Foot-and-Mouth Disease (FMD)

Note: "FMD" classically refers to the animal disease caused by Aphthovirus (a picornavirus affecting cloven-hoofed animals). It is distinct from Hand-Foot-and-Mouth Disease (HFMD), a human disease caused by coxsackieviruses/enteroviruses. Both are covered below.

Part A: Foot-and-Mouth Disease (FMD) - Classic Animal Disease

Etiology

• Caused by Aphthovirus, a member of the family Picornaviridae
• Small, nonenveloped, single-stranded RNA virus
• Acid-labile: particles are unstable below pH 6.8 (cesium chloride buoyant density: 1.43 g/mL)
• At least 7 serotypes (O, A, C, SAT1, SAT2, SAT3, Asia-1) with >50 subtypes - this antigenic diversity complicates vaccine development
• Virus is highly resistant to inactivation in the environment; excreted material remains infectious for extended periods

Pathogenesis

• Reservoir and hosts: Cloven-hoofed animals - cattle, sheep, pigs, goats; virus recovered from at least 70 mammalian species
• Transmission: Highly contagious via direct contact, ingestion of contaminated material, or inhalation of aerosols
• Disease course in animals:
  • Viremia is present in early stages; disease is most contagious at this point
  • Vesicle formation occurs in the mouth and on the feet; when vesicles rupture, large amounts of virus are liberated
  • Many cattle remain foci of infection for up to 8 months after recovery
  • Immunity after infection is short-lived
  • Mortality is usually low but can reach 70% in some outbreaks
• In humans: Rare; transmitted by direct contact or ingestion. Manifests as fever, salivation, and vesiculation of oropharyngeal mucous membranes and skin of the feet
• Typical disease can be experimentally reproduced by inoculating virus into foot pads

Diagnosis

• Clinical: Fever + characteristic vesicular lesions on mouth/feet in cloven-hoofed animals
• Virological:
  • Virus isolation from vesicular fluid, epithelial tissue, esophago-pharyngeal (OP) fluid
  • Serotyping is essential (guides vaccine selection) - done by complement fixation or ELISA
  • RT-PCR for rapid detection and serotyping
  • Antigen-detection ELISA (most widely used in field labs)
  • Serology: virus neutralization test, liquid-phase blocking ELISA
• Key point: Because of the multiple serotypes, lab confirmation + typing is mandatory before vaccination

Control

• Jawetz, Melnick & Adelberg's Medical Microbiology, 28e, p. 549

Part B: Hand-Foot-and-Mouth Disease (HFMD) - Human Enteroviral Disease

Etiology

• Caused by Coxsackievirus A16 (most common), Enterovirus A71 (EV-A71), and Coxsackievirus A6 (emerging cause of severe disease)
• Also: Coxsackievirus B1 and other Enterovirus A species
• Family Picornaviridae, genus Enterovirus
• Not related to the animal FMD Aphthovirus

Pathogenesis

• Humans are the only reservoir
• Transmission: fecal-oral route, respiratory droplets, direct contact with lesion fluid
• Predominantly affects children under 5 years; >80% of infections occur in those under 20
• Virus replicates in the oropharynx and gastrointestinal tract, then spreads hematogenously to skin and other organs
• EV-A71 is associated with severe neurological complications: brainstem encephalomyelitis (rhombencephalitis), acute flaccid myelitis - can be life-threatening
• Coxsackievirus A6 causes a more widespread rash and is associated with onychomadesis (nail shedding) 1-2 months post-infection

Diagnosis

• Low-grade fever, malaise, anorexia, oral soreness
• After 1-2 days: oral macules rapidly vesiculate and ulcerate (buccal mucosa, tongue, palate)
• Exanthem in ~2/3 of patients: tender 3-7 mm vesicles on dorsum of hands and feet, especially palms and soles
• Lesions may appear on buttocks (usually non-vesicular)
• Vesicles heal without crusting - distinguishes HFMD from herpesviruses and poxviruses

• Nucleic acid amplification (PCR): method of choice; highly sensitive; can detect from stool, throat swab, vesicular fluid, CSF
• Virus culture: from stool, pharyngeal secretions, vesicular fluid
• Serology: for outbreak investigation
• Clinical diagnosis is usually sufficient in typical cases

Control / Treatment

• No specific antiviral therapy exists for most enteroviral HFMD
• Supportive care: hydration (IV fluids if needed), analgesics, antipyretics
• Disease usually resolves in <1 week; herpangina resolves in ~10 days
• Hospitalization for infants/young children with inability to maintain oral intake
• EV-A71 vaccine: Available (approved in China); effective for prevention of EV-A71-associated HFMD
• Poliovirus vaccine (IPV/OPV) does not protect against HFMD serotypes
• Infection control: Hand hygiene, avoiding contact with infected individuals, disinfection of fomites
• Goldman-Cecil Medicine, International Edition, p. 3632