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Vol. I, No. 9 ~~~ EINet News Briefs ~~~ 24㪝㫺

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  1. Highlight on dengue in Asia

    + The epidemic: scope and magnitude + Geographic distribution and epidemiology
    + Factors of reemergence
    + Diagnosis: new patterns
    + Treatment
    + Dengue control efforts and policy
    + Dengue serotypes and DHF: lessons from Cuba

  2. How to add colleagues to the EINet listserv


The epidemic: scope and magnitude

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.

Geographic distribution and epidemiology

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>

Factors of reemergence

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."

Diagnosis: new patterns

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."

Dengue control efforts and policy

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.


Dengue serotypes and DHF: lessons from Cuba

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>


(1) Monath TP: Yellow fever and dengue––The interactions of virus, vector and host in the emergence of epidemic disease. Semin Virol 5:133𤪁, 1994.


Associated Press, 01/05/98
Associated Press, 25/04/98
Bangkok Post, 19/10/97. Doctor warns that symptoms overlooked Bangkok Post, 24/04/98. Dengue fever risk highest in 40 years.
Bangkok Post, 31/12/97. El Nino affecting pattern of diseases: Dengue fever on the rise
CNN Interactive – 24㪜㫺
CNN Interactive – 4㪝㫺
CNN Interactive News – SINGAPORE, May 10 (Edited)
CNN International (Edited) 11㪝㫺
CNN Internet News – 20 April 98 Diario de Pernambuco, 09/05/98
Emerging Infectious Diseases, Vol 1, #2 Apr–June 1995
Emerging Infectious Diseases, Vol 4 number 1 Jan–Mar 1998.
Dengue and Dengue Hemorrhagic Fever (DHF).
Emerging Infectious Diseases, Vol 4, #2 Apr–June 1998
Pacific Public Health Surveillance Network (PACNET@LISTSERV.SPC.ORG.NC) & Tom Kiedrzynski <TomK@SPC.ORG.NC>
PROMED Indonesia – Dengue (04㪟) Dengue – New Caledonia (03) Dengue viruses, transmission by _Aedes Albopictus_ (03㪜, 06㪠)
South China Morning Post Straits Times Interactive, 17/3/98


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June 25, 1998

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