Excerpts: Health Agencies Describe Dengue Fever as Major Concern

27 August 2001

Excerpts: Health Agencies Describe Dengue Fever as Major Concern

Venezuelan president declares health emergency

Venezuelan President Hugo Chavez declared a health emergency August 23 in response to the growing number of cases of dengue fever in his country. The mosquito-borne disease has caused some 600 deaths in Venezuela, with more than 24,000 infections, according to news reports.

Dengue fever has not received the attention devoted to more life-threatening conditions like HIV/AIDS, but public health agencies have been watching its increasing occurrence across the globe with growing concern.

In a 1997 document about dengue, the U.S. Centers for Disease Control and Prevention (CDC) said the spread of the illness "as a major public health problem has been most dramatic in the American region."

A fact sheet about the disease from the World Health Organization (WHO) notes that about 2,500 million people are at risk of the disease in more than 100 nations. Prior to 1970, WHO reports, dengue fever occurred in only nine nations.

Four distinct virus cause dengue and the related condition dengue hemorrhagic fever (DHF). Dengue is a severe flu-like illness that is rarely fatal, but DHF is a more serious complication that can lead to sudden death. Surviving a bout of the disease caused by one virus does not provide immunity to the disease. On the contrary, the WHO fact sheet says that serial infection may make the patient more susceptible to DHF.

Both CDC and WHO report that control of mosquito populations is the best way to control and prevent dengue fever. In the rapidly expanding cities of developing world nations in tropical climes, mosquito control becomes increasingly difficult and both health agencies cite that demographic shift as a likely cause of the rapid spread of the disease in the last two decades.

Further information is available at http://www.who.int/emc/diseases/ebola/Denguepublication/index.html

The full text from the CDC is available at www.cdc.gov/ncidod/dvbid/dengue.htm

Following are excerpted text from CDC and WHO providing background on the history, spread, symptoms and outlook for dengue fever:

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WORLD HEALTH ORGANIZATION

Fact Sheet

Revised November 1998

DENGUE AND DENGUE HAEMORRHAGIC FEVER

Dengue is a mosquito-borne infection which in recent years has become a major international public health concern. Dengue is found in tropical and sub-tropical regions around the world, predominately in urban and peri-urban areas. Dengue haemorrhagic fever (DHF), a potentially lethal complication, was first recognized during the 1950s and is today a leading cause of childhood mortality in several Asian countries. There are four distinct, but closely related, viruses which cause dengue. Recovery from infection by one provides lifelong immunity against that serotype but confers only partial and transient protection against subsequent infection by the other three. Indeed, there is good evidence that sequential infection increases the risk of more serious disease resulting in DHF.

Prevalence

The global prevalence of dengue has grown dramatically in recent decades. The disease is now endemic in more than 100 countries in Africa, the Americas, the Eastern Mediterranean, South-East Asia and the Western Pacific (see Table 1). South-East Asia and the Western Pacific are most seriously affected. Before 1970 only nine countries had experienced DHF epidemics, a number which had increased more than four-fold by 1995. Some 2500 million people -- two fifths of the world's population -- are now at risk from dengue. WHO currently estimates there may be 50 million cases of dengue infection worldwide every year. In 1998 alone, there were more than 616,000 cases of dengue in the Americas, of which 11,000 cases were DHF. This is greater than double the number of dengue cases which were recorded in the same region in 1995. Not only is the number of cases increasing as the disease is spreading to new areas, but explosive outbreaks are occurring. In Brazil nearly 475,000 cases were reported between January and October 1998 - more than were reported from the entire continent in previous years.

Some other statistics:

-- During epidemics of dengue, attack rates among susceptibles are often 40 - 50%, but may reach 80 - 90%.

-- An estimated 500,000 cases of DHF require hospitalisation each year, of whom a very large proportion are children and roughly 5% die.

-- Without proper treatment, DHF case fatality rates can exceed 20%. With modern intensive supportive therapy, can be reduced to less than 1%.

The spread of dengue is attributed to expanding geographic distribution of the four dengue viruses and of their mosquito vectors, the most important of which is the predominantly urban species Aedes aegypti. A rapid rise in urban populations is bringing ever greater numbers of people into contact with this vector, especially in areas which are favourable for mosquito breeding e.g., where household water storage is common and where solid waste disposal services are inadequate.

