Dengue fever (DF) is an acute febrile viral disease frequently presenting with headaches, bone or joint and muscular pains, rash and leukopenia as symptoms. Dengue haemorrhagic fever (DHF) is characterized by four major clinical manifestations: high fever, haemorrhagic phenomena, often with hepatomegaly and, in severe cases, signs of circulatory failure. Such patients may develop hypovolaemic shock resulting from plasma leakage. This is called dengue shock syndrome (DDS) and can be fatal.
Dengue or dengue-like epidemics were reported throughout the nineteenth and early twentieth centuries in the Americas, southern Europe, North Africa, the eastern Mediterranean, Asia and Australia, and on various islands in the Indian Ocean, the south and central Pacific and the Caribbean. DF and DHF have steadily increased in both incidence and distribution over the past 40 years. Annually, it is estimated that there are 20 million cases of dengue infection, resulting in around 24 000 deaths.
Dengue virus infection may be asymptomatic or may cause undifferentiated febrile illness (viral syndrome), dengue fever (DF), or dengue haemorrhagic fever (DHF) including dengue shock syndrome (DSS). Infection with one dengue serotype gives lifelong immunity to that particular serotype, but there is no cross-protection for the other serotypes. The clinical presentation depends on age, immune status of the host, and the virus strain.
Undifferentiated fever: Infants, children and some adults who have been infected with dengue virus for the first time (i.e. primary dengue infection) will develop a simple fever indistinguishable from other viral infections. Maculopapular rashes may accompany the fever or may appear during defervescence.
Dengue fever: Dengue fever is most common in older children and adults. It is generally an acute biphasic fever with headache, myalgias, arthralgias, rashes and leucopenia. Although DF is commonly benign, it may be an incapacitating disease with severe muscle and joint pain (break-bone fever), particularly in adults, and occasionally with unusual haemorrhage. In dengue endemic areas, DF seldom occurs among indigenous people.
Dengue haemorrhagic fever: Dengue haemorrhagic fever is most common in children less than 15 years of age, but it also occurs in adults. DHF is characterized by the acute onset of fever and associated non-specific constitutional signs and symptoms. There is a haemorrhagic diathesis and a tendancy to develop fatal shock (dengue shock syndrome). Abnormal haemostasis and plasma leakage are the main patho-physiological changes, with thrombocytopenia and haemoconcentration presenting as constant findings. Although DHF occurs most commonly in children who have experienced secondary dengue infection, it has also been documented in primary infections.
Policy, Strategy and Objectives
There is no specific treatment for dengue fever. Moreover, vaccine development is difficult since any of four different dengue serotypes may cause the disease, and because protection against only one or two of these serotypes might actually increase the risk of more serious disease. Nevertheless, progress is being made in the development of vaccines that may protect against all four serotypes.
At present, the only method of controlling or preventing dengue and DHF is to combat the vector mosquito which, in Asia and America, breeds primarily in man-made containers such as domestic water storage vessels, bottles, cans, used tyres and other items that retain water. In Africa, however, it breeds both in artificial containers as well as in natural habitats.
Elements of a global strategy must include:
Although governments express concern about the continual spread and increase in dengue transmission and the increasing number of cases of DHF with its attendant mortality, this concern has yet to result in the development of efficient control programmes using all means available for vector control, which must include heightened awareness of the public and its full participation in vector control and prevention efforts.
Prevention and Control Options
The options available for prevention and control of epidemic dengue are rather limited. They include the following: Aedes aegypti eradication, ultra-low volume (ULV) insecticide application, regulation of air travel, development and use of dengue vaccines, preventive measures keyed to improved surveillance, and routine mosquito control efforts.
Obviously, the most effective preventive measure would be eradication of the Ae. aegypti vector. Unfortunately, experience in the Americas and elsewhere indicates that eradication is not a very realistic option at this time. To begin with, even though the technology is available, such eradication is a very expensive process. Moreover, in order to be effective over the long run, eradication must be achieved by all countries in the region.
