Most Common Viruses Causing Hand, Foot, and Mouth Disease
The most common viruses responsible for hand, foot, and mouth disease (HFMD) are coxsackievirus A16 (CV-A16) and enterovirus 71 (EV-A71), though coxsackievirus A6 (CV-A6) has emerged as an increasingly important pathogen causing more severe outbreaks worldwide. 1, 2
Primary Causative Agents
Traditional Pathogens
- Coxsackievirus A16 (CV-A16) and Enterovirus 71 (EV-A71) have historically been the predominant pathogens causing HFMD outbreaks worldwide 3, 4, 5
- CV-A16 typically causes milder disease, with patients recovering without special medical attention 5
- EV-A71 is associated with more severe outbreaks and has been responsible for large HFMD outbreaks with rare but severe cases of rhomboencephalitis, particularly in Asia and more recently in Europe 1
Emerging Pathogen
- Coxsackievirus A6 (CV-A6) has become a major cause of HFMD outbreaks since 2008, particularly in Finland, Europe, North America, and Asia 6, 4
- CV-A6 causes more severe disease with unique clinical findings compared to traditional strains, including higher fever, longer disease duration, and more extensive skin manifestations spreading beyond the typical hand-foot-mouth distribution 6
- This strain affects broader demographics, including adults, which is atypical for traditional HFMD 6
Other Enterovirus Serotypes
- Coxsackievirus A10 (CV-A10) has been identified as causing more infections in recent epidemiological shifts 2
- Coxsackievirus A5 (CV-A5) can also cause HFMD, though less commonly 5
- Other human enterovirus A (HEV-A) serotypes tend to cause only sporadic HFMD cases rather than outbreaks 4
Clinical Significance by Viral Type
EV-A71 carries the highest risk for severe complications, including brain stem encephalitis, meningoencephalitis, acute flaccid paralysis, and pulmonary edema 7, 2
- Mortality has increased particularly in children under 3 years of age and teenagers with brain stem encephalitis 2
- Neurological complications such as encephalitis/meningitis and acute flaccid myelitis (AFM) are potential severe outcomes 7
CV-A6 presents with atypical features that distinguish it from classic HFMD:
- Widespread exanthema beyond classic distribution, involving the legs 7
- More severe skin manifestations requiring intensive skin care 7
- Association with onychomadesis (nail shedding) occurring 1-2 months after fever onset 1
Epidemiological Shifts
Recent molecular epidemiology studies reveal important changes in HFMD causative agents 2:
- A shift from EV-A71 and CV-A16 dominance to increased prevalence of CV-A6 and CV-A10 2
- Extensive recombination events among enterovirus strains may contribute to faster evolution and extinction of dominant serotypes 2
- These changes necessitate updated prevention strategies, including consideration of multivalent vaccines combining EV-A71, CV-A16, and CV-A6 4
Important Diagnostic Considerations
Vesicle fluid samples have the highest viral loads and are ideal for testing using reverse transcriptase PCR (RT-PCR) targeting the 5′ non-coding region 7