Transmission

Dengue viruses are transmitted to humans through the bites of infective female Aedes mosquitoes. Mosquitoes generally acquire the virus while feeding on the blood of an infected person. Once infective a mosquito is capable of transmitting the virus to susceptible individuals for the rest of its life, during probing and blood feeding. Infected female mosquitoes may also transmit the virus to the next generation of mosquitoes by transovarial transmission i.e. via its eggs, but the role of this in sustaining transmission of virus to humans has not yet been delineated. Humans are the main amplifying host of the virus, although studies have shown that in some parts of the world monkeys may become infected and perhaps serve as a source of virus for uninfected mosquitoes. The virus circulates in the blood of infected humans for 2-7 days, at approximately the same time as they have fever; Aedes mosquitoes may acquire the virus when they feed on an individual at this time.

Characteristics

Dengue fever is a severe, flu-like illness that affects infants, young children and adults but rarely causes death. The clinical features of dengue fever vary according to the age of the patient. Infants and young children may have a non-specific febrile illness with rash. Older children and adults may have either a mild febrile syndrome or the classical incapacitating disease with abrupt onset and high fever, severe headache, pain behind the eyes, muscle and joint pains, and rash. Dengue haemorrhagic fever is a potentially deadly complication that is characterized by high fever, haemorrhagic phenomena-often with enlargement of the liver-and in severe cases, circulatory failure. The illness commonly begins with a sudden rise in temperature accompanied by facial flush and other non-specific constitutional symptoms of dengue fever. The fever usually continues for 2-7 days and can be as high as 40-41��C, possibly with febrile convulsions and haemorrhagic phenomena. In moderate DHF cases, all signs and symptoms abate after the fever subsides. In severe cases, the patient's condition may suddenly deteriorate after a few days of fever; the temperature drops, followed by signs of circulatory failure, and the patient may rapidly go into a critical state of shock and die within 12-24 hours, or quickly recover following appropriate volume replacement therapy.

Treatment

There is no specific treatment for dengue fever. However, careful clinical management by experienced physicians and nurses frequently save the lives of DHF patients. With appropriate intensive supportive therapy, mortality may be reduced to less than 1%. Maintenance of the circulating fluid volume is the central feature of DHF case management

Immunization

Vaccine development for dengue and DHF is difficult because any of four different viruses may cause disease, and because protection against only one or two dengue viruses could actually increase the risk of more serious disease. Nonetheless, progress is gradually being made in the development of vaccines that may protect against all four dengue viruses. Such products could be commercially available within several years.

Prevention and Control

At present, the only method of controlling or preventing dengue and DHF is to combat the vector mosquitoes. In Asia and the Americas, Aedes aegypti breeds primarily in man-made containers like earthenware jars, metal drums and concrete cisterns used for domestic water storage, as well as discarded plastic food containers, used automobile tyres and other items that collect rainwater In Africa it also breeds extensively in natural habitats such as tree holes and leaf axils. In recent years, Aedes albopictus, a secondary dengue vector in Asia, has become established in the United States and several Latin American and Caribbean countries as well as two European and one African state. The rapid geographic spread of this species has been largely attributed to the international trade in used tyres.

Vector control is implemented using environmental management and chemical methods. Proper solid waste disposal and improved water storage practices, including covering containers to prevent access by egg laying female mosquitoes are among methods which are encouraged through community-based programmes. The application of appropriate insecticides to larval habitats, particularly those which are considered useful by the householders, e.g. water storage vessels, prevent mosquito breeding for several weeks but must be re-applied periodically. Small, mosquito-eating fish have also been used with some success. During outbreaks, emergency control measures may also include the application of insecticides as space sprays to kill adult mosquitoes using portable or truck-mounted machines or even aircraft. However, the killing effect is only transient, variable in its effectiveness because the aerosol droplets may not penetrate indoors to microhabitats where adult mosquitoes are sequestered, and the procedure is costly and operationally very demanding. Regular monitoring of the vectors' susceptibility to the most widely used insecticides is necessary to ensure the appropriate choice of chemicals. Active monitoring and surveillance of the natural mosquito population should accompany control efforts in order to determine the impact of the programme.

