiwan (over 6,000 herds in 1997).
Transmission by human has always been important in FMD outbreaks and is still important today. This is evidenced by the suspected methods of incursion of the disease, in the above 24 outbreaks. There was a somewhat even distribution by the following mechanisms: the spread from an infected neighbouring country by non-animal fomites, by illegal animal importation, by swill feeding, by legal animal importation, and by undetermined means. The disease in these outbreaks was most often detected in cattle, on farms by the farmer, and in some other cases, by routine surveillance. FMDV infection is usually first noticed in cattle because of a combination of husbandry practices and the obvious nature of the lesions produced. The time from introduction to detection was more than two weeks in half of the outbreaks; all but one was less than 30 days; and for one outbreak, the time from introduction to detection was over 100 days.
A larger study (Sources of Outbreaks and Hazard Categorization of Modes of Virus Transmission, by the USDA) of over 880 primary outbreaks reported around the world between 1870 and 1993 shows the relative importance of these transmission methods in initiating an outbreak:
- 66% from meat products;
- 22% from airborne sources;
- 6% from livestock importations;
- 4% from fomites; and
- 3% from contaminated vaccines.
Note: the last is not an issue with the antigens held by the North American Foot-and-Mouth Disease Vaccine Bank (NAFMDVB) and not an issue for current high-quality vaccines, as the procedure of virus inactivation for vaccine production has changed from using formaldehyde (incomplete inactivation kinetics) to using aziridines, such as binary ethylene-imine (BEI) effectively and fully inactivating the virus.
It is worth noting that no outbreaks between 1870 and 1993 were attributed to the movement of international travellers, except through their transporting of contaminated fomites or meat products.
Despite the various means of potential transmission, once FMD is introduced into a country, the primary means of spread is directly through movement of infected yet subclinical animals prior to recognition of the disease and by contaminated fomites. It is believed that, during the UK 2001 outbreak, 85%-90% of the infections of new premises could have been prevented by movement controls. Epidemiologists postulate that, had a national standstill been put in place two days earlier than it was, the outbreak would have been 50% smaller. Generally, up to 95% of outbreaks are the result of direct contact between infected and susceptible animals.
FMD is transmitted between animals by inhalation, by entry through cuts and abrasions in the skin or mucosa, or by ingestion of the virus. All secretions and excretions become infectious during the course of the disease, and some contain virus before the animals develop clinical signs. The virus spreads rapidly between animals within an unvaccinated herd. Higher doses of virus are required for oral infection, and ruminants are more resistant to oral infection than are pigs.
Natural aerosols from infected animals contain large, medium, and small particles which are excreted as droplets and droplet nuclei in the breath. When inhaled by recipient animals, a proportion of these particles are deposited in the respiratory system, with the sites of deposition determined mainly by the diameter and mass of the particles. Large particles are deposited in the upper respiratory tract (nares), medium-sized particles in the middle to upper respiratory tract (pharynx, trachea, bronchi), and small particles in the lower regions (small bronchioles and alveoli). The regions in the respiratory tract of recipient animals that will be exposed to virus initially depend on the distance between the recipient animals and the source of airborne virus, and on the amount of air turbulence. Larger droplets are affected by gravity and tend to sediment rapidly. In still air, the rate of fallout of such droplets is high, but turbulence keeps them suspended longer. Particles of less than 6 mm diameter are not greatly affected by gravity and therefore can be transported over long distances. These are the particles that contain high amounts of FMDV and that are most likely deposited in the upper and middle to upper regions of the respiratory tract. Particles landing in the nares are taken backwards toward the pharynx along the mucociliary escalator. Similarly, smaller particles lodging in the trachea and bronchi are taken upwards toward the pharynx.
The earliest sites of FMDV infection and replication in contact-exposed animals appear to be in the pharynx, as detailed above. Viral replication may reach a peak as early as 2-3 days after exposure. Recent data indicate that, after initial replication, the virus enters through regional lymph nodes and into the bloodstream. The greater part of the viral amplification occurs subsequently within the cornified stratified squamous epithelia of the skin (including the feet and the mammary gland) and mouth (including the tongue), or in the myocardium of young animals. Although some viral replication occurs in the epithelia of the pharynx, it is much less than in the skin and mouth during the acute phase of the disease.
