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Hand, Foot and Mouth Disease

GMJ News knowledge hub · last reviewed August 2026 · Georgian Medical Journal

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Hand, foot and mouth disease (HFMD) — caused primarily by Coxsackievirus A16 and Enterovirus A71 (EV-A71) — is an extremely common childhood infection causing oral ulcers and vesicular rash on hands, feet and buttocks, with most cases self-resolving in 7-10 days; however, EV-A71 causes severe neurological complications (brainstem encephalitis, neurogenic pulmonary oedema) that kill thousands of children annually during major Asia-Pacific outbreaks (WHO). China reported millions of HFMD cases annually in the 2000s-2010s. A related enterovirus — EV-D68 — causes acute flaccid myelitis (AFM), a polio-like spinal cord disease in children, with US clusters in 2014, 2016 and 2018. China licensed the first EV-A71 vaccine in 2016.

Key messages

Millions of children annually — EV-A71 causes severe disease
Hand, foot and mouth disease (HFMD) affects millions of children annually — predominantly under 5. While most cases are mild and self-limiting, Enterovirus A71 (EV-A71) causes severe neurological complications (brainstem encephalitis, neurogenic pulmonary oedema) that kill hundreds of children per year in Asia-Pacific (WHO).
EV-D68 — acute flaccid myelitis
Enterovirus D68 (EV-D68) — a distinct enterovirus — causes acute flaccid myelitis (AFM), a polio-like spinal cord condition causing acute limb paralysis in children. US clusters in 2014, 2016 and 2018. AFM is associated with respiratory EV-D68 illness 1-4 weeks before paralysis.
China EV-A71 vaccine — 2016
China licensed the world's first EV-A71 inactivated vaccine in 2016 (approved for children 6 months to 5 years) — substantially reducing EV-A71-associated deaths and severe disease in vaccinated populations. WHO has called for broader EV-A71 vaccine access.
Contact and respiratory precautions
HFMD spreads through respiratory droplets, saliva, vesicle fluid and faeces. Standard hygiene (handwashing, surface disinfection, isolating infected children from daycare) reduces transmission. No specific antiviral treatment.
Outbreaks predominantly Asia-Pacific
HFMD causes major periodic outbreaks in East and Southeast Asia — China (millions of cases/year), Vietnam, Malaysia, Korea, Japan, Taiwan. Temperate regions (North America, Europe) experience milder, less frequent outbreaks.
Bivalent or quadrivalent vaccines in development
Multiple broader-coverage enterovirus vaccines — covering both EV-A71 and Coxsackievirus A16 (the two main HFMD agents) — are in development and clinical trials globally.

Key statistics

Millions
HFMD cases reported annually in China alone
Chinese CDC/WHO
2016
year China licensed first EV-A71 vaccine (world's first)
WHO/China
Hundreds
of children die annually from EV-A71 severe disease in Asia
WHO
AFM
acute flaccid myelitis: EV-D68 clusters in US 2014/2016/2018
CDC/WHO
7-10 days
typical self-limiting course of uncomplicated HFMD
WHO
<5yr
peak age group for HFMD (highest incidence and mortality)
WHO

HFMD key enteroviruses — serotypes, disease severity and vaccine status

Source: WHO. EV-A71 causes the most severe HFMD; EV-D68 causes AFM; Coxsackievirus A16 is most common but milder.

Glossary of key terms

Enteroviruses (HEV)
WHOA genus of positive-sense RNA viruses — including polioviruses, coxsackieviruses, echoviruses and numbered enteroviruses (EV-A71, EV-D68 etc). Over 100 serotypes infect humans. Transmitted fecal-oral and respiratory routes. Enteroviruses are second only to rhinoviruses as causes of human viral infection globally.
Coxsackievirus A16 (CV-A16)
WHOThe most common HFMD agent — causes classic mild HFMD with oral ulcers and vesicular rash on hands, feet and buttocks. Self-limiting in 7-10 days; rarely causes severe complications. Co-circulates with EV-A71.
Enterovirus A71 (EV-A71)
WHO/ChinaThe most clinically significant HFMD pathogen — associated with severe neurological complications: aseptic meningitis; rhombencephalitis (brainstem encephalitis — presenting with myoclonus, tremor, ataxia → rapid deterioration); and neurogenic pulmonary oedema (a catastrophic complication causing rapid respiratory failure). Mortality in EV-A71 neurological disease: approximately 5-30%. China's EV-A71 vaccine is protective against this serotype specifically.
Acute flaccid myelitis (AFM)
WHO/CDCA rare but serious condition — predominantly affecting children — characterised by sudden onset of limb weakness (acute flaccid paralysis) from spinal cord grey matter inflammation. Strongly associated with EV-D68 respiratory illness 1-4 weeks before. Distinct from polio but clinically similar. US cases cluster every 2 years (2014: 120 cases; 2016: 149 cases; 2018: 238 cases). Recovery is incomplete in many.
EV-D68 (Enterovirus D68)
WHO/CDCAn enterovirus causing severe respiratory illness (wheezing, asthma exacerbation, bronchiolitis) and acute flaccid myelitis (AFM). Major US respiratory outbreak 2014 preceded the first AFM cluster. Children with asthma/wheezing history are at highest risk of severe respiratory EV-D68 disease.
China EV-A71 vaccine
WHO/China NDAThree inactivated EV-A71 vaccines licensed in China (2016): EV71 vaccine (Sinovac), BMEI EV71 vaccine and Vigoo EV71 vaccine. Target group: children 6 months to 5 years. Efficacy against EV-A71-associated HFMD approximately 90%; against severe EV-A71 disease approximately 80%. Significantly reduced EV-A71-related deaths in China.

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Polio (AFM parallel)Child healthEV-A71 vaccinationEV-D68 respiratory diseaseAFM disabilityViral meningitis

About this hub. Produced by the GMJ News Editorial Team as a public-good service. Every statistic is linked to its primary source. Documents are preserved in the GMJ Repository with full attribution. Georgian Medical Journal · Contact the editorial team
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