Foot-and-Mouth Disease (FMD) in Cattle

1. Etiology

• A small, non-enveloped, single-stranded positive-sense RNA virus
• Acid-labile: unstable below pH 6.8, inactivated by acids and alkalis
• Buoyant density in cesium chloride: ~1.43 g/mL
• 7 serotypes: O, A, C, Asia 1, SAT 1, SAT 2, SAT 3 (Southern African Territories)
  • Serotype C is considered possibly extinct in the wild
  • Over 50 subtypes exist across these serotypes
• No cross-protection between serotypes; immunity after natural infection is short-lived
• Recovered from at least 70 mammalian species

• Cloven-hoofed artiodactyls: cattle, pigs, sheep, goats
• Wildlife: African buffalo, bison, giraffes, Bactrian camels, deer, antelope
• Asian elephants are also susceptible
• Horses, dogs, and cats are NOT susceptible

2. Epidemiology and Transmission

• Endemic in parts of Africa, the Middle East, Asia, and South America
• Free countries include the USA, Australia, Canada, UK (after 2001 outbreak), most of Europe

• Direct contact - nose-to-nose, contact with vesicular fluid, secretions, excretions
• Aerosol - especially from pigs, which amplify and excrete enormous quantities of virus; aerosols can spread several kilometers under favorable meteorological conditions
• Fomites - contaminated equipment, vehicles, clothing, feed
• Animal products - movement of infected live animals, raw meat, unpasteurized milk
• Biological products - contaminated vaccines, embryos

3. Pathophysiology

• Virus enters via the respiratory tract (inhalation) or through abraded skin/mucous membranes
• Primary replication occurs in the epithelium of the pharynx (specifically the dorsal soft palate in cattle)
• A primary vesicle may form at the site of entry

• After local replication, the virus disseminates via the bloodstream (viremia) - this phase lasts roughly 1-4 days and is when the animal is most infectious
• During viremia, virus spreads hematogenously to target tissues

• Virus replicates in stratum spinosum of stratified squamous epithelium
• Cytopathic effect: epithelial cell death, intercellular edema, and intracellular edema cause cleavage between the stratum spinosum and stratum corneum
• Fluid accumulates to form macroscopic vesicles (blisters) filled with clear/straw-colored fluid containing very high viral titers
• Vesicles rupture, releasing virus and leaving painful, raw erosions

• In calves <6 months: virus causes direct myocarditis - necrosis of myocardial fibers produces pale streaks ("tiger heart"), leading to acute heart failure and sudden death, sometimes before vesicles even appear

• FMDV encodes proteases (Lpro, 3Cpro) that cleave host innate immune signaling factors, suppressing type I interferon responses
• The high antigenic variability across serotypes allows reinfection with different serotypes

4. Clinical Signs and Symptoms in Cattle

• High fever: ~40-41°C (104-106°F)
• Depression, anorexia, cessation of rumination
• Sudden drop in milk production in lactating cows
• Animals may appear dull and separate from the herd

• Profuse salivation - ropy, frothy saliva hanging from the lips (very characteristic)
• Characteristic smacking/sucking noises due to oral pain
• Vesicles (blisters 1-2 cm or larger) on the tongue, dental pad, hard palate, gums, and inside the lips
• Ruptured vesicles leave raw, painful erosions that heal within 1-2 weeks

• Stamping of feet, reluctance to move, preference to lie down
• Vesicles at the coronary band and in the interdigital cleft
• Lameness - can be severe
• Ruptured lesions may become secondarily infected with bacteria, leading to chronic lameness, foot rot, or even loss of the hoof

• Vesicles on the teats of lactating cows
• Predisposes to mastitis via secondary bacterial infection
• Milk production may remain suppressed for weeks to months after recovery

• Nasal discharge
• Weight loss, loss of condition
• Young calves (<6 months): sudden death from myocarditis (may die before oral/foot lesions appear)

• Most adult animals recover in 2-3 weeks
• Persistent problems: chronic lameness, reduced milk production, poor body condition, reduced fertility

