Published Date: 1998-07-18 23:50:00
Subject: PRO> HFMD-related deaths, role of EV71 - Malaysia
Archive Number: 19980718.1347

HFMD-RELATED DEATHS; ROLE OF EV71 - MALAYSIA
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A ProMED-mail post
<http://www.healthnet.org/programs/promed.html>

[We are posting this message because the articles appear to contain
information we had not previously received. - Mod.CHC]
Date: Thu, 16 Jul 1998 16:38:01 +0800
Source: July 1998 issue of Infectious Agents Surveillance Reports, Japan.
Via: C.L. Wong <wongcl@pop.jaring.my>

I came across two interesting articles published on a Japanese website last
weekend. They are concerned with the outbreak of HFMD in Malaysia in 1997
which resulted in 30 deaths in Sarawak and another 17 or so in Peninsular
Malaysia. At the time, CDC epidemiologists and Japanese experts were asked
to come to Sarawak to help in the investigation of the outbreak.
So far, we have not heard any official news about the CDC findings. The 2
Japanese articles posted in the July 1998 issue of Infectious Agents
Surveillance Reports document the findings of the Japanese team involved in
the Malaysian outbreak.
I downloaded the articles in Japanese and enlisted the assistance of Dr.
Flora Ong of the Sarawak Medical and Health Department in asking a visiting
Japanese medical student to help translate the 2 articles into English. I
believe they will provide us with a greater understanding of the outbreak
in Malaysia in 1997, and may be of some help in understanding the present
Taiwanese outbreak as well.
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Translated from the original Japanese by Kaede I <kaedesyrup@yahoo.com>,
Monday, 13 July 1998.

Article 1:
MOLECULAR EPIDEMIOLOGY OF ENTEROVIRUS 71 ISOLATED IN MALAYSIA AND JAPAN
Enterovirus 71 (EV71) is one of the major agents of hand-foot-and-mouth
disease (HFMD) along with enteroviruses Group A Coxsackievirus 16 (CA16)
and Group A Coxsackievirus 10 (CA10). EV71 is a common virus that has been
isolated from all regions in Japan on an annual basis. More than 40 fatal
incidences of EV71 infections were reported both in Bulgaria (1975) and
Hungary (1978). Occasionally EV71 is known to cause severe neural
complications. In Australia and the US, incidences of complications of
disorders involving the central nervous system have been linked with EV71.
In Sarawak, Malaysia, an enterovirus infection among children involving
fatal cases was reported in 1997. (See other page). The Japanese National
Institute of Infectious Diseases and the Malaysian National Institute of
Medical Research jointly collaborated to isolate the enterovirus from fatal
cases and HFMD patients in Sarawak and Peninsular Malaysia. Up to date, 15
strains have been isolated. According to molecular epidemiological
analysis, the isolated Malaysian EV71 (Sarawak type) strains from fatal and
HFMD cases were identified to be all from the same genotype. The Malaysian
Sarawak type EV71 compared with the known nucleotide sequences of the
previous isolates (prototype strain BrCr and the 7423/MS strain (US 1987))
showed 80-86% RNA and 95% amino acid match indicating that the EV71 belongs
to a different genotype group.
To compare the pathogenicity and viral characteristics of EV71 causing HFMD
in Japan and the EV71 isolated in Malaysia, a molecular epidemiological
comparative analysis of each enterovirus was performed. The strain that
caused a small scale HFMD epidemic with fatal cases in Osaka showing
encephalitis presumably due to EV71 infection was also analyzed. When the
40 EV71 strains isolated in the past and the strain found in Osaka were
analyzed, it was found that they could be grouped largely into two. About
10 strains showed genotypic similarities with the EV71 isolated in
Malaysia. The strain causing the fatal cases in Osaka was found to belong
to the same genotype group as above. The rest of the Japanese EV71 strains
showed considerable difference with the EV71 Sakura type.
Varying pathogenicity and symptoms depending on regions and seasons have
lead researches to believe that different EV71 strains have different
pathogenicities. Along with further research on EV71 isolated in Japan and
other regions of the world, careful monitoring of the Japanese EV71 and
their genotypes seems to be very important.
National Institute of Infectious Diseases, Viral Division 2: Hiroshi
Shimizu, Andi Utama, Hiroshi Yoshida, Teruo Hagiwara, Tatsuo Miyamura

Article 2:
AN OUTBREAK OF HAND-FOOT-AND MOUTH DISEASE AND SUDDEN DEATHS AMONG CHILDREN
IN MALAYSIA
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 [? - Mod CHC] from HFMD patients. The
serum studies identified Group B enteroviruses [Coxsackie B viruses? -
Mod.CHC]. 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
--
Dr. C.L. Wong
M.B.,B.S. (London), M.R.C.P. (U.K.)
Physician in private practice
Kuching, Sarawak
Malaysia
e-mail: wongcl@pop.jaring.my
[These articles do not address the possibility that more than EV71 virus
was involved in this epidemic. Nonetheless, we are grateful to Dr. Wong
for having gone to all the trouble of having these papers translated and
for sending them to ProMED-mail.
The sentence "The cause of the outbreak of sudden deaths among children in
Malaysia has not been identified." may be all the more remarkable for what
it does not say. We look forward to obtaining an official report of the
key information still missing from this puzzle. - Mod.CHC]
......................................chc/es
--
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