That is not likely to occur any time soon. Finally, previous experience has shown that the large vertically structured programs which succeeded in eradicating Ae. aegypti from much of Central and South America in the 1950s and 1960s were not sustainable because ultimate responsibility for continued control was not transferred from the central government to local community residents (10).
A second option is to continue spraying insecticides, using ultra-low volume (ULV) applications, to kill adult mosquitoes. This has been the recommended way of controlling epidemic dengue for nearly 20 years (4). However, recent work in Puerto Rico, Trinidad, and Jamaica has shown ULV spraying to have little lasting impact on the natural wild mosquito population (11-13). This conclusion is supported by the fact that over the 20 years ULV spraying has been the recommended epidemic dengue control method, the distribution of DHF has expanded into the Pacific, Central America, and South America, and the incidence of severe and fatal hemorrhagic disease has increased dramatically (3, 6, 10). Hence, the available evidence strongly indicates that we should not continue to rely on this approach.
A third possibility might be to improve quarantine measures for air travelers, since we know that most dengue viruses are introduced into new areas by people who have visited places where those viruses are endemic. In the 1990s, however, that is probably not a viable option.
Ultimately, prevention of epidemic DHF may depend on vaccination. At present, however, no vaccines against dengue viruses are available for general use. Although several laboratories are working on development of both live attenuated and genetically engineered vaccines (14), the best available estimates suggest it will take at least 10 years before a safe, effective, and economical vaccine becomes available. That leaves only improved surveillance and integrated community-based mosquito control measures. Our program in Puerto Rico is based on making effective use of these options--by developing a proactive surveillance system sensitive enough to provide "early warning" of an impending dengue epidemic (15) and by establishing a rapid-response emergency vector control program that can supplement routine community-based mosquito control when evidence of a pending epidemic surfaces. Such an approach may not interrupt dengue transmission, but it doesn't have to. Rather, the goal is to prevent major dengue epidemics by reducing dengue incidence, the rationale being that if we can decrease incidence, we will automatically reduce the likelihood of DHF/DSS occurring in the Puerto Rican population.
The program in Puerto Rico and the U.S. Virgin Islands has five components: proactive surveillance; rapid-response emergency vector control; long-term, integrated community-based mosquito control; education of the medical community; and an emergency hospitalization plan. These components are being developed asdescribed below.
Surveillance for dengue and DHF/DSS can be of two basic types, reactive or proactive (15). Most endemic countries conduct reactive surveillance, with health authorities waiting until the medical community recognizes transmission before reacting to implement control measures. Unfortunately, this type of surveillance is very insensitive--because in the absence of epidemic transmission there is a low index of suspicion among physicians, and dengue is rarely diagnosed. Indeed, in most cases epidemics are near peak transmission before they are recognized and confirmed as dengue. By then it is generally too late to implement effective preventive measures that impact on transmission and thus on the course of the epidemic.
Our program seeks to employ a proactive surveillance system that will permit prediction of epidemic dengue (15). The most important component of this proactive system is virologic surveillance that is designed to monitor dengue virus transmission on the island, especially during interepidemic periods, and to continually provide information on where transmission is occurring, what virus serotype or serotypes are involved, and what type of illness is associated with the dengue infection. If this type of information is available, then without too much delay we should be able to detect the introduction of new dengue virus serotypes.
During periods of low dengue activity, cases of dengue-like illness are frequently not recognized as suspected dengue; many dengue infections present clinically as nonspecific viral illness, and physicians tend not to be on the lookout for dengue during interepidemic periods. For all these reasons, the surveillance program cannot rely on the medical community to monitor dengue virus introductions and transmission. Instead, the program depends upon regular monitoring of patients with viral syndrome to provide increased sensitivity and detect changes in the dengue virus picture.
