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The EINet listserv was created to foster discussion, networking, and collaboration in the area of emerging infectious diseases (EID's) among academicians, scientists, and policy makers in the Asia–Pacific region. We strongly encourage you to share their perspectives and experiences, as your participation directly contributes to the richness of the "electronic discussions" that occur. To respond to the listserv, use the reply function. SPECIAL DENGUE EDITION
1. HIGHLIGHT ON DENGUE IN ASIA Dengue is by far the most common vector borne disease worldwide, with
an expanding geographic and serotype distribution; therefore the EINet
decided to consolidate recent information on dengue in Asia into this
special edition. About two thirds of the world's population live in environments
where DHF is either endemic or epidemic, and an estimated 80 million persons
are infected with dengue viruses each year (1).
At the 46th World Health Assembly held in Geneva in May 1993, a resolution
was passed to make the prevention and control of dengue a priority. Since
then, SE Asia has witnessed a dramatic increase in the number of dengue
cases in many economies. Dengue is reaching the peak of a roughly five–year
cycle in Southeast Asia, striking people with low immunity levels.
The geographic distribution of dengue hemorrhagic
fever/dengue shock syndrome (DHF/DSS) has been expanding and
now can be found in tropical areas of Asia, the Pacific, and
the Americas, including Latin America and Mexico. In
Southeast Asia, epidemic DHF was first recognized as a new
disease in the Philippines in 1953, and by 1975 it had
become a leading cause of hospitalization and death among
children in many countries. In the 1980s, DHF began a second
expansion into Asia when Sri Lanka, India, and the Maldive
Islands had their first major DHF epidemics; Pakistan first
reported an epidemic of dengue fever in 1994.
DHF has been seen in Thailand, Vietnam, Cambodia,
Malaysia, Singapore, Indonesia, Sri Lanka, India, and PRC.
Thailand has been facing an unusually high incidence of
dengue fever. In the first three months of this year, dengue
took 31 lives and affected 10,197 patients, a threefold
increase over the previous year (Bangkok Post, 24/4/98).
Thailand recorded more cases than its neighbouring countries
because of the presence of all four strains of the virus,
while other countries such as Malaysia and Indonesia have
reported only three strains (Bangkok Post 19/4/98). Although
in any year, there is usually a predominant type of virus
isolated from patients with DHF, the proportion attributable
to the dominant type is usually <50%. Every 2ן years,
the dominant type changes; most frequently, DENמ virus has
been the dominant type, but the largest annual epidemic
before 1997פ was in 1987, caused by DENן virus (Colonel
Bruce Innis, Walter Reed Army Institute of Research
Washington, DC, PROMED).
In Vietnam, numbers of dengue cases were an increase of
13% over last April. In Malaysia, where the disease is
endemic, dengue cases have risen 6% since last year. In
addition, encephalitis cases associated with dengue viruses
have been documented, and vertical transmission has also
been reported in the last two years. Singapore also had a
resurgence of dengue/DHF from 1990 to 1994, after a
successful control program had prevented significant
transmission for over 20 years. In fact, cases reported so
far this year are double that in the same period last year
(Associated Press, 1/5/98).
In Indonesia, there seems to be no sign of decrease in
cases. The number of deaths recorded is believed to be only
a fraction of the actual number of fatalities throughout the
country. In Jakarta, the epidemic has triggered a blood
transfusion crisis. The death toll is expected to rise, as
government–run hospitals and blood donor agencies in Jakarta
do not have a sufficient supply of blood badly needed by the
dengue patients. In Vietnam, dengue is the largest killer in
the country, and dengue–infected people numbered 13,528 in
the first quarter of 1998, or 238.8% higher than in the same
period last year (Vietnam News).
Sri Lanka reported its first outbreak in 1989. The recent
epidemics in Sri Lanka and India were associated with
multiple dengue virus serotypes, but DENן was predominant
and was genetically distinct from DENן viruses previously
isolated from infected persons in those countries. Epidemic
dengue fever resurfaced in both Chinese Taipei and the PRC
in the 1980s after being absent for 35 years. The PRC had a
series of epidemics caused by all four serotypes, and its
first major epidemic of DHF, caused by DENמ, was reported
on Hainan Island in 1985.