Replication in epithelial tissues mainly occurs in the stratum spinosum. It results in the accumulation of intracellular and extracellular fluid, leading to the development of a vesicle. Sometimes, early rupture of this layer results in escape of fluid and a desiccated lesion. Other important secondary sites of replication may include the mammary gland and heart. In young animals, sudden death from myocardial necrosis may occur before the development of vesicles. Apart from the identification of vesicles and heart lesions, pathological examination is important, mainly to establish a potential differential diagnosis of other diseases from FMD.
Once a herd is infected and other animals are exposed to larger amounts of virus, infection can occur via other routes, particularly through minor abrasions to the integument of the feet, mouth, muzzle, nose, and udder.
2.6.1 Clinical Signs
This section describes the classical signs and lesions of FMD. However, a wide range of clinical syndromes may occur, ranging from inapparent disease with minimal lesions to severe clinical disease, depending on the virus strain, the species, and the breed of animal infected.
In cattle, the earliest clinical signs are dullness, poor appetite, and a rise in temperature to 40°C-41°C. In dairy cows, milk yield drops considerably. Salivation and lameness may be observed, depending on the stage of infection. Affected animals move away from the herd, and may be unwilling or unable to stand.
Vesicles may appear inside the mouth, on the tongue, cheeks, gums, lips, and/or palate. At first, they are small blanched areas. Fluid accumulates under these areas to form vesicles, which develop quickly and may reach 30 mm or more in diameter, especially on the dorsum of the tongue. Two or more blisters may coalesce to form a larger one, sometimes covering as much as half of the surface of the tongue. However, intact vesicles are not often seen, because they usually burst easily and within 24 hours, leaving a raw surface fringed by blanched flaps of epithelium. Alternatively, the fluid may drain, leaving an intact area of blanched epithelium. There may be profuse frothy saliva around the mouth and, at intervals, a smacking or sucking sound. The profuse salivation is caused by failure to swallow, not hypersalivation. The lesions heal rapidly over several days.
Lesions on the feet cause acute lameness, a tucked-up stance, a reluctance to move, and intermittent leg flicking as if to dislodge some object wedged between the claws. In the early stages, when affected feet are palpated, they will be warm and painful. Vesicles usually develop first along the coronary bands near the interdigital cleft or at the bulbs of the heel. Vesicles may extend into and through the length of the interdigital space. The epithelium is white and necrotic. Generally, vesicles on the feet take a day or so longer to rupture than those in the mouth. In addition, in the acute stage of the disease, affected animals generally have nasal and ocular discharges. Nasal discharges are usually serous at first, and later become mucopurulent.
Lesions may also occur on the teats and udder, and reduced lactation, mastitis, and abortion are common.
In pigs, reluctance to move, vocalization when forced to get up, and whitening of the coronary band (often of the four feet) are the most significant signs to look for. After blisters occur, the main sign is lameness, due to vesicles on the coronary band and heel. It is especially noticeable if the pigs are housed on hard cement floors, but may be masked if the affected animals are on soft ground. Blisters form around the top of the foot, on the heels, and between the claws. The epithelium may appear blanched, or raw and ragged at the coronary band at the top of the hoofs. As the disease progresses, the pigs' reluctance to move about means that they defecate and urinate in-situ and therefore become very dirty. Thus, foot lesions may also be masked by dirt, necessitating careful examination of feet in muddy or dirty conditions. Affected pigs prefer to lie down and, when made to move, hobble painfully and squeal loudly. Cracks in the heels may take a long time to heal in some animals, causing chronic lameness and weight loss. A pig-adapted virus strain can cause high morbidity and mortality in swine, but does not affect cattle.
Snout lesions may develop but quickly rupture, and mouth lesions are difficult to see. Blisters may develop on the teats and spread over the skin of the mammary glands. Abortion is common and may even be the presenting clinical problem. Significant mortality can occur in piglets due to multifocal myocarditis.
Sheep and Goats
The severity of FMD in sheep and goats varies considerably with the strain of virus, the breed of animal, and environmental conditions. Some strains cause relatively severe lesions, but in most situations, the clinical signs will be mild, and a careful individual examination of a high proportion of the animals in the flock or herd will be required to detect the disease. It has been reported that goats indigenous to East and South Africa generally suffer completely inapparent infection.
