Foot and Mouth Disease

FMD FMDV

Morphology

• Very small (25nm) +ss RNA virus, unenveloped
• 12 capsomeres (1 per vertex)
• 5 subunits per capsomere
• 1 molecule of virus protein (VP) per subunit
• 4 virus proteins (VP1-VP4)
• VP1 is the attachment protein

Antigenicity

• FMDV was the first animal virus in which serotypes were isolated
• To date, there are (important in bold):
  • Oise (O)
  • Allemagne (A)
  • C (also German)
  • South African Territories (SAT) 1, 2, and 3
  • India (Asia-1)
• Each serotype has at lease three subtypes
• Serotype and subtype can be quickly identified by ELISA using guinea pig antisera
• All isolates are virulent

Hosts

• Cloven-hoofed animals, EXCLUDING the horse
  • Cattle
  • Sheep
  • Goats
  • Pigs
  • Deer
  • Elephants
  • Wild ruminants: buffalo, kudu, impala, etc

Pathogenesis

• Primary replication in the upper respiratory tract, tonsils, or upper alimentary tract
• Aerosol excretion during this incubation period
• Viremia
• Virus targets stratum spinosum of stratified squamous epithelia and mucus mebranes
• Secondary vesicles appear after incubation of 2-14 days
• Appearance of lesions by age:
  • 0-2 days: unruptured vesicles
  • 1-3 days: newly ruptured vesicles with adherent epithelia at margins
  • 3-7 days: ruptured vesicles, loss of epithelia, no marked fibrous margin
  • 7-10+ days: open lesions with marked fibrous margin
• Lameness
  • Also produces cutaneous erosions in interdigital cleft, at coronet and bulbs of heals
  • These feet lesions often take a long time to heal as secondary bacterial infections may ensue and produce true deep ulcerative dermatitis
• Teats on animals that are suckling may also develop vesicles
• In the young, without maternal antibody, virus will localize in the heart and cause death by myocarditis
• FMDV causes loss of condition and productivity but is NOT typically fatal

Pathogenesis by species

• Pigs and Sheep:
  • Lesions less obvious, but vesicles around nose, mouth, and coronary band
  • Pigs have vesicles on snout, which are quickly traumatised to leave an eroded lesion
  • Lesion at coronary band means infection is usually less than a week old
  • Lesions grow down claw at a rate of 1mm per week
• Cattle
  • Lesions are seen inside mouth, around muzzle, in the interdigital cleft, around coronary band, and on teats
  • Excessive salivation, anorexia, secondary mastitis
  • PM: lesions in oesophagus and forestomachs

Epidemiology

• Highly contagious virus that is spread by aerosol, saliva, infected swill, direct contact, and fomites
• Pigs produce 3000 times more aerosol virus than cows
• Cows are much more susceptible to infection than pigs
  • Persistent infection of cattle can occur in unkeratinized lesions, but subclinical carriers do not usually transfer infection
  • Subclinical buffalo CAN transmit the disease
• 1967 + 2001 major outbreaks in UK
• Still widespread in many parts of world especially S. America, far East
• Foot and Mouth disease is NOT a highly fatal disease: approximately 5% mortality (usually young animals); older animals recover

Diagnosis

• Clinical signs for provisional diagnosis
• Confirmed by ELISA for virus antigen
  • ELISAs are serotype-specific
• Should soon be replaced by immunochromatography-bedside ELISA to allow on-farm diagnosis
• Virus isolation can also be performed in kidney culture cells, and then serotyped by ELISA
• Serology for virus antibody can determine past infection
  • ELISAs used to detect subclinical carrier sheep
  • Cannot be done on vaccinated animals
• RT-PCR has been suggested for on-farm diagnosis, but has flaws:
  • RNA is readily degraded by tissue enzymes
  • RNA must be purified before converting to DNA for PCR
  • False positives can occur easily by contamination with previously amplified DNA
• May see animals that have discoloration of tongue due to having had FMD
  • In these cases take scraping of retropharyngeal region, put scrapings in transport medium and send for testing

Control

• Recovered animals show immunity ONLY to the subtype of first exposure, and even this is relatively short-lived
• Re-exposure to the original serotype after immunity as waned will still result in virus excretion, even without clinical symptoms
• Infection by a second serotype will result in clinical disease
• For these reasons, vaccination is not practiced in the UK
  • Further, vaccination would mean a loss of meat export markets

Prevention in the UK

• Imported stock must come from virus-free countries that DO NOT vaccinate
• Meat imported from endemic countries must be de-boned

In an Outbreak

• ANY sign of lesions in a susceptible animal is NOTIFIABLE to the Divisional Veterinary Officer and local police
• Once diagnosis is confirmed, all animals on the premises must be slaughtered and incinerated
• Further disinfection of the premises
• Movement is controlled within a 10-mile radius
• Follow-up serology must be performed to ensure no spread has taken place
• Ring vaccination with relevant subtype to create a barrier of immune animals (although this was not done in the 2001 outbreak)

In Endemic Areas

• Disease cannot be prevented by slaughter due to large numbers of carrier stock
• Annual Inactivated whole virus vaccination using local subtypes
  • Inactivated by azuridines, using alhydrogel adjuvant for cows, and oil for pigs
  • Attenuated virus reverts to virulence
  • Subunit vaccines ineffective
  • Expensive
  • 2 initial injections at 4 months (if dams vaccinated), followed by boosters every 6-12 months
  • Induces virus-neutralizing antibodies
• Vaccination DOES NOT render meat harmful to consumers, but does affect when it can be exported

Pathology

Gross

1. Initially - hyperaemia of mucosa (e.g. catarrhal inflammation) then within 12 hours produces fluid filled vesicles on dorsum of tongue, may be other places
2. Small vesicle coalesce to produce big ones -i.e. Bullae
3. Very quickly rupture; epithelium appears dirty grey in colour because of necrosis - sloughed skin, very good for diagnosis
4. Leave painful, hyperaemic epithelium
5. Looks like "ulcer "with ragged edge but not a true ulcer as stratum germinativum retained and will rapidly heal completely in about 2 weeks unless becomes secondarily infected

Microscopic lesions

• Degeneration of prickle cells
• Cells "balloon" as fill with fluid and then die to produce vesicle containing straw coloured or clear fluid

For more information

DEFRA

• Caused by Apthovirus
• Main presentation are vesicles
• May also involve skeletal and heart muscle
• Grossly:
  • Yellow streaks and grey foci
• Histologically:
  • Segmental myofibre necrosis
  • Infiltration of lymphocytes and neutrophils