What are the specific causes of Hand, Foot, and Mouth (HFM) disease?

Specific Causes of Hand, Foot, and Mouth Disease

Hand, Foot, and Mouth Disease (HFMD) is primarily caused by enteroviruses, with Coxsackievirus A16 (CV-A16) and Enterovirus A71 (EV-A71) being the most common causative agents, though recent epidemiological shifts have shown increasing prevalence of Coxsackievirus A6 and Coxsackievirus A10. 1, 2

Primary Causative Agents

• Coxsackievirus A16 (CV-A16): Traditionally one of the most common causes of typical HFMD 1, 3
• Enterovirus A71 (EV-A71): Another major cause, often associated with more severe cases 2, 3
• Coxsackievirus A6 (CV-A6): Emerging as a significant cause with recent worldwide outbreaks 3
  • Associated with more extensive cutaneous manifestations
  • Can cause atypical presentations including vesicobullous eruptions and involvement of areas of atopic dermatitis ("eczema coxsackium")
• Coxsackievirus A10: Increasingly identified in HFMD cases 2
• Other enteroviruses: Less commonly, other enterovirus serotypes can cause HFMD 4, 5

Transmission Mechanisms

HFMD spreads through multiple routes:

• Fecal-oral transmission: Primary route, especially in household settings 4, 5
• Oral-oral contact: Direct transmission through saliva 4
• Respiratory droplet contact: Transmission through coughing and sneezing 4
• Contact with contaminated surfaces and fomites: Virus can persist on surfaces 4

Molecular and Epidemiological Factors

• Viral recombination: Extensive recombination events among enterovirus strains contribute to:

  • Faster viral evolution
  • Extinction of previously dominant serotypes
  • Emergence of new variants with potentially different clinical presentations 2

• Seasonal patterns: Outbreaks typically occur during spring to fall in North America 2, 4

• Changing epidemiology: Recent surveillance has shown shifts in the predominant causative agents:

  • CV-A6 has emerged as a significant cause in outbreaks across the United States, Japan, Southeast Asia, and Europe 3
  • This shift has been associated with more extensive and varied clinical presentations 3

Diagnostic Considerations

For definitive identification of the causative agent:

• Reverse transcriptase PCR (RT-PCR) targeting the 5′non-coding regions is recommended for initial diagnosis 1
• Sequencing of the VP1 capsid protein gene is recommended for enterovirus typing due to frequent recombination events 1
• Appropriate samples for testing include:
  • Vesicle fluid
  • Respiratory samples
  • Stool samples 1

Prevention

The most effective methods to prevent HFMD transmission include:

• Handwashing: Thorough and frequent handwashing, especially after diaper changes and before handling food 4
• Surface disinfection: Regular cleaning of potentially contaminated surfaces and fomites 4
• Isolation: Children are particularly infectious until blisters have disappeared, though the virus may remain present in feces for several weeks 5

Understanding the specific viral causes and transmission mechanisms of HFMD is essential for accurate diagnosis, appropriate management, and effective prevention strategies.