Often, the first signs in an infected flock of sheep or herd of goats are a rapidly increasing incidence of lameness, accompanied by some depression, anorexia and pyrexia; or the sudden death of young stock, if lambs or kids are present. The mortality rate among lambs and kids may be high. The cause of death, as in other cases of acute fatal infection in young stock, is heart failure due to multifocal necrosis of the myocardium. In the early stages of disease, milking animals, especially goats, show a sudden drop in production. Vesicles may be present on the teats and vulva. Rams may develop vesicles on the prepuce and be unable or unwilling to serve. Closer examination of lame animals is likely to show that their feet (or it may be only one foot) are hot and painful when handled. Vesicles may be found in the interdigital space, at the bulbs of the heel, and along the coronary band. To see lesions along the coronary band, cleaning of the feet and careful reflection of the hair above the hoof may be required. Vesicles on the outer coronary band are more common than in cattle. Coronary band lesions usually rupture quickly, leaving shallow erosions. FMD may cause severe abortion in sheep.
Early lesions in the mouths of sheep or goats are typically seen as small blanched areas of necrotic epithelium – most often on the dental pad. The superficial necrotic layer is quickly lost, resulting in the formation of erosions. Fluid-filled vesicles are unusual, and if they occur, are very transient, as the superficial epithelium is thin and readily ruptured. Erosions may also be seen on the gums, inside the lips, and occasionally on the tongue. Tongue erosions generally occur as multiple small areas (0.5 to 1.0 cm) on the dorsum.
Lesions in goats are usually fewer in number and less severe than in sheep. In cases where no secondary infection has occurred, the healing of lesions is rapid, especially in the mouth. On the feet, resolution proceeds, and there is scabbing and granulation, both on the coronary band and in the interdigital space. At this stage, it is difficult to be certain that the lesions are those of FMD. However, if there is secondary infection, lameness may continue and be severe, causing affected animals to hobble on their knees or remain recumbent. In milking animals, reduced production and mastitis may be a sequel.
During the 2001 epidemic in the UK, signs in sheep were sometimes so mild that the presence of the disease was revealed only by very close examination of all sheep in a flock.
As indicated in section 2.2 above, early studies in 1974 (Plum Island) confirmed the susceptibility of white-tailed deer to FMD through contact. Red, fallow, and roe deer are experimentally susceptible and exhibit lesions similar to sheep in studies done in the UK in 1974. Persistence of the virus beyond 14 days was uncommon in red or roe deer, but virus was isolated from experimentally infected fallow deer at 63 days. In the 2001 UK outbreak, no positive deer were detected in over 50 samples submitted from farmed and wild deer. One farm had a deer with consistent lesions, with no virus confirmed. It was concluded that deer do not generate significant aerosol infection and offer a low risk to other species.
After 2000, Plum Island did experimental work on bison, elk, pronghorn, and mule deer using serotype O1 Manisa. Bison developed severe disease and evidenced transmission between bison and cattle, and within bison. There was no conclusive evidence of carrier status in bison. Elk developed mild lesions. Transmission occurred between elk and one exposed elk (laboratory evidence), but apparently not between cattle and elk. It was concluded that elk, while susceptible to inoculation with FMD, are not efficient transmitters. Pronghorn had severe foot lesions and mild oral lesions. Transmission occurred between pronghorn and cattle, as well as within pronghorn. Similarly, mule deer developed lesions and mortality during the study. Transmission occurred between mule deer and cattle, and within mule deer. In their natural habitat, pronghorn and mule deer would suffer moderate to severe mortality.
In 2009, using A24 Cruzeiro in feral swine, research at Plum Island found lesions similar to those in domestic swine, although developing later. All feral swine seroconverted in 6-8 days and were confirmed to have cleared the infection by virus isolation (not polymerase chain reaction, or PCR) by 35 days. Similar to domestic swine, feral swine generated aerosols with air samples positive up to day 22 of the experiment.
2.6.2 Aging of Lesions
An effort should be made to find the oldest lesions in the herd, and backdate the time of introduction. Aging of lesions, used to determine the date of entry of the virus into the herd, is more important in the index case to determine the entry into the country, rather than in subsequent cases once the area involved is well defined. Table 2 shows how to estimate the age of FMD lesions in ruminants and pigs, based on those of Kitching and MacKay (1995). The illustrated form may be found in a 2005 publication entitled Foot and Mouth Disease Ageing of Lesions - PDF (1,34 kb) on the UK's Department for Environment, Food and Rural Affairs (DEFRA) website.
|Days of Clinical Disease||Appearance of Lesions|
|Day 1||Blanching of epithelium, followed by formation of fluid-filled vesicles.|
|Day 2||Freshly ruptured vesicles, characterised by a raw epithelium, a clear edge to the lesion and no deposition of fibrin.|
|Day 3||Lesions start to lose their sharp demarcation and bright red colour. 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.|
Australian Veterinary Emergency Plan (AUSVETPLAN) 2010
Lesions in sheep are too transient to be used for gauging the time of infection.
