Dengue is a mosquito-borne disease caused by a flavivirus. Dengue fever usually results in abrupt onset of high fever, headache, myalgias, arthralgias, and generalized lymphadenopathy, followed by a rash that appears with a recurrent fever after an afebrile period. Respiratory symptoms, such as cough, sore throat, and rhinorrhea, can occur. Dengue can also cause potentially fatal hemorrhagic fever with a bleeding tendency and shock. Diagnosis involves serologic testing and polymerase chain reaction (PCR). Treatment is symptomatic and, for dengue hemorrhagic fever, includes meticulously adjusted intravascular volume replacement.
Dengue is endemic to the tropical regions of the world in latitudes from about 35° north to 35° south. Outbreaks are most prevalent in Southeast Asia but also occur in the Caribbean, including Puerto Rico and the US Virgin Islands, Oceania, and the Indian subcontinent; more recently, dengue incidence has increased in Central and South America. Each year, only about 100 to 200 cases are imported to the United States by returning tourists, but an estimated 50 to 100 million cases occur worldwide, with about 20,000 deaths. Limited local transmission has occurred most recently in Hawaii (2015), Florida (2013, 2020, 2022), and Texas (2013).
The causative agents, enveloped single-strand RNA viruses from the genus Flavivirus with 4 serotypes, are transmitted by the bite of Aedes mosquitoes. Individual mosquitoes may bite repeatedly, potentially exposing multiple people to infection. The virus circulates in the blood of infected humans for 2 to 7 days; Aedes mosquitoes may acquire the virus when they feed on humans during this period.
A pregnant woman can pass the dengue virus to her fetus during pregnancy or around the time of birth, although the rate of vertical transmission appears low (see World Health Organization [WHO]: Dengue and severe dengue). There has been one report of potential dengue transmission through breast milk (1).
Reference
1. Barthel A, Gourinat AC, Cazorla C, et al: Breast milk as a possible route of vertical transmission of dengue virus? Clin Infect Dis 57(3):415-417, 2013. doi:10.1093/cid/cit227
Symptoms and Signs of Dengue
After an incubation period of 3 to 15 days, fever, chills, headache, retro-orbital pain with eye movement, lumbar backache, and severe prostration begin abruptly. Extreme aching in the legs and joints occurs during the first hours, accounting for the traditional name of breakbone fever. The temperature rises rapidly to up to 40° C, with relative bradycardia. Bulbar and palpebral conjunctival injection and a transient flushing or pale pink macular rash (particularly of the face) may occur. Cervical, epitrochlear, and inguinal lymph nodes are often enlarged.
Fever and other symptoms persist 48 to 96 hours, followed by rapid defervescence with profuse sweating. Patients then feel well for about 24 hours, after which fever may occur again (saddleback pattern), typically with a lower peak temperature than the first. Simultaneously, a blanching maculopapular rash spreads from the trunk to the extremities and face.
Sore throat, gastrointestinal symptoms (eg, nausea, vomiting), and hemorrhagic symptoms can occur. Some patients develop dengue hemorrhagic fever.
Neurologic symptoms are uncommon and can include encephalopathy and seizures; some patients develop Guillain-Barré syndrome.
Mild cases of dengue, usually lacking lymphadenopathy, remit in < 72 hours. In more severe disease, asthenia may last several weeks. Death is rare. Immunity to the infecting strain is long-lasting, whereas broader immunity to other strains lasts only 2 to 12 months.
More severe disease may result from antibody-dependent enhancement of infection, in which patients have a non-neutralizing antibody from a previous infection with one dengue serotype and then have another infection with a different dengue serotype.
Diagnosis of Dengue
Acute and convalescent serologic testing
Dengue fever is suspected in patients who live in or have traveled to endemic areas if they develop sudden fever, severe retro-orbital headache, myalgias, and adenopathy, particularly with the characteristic rash or recurrent fever. Evaluation should rule out alternative diagnoses, especially malaria, Zika virus infection, chikungunya disease and leptospirosis.
Diagnostic studies include acute and convalescent serologic testing, antigen detection, and virus genome detection by polymerase chain reaction (PCR) of blood (1). Serologic testing involves hemagglutination inhibiting or complement fixation tests using paired sera, but cross-reactions with other flavivirus antibodies, especially to Zika virus, are possible. Plaque-reduction neutralization tests are more specific and are considered the gold standard for serologic diagnosis. Antigen detection is available in some parts of the world (not in the United States), and PCR is usually done only in laboratories with special expertise.
Although rarely done and difficult, cultures can be done using inoculated Toxorhynchites mosquitoes or specialized cell lines in specialized laboratories.
Complete blood count may show leukopenia by the 2nd day of fever; by the 4th or 5th day, the white blood cell count may be 2000 to 4000/mcL with only 20 to 40% granulocytes. Urinalysis may show moderate albuminuria and a few casts. Thrombocytopenia may also be present.
Diagnosis reference
Treatment of Dengue
Supportive care
Reye syndrome in children and should be avoided for that reason.
Prevention of Dengue
People in endemic areas should try to prevent mosquito bites. Dengue-endemic areas include the United States territories of American Samoa, Puerto Rico, and the U.S. Virgin Islands, and freely associated states, including the Federated States of Micronesia, the Republic of Marshall Islands, and the Republic of Palau. To prevent further transmission by mosquitoes, patients with dengue should be kept under mosquito netting until the 2nd bout of fever has resolved.
In the United States, the dengue vaccine CYD-TDV is approved for use in children and adolescents 9 to 16 years of age who have laboratory-confirmed previous dengue virus infection and are living in an area where dengue is endemic (1). The vaccine decreases the risk of hospitalization and severe disease in seropositive recipients. However, vaccinating children who have never had dengue appears to result in risk of more severe disease if the children become infected with dengue later. The World Health Organization (2) and the US Food and Drug Administration (FDA) recommend doing pre-vaccination screening for serologic evidence of previous dengue infection and vaccinating only seropositive patients. Three doses are given at 6-month intervals.
The FDA is evaluating another dengue vaccine candidate (TAK-003) for the prevention of the viral disease caused by any serotype. TAK-003 is approved for use in Indonesia, the European Union, and the United Kingdom. See CDC: TAK-003 (tetravalent dengue vaccine candidate).
Prevention references
1. Centers for Disease Control and Prevention: Dengue Vaccine: Recommendations of the Advisory Committee on Immunization Practices, United States, 2021. Accessed March 20, 2023.
2. World Health Organization: Dengue vaccines: WHO position paper – September 2018. Accessed March 20, 2023.
Key Points
The dengue virus is transmitted by the bite of Aedes mosquitoes.
Dengue fever typically causes sudden fever, severe retro-orbital headache, myalgias, adenopathy, a characteristic rash, and extreme aching in the legs and joints during the first hours.
Dengue fever can cause a potentially fatal hemorrhagic fever with a bleeding tendency and shock (dengue hemorrhagic fever and dengue shock syndrome).
Suspect dengue fever if patients who live in or have traveled to endemic areas if they have typical symptoms; diagnose using serologic tests, antigen tests, or PCR of blood.
