The Topic of This Month Vol.19 No.7(No.221)

Hand-foot-and-mouth disease (HFMD) exhibits such principal symptoms as vesicular exanthemas developing on oral mucosa and extremities. It is a common acute viral infection, affecting mostly young children in the summer season and has been a clinical entity since approximately 1967 in Japan. The major agents of HFMD are such enteroviruses as group A coxsackievirus 16 (CA16), enterovirus 71 (EV71), and group A coxsackievirus 10 (CA10). Since the symptoms developing after infection with any of these viruses are the same, the etiologic diagnosis depends basically on virus isolation and serotype identification of the isolate. Primarily the virus excreted from the pharynx causes person-to-person transmission. It is one of the characteristics of enteroviruses that the virus is excreted in stools for 3 to 4 weeks even after disappearance of the main symptoms. Acute meningitis is seen occasionally, but a benign prognosis has generally been reported. It is known, however, that the incidence of complications of disorders involving the central nervous system is higher with EV71 than with other viruses.

The trend of HFMD cases during the period from 1982 through 1997 in this country according to the National Epidemiological Surveillance of Infectious Diseases is shown in Fig. 1. A large-scale epidemic occurred recently in 1995. Although the peak of epidemic is usually seen in summer, Fig. 1 indicates the occurrence of HFMD also from autumn to winter. The incidence of HFMD during 1993-1997 by the prefectures is shown in Fig. 3. The incidence differed from one prefecture to another every year; nevertheless this disease is seen usually in all districts. As seen in Fig. 4, HFMD patients aged 2 years or less accounted for half of all patients.

The initial clinical diagnoses of the patients from which one of the main virus agents of HFMD, CA16, EV71, or CA10 was isolated at prefectural and municipal public health institutes (PHIs) were recorded (Table 1). For those yielding CA16, HFMD was most frequent accounting for 89%, followed by herpangina 3.3%. For those yielding EV71, HFMD was most frequent accounting for 83%, followed by meningitis 11%, and herpangina 1.2%. Contrastingly, for those yielding CA10, herpangina was most frequent accounting for 79%, HFMD being infrequent accounting for 16%, and meningitis 2.6%. From the monthly isolation of each virus after 1982 (Fig. 2), it is understood that isolation of either CA16 or EV71 was frequent in agreement with the high prevalence of HFMD patients, but the frequency of CA10 isolation did not necessarily agree with HFMD patients. The epidemics occurring three years ago in 1995 were caused by CA16; EV71 was isolated mainly in 1997 (see p. 153 of this issue).

Complications of HFMD

In Sarawak, Malaysia, large-scale HFMD epidemics started in February 1997 among young children involving 30 fatal cases. Although not finally concluded, the followings have been revealed: there may be sudden death in the course of HFMD, autopsy detected such acute neurological involvement as brainstem encephalitis, and EV71 may have served as an etiological virus agent (see p. 152 of this issue).

There was an HFMD epidemic of slightly smaller scale than usual in Osaka City, in 1997. In this epidemic, three sudden death cases of children related to HFMD or EV71 infection were reported (see IASR, Vol. 19, No. 3, 1998). The viruses isolated at Osaka PHI were subjected to nucleotide sequencing at the National Institute of Infectious Diseases (NIID). The nucleotide sequence was compared with those of previous isolates. The EV71 strains isolated in the past one or two years in Japan were grouped largely into two: the major and minor genotypes. The EV71 strain isolated from a fatal case in Osaka City was identified as the minor genotype. The EV71 strains isolated last year in Sarawak also resembled to the minor genotype (see p. 152 of this issue).

According to the reports to IASR, encephalitis was diagnosed in 14 of 2,337 cases from which EV71 was isolated during the period from 1982 to 1997. In 1993, a fatal case complicated with encephalitis in the course of HFMD was reported in Toyama Prefecture (IASR, Vol. 14, No. 11, 1993).

Recent reports published or presented at academic meetings demonstrated serious complications of HFMD; a case of localized encephalitis presumably due to EV71 infection (serodiagnosed) in Okayama Prefecture in 1995 (Infection and Immunity in Childhood, 10: 19-22, 1998), seven cases of encephalitis presumably due to EV71 infection (serodiagnosed) in Shiga Prefecture in 1997 (Annual Meeting of Japan Pediatric Society, 1998), and 15 cases of acute cerebellar ataxia in Osaka Prefecture in 1997 (Annual Meeting of Japanese Society of Child Neurology, 1998).

Since May 1998, death cases seemingly due to HFMD or EV71 infection have increased among infants and young children in Taiwan (see p. 160 of this issue). NIID and its counterparts in Taiwan are exchanging information and proceeding a joint research project on the viral agents. According to Taiwanese health authorities, HFMD or suspected cases registered as fatal ones numbered 50 and severe ones 248 as of June 24. The ages of these cases peaked at 1 to 3 years with skirts ranging from 0 to 15 years. The health authorities decided on intensifying general public health measures, discouraging holding events for children (e. g., camping), intensifying surveillance, and starting active epidemiological investigations.

The Japanese Ministry of Health and Welfare immediately informed the incidence of HFMD in Taiwan as well as in Malaysia and Japan to Japan Medical Association on June 8, 1998. HFMD is fundamentally a mild disease, healing spontaneously, with a good prognosis, and accompanied very rarely with serious complications at present. Nevertheless, careful monitoring of the incidence of HFMD in the coming summer in Japan and of the virus agents (CA16 and EV71) seems to be very important. The Infectious Disease Surveillance Center provides information on the incidence of HFMD and virus isolation by prefectures on a homepage (http://idsc.nih.go.jp/kanja/index-e.html).

Update: HFMD patients in 1998 started to increase in number earlier than usual (as of the 23rd week) as was the case in the previous years giving large-scale epidemics (1995, 1990, and 1988). CA16 was isolated from HFMD cases in Iwate (April-May), and Shimane Prefectures (April-May); EV71 in Tottori Prefectures (April) (see p. 154 of this issue).

idsc-query@nih.go.jp

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