Dengue Fever

Dengue

Clinical Description

Identification

An acute febrile viral disease characterized by sudden onset, fever for 2–7 days (sometimes biphasic), intense headache, myalgia, arthralgia, retro-orbital pain, anorexia, nausea, vomiting and rash. Early generalized erythema occurs in some cases. A generalized maculopapular rash may appear about the time of defervescence. Rash is frequently not visible in dark-skinned patients. Minor bleeding phenomena, such as petechiae, epistaxis or gum bleeding, may occur at any time during the febrile phase. With underlying conditions, adults may have major bleeding phenomena, such as GI hemorrhage in peptic ulcer cases or menorrhagia. Dengue fever with unusual hemorrhage should be differentiated from DHF* with increased vascular permeability, bleeding manifestations and involvement of specific organs. Recovery may be associated with prolonged fatigue and depression. Lymphadenopathy and leukopenia with relative lymphocytosis are usual; mild thrombocytopenia (less than 100 × 103 cells per mm3; or 100 SI units × 109 per L) and elevated transaminases occur less frequently. Epidemics are explosive, but fatalities, usually rare, can be minimized by timely medical intervention.

*Note: Dengue Hemorrhagic Fever (DHF) is now known as severe dengue.  For more information, see: http://www.who.int/mediacentre/factsheets/fs117/en/index.html

Infectious Agent

The viruses of dengue fever are flaviviruses and include serotypes 1, 2, 3 and 4 (dengue-1, -2, -3, -4). The same viruses are responsible for dengue hemorrhagic fever.


Diagnosis

Laboratory confirmation of dengue infection is through detection either of virus in acute phase blood/serum within 5 days of onset of illness, or of specific antibodies in convalescent phase serum obtained 6 days or more after onset of illness. Virus identification in blood is by reverse transcriptase polymerase chain reaction (RT-PCR), culture in mosquito cell lines, or inoculation to mosquitoes then identified through immunofluorescence with serotype-specific monoclonal antibodies. These procedures provide a definitive diagnosis, but practical considerations limit their use in endemic countries. The IgM capture ELISA is the most commonly used serological procedure for diagnosis, and is particularly suitable for high-volume testing. IgM antibody, indicating current or recent infection, is usually detectable 6–7 days after onset of illness. A positive test result in a single serum indicates presumptive recent infection; a definitive diagnosis requires increased antibody levels in paired sera. New immunoassays that detect dengue non-structural protein-1 (NS1) show some promise in diagnosis early in the febrile phase, prior to IgM rise. RT-PCR amplification protocols using dengue oligonucleotide primers can also detect dengue virus RNA in tissue from fatal cases. PCR with specific primers can distinguish among the dengue virus serotypes; PCR with nucleotide sequencing can characterize dengue strains and genotypes. Since these genome-based assays are costly, demand meticulous technique, and are highly prone to false-positives through contamination, they are not yet applicable for wide use in all settings.

Differential diagnosis includes chikungunya and other epidemiologically relevant diseases listed under arthropod-borne viral fevers; influenza; measles; rubella; malaria; leptospirosis; typhoid; scrub typhus; and other systemic febrile illnesses, especially those accompanied by rash.


Epidemiology

Mode of Transmission

Bite of infective mosquitoes, principally Aedes aegypti. This is a day-biting species, with increased biting activity for 2 hours after sunrise and several hours before sunset. Dengue outbreaks have been attributed to Ae. aegypti and Ae. albopictus, an urban species abundant in Asia that has now spread to Latin America and the USA, the Caribbean, and the Pacific parts of southern Europe and Africa. Ae. albopictus is less anthropophilic than Ae. aegypti and hence a less efficient epidemic vector. In Polynesia, one of the Ae. scutellaris spp. complex serves as the vector. Mosquitoes of Ae. nivaeus complex in Malaysia and Ae. furcifer-taylori complex in western Africa are involved in enzootic monkey/mosquito transmission.

Incubation Period

From 3 to 14 days, commonly 4–7 days.

Period of Communicability

No direct person-to-person transmission. Patients are infective for mosquitoes during the period of high viremia, from shortly before the febrile period to the end thereof, usually 3–5 days. The mosquito becomes infective 8–12 days after the viremic blood-meal, and remains so for life.

Reservoir

The viruses are maintained in a human/Aedes aegypti mosquito cycle in tropical urban centers; a monkey/mosquito cycle may serve as a reservoir in the forests of southeastern Asia and western Africa.

Susceptibility

Susceptibility in humans is universal, but children usually have a milder disease than adults. Asymptomatic infections can occur. Recovery from infection with one serotype provides lifelong homologous immunity, but only short-term protection against other serotypes, and may exacerbate disease upon subsequent infections— presumably through immune enhancement, though this is not well understood. Given a particular patient who presents with dengue, it may be difficult, especially at the early stages, to predict its eventual severity.