More information

For more information on Dengue, including a list of those countries where outbreaks have occurred, please consult WHO's publication on the subject at the following website:

http://www.who.int/emc/diseases/ebola/Denguepublication/index.html

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U.S. CENTERS FOR DISEASE CONTROL AND PREVENTION

Division of Vector-Borne Infectious Diseases
National Center for Infectious Diseases

Revised June 1997

Information on Dengue Fever and Dengue Hemorrhagic Fever

Perspectives

Dengue and dengue hemorrhagic fever (DHF) are caused by one of four closely related, but antigenically distinct, virus serotypes (DEN-1, DEN-2, DEN-3, and DEN-4), of the genus Flavivirus. Infection with one of these serotypes does not provide cross-protective immunity, so persons living in a dengue-endemic area can have four dengue infections during their lifetimes. Dengue is primarily a disease of the tropics, and the viruses that cause it are maintained in a cycle that involves humans and Aedes aegypti, a domestic, day-biting mosquito that prefers to feed on humans. Infection with dengue viruses produces a spectrum of clinical illness ranging from a nonspecific viral syndrome to severe and fatal hemorrhagic disease. Important risk factors for DHF include the strain and serotype of the infecting virus, as well as the age, immune status, and genetic predisposition of the patient.

History of Dengue

The first reported epidemics of dengue fever occurred in 1779-1780 in Asia, Africa, and North America; the near simultaneous occurrence of outbreaks on three continents indicates that these viruses and their mosquito vector have had a worldwide distribution in the tropics for more than 200 years. During most of this time, dengue fever was considered a benign, nonfatal disease of visitors to the tropics. Generally, there were long intervals (10-40 years) between major epidemics, mainly because the viruses and their mosquito vector could only be transported between population centers by sailing vessels.

A global pandemic of dengue began in Southeast Asia after World War II and has intensified during the last 15 years. Epidemics caused by multiple serotypes (hyperendemicity) are more frequent, the geographic distribution of dengue viruses and their mosquito vectors has expanded, and DHF has emerged in the Pacific region and the Americas. In Southeast Asia, epidemic DHF first appeared in the 1950s, but by 1975 it had become a leading cause of hospitalization and death among children in many countries in that region.

Current Trends

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. The recent epidemics in Sri Lanka and India were associated with multiple dengue virus serotypes, but DEN-3 was predominant and was genetically distinct from DEN-3 viruses previously isolated from infected persons in those countries. After an absence of 35 years, epidemic dengue fever occurred in both Taiwan and the People's Republic of China in the 1980s. The People's Republic of China had a series of epidemics caused by all four serotypes, and its first major epidemic of DHF, caused by DEN-2, was reported on Hainan Island in 1985. 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 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.

Despite poor surveillance for dengue in Africa, epidemic dengue fever caused by all four serotypes has increased dramatically since 1980. Most activity has occurred in East Africa, and major epidemics were reported for the first time in the Seychelles (1977), Kenya (1982, DEN-2), Mozambique (1985, DEN-3), Djibouti (1991-92, DEN-2), Somalia (1982, 1993, DEN-2), and Saudi Arabia (1994, DEN-2). Epidemic DHF has been reported in neither Africa nor the Middle East, but sporadic cases clinically compatible with DHF have been reported from Mozambique, Djibouti, and Saudi Arabia.

The emergence of dengue/DHF as a major public health problem has been most dramatic in the American region. In an effort to prevent urban yellow fever, which is also transmitted by Ae. aegypti, the Pan American Health Organization organized a campaign that eradicated Ae. aegypti from most Central and South American countries in the 1950s and 1960s. As a result, epidemic dengue occurred only sporadically in some Caribbean islands during this period. The Ae. aegypti eradication program, which was officially discontinued in the United States in 1970, gradually eroded elsewhere, and this species began to reinfest countries from which it had been eradicated. In 1997, the geographic distribution of Ae. aegypti is wider than its distribution before the eradication program. . . .

In 1970, only DEN-2 virus was present in the Americas, although DEN-3 may have had a focal distribution in Colombia and Puerto Rico. In 1977, DEN-1 was introduced and caused major epidemics throughout the region over a 16-year period. DEN-4 was introduced in 1981 and caused similar widespread epidemics. Also in 1981, a new strain of DEN-2 from Southeast Asia caused the first major DHF epidemic in the Americas (Cuba). This strain has spread rapidly throughout the region and has caused outbreaks of DHF in Venezuela, Colombia, Brazil, French Guiana, Suriname, and Puerto Rico. By 1997, 18 countries in the American region had reported confirmed DHF cases, and DHF is now endemic in many of these countries. . . .

DEN-3 virus recently reappeared in the Americas after an absence of 16 years. This serotype was first detected in association with a 1994 dengue/DHF epidemic in Nicaragua. Almost simultaneously, DEN-3 was confirmed in Panama and, in early 1995, in Costa Rica. In Nicaragua, considerable numbers of DHF cases were associated with the epidemic, which was apparently caused by DEN-3. In Panama and Costa Rica, the cases were classic dengue fever.