Each week throughout the year, regardless of dengue activity, Puerto Rico Health Department clinics are asked to take blood samples from selected patients with viral syndrome whose illnesses had their onset three to 14 days earlier. These samples are picked up by Puerto Rico Health Department employees and taken to the laboratory, where they are processed on a weekly basis to isolate dengue virus and detect the presence of dengue-specific IgM antibody (15, 16).
In addition to this clinic work, a collaborative program with a small group of selected private physicians who are interested and who provide high-quality specimens and information has been initiated. All collaborators, both private physicians and clinics, are also asked to take samples from any patient with classical dengue or hemorrhagic manifestations in addition to viral syndrome.
This is a very hard type of surveillance to maintain, because many physicians refuse to take blood samples from patients they are "sure do not have dengue infection". It requires constant communication and encouragement, and even then many physicians do not take the blood samples requested. It is, however, the most critical part of a proactive surveillance system designed to detect new virus introductions.
Because dengue frequently presents as nonspecific febrile illness, especially in children, another component of the proactive system is surveillance designed to detect increased febrile illness in the community (15). Through a network of nurse epidemiologists, physicians, and environmental health workers on the island, any observed increase in febrile illness is reported and investigated immediately. Blood samples are obtained from representative cases, taken to the laboratory, and processed to isolate dengue virus and detect dengue-specific IgM antibody.
The proactive surveillance system also monitors all cases of hemorrhagic disease and all cases of viral illness that have a fatal outcome (17). This is done working in close collaboration with infectious disease physicians who would normally see such cases of severe and fatal disease. All cases reported are investigated, and blood specimens-as well as tissue specimens in fatal cases-are obtained for virologic and serologic study. Fresh-frozen tissue and formalin-fixed tissue may be examined by immunofluorescence, immunoperoxidase, or specific hybridization probes for specific dengue viral antigen.
Each of the above surveillance components has limitations and may not be very sensitive by itself. Collectively, however, they provide a relatively good early warning capability that has been sensitive enough to predict epidemic dengue activity in Puerto Rico. It should be noted that entomologic surveillance is not routinely carried out as part of this program because Ae. aegypti densities are usually well in excess of the level needed for epidemic transmission.
Rapid-response Emergency Vector control
The rationale for rapid-response emergency vector control depends on two points. These are as follows: (1) routine mosquito control will not reduce vector populations below the threshold levels required for epidemic transmission; and (2) there is a "lag time" of one to six months between introduction of a new dengue virus and peak epidemic transmission (17). Hence, to follow up on the surveillance program's early warning--if that program is sensitive enough to detect new viruses shortly after their introduction, or to detect increased dengue activity well in advance of epidemic transmission we must have an effective emergency vector control capacity that can be activated quickly. The aim of this activity is to contain an incipient epidemic in a limited area before it spreads to other parts of the island.
Baseline data required for this work include delineation of the most important and productive Ae. aegypti larval habitats in every major town and city, species associations with other potential mosquito vectors, and identification of major problem areas. This island survey was completed in 1985, and the results of the survey were computerized to improve rapid access to information on mosquito breeding sites in all major towns and cities in Puerto Rico and the U.S. Virgin Islands (San Juan Laboratories, unpublished data).
At the time of this writing (1991), details of the rapid-response program ha not been fully elaborated. Unfortunately the principal emergency control method, ULV application of insecticide for adult mosquito control, does not work very well (10-13). So, while research to improve the efficacy of adulticiding is under way, we must rely on other approaches as well.
The basic method employed is as follows: When surveillance data suggest increased dengue transmission or introduction of a new dengue virus serotype or strain, the situation is investigated immediately. Epidemiologic data are collected in an attempt to determine where the infection or infectons occurred and where it or they may have been transported. At the same time, a fully integrated mosquito control effort is launched on the basis of information taken from the computerized survey results.