Morbidity is usually very high (close to 100%) in fully susceptible cloven-hoofed domestic animals. However, it does depend on the conditions under which the animals are kept. Consequently, sheep kept under intensive conditions indoors may have a high morbidity, while sheep kept under low-intensity conditions outside may have a much lower morbidity. Morbidity in susceptible wildlife is quite variable, from high to very low, depending on the FMD virus subtype and the species involved.
However, the disease may also be mild or inapparent, particularly in Bos indicus (zebu) breeds.
In tropical areas, some cattle that have recovered from acute FMD suffer from a wasting syndrome in which they have a staring coat (a dry haircoat lacking in luster, usually carrying dandruff or scurf) and dyspnea. They have been called "hairy panters." The underlying pathology has not been determined, but its link to hyperactive thyroid-adrenal function has been hypothesized.
Mortality in adult animals is usually low to negligible. Up to 50% of calves may die due to cardiac involvement and complications such as secondary infection, exposure, or malnutrition. Mortality in suckling pigs and lambs ranges from 20% to 75% in the most extreme cases. Mortality is highly age-dependant; in fact, for animals under four weeks of age, mortality is high, and decreases rapidly as animals get older (> 4 weeks). Deaths are generally associated with cardiac lesions. FMDV can cause transplacental infection and death in fetal lambs.
2.6.4 Laboratory Diagnosis
During an initial investigation, submit samples to the National Centre for Foreign Animal Disease (NCFAD). However, to avoid possible delays in transporting samples and to ensure an early preliminary diagnosis, submit duplicate samples to the nearest Canadian Animal Health Surveillance Network (CAHSN) laboratory that is approved for FMD testing. Consultation with your Area FAD specialist is required prior to sending samples. Final index case diagnosis, positive or negative, is the responsibility of the NCFAD.
Laboratory tests are divided into what CFIA inspectors can select in the Laboratory Sample Tracking System (LSTS), along with those additional tests that the laboratory may run to confirm a diagnosis.
CFIA inspectors are to select only the following two laboratory tests when submitting samples for vesicular disease investigation:
- virus isolation (FMD-ISOL; Foot and Mouth Disease – Isolation); and/or
- 3 ABC competitive ELISA, which is serotype independent, as it detects antibodies to a relatively conserved non-structural protein in serum (FMD-C_ELI; Foot and Mouth Disease – Competitive ELISA).
It is required that a complete history accompany any samples submitted to NCFAD, including any samples received as lab referral.
A positive FMD diagnosis for the index case normally will be based on virus isolation (VI) in cell culture only. The demonstration of nucleic acid specific to FMD by NCFAD in samples of tissue or fluids will also be considered positive for FMD, if accompanied by either the presence of clinical signs specific for FMD in susceptible animals or a strong epidemiological link to a confirmed case.
Subsequent to the index case, a positive diagnosis will be based on VI in cell culture or demonstration of nucleic acid specific to FMD in samples of tissues or fluids, by reverse transcriptase (RT) RT-PCR, or by detection of FMD viral antigen by a double antigen sandwich (DAS) ELISA. The RT-PCR and the DAS-ELISA will be performed, at the discretion of NCFAD, on any vesicular submission, even without a request from CFIA inspectors.
The time needed to confirm the diagnosis of the index case depends on the number, volume and quantity, and the quality and type of samples received by the laboratory.
All vesicular submissions should only be submitted under Reason for Test as Disease Investigation or Lab Referral. Under Disease Category, choose Foreign Animal Disease – Mammalian. Under Submission Priority, select either confirmatory Negative or High Risk. No other choices are acceptable.
Preclinical detection of FMD is possible with conventional RT-PCR or real-time (kinetic) RRT-PCR (serum, tissues, or vesicular fluid), which will be used after the index case.
2.6.5 Differential Diagnosis
AUSVETPLAN provides a comprehensive list of diseases where signs or lesions are somewhat similar to those of FMD:
- Exotic viral diseases: swine vesicular disease, bluetongue, vesicular stomatitis, rinderpest, peste des petits ruminants, vesicular exanthema of swine.
