Hand, foot and mouth disease (HFMD) is a common acute viral infection that typically presents as a vesicular exanthema of the oral mucosa and peripheral extremities. It predominately affects young children during the summer season. Enteroviruses, such as group A coxsackievirus 16 (CA16) and enterovirus 71 (EV71) are most commonly isolated from HFMD cases; virus isolation and type identification are essential for etiological diagnosis. During previous large-scale epidemics of herpangina due to group A coxsackievirus 10 (CA10), CA10 was also isolated from HFMD cases. Enteroviruses are spread primarily from person-to-person through viruses excreted from the oropharynx. Enteroviruses are also excreted in stools for up to 3 to 4 weeks after the disappearance of primary symptoms; attention therefore must be also paid to fecal-oral infection. Although prognosis of neurological complications has been considered good, deaths and severe cases occurring during epidemics of HFMD have been reported, therefore elevating the importance of surveillance for HFMD and EV71 infections (see IASR, Vol. 19, No. 7; Vol. 20, No. 6 and Vol. 21, No. 10).

Trends of HFMD epidemics and virus isolation/detection: Weekly reports of HFMD cases by the National Epidemiological Surveillance of Infectious Diseases (NESID) (Fig. 1) demonstrate that the peak of each epidemic occurs in the summer. However, epidemics may also occur in the autumn and winter. After 1994, large-scale outbreaks occurred in 1995 (annual reports counted at 158,677; 65.03 per sentinel), 2000 (205,365; 68.96) and 2003 (172,456; 56.71). About 90% of HFMD cases were 5 years of age or less, showing very little changes (Fig. 2). Reports of HFMD cases 15 years of age and older account for about 1% every year; the proportion of adult HFMD cases is not known because this sentinel surveillance is performed only at pediatric clinics.

Monthly reports of isolation/detection of CA16 and EV71 by prefectural and municipal public health institutes (PHIs) are shown in Fig. 3. After 1994, EV71 has been prevalent every three years. The primary causative agent of HFMD was EV71 in 2000 and 2003, and CA16 in 2001-2002.

Incidence of HFMD by prefecture from 2000 to 2003 is shown in Fig. 4. Incidence and years of epidemics differed from region to region. Isolation/detection of EV71 and CA16 by prefecture (Fig. 5) shows that nationwide epidemics of either EV71 or CA16 alone have not occurred in recent HFMD epidemics (for epidemics in several different regions in 2003, see IASR, Vol. 24, Nos. 5, 7, 8 and 9).

Diagnoses of EV71- or CA16-detected cases (Table 1) show that as EV71-detected cases increased in 2000 and 2003, so did reports of meningitis and encephalitis/encephalopathy. On the other hand, reports of meningitis and encephalitis/encephalopathy have been few among CA16-detected cases.

Serious complications of HFMD: Sudden deaths occurred in succession among infants and children during epidemics of HFMD in Malaysia in 1997 and in Taiwan in 1998 and 2000. In Japan, three sudden death cases of young children from HFMD or EV71 infection were reported in Osaka in 1997 (see IASR, Vol. 19, No. 3, 1998). Subsequently, the Ministry of Health and Welfare conducted a nationwide survey on clinical complications of HFMD/herpangina (encephalitis, encephalopathy, myocarditis, acute flaccid paralysis, or acute respiratory failure) and other sudden deaths of unknown etiology. Four cases of severe complications were found (see IASR, Vol. 20, No. 6, 1999). Thereafter, a questionnaire survey lead by T. Iwasaki of the Health Science Study Group was conducted on cases hospitalized for 24 hours or more during the course of HFMD or herpangina from 2000 to 2002. According to the 2000-2001 interim report, in 2000, when EV71 was circulating, hospitalized cases increased, with occurrence of the following serious complications of HFMD: two deaths, seven cases of encephalitis/encephalopathy, 18 cases of cerebellar ataxia, five cases of myoclonus, three cases of acute flaccid paralysis, two cases of cardio-respiratory failure, and two cases of pulmonary edema/pulmonary hemorrhage/shock (see p. 226 of this issue).

There are many genotypes of EV71, and it has been shown that virus transmission occurs frequently in wide regions without any relation between the genotype of EV71 and disease severity (see p. 228 of this issue). Experimental infection of cynomolgus monkeys with EV71 has demonstrated that virus derived from cases of HFMD, aseptic meningitis, or encephalitis causes serious neurological manifestations (see p. 229 of his issue).

Although cases of HFMD have mostly good prognoses, close attention must be paid to symptomatic changes and complications during EV71 epidemics. Surveillance for complications, including etiological viruses, must be intensified and the importance of feedback of results to clinical and public health fields stressed.

In the amendment to the Infectious Diseases Control Law in November 2003, acute encephalitis (excluding West Nile encephalitis and Japanese encephalitis) was changed from a Category IV infectious disease reported by sentinel hospitals to a new Category V infectious disease, in which all cases are to be notified. Acute encephalitis, accompanied by infectious diseases with separate reporting criteria (e.g. influenza, HFMD, and mumps) must also be reported (IDWR, Vol. 6, No. 9, 2004). Etiological diagnosis should be pursued as much as possible, including cases of acute encephalopathy that fit to the reporting criteria (see http://www.mhlw.go.jp/topics/bukyoku/kenkou/kansensyo/kijun5a.html#3). The national surveillance system for central nervous system complications of HFMD (particularly acute encephalitis) is now ready and in operation. Results obtained through cooperation of various channels will provide valuable information in the future for early detection of community outbreaks, investigation of causative agents, and development of countermeasures.

Update 2004: The incidence of HFMD has been maintained at a low level (see Fig. 1 and http://idsc.nih.go.jp/idwr/kanja/weeklygraph/06HFMD.html). As the etiological virus, CA16 has been detected in Akita (March), Kitakyushu (June-July), Aichi (June-July, see p. 231 of this issue), Saitama (July), Ehime (July), Nagano (July-August) and Kawasaki (August), and EV71 in Nara (February), and Tokyo (May-July, see IASR, Vol. 25, No. 8) (as of September 8, 2004, see http://idsc.nih.go.jp/iasr/prompt/s2graph-k.html).

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