Viral envelope gene sequence data from the DEN-3 strains isolated from Panama and Nicaragua have shown that this new American DEN-3 virus strain was likely a recent introduction from Asia since it is genetically distinct from the DEN-3 strain found previously in the Americas, but is identical to the DEN-3 virus serotype that caused major DHF epidemics in Sri Lanka and India in the 1980s. As suggested by the finding of a new DEN-3 strain, and the susceptibility of the population in the American tropics to it DEN-3 spread rapidly throughout the region caused major epidemics of dengue/DHF in Central America in 1995.

In 1997, dengue is the most important mosquito-borne viral disease affecting humans; its global distribution is comparable to that of malaria, and an estimated 2.5 billion people live in areas at risk for epidemic transmission). Each year, tens of millions of cases of dengue fever occur and, depending on the year, up to hundreds of thousands of cases of DHF. The case-fatality rate of DHF in most countries is about 5%; most fatal cases are among children and young adults. . . .

There is a small, but significant, risk for dengue outbreaks in the continental United States. Two competent mosquito vectors, Ae. aegypti and Aedes albopictus, are present and, under certain circumstances, each could transmit dengue viruses. This type of transmission has been detected three in the last 16 years in south Texas (1980, 1986, and 1995) and has been associated with dengue epidemics in northern Mexico. Moreover, numerous viruses are introduced annually by travelers returning from tropical areas where dengue viruses are endemic. From 1977 to 1994, a total of 2,248 suspected cases of imported dengue were reported in the United States. Although some specimens collected were not adequate for laboratory diagnosis, 481(21%) cases were confirmed as dengue. Many more cases probably go unreported each year because surveillance in the United States is passive and relies on physicians to recognize the disease, inquire about the patient's travel history, obtain proper diagnostic samples, and report the case. These data suggest that southern Texas and the southeastern United States, where Ae. aegypti is found, are at risk for dengue transmission and sporadic outbreaks.

The reasons for this dramatic global emergence of dengue/DHF as a major public health problem are complex and not well understood. However, several important factors can be identified. First, effective mosquito control is virtually nonexistent in most dengue-endemic countries. Considerable emphasis for the past 20 years has been placed on ultra-low-volume insecticide space sprays for adult mosquito control, a relatively ineffective approach for controlling Ae. aegypti. Second, major global demographic changes have occurred, the most important of which have been uncontrolled urbanization and concurrent population growth. These demographic changes have resulted in substandard housing and inadequate water, sewer, and waste management systems, all of which increase Ae. aegypti population densities and facilitate transmission of Ae. aegypti-borne disease. Third, increased travel by airplane provides the ideal mechanism for transporting dengue viruses between population centers of the tropics, resulting in a constant exchange of dengue viruses and other pathogens. Lastly, in most countries the public health infrastructure has deteriorated. Limited financial and human resources and competing priorities have resulted in a "crisis mentality" with emphasis on implementing so-called emergency control methods in response to epidemics rather than on developing programs to prevent epidemic transmission. This approach has been particularly detrimental to dengue control because, in most countries, surveillance is (just as in the U.S.) very inadequate; the system to detect increased transmission normally relies on reports by local physicians who often do not consider dengue in their differential diagnoses. As a result, an epidemic has often reached or passed transmission before it is detected.

Future Outlook

No dengue vaccine is available. Recently, however, attenuated candidate vaccine viruses have been developed in Thailand. These vaccines are safe and immunogenic when given in various formulations, including a quadrivalent vaccine for all four dengue virus serotypes. Efficacy trials in human volunteers have yet to be initiated. Research is also being conducted to develop second-generation recombinant vaccine viruses; the Thailand attenuated viruses are used as a template. Therefore, an effective dengue vaccine for public use will not be available for 5 to 10 years.

Prospects for reversing the recent trend of increased epidemic activity and geographic expansion of dengue are not promising. New dengue virus strains and serotypes will likely continue to be introduced into many areas where the population densities of Ae. aegypti are at high levels. With no new mosquito control technology available, in recent years public health authorities have emphasized disease prevention and mosquito control through community efforts to reduce larval breeding sources. Although this approach will probably be effective in the long run, it is unlikely to impact disease transmission in the near future. We must, therefore, develop improved, proactive, laboratory-based surveillance systems that can provide early warning of an impending dengue epidemic. At the very least, surveillance results can alert the public to take action and physicians to diagnose and properly treat dengue/DHF cases.

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