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Hand-Foot-Mouth Disease related to Enterovirus 71

Hand-foot-mouth disease (HFMD) or vesicular stomatitis with exanthem is a common childhood condition. It results from infection with non-polio enteroviruses such as coxsackie viruses A16, A4, A5, A9, A10, B2 and B5 and enterovirus 71. Its most common causes are coxsackie virus A16 (CAV 16) and enterovirus 71 (EV 71).

Large outbreaks of HFMD related to CAV 16 and EV 71 have both been documented. Outbreaks of HFMD due to CAV 16 have not been associated with significant complications or mortality. Interestingly, certain outbreaks of HFMD due to EV 71 have been associated with severe neurological complications and significant mortality while others have been associated with relatively fewer complications and little mortality.

Hand-Foot-Mouth Disease

HFMD generally affects children aged 11 years old and younger. It characteristically presents with fever, oral lesions and rash on the hands, feet and buttocks. The oral lesions consist of rapidly-ulcerating vesicles on the buccal mucosa, tongue, palate and gums. The rash consists of papulovesicular lesions on the palms, fingers and soles which generally persist for seven to 10 days and maculopapular lesions on the buttocks. Malaise, sore throat, vomiting and/or diarrhea may also be present. The disease is considered benign and self-limited but complications may arise, particularly when the illness results from infection with EV 71. Complications include encephalitis, aseptic meningitis, acute flaccid paralysis, pulmonary edema or hemorrhage and myocarditis. Most deaths in HFMD occur as a result of pulmonary edema or hemorrhage.

Enterovirus 71

EV 71 is a non-polio enterovirus. Non-polio enteroviruses are common ribonucleic acid (RNA) viruses that are found worldwide. Infection is usually asymptomatic or associated with a mild non-specific illness. More severe presentations do occur, particularly in children. Presentations include exanthems (including HFMD), herpangina, conjunctivitis, encephalitis, aseptic meningitis, acute flaccid paralysis, acute respiratory problem and myopericarditis. It should be noted that infection with EV 71 may result in complications without producing clinically-evident HFMD. This occurred in the context of a large outbreak of EV 71 in Bulgaria.

EV 71 is transmitted through direct contact with discharge from the nose and throat, saliva, fluid from blisters or the stools of an infected person. Cases are most infectious during the first week of acute illness but may continue to shed virus in stool for weeks. The incubation period is three to five days. The epidemiological pattern varies by geographical region and climate, but the incidence of infection is higher in the summer and autumn months in temperate climates while remaining prevalent year-round in tropical climates.

Laboratory Diagnosis

Laboratory diagnosis is generally not required for uncomplicated cases of HFMD. In complicated cases, diagnosis can be made by isolation of virus by culture of upper respiratory tract or faecal specimens or from specimens of cerebrospinal fluid, biopsy material or skin lesions. Viral culture and/or molecular techniques, such as polymerase chain reaction (PCR) and sequencing can both be used; however culture to obtain a viral isolate is preferred for accurate typing of the virus strain. The National Microbiology Laboratory (NML) in Winnipeg performs typing for enteroviruses and asks that provinces and territories send all isolates to NML as part of ongoing enterovirus surveillance. A four-fold rise in the level of neutralizing antibody in blood specimens collected during the acute and convalescent phases of illness can provide evidence of recent infection. However, this is often difficult in practice since patients may already have started to seroconvert on presentation of symptoms.

Treatment

No specific antiviral agent is available for therapy or prophylaxis of EV 71 infection. Treatment is supportive and focuses on management of complications. Intravenous administration of immune globulin may have a use in preventing severe disease in immunocompromised patients or those with life-threatening disease.

Prevention

During outbreaks of HFMD related to EV 71, transmission is thought to occur predominantly via the respiratory route. Transmission of enteroviruses may be increased by poor hygiene and overcrowded living conditions. Improved sanitation and general hygiene are important preventive measures. Measures that can be taken to avoid getting infected with enteroviruses include frequent handwashing, especially after diaper changes or going to the toilet; disinfection of contaminated surfaces with bleach (20 ml/litre of water); and washing soiled articles of clothing. The viruses are resistant to many disinfectants so it is important to use chlorinated (bleach) or iodized disinfectants. During epidemics, closure of schools or child care facilities may be considered in order to reduce transmission especially among young children. It is not necessary to restrict travel or trade.

References

Bible JM, Pantelidis P, Chan PKS et al. Genetic evolution of enterovirus 71: Epidemiological and pathological implications. Rev. Med. Virol. 2007;17:371-379.

Chen KT, Chang HL, Wang ST et al. Epidemiologic features of hand-foot-mouth disease and herangina cause by enterovirus 71 in Taiwan 1998-2005. Pediatrics 2007;120(2):e244-252.

Heymann DL. “Coxsackievirus Diseases” in Control of Communicable Diseases Manual 18th Ed. American Public Health Association, 2004.

Ho M, Chen ER, Hsu KH et al. An epidemic of Enterovirus 71 infection in Taiwan. NEJM 1999;341(13):929-935.

Huang CC, Liu CC, Chang YC et al. Neurological Complications in Children with enterovirus 71 infection. NEJM 1999;341(13):936-942.

Lin TY, Twu JS, Ho MS et al. Enterovirus 71 outbreaks, Taiwan: Occurrence and recognition. EID;9(3):291-293.

Other Fact Sheets

CDC Q&A's: Non-polio Enteroviruses. CDC Nov 2000.

WHO Fact Sheet: Enteroviruses - non-polio. WHO May 2002.