5. Diagnosis

Clinical Suspicion

• Any vesicular disease in cloven-hoofed animals must be immediately investigated as a potential FMD case (it is an OIE/WOAH List A disease requiring immediate notification)
• Differential diagnoses to exclude: vesicular stomatitis, malignant catarrhal fever, mucosal disease/BVD, bluetongue, epizootic hemorrhagic disease, contagious ecthyma (orf), rinderpest (eradicated)

Sample Collection

• Vesicular epithelium and fluid are the best samples
• Nasopharyngeal swabs, blood (EDTA and serum), oesopharyngeal (OP) fluids (probang samples)

Laboratory Tests

• DIVA (Differentiating Infected from Vaccinated Animals): using NSP-ELISA is important in countries using vaccination, to distinguish natural infection from vaccine response

6. Treatment

• Wound care: Clean and disinfect oral and foot lesions; antiseptic sprays or footbaths with copper sulfate, formalin, or iodine solutions
• Pain relief: NSAIDs (e.g., flunixin meglumine, aspirin) to reduce fever and pain, encourage eating and movement
• Antibiotics: Not for FMDV itself, but for secondary bacterial infections (e.g., mastitis, foot rot) - commonly penicillin/streptomycin or tetracyclines
• Nutritional support: Soft, palatable feed (e.g., silage, soaked hay) for animals with oral lesions; access to clean water
• Rest and housing: Separate affected animals; reduce standing time; soft bedding to protect feet
• Lactating cows: Continue milking to prevent mastitis; disinfect teat dip cups between animals
• Young calves: Monitor closely for cardiac complications; high mortality risk

Note: In FMD-free countries (USA, UK, Australia), the standard control policy on detection of an outbreak is slaughter of all infected and contact animals ("stamping out") rather than treatment, combined with strict quarantine and movement controls.

7. Prevention and Control

Vaccination

• Inactivated (killed) virus vaccines are the primary preventive tool in endemic regions
• Must match the circulating serotype(s) - no cross-protection between serotypes
• Provides protection for approximately 6 months - requires biannual boosters
• Emergency ring vaccination used during outbreaks to create an immune buffer zone
• Limitations: Does not prevent carrier state; limited shelf life; requires cold chain
• Emerging technology (2024-2025): mRNA vaccines (Australia announced domestic production plans in 2024) and recombinant subunit vaccines are under development, offering faster production, no live virus risk, and DIVA compatibility
• Formalin-treated tissue culture vaccines have been used for decades (as noted in Jawetz Melnick - Adelberg's Medical Microbiology, p. 549), though recombinant approaches are advancing

Biosecurity Measures

• Movement controls: Strict regulation and restriction of animal, vehicle, and personnel movement
• Border controls: Prohibition of importation of potentially infective materials (fresh meat, live animals, untreated hides) from FMD-endemic regions - the foundation of freedom in the USA and Australia
• Farm hygiene: Regular disinfection of premises, vehicles, and equipment; footbaths at farm entry points (sodium carbonate or citric acid are effective FMDV disinfectants)
• Quarantine: Immediate isolation of suspected cases; movement bans within affected zones
• Surveillance: Passive surveillance (farmer/vet reporting of clinical signs) and active surveillance (serological testing in target populations)

Outbreak Response (FMD-free countries)

1. Immediate notification to competent authority and WOAH (mandatory)
2. Stamping out - slaughter of infected and in-contact animals
3. Quarantine of premises; movement ban on animals, products, people
4. Trace-forward and trace-back epidemiological investigation
5. Decontamination of premises, equipment, and vehicles
6. Surveillance zone established around outbreak; susceptible animals monitored for 30 days post-slaughter before area declared safe
7. Emergency vaccination may be used as a complementary measure

Zoonotic Risk

Summary Table

• Merck Veterinary Manual - FMD in Animals (updated Feb 2026)
• WOAH - Foot-and-Mouth Disease
• Jawetz, Melnick & Adelberg's Medical Microbiology, 28th Ed., p. 549
• Arzt J, Sanderson MW, Stenfeldt C. Foot-and-Mouth Disease. Vet Clin North Am Food Anim Pract. 2024 Jul. [PMID: 38462419]
• Stenfeldt C et al. Pathogenesis of FMDV: current understandings and knowledge gaps. Vet Res. 2025. [PMID: 40524230]