Translated from the original Japanese by:-Kaede I <>

Monday 13 July 1998.


In Sarawak (Borneo Island), Malaysia, an outbreak of Hand-foot-and-mouth disease (HFMD) and sudden deaths among children was reported in February 1997. Until then, there were no reported epidemics of HFMD in Malaysia and the unfamiliar disease puzzled the public. No previous clinical studies nor virus surveillance had been conducted for HFMD and enteroviruses and past records of epidemics are unknown. Sporadic incidences of infants showing symptoms of fever and rashes followed by sudden deterioration of the body causing sudden deaths after one to two days of hospitalization were reported from Sarawak on April 15, 1997. In May, the number of incidences reported increased amounting to 11 by the end of the month. Initial speculations of Kawasaki Disease were contradicted by the clinical findings of acute myocardial infection.  The epidemic of sudden infant death due to an unknown cause terrorized the nation.

The WHO sent a request to the Japanese Ministry of Health and Welfare to investigate the cause of the epidemic and two researcher from the National Institute of Infectious Disease (NIID) were sent immediately. Also, CDC (Center for Disease Control and Prevention) dispatched an epidemiologist upon the request of the Malaysian government. 

On a weekly basis, one to two hundred patients were hospitalized and two to three hundred came to clinics to get treated for HFMD. However, in July the number of cases started to decline. According to NIID's report, 30 fatal cases were recorded, ages between one and two, more infant boys than girls, and they died suddenly after 1 to 2 days of hospitalization. Among the 27 patients that showed HFMD rashes, the cell count in the marrow were high in 6 out of 8 cases. A circulatory specialist for children, quoted that Echo references show myocardial disorder in fatal cases (Sarawak General Hospital, Sibu Division ,Pediatrics).

Out of the 30 reported fatalities, Sarawak General Hospital, the CDC and the medical team of the NIID investigated 7 heart biopsies and 4 autopsies. All cases showed no signs of myocardial infection. Out of the 4 autopsies, 3 showed slight edema and infection in the central nervous system and one case of encephalitis.

At the Malaysian National Institute of Medical Research and the NIID, researchers isolated EV71, Group A coxsackievirus 16 (CA16) and other enteroviruses such as the Echovirus from HFMD patients. The serum studies identified Group B enteroviruses. Various types of enteroviruses were seen in this epidemic. EV71 was isolated from thoracic and fecal specimens of the bodies. CDC also identified EV71 infection in the fatal cases.

The cause of the outbreak of sudden deaths among children in Malaysia has not been identified. However, from the facts that (1) sudden death occurs during an incidence of HFMD and (2) autopsies show infection in the central nervous system and signs of encephalitis, there is a strong likelihood that EV71 is one of the causal viral agents. Careful monitoring of the incidence in children seems to be very important.

National Institute of Infectious Disease,
Infectious Disease Information Center:
Nobuhiko Okabe
National Institute of Infectious Disease,
Viral Division 2: Hiroshi Shimizu, Hiroshi Yoshida


PRO> HFMD-related deaths, role of EV71 - Malaysia: revised



A ProMED-mail post


[see also:

HFMD-related deaths, role of EV71 - Malaysia           980718094233]

Date: Wed, 5 Aug 1998 09:28:35 +1000

From: Nobuhiko Okabe, MD, PhD <>

Reference is made on the ProMED-mail post:


Dr.C.L.Wong quoted our articles on HFMD-related death experienced in

Sarawak, Malaysia, in 1997, published in Japanese in Infectious Agents

Surveillance Reports (IASR), Japan, translated into English by Kaede I.

<>, visiting Japanese medical student in Sarawak.   

I appreciate his(her) voluntary translation, however,  I would request you

to insert the following report which was revised by Dr. N. Okabe, the

author of that article,  to clear and correct some errata.  

A full report on Malaysian issue related HFMD and sudden death would be

expected to be published on the appropriate international journal by

Malaysian [authors]. 


Nobuhiko Okabe, MD, PhD

Infectious Disease Surveillance Center

National Institute of Infectious Diseases



Hiroshi Shimizu, PhD,  Hiroshi Yoshida,  PhD

Viral Division 2

National Institute of Infectious Diseases,

Tokyo Japan


[The first 4 paragraphs were essentially unchanged.  The revised version of

the remainder is given below - Mod.JW] 

"Among the 27 patients that showed HFMD rashes, the cell count in the

cerebrospinal fluid was high in 6 out of 8 cases.  Pediatric cardiologists

quoted that Echo cardiogram examination was identical with myocardial

disorder in some fatal or serious cases (Pediatrics/Sarawak General

Hospital, Pediatrics, Sibu Hospital).  

"Out of 30 registered fatalities, Sarawak General Hospital and the CDC team

investigated 7 heart tissues obtained by biopsy from fatal cases and 4

total autopsies. Some of these were examined in the NIID also.  None of the

pathologically investigated cases showed any evidence of myocardial

inflammation. Of the 4 with total autopsies, 3 showed slight edema and

infection in the central nervous system and one had brainstem encephalitis.  

"At the Department of Virology, IMR, and the NIID, EV71,  Coxsackie  A16

(CA16) and other enteroviruses such as the Echovirus [sic - there  at least

30 types - Mod.JW] were isolated from HFMD and other  related cases. The

serological studies from some patients revealed Coxsackie B virus infection

also.  These virological examinations showed that various types of

enterovirus existed [together] in this epidemic.  EV71 was also isolated

from throat swab and fecal specimens obtained from some fatal cases. CDC

also identified EV71 infection in the fatal cases.   

Although not finally concluded, the following have been revealed: there may

be sudden deaths in the course of HFMD, autopsy detected acute neurological

involvement such as brainstem encephalitis, and EV71 may have served as one

of the etiological viral agents.  Careful monitoring of the incidence in

children seems to be very important." 




[Note this disclaimer to the effect that a viral cause of the deaths in 

Malaysia has not yet been definitely established - Mod.JW]




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