- Endemic infectious diseases: mucosal disease (BVD), contagious ecthyma (ORF), infectious bovine rhinotracheitis/infectious pustular vulvovaginitis, bovine papular stomatitis, malignant catarrhal fever, bovine ulcerative mammalitis, pseudocowpox, dermatophilosus infection, idiopathic vesicular disease. (The latter is a relatively new differential, which can be caused by swine enteroviruses, teschoviruses, and Seneca Valley virus [e.g. responsible for the FMD suspect pigs in Manitoba 2007]).
- Dermatitis: scalding, chemicals, acid/alkaline substances, contact dermatitis, photosensitization.
- Phytophotodermatitis: contact with certain plants containing furocoumarins (especially umbelliferae – parsnips, celery, parsley).
- Trauma and lameness: laminitis, hoof abscess, foot rot, bad floors, new concrete, mud.
2.7 OIE Definition of FMD Virus Infection and Eradication Strategies
The OIE's Terrestrial Animal Health Code 2011, section 8.5.1, defines the occurrence of FMD virus infection as follows:
- FMD virus has been isolated and identified as such from an animal or a product derived from that animal; or
- viral antigen or viral ribonucleic acid (RNA) specific to one or more of the serotypes of FMD virus has been identified in samples from one or more animals, whether showing clinical signs consistent with FMD or not, or epidemiologically linked to a confirmed or suspected outbreak of FMD, or giving cause for suspicion of previous association or contact with FMD virus;or
- antibodies to structural or non-structural proteins of FMD virus that are not a consequence of vaccination, have been identified in one or more animals showing clinical signs consistent with FMD, or epidemiologically linked to a confirmed or suspected outbreak of FMD, or giving cause for suspicion of previous association or contact with FMD virus.
The OIE recognizes four strategies (Table 3) to eradicate FMD in domestic livestock (Terrestrial Animal Health Code 2011, section 8.5.47). Three of these include stamping-out (the slaughter of clinically affected and in-contact susceptible animals), with or without emergency vaccination and with or without the slaughter of vaccinated animals.
|Slaughter of all clinically affected and in-contact susceptible animals. (Stamping-out)||UK 2001|
|Slaughter of all clinically affected and in-contact susceptible animals and vaccination of at-risk animals, with subsequent slaughter of vaccinated animals. (Stamping-out modified with emergency vaccination-to-slaughter)||Japan 2010|
|Slaughter of all clinically affected and in-contact susceptible animals and vaccination of at-risk animals, without subsequent slaughter of vaccinated animals. (Stamping-out modified with emergency vaccination-to-live)||South Korea 2010-2011|
|Vaccination used without slaughter of affected animals or subsequent slaughter of vaccinated animals. (Emergency vaccination-to-live without stamping-out)||Ecuador 2011,
South Korea 2010-2011
The use of vaccination as a control strategy is discussed further in section 2.8.3 and section 3.3.6.
2.8 Natural Resistance and Immunity
2.8.1 Innate and Passive Immunity
In endemic countries, zebu breeds of cattle (Bos indicus) usually show milder clinical signs in comparison to introduced European breeds (Bos taurus). However, they can still become infected and transmit infection. Camelids, apart perhaps from Bactrian (two-humped) camels, appear to have a high natural resistance to infection. Very young animals tend to have higher mortality due to myocarditis that can be caused by FMD, unless protected by passive colostral immunity. Young animals, once past the first four weeks of age when they are highly susceptible to myocarditis, tend to get a much milder form of FMD compared with their adult herdmates. In fact, six-month-old calves may show mild clinical signs, whereas adult milking cows or heavy bulls may show severe vesicular disease.
2.8.2 Active Immunity
The immunity conferred by natural infection or vaccination is largely serotype-specific. There is variable cross-protection between strains of FMD virus within the same serotype, and none between different serotypes. Animals can be infected by multiple serotypes. Ruminants, but not pigs, can develop a carrier status in which virus persists in the pharynx in the presence of circulating antibody. (Refer to section 2.4.3.)
