Dengue Fever

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Introduction and Definitions

Dengue virus is at present the most important arboviral cause of illness and death in humans. The four serotypes of Dengue virus, a subgroup of the genus Flavivirus, are distributed widely throughout the tropics and warm climate regions of Africa, Asia, Australia, the Pacific Islands, India, the Caribbean Islands, and the Americas, involving several million people each year. The incidence of the disease corresponds to the distribution of the principal vector, the Ae. aegypti mosquito, which maintains the virus in a human-mosquito-human cycle. The incidence of dengue is increasing, with more frequent epidemics and greater severity, and spread to new areas.

Nature of the Infectious Agent

Dengue virus is a distinct antigenic subgroup of the genus Flavivirus. There are four serotypes with extensive cross-

reactivities and strain variation. After infection, protective immunity is homotypic so that individuals can be infected simultaneously or serially by more than one serotype.

Epidemiology and Geographical Distribution

Reference has been made to the extensive geographical distribution of dengue throughout the tropics and warm climate regions of Africa, Asia, Australia, Oceania, India, the Caribbean Islands and the Americas. Extension to new areas is the result of uncontrolled poor housing settlements, slums and squatter camps on the peripheries of cities, resurgence of infestation with Aedes mosquitoes and failure of vector control.

The principal vector is Ae. aegypti. Other Aedes species of the subgenus Stegomyia are also implicated as vectors in Asia and in the Pacific region. Although there are many similarities with the epidemiology of yellow fever, the urban cycle involving domesticated Aedes mosquitoes is the most common and most important for both endemic and epidemic dengue. The incubation period is 3-14 days.

Reservoir of Infection

Humans together with the mosquito.


All four dengue virus serotypes cause three distinct syndromes: dengue fever, dengue haemorrhagic fever and dengue shock syndrome. The virus replicates in macrophages at the site of the mosquito bite, in the regional lymph nodes and subsequently the reticuloendothelial system. Viraemia is associated with circulating mono-cytes, and there is often severe leucopenia. A maculo-papular rash on the trunk appears on day 3-5 of the illness and spreads to the face and limbs, accompanied frequently by lymphadenopathy, granulocytopenia and thrombocytopenia. Minor mucocutaneous bleeding may occur.

Dengue haemorrhagic fever is the result of increased vascular permeability, unusual bleeding manifestations and involvement of the gut and the liver, with or without encephalopathy, and disseminated intravascular coagulation. In dengue shock syndrome, increased vascular permeability causes decreased plasma volume and clinical shock, which, if uncorrected, may lead to acidosis, hyperkalaemia and death. Most cases of dengue haemor-rhagic fever and dengue shock syndrome occur in children and adolescents under the age of 15 years, with a fatality rate of 3-10%.

Dengue haemorrhagic fever and dengue shock syndrome are believed to be the result of 'immune enhancement', whereby homologous and heterologous antibodies binding to the virus, including subprotective levels of maternal dengue antibodies in infants, enhance infection of macrophages via cellular Fc receptors. Another possible explanation is that T cells exacerbate the antibody-enhanced cascade by concomitant release of cytokines by both T cells and damaged macrophages. The alternative hypothesis is that the severe complications of dengue are caused by unusually virulent strains of dengue, particu larly serotype 2; however, there is no consistent relationship between strain variation and increased virulence or infectivity.

Clinical Features and Diagnosis

Dengue fever is characterised by sudden fever, headache, vomiting and severe muscle and bone pain of increasing severity. The fever is biphasic, remitting on day 3-5 of the illness, followed by a maculopapular or morbilliform rash, which spreads from the trunk to the limbs and face. This second phase of the illness, which is often accompanied by recurrence of fever, is associated with lym-phadenopathy, granulocytopenia and thrombocyto-penia. Minor mucocutaneous bleeding may occur. The fever lasts for 3-9 days and is self-limiting.

The clinical features of dengue haemorrhagic fever are characterised by fever, rash and anorexia lasting 3-5 days, followed by hepatomegaly, hypotension and a haemorrhagic diathesis. The dengue shock syndrome is due to decreased plasma volume following increased vascular permeability, and is associated with a significant mortality of up to 10%, but which can be as high as 40-50% if untreated. Diagnosis in returning travellers may be difficult. Serological diagnosis is based on haema-gglutination-inhibition and IgM antibody-capture ELISA. Definitive diagnosis is by way of virus isolation and PCR-based techniques.

Treatment is symptomatic and, in case of complications, careful management of clinical shock.

Protective Measures and Prevention

Live attenuated dengue vaccines are undergoing clinical trials. There is no licensed dengue vaccine.

Epidemiological monitoring is important and also provides means of education and control. Vector control is essential, with the aim of eliminating the domesticated Aedes mosquitoes. It appears that the results of insecticide and larvicide treatment of stagnant water are temporary, and indeed reinfestations are inevitable. Nevertheless, these are essential tools for control. The traveller should employ the usual measures for the prevention of insect bites.

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