This latter control activity, conducted by the environmental health program of the Puerto Rico Department of Health, is directed at the whole community. It uses radio, television, and newspaper public service announcements to inform the people of the problem and what to do about it. A targeted source reduction program is undertaken that emphasizes removing those larval habitats that are the most productive and treating those that cannot be removed with ABATE or other insecticide. In addition, ULV malathion spraying of the entire city where the case was detected may be carried out using truck-mounted equipment. Perifocal ULV spraying in the vicinity of the case, as is done in many countries, is not recommended because it is felt likely that by the time a case is detected and a response mounted the infection will have spread to a wider area.
Other government and civic organizations such as Civil Defense, the Civil Air Patrol, the Boy Scouts, primary and secondary schools, and Rotary Clubs are used in those communities where they are active and agree to participate. Specifically, these organizations help by distributing educational material and providing the public with information about where mosquitoes can be found and how to control them so as to prevent transmission.
In general, it is felt that the response to news of a threatening epidemic should involve community participation. Ultimate success of the program will depend on community participation and cooperation by citizens (most transmission occurs in the home) (10). Therefore, considerable effort is being placed on community education.
One major problem with this approach is the need for government approval in order to use the above community mobilization methods to help control the mosquitoes. Most governments are regrettably reluctant to give such approval, because they like to be 100% sure there is an epidemic before declaring an emergency. This type of thinking must change before an effective emergency response can be mounted.
Contingency Planning, Education of the Medical Community
Because the above long-term program for prevention and control of epidemic dengue will take several years to implement and refine, it has been necessary to develop contingency plans in case a DHF/ DSS epidemic should occur before the program is effectively established. One important aspect of these plans is education of the medical community--to make physicians in Puerto Rico and the U.S. Virgin Islands more aware of dengue and to train them in DHF/DSS diagnosis and treatment.
An international seminar on DHF in the Americas was organized in 1985 and was followed by a series of local seminars in all major Puerto Rican cities that gave emphasis to the need for clinical diagnosis and treatment of DHF/DSS. A program continuing these seminars, which has been under way ever since, now relies primarily on a "peer education" system that recruits and trains highly respected physicians in a community to become the local DHF/DSS experts. These physicians give lectures and seminars employing visual materials provided to them by CDC/PRHD,including a video on clinical diagnosis and treatment of DF/DSS written by us and produced by the San Juan Rotary Club for use by physicians and medical associations.
Current plans call for maintaining this program indefinitely. Fortunately, evidence including the improved quality of clinical data received by the surveillance program indicates that progress has been made. In contrast to the situation prevailing in 1985, many physicians now routinely do the official laboratory tests critical for early diagnosis of DHF/DSS. The program has also turned out to have a worthwhile added benefit in that informed physicians are themselves helping to educate the lay community.
Emergency Hospitalization Plan
A second contingency plan dealing with emergency hospitalization has sought to pave the way for making the most effective use of hospital and treatment facilities in case a DHF/DSS epidemic should occur before the medical community is fully aware of the disease and ready for it. This program is being implemented as follows: First, an overall emergency hospitalization plan (see Annex) that outlines basic principles and requirements based on the WHO Technical Guide (4) was drafted and sent to each of the island's eight medical regions. Second, hospitals and potential treatment centers in each region have been identified according to the type of facility and number of beds available. Plans call for entering the names of physicians and paramedics in the area into a computer data base and keeping the list current at the regional level.
Each region will use this information to develop a contingency plan for a "worst case" situation where there is one DHF/DSS case for every 100 cases of dengue infection. If adequate numbers of beds are not available in hospitals and public clinics, plans will be made to convert other public buildings into temporary treatment centers. Each region is responsible for determining needed equipment and supplies and ensuring that these are available in an emergency. Finally, a central committee advises and consults with regional committees appointed to oversee the program.
Long-term, Integrated, Community-Based Mosquito Control
Ultimately, prevention of epidemic dengue and DHF/DSS will depend upon effective, long-term mosquito control. To be cost-effective and sustainable, such control must be achieved through integrated community-based action.