Inactivated FMD vaccines have been used successfully in many parts of the world to control, and at times eradicate, FMD. However, earlier improperly inactivated vaccines contributed to the spread of the disease. In the early years, the primary method to inactivate the FMD virus was formalin inactivation. This procedure was discontinued in the late 1980s, as problems occurred with complete inactivation, even with prolonged exposure times. A number of better methods are being employed to ensure complete inactivation. Therefore, it is necessary to acquire quality vaccines that have been safety tested before being used. The NAFMDVB maintains a supply of emergency quality vaccine antigen concentrates (VAC) that have at least twice the potency of commercial vaccine; these are targeted for testing every 5-10 years to ensure that quality vaccines are available. Most of the newer vaccines use a double oil-in-water emulsion which has low viscosity, low tissue reactivity, and a higher potency, compared to previous vaccines.
A vaccine will stimulate a predominantly humoral immune response and, in cattle, offers good protection against disease after live virus challenge, using the antigenically related strain of FMD virus. To achieve maximum advantage from a FMD vaccine, the virus strain used to produce the vaccine must share as many antigenic characteristics with the outbreak strain as possible. Resistance to clinical disease induced by these vaccines wanes rapidly after 4-6 months, which warrants repeat vaccination at intervals to maintain an acceptable protection level.
FMD virus frequently mutates during natural passage through various animal species, or by passage through animals with varying levels of antibody. If vaccination is used, it is necessary to check the strain variation of field isolates and to be prepared to adjust the viral composition of the vaccine accordingly during the course of a prolonged outbreak.
Emergency vaccination for FMD is no longer a last-resort measure in previously free countries, as evidenced by the two recent experiences in Japan and Korea. Both used FMD vaccines to gain control of outbreaks that could not be controlled using stamping-out alone. Given the high-quality, reasonably priced vaccines that are now available, emergency vaccination has become an alternative that warrants consideration. Concurrent with this development, the OIE has officially recognized the four strategies for control (Table 3), thus making emergency vaccination more appealing. This appeal may be directly linked to the availability of effective diagnostic tools, substantiating that vaccinated animals, or meats and other products obtained from vaccinated animals, are free from pathogens and can be traded safely. The EU commissioned an expert group that developed the Strategic Planning Options for Emergency Situations or Major Crises, recommending that emergency vaccination be a vaccination-to-live strategy, which means that vaccinated animals are kept to the end of a normal production cycle and that their meat and other products are marketed.
Implementing vaccination strategies can reduce animal destruction losses; however, it complicates the process of establishing freedom from FMD following an outbreak. The availability of quality diagnostic tests recognized by the OIE to differentiate infected from vaccinated animals (DIVA) has been crucial to proving freedom from disease. It also allows reinstatement of FMD-free without vaccination status by the OIE following six months versus three months with a vaccinate-to-slaughter strategy. The remaining difficulty could be the unwillingness of trading partners to accept a vaccinate-to-live strategy, or rather their unwillingness to accept the evidence provided to show absence of active virus infection (i.e. absence of risk).
Development of genetically engineered vaccines that contain virus protein subunits is in progress but is still in the experimental stages, as is the use of synthetic polypeptide fragments of the immunogenic section of the FMD virus. There is no indication that a new-generation vaccine will become available in the immediate future. Until such bioengineered and synthetic vaccines are available, correctly inactivated and licensed FMD vaccines are the best option, if vaccination must be employed.
2.9 Public Health
FMD is not considered zoonotic at the exposure levels that would be experienced by response personnel. In 1968, the World Health Organization (WHO) dropped FMD from its list of zoonoses, and it is considered a rare human disease, rather than a public health problem.
FMDV infections in humans are very rare, with about 40 cases reported in the literature since 1921. The majority of these cases were diagnosed without laboratory confirmation and are thus viewed with scepticism by some FMD researchers. Most of these cases existed as subclinical infections. Humans are believed to become infected through skin wounds or through the mucosa by handling infected livestock, contacting the virus in the laboratory, or drinking infected milk. Infection does not occur through eating cooked or normally prepared meats. These rare infections are temporary and mild, and FMD is not considered a public health problem.
More frequently, humans are afflicted with hand, foot and mouth disease (HFMD), caused by human intestinal viruses of the Picornaviridae family. The most common strains causing HFMD are Coxsackie A virus and Enterovirus 71 (EV-71).
A FMD outbreak may nevertheless have public health implications, given the mental health effects on personnel and individuals associated with the response effort, particularly depopulation and disposal. The effects of a FMD outbreak on mental health may include post-traumatic stress disorder and depression. Support should be made available to those involved, particularly responders and owners of affected livestock.
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