Dengue Virus
المؤلف:
Stefan Riedel, Jeffery A. Hobden, Steve Miller, Stephen A. Morse, Timothy A. Mietzner, Barbara Detrick, Thomas G. Mitchell, Judy A. Sakanari, Peter Hotez, Rojelio Mejia
المصدر:
Jawetz, Melnick, & Adelberg’s Medical Microbiology
الجزء والصفحة:
28e , p569-570
2025-12-20
14
Dengue (breakbone fever) is a mosquito-borne infection caused by a flavivirus that is characterized by fever, severe headache, muscle and joint pain, nausea and vomiting, eye pain, and rash. Severe forms of the disease, dengue hemorrhagic fever and dengue shock syndrome, principally affect children. Dengue is endemic in more than 100 countries.
Clinical Findings
Clinical disease begins 4–7 days (range, 3–14 days) after an infective mosquito bite. The onset of fever may be sudden or there may be prodromal symptoms of malaise, chills, and headache. Pains soon develop, especially in the back, joints, muscles, and eyeballs. Fever lasts from 2 to 7 days, corresponding to peak viral load. The temperature may subside on about the third day and rise again about 5–8 days after onset (“saddleback” form). Myalgia and deep bone pain (breakbone fever) are characteristic. A rash may appear on the third or fourth day and last for 1–5 days. Lymph nodes are frequently enlarged. Classic dengue fever is a self-limited disease. Convalescence may take weeks, although complications and death are rare. Especially in young children, dengue may be a mild febrile illness lasting a short time.
A severe syndrome—dengue hemorrhagic fever or dengue shock syndrome—may occur in individuals (usually children) with passively acquired (as maternal antibody) or preexisting nonneutralizing heterologous dengue antibody caused by a previous infection with a different serotype of virus. Although initial symptoms simulate normal dengue, the patient’s condition worsens. The key pathological feature of dengue hemorrhagic fever is increased vascular permeability with plasma leakage into the interstitial spaces associated with increased levels of vasoactive cytokines. This can lead to life-threatening shock in some patients.
Laboratory Diagnosis
Reverse transcriptase PCR (RT-PCR)-based methods are available for rapid identification and serotyping of dengue virus in acute-phase serum, roughly during the period of fever. Isolation of the virus is difficult. The current favored approach is inoculation of a mosquito cell line with patient serum coupled with nucleic acid assays to identify a recovered virus.
Serologic diagnosis is complicated by cross-reactivity of IgG antibodies to heterologous flavivirus antigens. A variety of methods are available; the most commonly used methods are envelope/membrane viral protein-specific capture IgM or IgG ELISA and the HI test. IgM antibodies develop within a few days of illness. Neutralizing and hemagglutination-inhibiting antibodies appear within a week after the onset of dengue fever. Analysis of paired acute and convalescent sera to show a significant rise in antibody titer is the most reliable evidence of an active dengue infection.
Immunity
Four serotypes of the virus exist that can be distinguished by molecular-based assays and by neutralization tests. Infection confers lifelong protection against that serotype, but cross protection between serotypes is of short duration. Reinfection with a virus of a different serotype after the primary attack is more apt to result in severe disease (dengue hemorrhagic fever).
The pathogenesis of the severe syndrome involves preexisting dengue antibody. It is postulated that virus–antibody complexes are formed within a few days of the second dengue infection and that the nonneutralizing enhancing antibodies promote infection of higher numbers of mononuclear cells followed by the release of cytokines, vasoactive mediators, and procoagulants, leading to the disseminated intravascular coagulation seen in the hemorrhagic fever syndrome. Cross reactive cellular immune responses to dengue virus may also be involved.
Epidemiology
Dengue viruses are distributed worldwide in tropical regions. Most subtropical and tropical regions around the world where Aedes vectors exist are endemic areas. In the past 20 years, epidemic dengue has emerged as a problem in the Americas. In 1995, more than 200,000 cases of dengue and more than 5500 cases of dengue hemorrhagic fever occurred in Central and South America. The changing disease patterns are probably related to rapid urban population growth, overcrowding, and lax mosquito control efforts.
In 2008, dengue was the most important mosquito borne viral disease affecting humans. There are an estimated 50 million or more cases of dengue annually worldwide, with 400,000 cases of dengue hemorrhagic fever. The latter is a leading cause of childhood death in several Asian countries.
The risk of the hemorrhagic fever syndrome is about 0.2% during the first dengue infection but is at least 10-fold higher during infection with a second dengue virus serotype. The fatality rate with dengue hemorrhagic fever can reach 15% but can be reduced to less than 1% with proper treatment.
The ratio of inapparent to apparent infections is variable but may be about 15 to one for primary infections; the ratio is lower in secondary infections.
In urban communities, dengue epidemics are explosive and involve appreciable portions of the population. They often start during the rainy season, when the vector mosquito, A. aegypti, is abundant. The mosquito breeds in tropical or semitropical climates in water-holding receptacles or in plants close to human dwellings.
A. aegypti is the primary vector mosquito for dengue in the Western Hemisphere. The female acquires the virus by feeding upon a viremic human. After a period of 8–14 days, mosquitoes are infective and probably remain so for life (1–3 months). In the tropics, mosquito breeding throughout the year maintains the disease.
World War II was responsible for the spread of dengue from Southeast Asia throughout the Pacific region. Only dengue type 2 was present in the Americas for years. Then, in 1977, a dengue type 1 virus was detected for the first time in the Western Hemisphere. In 1981, dengue type 4 was first recognized in the Western Hemisphere followed in 1994 by dengue type 3. The viruses are now spread throughout Central and South America, and dengue hemorrhagic fever is endemic in many countries.
Endemic dengue in the Caribbean and Mexico is a constant threat to the United States, where A. aegypti mosquitoes are prevalent in the summer months. Concurrent with the increased epidemic activity of dengue in the tropics, there has been an increase in the number of cases imported into the United States. By 2010, dengue was the leading cause of febrile illness among travelers returning from the Caribbean, Latin America, and Asia. The first locally acquired case of dengue hemorrhagic fever in the United States occurred in south Texas in 2005. From 2009 to 2010, 28 cases of locally acquired dengue occurred in Key West, Florida.
Aedes albopictus, a mosquito of Asian origin, was discovered in Texas in 1985; by 1989 it had spread throughout the southeastern United States, where A. aegypti, the principal vector of dengue virus, is prevalent. In contrast to A. aegypti, which cannot overwinter in northern states, A. albopictus can overwinter farther north, increasing the risk of epidemic dengue in the United States.
Treatment and Control
There is no antiviral drug therapy. Dengue hemorrhagic fever can be treated by fluid replacement therapy. There is no vac cine, but candidate vaccines are under development. Vaccine development is difficult because a vaccine must provide protection against all four serotypes of virus. Therapeutic anti bodies able to neutralize multiple genotypes of dengue are also under development.
Control depends on antimosquito measures, including elimination of breeding places and the use of insecticides. Screened windows and doors can reduce exposure to the vectors.
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