In other countries of Asia where DHF is endemic, the
epidemics have become progressively larger in the last 15
years. In the Pacific, dengue viruses were reintroduced in
the early 1970s after an absence of more than 25 years.
Epidemic activity caused by all four serotypes has
intensified in recent years with major epidemics of DHF on
several islands. DHF/dengue shock syndrome has also been
reported for the first time in New Caledonia, Tahiti, and
Saipan (N. Marianas). In New Caledonia, about half the 1,819
dengue cases reported in the 1st quarter of 1998 were new
cases, 99% of which were confirmed DENמ (the remaining ones
were type DENן). Early this year, there were larger than
normal outbreaks of dengue fever in the Australian coastal
city of Cairns as well as Fiji and other South Pacific
islands.
On the positive side, dengue cases have decreased in some
areas. Manila City Government recently announced a
significant decrease in the number of cases. In other areas,
well organised control efforts have proven to be effective
in slowing down transmission, such as in the Western
Division of Fiji.
Dengue fever is predominantly spread by the striped
_Aedes aegypti_ mosquito, capable of urban endemicity,
though the less efficient rural vector, _Aedes albopictus_,
is native to the region. Duane Gubler recently commented
that there are three excellent natural experiments with
_Aedes albopictus_ and dengue. Hawaii and Guam have had only
_Ae. albopictus_ for more than 50 years, with no _Ae.
aegypti_. Although epidemic dengue has occurred all around
them on islands where _Ae. aegypti_ was present, neither has
had an outbreak of dengue since 1944. In Taiwan,
_Ae.aegypti_ occurs only in the south of the island, while
_Ae. albopictus occurs all over the island. The epidemics of
dengue in Taiwan, since reintroduction of dengue in 1981,
have all been in the south. In 1996 and 1997, there was
local transmission of dengue in Taipei where only _Ae.
albopictus_ supposedly occurred, but the cases were sporadic
and few in number. <PROMED, 11㪝㫺>
The rise of dengue in tropical and subtropical areas of
the world is explained by factors such as rapid population
growth associated with urbanization in tropical regions,
inadequate municipal waste water disposal and drainage,
difficulties in refuse disposal, lack of effective mosquito
control, viral serotypes that followed human migration among
tropical urban centers due to increasing international air
travel, and development of hyperendemicity (multiple
serotypes) in the Pacific Region and the Americas.
Since dengue tends to occur during the October–April
monsoons season in SE Asia, El Nino has been recently blamed
for prolonging and spreading dengue through the winter
season.
Country specific conditions also apply. For example, Dr
Sujitra, technical consultant to the Thai CDC, believes that
the rise in dengue cases in Thailand last year can also be
attributed to insufficient publicity about the disease and
"() failure of political will, (which) has obstructed public
support in controlling the spread of dengue." In addition,
Dr Prayura, the Thai CDC`s former director general explained
that another obstacle in addressing the importance of
controlling DHF in Thailand is its continuously fluctuating
trend: "Since the reported rate of incidence of dengue fever
rises and falls every alternate year, its statistics often
show average numbers that are not considered high. The
severity of the illness is often ignored and only its
statistics, calculated on the base of fluctuation in
reported cases, is taken into account in formulating
policies."
Rapid and accurate diagnosis leads to earlier treatment.
In the case of dengue, however, because clinical symptoms
are initially nonspecific, dengue can be difficult to
distinguish from other viral, bacterial, and parasitic
infections. Correct diagnosis requires a detailed clinical
summary, thorough epidemiologic information (including
recent travel history), and a diagnostic laboratory
test.
Demographic changes in the population most affected by
dengue has been observed in Thailand. Dr Sujitra Nimmanmit,
a pediatrician and technical consultant to the Thai CDC,
said many Thai doctors tend to overlook the possibility of
dengue fever with older children and adults. This is because
in Thailand dengue fever previously occurred among young
children under 5 years old, while recent cases of dengue
fever have occurred more among older children. Reports of
patients treated in state hospitals show that 70㫣% of
patients with dengue fever are between 5 and 14 years of age
(Bangkok Post, 24㪜㫺). DHF is often found to be more
severe among adolescents and can lead to shock and death
because of slow diagnosis of the infection. In addition,
many cases in Thailand last year were reported among adults
up to 40 years old, including cases of severe dengue. Theory
on the susceptibility of adults is discussed in the last
section of this bulletin (Dengue Serotypes And DHF: Lessons
From Cuba).
Dr. Sujitra advises that it is very important to suspect
dengue fever if a patient is suffering from a constantly
high fever for two to four days. In the case of dengue, the
condition can lead to a shock syndrome when the fever
recedes four to eight days later. Other unusual
manifestations include acute renal failure and hemolytic
uremic syndrome. The emergence of such unusual clinical
manifestations should also be monitored and documented in
other dengue–endemic countries. Despite intensive efforts by
the countries in the region to control the vectors, the
disease is still on the rise.
Correct and timely treatment is integral to the control
of the human toll of dengue. The severe hemorrhagic form,
DHF/dengue shock syndrome (DSS), has an average incubation
period of 4 to 6 days before sudden onset of fever and
nonspecific signs and symptoms. Because the major
pathophysiologic abnormality observed in DHF/DSS is
increased vascular permeability and leakage of plasma from
the vascular compartment, early fluid replacement is
effective. In mild cases, normal saline with 5% glucose or
Ringer's lactate is recommended; for more serious cases,
plasma or colloids <Duane Gubler, Director of Division of
Vector Borne Infectious Diseases, NCID, US CDC>. Fresh
frozen plasma and/or concentrated platelets are indicated in
cases of massive bleeding. Acetaminophen is recommended to
control fever, and sedatives may be needed if the patient is
agitated. Oxygen therapy should be given to all patients in
shock. Treatment should be initiated immediately if any of
the following signs or symptoms of shock are present:
restlessness or lethargy, cold extremities or circumoral
cyanosis, rapid and weak pulse, narrowing of the pulse
pressure (20mm Hg or less), or hypotension <Infect Med
15(4):244𤫫, 1998>. Dr. Vichai Chokevivat, a senior
expert of the Thai CDC, warns that people with high fever
continuously for two–seven days and suspected of suffering
dengue fever should avoid aspirin, for it would cause more
bleeding in the stomach.
A tetravalent live attenuated vaccine developed at
Mahidol University, Thailand, is being field–tested, and the
preliminary results are promising. However, Dr Vichai
Chokeviwat, of the Thai CDC, said that though Thailand is
actively involved in the research of an anti–dengue vaccine,
"we should not only hope for a vaccine because it has yet to
start the third phase of its trial, and it would take at
least another five years to accomplish the task."
According to the CDC, the most cost–effective approach to
control dengue and DHF is larval source reduction in
disease–endemic areas. Programs should use both government
and community resources to integrate environmental
sanitation with the use of insecticides and biologic
controls, targeted to breeding grounds such as tire
dumps.
Many economies center control efforts on eliminating the
mosquitoes' favoured breeding grounds, an approach employed
in campaigns from Hong Kong to New Caledonia. In Thailand, a
mass campaign to destroy mosquitoes and sources of their
breeding will be launched in June. In Singapore, the
Environment Minister used the media to encourage families to
inspect their own premises. In addition, mosquito breeding
sites in Singapore are systematically counted–�
construction sites that were found breeding the _Aedes_
mosquito in 1997.
Health officials seem to agree that constant community
vigilance is imperative. In economies where dengue fever is
endemic, officials regularly urge people to empty stagnant
water from old tires, trash cans and flower pots. Singapore
Environment Minister Yeo Cheow Tong notes that "(our)
studies have shown that in a neighbourhood, all you need are
two homes out of a hundred homes to breed the Aedes
mosquitoes and there will a dengue outbreak risk there," he
said. "Ninety–eight families can be very vigilant but if two
families are complacent, you`ll get dengue in the
neighbourhood. This is why the public education programme
must be the lynchpin in the battle." Similarly, Dr Sujitra,
technical consultant to the Thai CDC, emphasized in a media
interview that dengue fever can be caused with only three
mosquitoes in the house, adding that community participation
and health education about controlling the vector is the
most important prevention measure.
Other dengue control policies are less common. In Brazil,
a northwestern state newspaper asserts that the government's
weapon to fight the dengue vector is a candle made of a
plant called andiroba, which functions as a repellant.
President Suharto of Indonesia has ordered a campaign in
which fumigation teams go door–to–door in neighborhoods of
Jakarta, where crowded slums with open sewers offer
mosquitoes a plethora of places to breed.
Research for new methods of control continues. The Thai
Public Health Minister Rakkiat Sukthana said that the Thai
Medical Services Department is working on testing the use of
a bacteria found in the soil, which when added to water
wards off mosquitoes and is not harmful to humans, said.
While the Bangkok Post report did not name the bacteria, it
noted simply that the side–effects of its use are being
tested.
The 1997 Cuban epidemic is once again clarifying our
understanding of the secondary infection/DHF phenomenon. A
recent thread in PRO–MED on how the epidemic supported the
sequential infection hypothesis that DHF can be elicited by
multiple different infection sequences.
Until the introduction of DEN 2 virus to Cuba in 1997, no
transmission had been documented since 1981. The 1997
epidemic included a pattern in which persons below age 20
did not have antibodies to DEN 1 virus, and persons 20 and
older were immune to DEN 1 virus. So in 1997, while the
younger cohort experienced primary infection, it was the
adult age group that experienced secondary infection and
severe disease. Classical DHF predominated. This illustrates
that enhanced dengue disease can occur at an interval of 20
years, and so that one could presume that the sensitizing
interval can be a lifetime. In other words, people who have
had multiple experiences with multiple dengue virus types
are immune to reinfection with these viruses but are the
very people who are at risk for DHF (unless they have had
all four types). In SE Asia, where all dengue types
circulate, adults are no longer susceptible to dengue virus
infections. According to Colonel Bruce Innis (Walter Reed
Army Institute of Research Washington, DC), transmission of
all 4 dengue types are so intense in some urban regions in
SE Asia that persons reaching adulthood are at little risk
of developing the disease. He explains this to be the case
of Thailand, Burma, Cambodia, and Vietnam, and perhaps to a
lesser degree, Indonesia.
However, one may be unable to predict a population`s risk
for DHF based purely upon past patterns of DEN exposure.
Exposure to a heterologous DEN infection even after a long
interval may be more risky for DHF than commonly estimated.
Additional information from India and Cuba outbreaks about
the risk factors for severe disease and death (and
information on the viruses implicated) would be quite useful
in guiding those interested in dengue vaccines. Next, with
access to clinical records and serological results, the
scientific community should be able to tease out the
clinical differences between primary DEN 2 illnesses and
secondary DEN 2 illnesses in adults. In some outbreaks, i.e,
New Delhi, 1996, gastrointestinal bleeding seemed to be a
major clinical sign. It was not clear whether bleeding
followed leaky capillary syndrome or was an independent
phenomenon. Closer study of the Cuba outbreak may help us
understand more precisely the pathophysiology of severe
dengue infections in adults. <COL Bruce L. Innis, Walter
Reed Army Inst. of Research, Washington, DC> <Scott
Halstead, halstes@ONR.NAVY.MIL>
Associated Press, 01/05/98
The APEC EINet listserv was established to enhance collaboration among academicians
and public health professionals in the area of emerging infections surveillance
and control. Subscribers are encouraged to share their own material with their
colleagues in the Asian–Pacific Rim by addressing comments to apec–ein@u.washington.edu.
To subscribe or unsubscribe, please contact Nedra Floyd Pautler at pautler@u.washington.edu.
Further information about the APEC Emerging Infections Network is available at
http://www.apec.org/infectious.
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© 1998, The University of Washington |
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