Community participation in Puerto Rico depends upon effective communication with a public that is diverse in terms of its socioeconomic and ethnocultural backgrounds (10). To develop effective community participation, the program seeks to inform the people of Puerto Rico and the U.S. Virgin Islands about DHF/DSS, the potential dangers and consequences of epidemic DHF/DSS, the fact that major epidemics can be prevented, and the fact that it is their responsibility to see that preventive measures are effective. Specifically, the message that must be communicated to all citizens is that (1) DHF/DSS is now endemic in Puerto Rico and the U.S. Virgin Islands; (2) the islands are at high risk of epidemic DHF/DSS because of the high Ae. aegypti densities in all major cities; (3) most dengue transmission occurs in and around the home; (4) this happens because people accumulate excessive trash around their homes, thereby creating mosquito breeding places; (5) dengue can be prevented by controlling these domestic larval habitats, but only the people involved can effectively clean up the areas around their own homes to prevent mosquito breeding; (6) control must be a community effort, because mosquitoes can fly from house to house; (7) insecticide spraying is expensive, is ineffective for routine mosquito control, and at most should only be used in emergency situations; and (8) it is the responsibility of the people, not the government, to prevent epidemic DHF/DSS in Puerto Rico and the U.S. Virgin Islands.
A major effort has been made to develop new and innovative educational materials that can effectively communicate this message to specific population groups. This effort has been based upon ongoing knowledge, attitude, and practices studies conducted by medical anthropologists, social scientists, and health educators who have been attached to the project since 1986 (10). The rationale here is to identify all the major ethnic, social, and cultural elements of the society, study their behavior and attitudes toward dengue and its prevention, and then develop educational materials directed at these groups. (Because one key population group is school-age children, major educational work has been directed toward the schools.) Details of the community-based component of this program will be reported elsewhere (San Juan Laboratories, unpublished data).
Disease control has historically been a responsibility of government. With a disease like dengue, however, most governments do not have the resources to maintain effective control. Because of certain resources available in the private sector, the influence civic organizations can have upon the public, and the marketing skills of those organizations, a plan was developed to involve the business community in dengue prevention and control (10). Briefly, civic organizations such as Rotary International have been encouraged to develop programs that will help government agencies educate the public about its responsibility for environmental sanitation and how to effectively control mosquitoes in the community.
WORLD HEALTH ORGANIZATION
FIFTY-FIFTH WORLD HEALTH ASSEMBLY
Provisional agenda item 13.14 4
Dengue Prevention and
Report by the Secretariat
1. Dengue is the most common and widespread arthropod-borne viral infection in the world. There are four distinct virus serotypes, each capable of producing a wide spectrum of signs and symptoms that characterize dengue fever, ranging from subclinical infection, to a debilitating but self-limiting illness with symptoms resembling influenza, to severe disease known as dengue haemorrhagic fever. Without proper hospital care, the latter can lead to clinical shock and death in less than 24 hours.
2. The geographical spread, incidence and severity of dengue fever and dengue haemorrhagic fever are increasing in the Americas, South-East Asia, the Eastern Mediterranean and the Western Pacific. Before 1970, only nine countries had experienced dengue haemorrhagic fever. Since then, the number has increased more than fourfold and continues to rise. Some 2500 million to 3000 million people live in areas where dengue viruses can be transmitted. A pandemic in 1998, in which 1.2 million cases of dengue fever and dengue haemorrhagic fever were reported from 56 countries, was unprecedented. Preliminary data for 2001 indicate a situation of comparable magnitude. However, only a small proportion of cases are reported to WHO; it is estimated that each year 50 million infections occur, with 500 000 cases of dengue haemorrhagic fever and at least 12 000 deaths, mainly among children, although fatalities could be twice as high.
3. Without proper clinical management, case-fatality rates for dengue haemorrhagic fever can exceed 20%. However, with intensive supportive therapy, rates can be reduced to less than 1%.
4. The resurgence of epidemic dengue fever and the emergence of dengue haemorrhagic fever as major public health problems are rooted in the demographic trends and socioeconomic policies of the twentieth century. During the past five decades, the population of the world has more than doubled, with the most rapid acceleration taking place in developing countries in the tropics and subtropics where the mosquito-borne dengue viruses are spread. Several factors have combined to produce epidemiological conditions that highly favour viral transmission by the main mosquito vector, Aedes aegypti: population growth, rural-urban migration, the inadequacy of basic urban infrastructure (e.g. unreliable water supply, which may lead householders to collect and store water close to homes) and the huge increase in volume of solid waste resulting from the new habits of consumers, for example, discarded plastic containers and other abandoned items which provide larval habitats in urban areas. The species thrives in intimate association with humans and is also the vector of the virus of urban yellow fever, a vaccine-preventable disease. A secondary vector of dengue virus, A. albopictus, which until the late 1970s was geographically limited to parts of Asia, has now become established in Africa, the Americas and Europe. Geographical expansion of this mosquito has been aided particularly by international commercial trade in used tyres which, with accumulated rainwater, are attractive habitats for egg-laying females of the species. Its role in the transmission of dengue and potentially also of yellow fever and other arthropod-borne viruses in these new epidemiological settings remains to be determined. The magnitude of the public health problem will continue to grow unless more effective measures are taken to reduce viral transmission.
5. In many countries, health-sector reform poses new challenges for programme delivery, including decentralization and issues of selection, purchase, procurement, use and monitoring of insecticide application. Moreover, few new cost-effective chemical pesticides suitable for public health use have been developed in recent years. This problem is particularly acute with regard to larvicides suitable for use in stored water for domestic consumption.
6. Although research on dengue vaccines for public health use is in process, currently the only method for the prevention and control of the disease is vector control. The global strategy enunciated in 19951 recommended the application of integrated vector-control measures, with community and intersectoral participation. An informal WHO consultation on strengthening implementation of the global strategy for prevention and control of dengue fever/dengue haemorrhagic fever (Geneva, 18-20 October 1999), the subsequent inclusion of dengue in the disease portfolio of the UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases in June 2000, and advances in regional strategy formulation in the Americas, South-East Asia and the Western Pacific during the 1990s have facilitated identification of the following four main priorities:
a. strengthening epidemiological surveillance for planning and response, including entomological surveillance and the monitoring of key human behaviors (such as inappropriate disposal of discarded household items) that contribute to the availability of mosquito larval habitats. Epidemiological surveillance includes the introduction of DengueNet, a global surveillance system for dengue fever on the Internet. This network includes a database which will be continually updated and which will allow remote data entry in order to provide a more comprehensive and current global picture;
b. reducing the disease burden through: accelerated training and the adoption of WHO standard clinical management guidelines for dengue haemorrhagic fever; improving emergency preparedness and response; and strengthening of national vector-control programmes;
c. promoting behavioural change through the development and implementation of a package of tools, approaches and guidelines for sustainable prevention and control of vectors at individual, household, community, institutional and political levels. The approaches will also foster intra- and inter-sectoral partnerships for programme implementation;
d. accelerating the research programme, with emphasis on mechanisms of pathogenesis, transmission dynamics, vaccine development, validation and improvement of existing or new vector-control methods and their application, partnership building, and formulation of guidelines for research in these strategic areas.
7. Given the worsening epidemiological trends, there is evident need to renew or intensify efforts to reduce the public health and economic burdens associated with this epidemic disease. In order to achieve this, the following will be required: the development, application and evaluation of new and improved tools and strategies for the prevention and control of dengue fever and dengue haemorrhagic fever; increased commitment and additional human and other resources for improved and sustainable prevention and control efforts; building and strengthening the capacity of health systems for dengue surveillance, laboratory diagnosis and disease management, and active intersectoral partnerships involving international, regional, national and local agencies and nongovernmental organizations.