Occurrence

Dengue viruses of multiple types are endemic in most countries in the tropics. In Asia, 2–5 year dengue/DHF epidemic cycles are established in southern Cambodia, China, Indonesia, Lao Democratic Republic, Malaysia, Myanmar, the Philippines, Thailand, and Viet Nam, with increasing epidemic activity and geographic spread in Bangladesh, India, Maldives, Pakistan, and Sri Lanka, and lower endemicity in New Guinea, Singapore and Taiwan (China). Dengue viruses of several types have regularly been reintroduced into countries of the Pacific Rim, and into northern Queensland, Australia, since 1981.

Dengue-1, -2, -3 and -4 are endemic in Africa. In large areas of western Africa, dengue viruses are probably transmitted epizootically in monkeys; urban dengue involving humans is also common in this area. In recent years, outbreaks of dengue fever have occurred on the eastern coast of Africa from Ethiopia to Mozambique, and on offshore islands such as the Comoros and the Seychelles, with a small number of dengue and DHF-like cases reported from the Arabian Peninsula.

Successive introduction and circulation of all 4 serotypes in tropical and subtropical areas of the Americas has occurred since 1977; dengue entered Texas in 1980, 1986, 1995, 1997, and 2005. As of 2007, two or more dengue viruses are endemic or periodically epidemic in virtually all of the Caribbean and Latin America, including Brazil, Bolivia, Colombia, Ecuador, the Guyanas, Mexico, Paraguay, Peru, Suriname, Venezuela, and Central America. There are now areas, such as Puerto Rico, parts of Venezuela and Mexico, where all 4 serotypes are co-circulating. Dengue was introduced into Easter Island, Chile, in 2002, and reintroduced into Argentina at the northern border with Brazil. Epidemics may occur wherever vectors are present and virus is introduced, whether in urban or rural areas.


Prevention and Control

1)    Preventive measures:

a)    Educate the public and promote behaviors to remove, destroy or manage mosquito vector larval habitats, which for Ae. aegypti are usually artificial water-holding containers close to or inside human habitations (e.g. old tires, flowerpots, and discarded containers for food or water storage).

b)    Survey the community to determine the abundance of vector mosquitoes, identify the most productive larval habitats, and promote and implement plans for their elimination, management or treatment with appropriate larvicides.

c)    Personal protection against day-biting mosquitoes through repellents, screening and protective clothing.

2)    Control of patient, contacts and the immediate environment:

a)    Report to local health authority: Obligatory report of epidemics; case reports, Class 4.

b)    Isolation: Blood precautions. Until the fever subsides, prevent access of day-biting mosquitoes to patients by screening the sickroom or using a mosquito bed net, preferably insecticide-impregnated, for febrile patients; or by spraying quarters with a knockdown adulticide or residual insecticide.

c)    Concurrent disinfection: Not applicable.

d)    Quarantine: Not applicable.

e)    Immunization of contacts: Not applicable. If dengue occurs near possible jungle foci of yellow fever, immunize the population against yellow fever, because the urban vector for the two diseases is the same.

f)    Investigation of contacts and source of infection: Determine patient's place of residence during the 2 weeks before onset of illness, and search for unreported or

undiagnosed cases.
g)    Specific treatment: Supportive, including oral rehydration. Acetylsalicylic acid (aspirin) is contraindicated because of its hemorrhagic potential. Severe illness is usually secondary to capillary leak syndrome, and requires appropriate intravenous fluid resuscitation.

3)    Epidemic measures:

a)    Search for and destroy Aedes mosquitoes in sites of human habitation, and eliminate or apply larvicide to all potential Ae. aegypti larval habitats. Adulticide should target indoor mosquitoes where most of the transmission takes place.

b)    Use mosquito repellents for people exposed to vector mosquitoes.

4)    Disaster implications:

Epidemics can be extensive and affect a high percentage of the population.

5)    International measures:

Enforce international agreements designed to prevent the spread of Ae. aegypti via ships, airplanes and land transport. Improve international surveillance and exchange of data between countries. WHO Collaborating Centres provide support as required. More information can be found at: http://www.who.int/collaboratingcentres/database/en/

6)    Further information can be found on the following websites:

a)    http://www.cdc.gov/ncidod/dvbid/dengue/

b)    http://www.who.int/denguenet

c)    http://www.who.int/health_topics/dengue/en

d)    http://www.paho.org/english/ad/dpc/cd/Dengue.htm

e)    http://www.searo.who.int/en/Section10/Section332/Section1026.htm
 

Source: Heymann (Ed.). (2008). Control of Communicable Diseases Manual, 19th edition. Washington, DC: American Public Health Association.
 

Common Disease Taxonomy: