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ev71
The Impact of Enterovirus 71 Epidemic in Taiwan
What is enterovirus?
Enteroviruses are a group of RNA viruses that
includes more the 60 types of viruses, including polio virus (3 types),
coxsackievirus A (23 types), coxsackievirus B (6 types), echo virus (30 types),
and enterovirus type 68 to 71. Unlike most respiratory viruses that can only
infect the respiratory tract, enteroviruses can also infect the gastrointestinal
tract. Therefore, they are named as enteroviruses. Herpangina (vesicles and
ulcers over the posterior part of the mouth) and hand–foot–and–mouth disease
(HFMD; oral ulcers, vesiculopapules of hands, foot, and buttock) are two
distinct clinical diseases caused by enteroviruses.
Routs of transmission
Enterovirus can be transmitted by
respiratory droplet, by fecal–oral route (virus excreted into the stool and then
ingested by someone else), or by person–to–person contact (important for
enterovirus 70 and coxsackievirus A24 that may cause acute hemorrhagic
conjunctivitis).
Epidemiology
In previous days, epidemics of enterovirus infection
occurred almost every year in Taiwan during warmer months. Because there are
more than 60 serotypes of enterovirus, a person may get similar diseases
repeatedly with different serotypes of the virus. The predominant serotype of
enterovirus in each epidemic usually differs from year to year.
Clinical Outcome
The enterovirus usually causes a mild disease
that can be recovered completely. For children with oral ulcers, the most
frequent complication is dehydration due to a poor oral intake. The infection is
occasionally complicated by meningitis, encephalitis, paralytic syndrome, and
myocarditis. The mortality rate is very low. In the past, the enterovirus may
endanger human life on two occasions: an invasion of the heart causing
myocarditis and heart failure, and a disseminated infection in infants less than
3ע months with septic pictures.
Enterovirus 71
Enterovirus 71 (EV71) is one distinct member of the
enterovirus family. Several reports on this virus indicated that it is
associated with a high rate of neurological complications, including
meningoencephalitis and nerve paralysis. In the literatures, there have been
three epidemics of EV71 infection with excess mortality. The first epidemic was
described in Bulgaria and caused 44 deaths in 1975. A mixed epidemic of EV71 and
a tick–borne encephalitis virus occurred in Hungary in 1978 and resulted in 45
deaths. Another epidemic of EV71 took place in Malaysia in 1997 and 29 deaths
were reported.
Epidemic of Enterovirus 71 in Taiwan
An epidemic of enterovirus infection occurred in Taiwan in 1998. Beginning
in late March, the number of cases of HFMD and herpangina reported by
sentinel physicians increased gradually. A total of 98,004 cases were
reported between March 29 and July 25, during the first wave of the epidemic.
The second wave was largely limited to the southern region, lasted from
September 6 to December 12, and included 24,166 cases. It peaked at 3177
cases during the week of October 4. The total number of cases reported
during the two waves from March 29 through the end of the year was 129,106,
which probably represents less than 10 percent of the estimated total
number of cases.(Fig.
1.)
There were 405 patients with severe disease, most of whom were five years
old or younger.
(Fig.2)
Complications included encephalitis, aseptic meningitis, pulmonary edema or
hemorrhage, acute flaccid paralysis, and myocarditis. Seventy–eight patients
died, 71 of whom (91 percent) were five years of age or younger. Among patients
from whom a virus was isolated, EV71 was present in 48.7 percent of outpatients
with uncomplicated HFMD or herpangina, 75 percent of hospitalized patients who
survived, and 92 percent of patients who died.
Among fatal and near fatal cases of enterovirus infection, almost all
isolates were EV71. Investigations on severe cases had identified only a few
significant risk factors, including a young age (89% of fatal cases were less
than 3 years of age), male sex (male: female = 6:4), location of residence
(severe cases clustered in Tao–Yuan, Tai–Chung and Chan–Hua area), and a history
of allergic disease.
The cause of excess mortality in the epidemic EV71 is a unique enterovirus in
that its infection is associated with a higher rate of neurological
complications than other types of enterovirus. This is true for all parts of the
world, including U.S.A., Australia, France, Japan, Sweden and so on. However, an
excess mortality of EV71 epidemic has been observed in only a few countries,
including Bulgaria (1975, 44 deaths), Hungary (1978, 45 deaths), and Malaysia
(1997, 31 deaths). The cause of different mortality rates in different areas
remains obscure. It is speculated that the neurovirulent potential of EV71
strains among these epidemics may be different. Analysis of fatal cases in
Taiwan indicated that EV71 can invade the brain stem and cause neurogenic
pulmonary edema that may lead to death within hours to days. Some authors
suggested that a viral sepsis syndrome may also contribute to the death.
Panic in the EV71 epidemic
The epidemic of EV71 infection resulted
in a panic in Taiwan. The news media reported new occurrences of severe cases
almost every day. Some parents took their children to other countries because of
an intense fear. Following the panic, there comes a chaos. The government was
blamed for the inability to control the epidemic. Physicians were blamed for the
inability to treat the disease. Some herbal drugs and various measures were
claimed to be effective for prevention or for treatment. Many people believed
that EV71 is a mutant of other pathogens, including avian influenza in Hong Kong
and foot–and–mouth disease in pigs. Patients were viewed as very dangerous and
no one would like to go near them. Some children did not go to school. Some
children were not vaccinated on schedule because their parents thought the
clinic was dangerous. The government closed swimming pools and other activities
for children, which action resulted in some economic loss.
Reasons of the panic
Several factors made EV71 epidemic hard to be
controlled and resulted in a panic:
- A rapidly fatal disease in previously healthy children: Most of the
fatal cases were below 3ס years of age and they were healthy in the past.
Some types of enterovirus infection may also be fatal in infants below 3ע
months. However, most fatal cases of EV71 were between 6 months and 3 years.
Among fatal cases, the duration between the onset of symptom and the admission
to a hospital ranged between 1.5 to 7 days (median 3 days), and 79% of fatal
cases expired within 24 hours after reaching a hospital. At the onset of
infection, there was not a clinical parameter that may predict a grave
outcome. Such a fulminant course of infection in a previously healthy child
was alarming and created an intense anxiety in the population.
- No effective treatment: There is no effective therapy against EV71
at present. Although an experimental antiviral agent, Pleconaril, can suppress
the growth of some enteroviruses, it has no effect on EV71 by in vitro test.
Intravenous immunoglobulin was given to some severe cases in the epidemic with
an aim to neutralize the disseminated virus in the body. However, there was no
apparent therapeutic effect. Many children still expired with such a
treatment.
- No effective means of prevention: Enterovirus infection is
difficult to prevent. Hand–washing and other means may lower the disease
incidence but not to the level of zero. Closing schools during an epidemic may
also be effective, but is not practical. Enterovirus may persist in
respiratory secretions of patients for up to 3נ weeks, and in stool of
patients for up to 6פ weeks. Closing schools means stopping the education of
all students for several months. The government could only recommend that
infected children should not attend a school for one week, in which period the
transmission potential is the greatest. A vaccine may provide an effective way
of prevention. However, the development of a vaccine needs several months and
this strategy is not practical for a sudden outbreak of EV71.
Lessons from the epidemic
According to some seroepidemiological
studies, about 50% of school–aged children had been infected by EV71 during the
epidemic. Seropositive rate for EV71 ranged between 10% and 40% in younger
children. Similar epidemic is not likely to occur in Taiwan in the next few
years. However, similar epidemic is likely to occur in other places and in
Taiwan in the future. The EV71 epidemic is a unique experience in medicine, not
only for Taiwan but also for the whole world. Our experiences suggest that a
conjoined effort of different countries is needed to combat EV71 infections.
Surveillance of EV71 in Southeast Asia may provide an early alarm system to
monitor the occurrence the epidemic. Conjoined efforts to study the virus in
detail will clarify the virulence potential of EV71, and the way to deal with
the infection. Development of a vaccine is also needed for us to be well
prepared before another epidemic occurs in the future.
Author: Ping–Ing Lee, MD, PhD
Department of Pediatrics
National Taiwan University Hospital
Contact: Data Center of Enterovirus Epidemic
Center for Disease
Control in Taiwan
http://www.cdc.gov.tw
clark@cdc.gov.tw
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