Foot-and-Mouth Disease (FMD)

Etiology

• Causative agent: Foot-and-mouth disease virus (FMDV), a member of the genus Aphthovirus, family Picornaviridae
• Virus structure: Small, non-enveloped, icosahedral, single-stranded RNA virus (positive sense). Buoyant density in CsCl: 1.43 g/mL. Acid labile - particles are unstable below pH 6.8
• Serotypes: 7 immunologically distinct serotypes - O, A, C, Asia 1, SAT 1, SAT 2, SAT 3 (SAT = Southern African Territories). Serotype C may now be extinct in the wild. More than 60 subtypes exist across these serotypes
• Cross-immunity: Immunity to one serotype does NOT protect against others - this complicates vaccination
• Host range: Primarily cloven-hoofed animals (order Artiodactyla) - cattle, pigs, sheep, goats, buffalo, deer, antelope, bison, giraffe, Bactrian camels, and wild artiodactyls. The virus has been recovered from at least 70 mammalian species. Asian elephants are also susceptible
• Zoonotic potential: Humans can be infected via direct contact or ingestion, but human disease is rare and usually mild (fever, salivation, vesicles in the oropharynx and on the feet)
• Epidemiology: Endemic in parts of Asia, Africa, the Middle East, and South America. North America, Australia, and much of Western Europe are FMD-free

Pathogenesis

1. Entry: The primary site of infection is the mucosa of the upper respiratory tract (nasopharynx). Virus also enters via skin abrasions and the oral/GI mucosa
2. Primary replication: FMDV replicates in epithelial cells at the site of entry, typically in the pharyngeal mucosa (pharynx is the initial replication site)
3. Viremia: Virus spreads via the bloodstream (viremia) to distant epithelial sites - the tongue, dental pad, lips, nares, coronary bands of the hooves, interdigital skin, teats, and udder
4. Vesicle formation: At these sites, viral replication causes intracellular and intercellular edema within the stratum spinosum of the epidermis, forming characteristic fluid-filled vesicles (aphthae). These vesicles rupture, releasing large quantities of virus and causing painful erosions
5. Shedding: During viremia and after vesicle rupture, virus is shed in enormous quantities through breath (aerosol), saliva, milk, urine, feces, semen, and vesicular fluid - making it extremely contagious
6. Carrier state: Cattle and some other species can become persistent carriers - virus can persist in the pharynx for up to 8 months post-infection, even in the absence of clinical signs. These animals serve as hidden foci of infection
7. Outcome: Mortality is usually low in adult animals but can reach 70% in young animals (myocarditis - "tiger heart" lesion). Survivors suffer significant production losses in milk and meat

Diagnosis

Clinical/Field Diagnosis

• Sudden onset fever, anorexia, salivation, and lameness in cloven-hoofed livestock
• Vesicles (blisters) on the tongue, dental pad, lips, gums, interdigital skin, coronary bands, and teats
• Characteristic "smacking" lip sound and drooling in cattle

Laboratory Diagnosis

• Samples: Epithelial tissue from fresh, unruptured vesicles is optimal; also esophageal-pharyngeal (OP) fluid ("probang" samples) for carrier detection
• All FMD laboratory work must be conducted in high-biosafety containment facilities (BSL-3 Ag or equivalent)
• Immediate reporting to national veterinary authorities is legally mandatory in most countries

Control

In FMD-Free Countries (e.g., USA, Australia, UK)

• Stamping out policy: Rapid slaughter (culling) of all infected and in-contact susceptible animals
• Carcass disposal: Incineration, deep burial, or rendering on or near the infected premises
• Movement restrictions/quarantine: Strict movement bans on animals, animal products, vehicles, and personnel from affected areas
• Decontamination: Premises disinfected with acidic (citric acid) or alkaline (sodium carbonate) disinfectants; people decontaminate clothing
• Surveillance: Susceptible animals introduced to the area after 30 days - if no disease develops, the area is declared safe
• Import restrictions: Prohibition on importing fresh meat and potentially infective animal products from FMD-endemic countries

In Endemic Countries

• Systematic vaccination: Formalin-inactivated (killed) vaccines prepared from virus grown in tissue culture; must be serotype-matched
• Vaccines do not produce long-lasting immunity, so repeated booster doses are required
• New generation vaccines: Recombinant DNA-based and virus-like particle (VLP) vaccines under development to provide better, longer immunity and allow DIVA (Differentiating Infected from Vaccinated Animals) testing
• Biosecurity measures: Quarantine of new animals, restricted access to farms
• Surveillance and early reporting: Rapid detection is key; sequencing of outbreak viruses can trace source and transmission pathways
• NSP (Non-Structural Protein) ELISA: Used in vaccinated populations to distinguish vaccinated-but-not-infected animals from those that were actually infected - important for demonstrating FMD-free status

Global Framework

• WOAH (formerly OIE) coordinates international FMD control under the Progressive Control Pathway (PCP-FMD)
• Countries achieve progressive stages from "uncontrolled endemic" to "provisionally free" to "free without vaccination"