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 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... read more ).
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 Dengue Hemorrhagic Fever/Dengue Shock Syndrome Dengue hemorrhagic fever is a variant presentation of dengue infection that occurs primarily in children < 10 years living in areas where dengue is endemic. Dengue hemorrhagic fever, which... read more .
Neurologic symptoms are uncommon and can include encephalopathy and seizures; some patients develop Guillain-Barré syndrome Guillain-Barré Syndrome (GBS) Guillain-Barré syndrome is an acute, usually rapidly progressive but self-limited inflammatory polyneuropathy characterized by muscular weakness and mild distal sensory loss. Cause is thought... read more .
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 Malaria Malaria is infection with Plasmodium species. Symptoms and signs include fever (which may be periodic), chills, rigors, sweating, diarrhea, abdominal pain, respiratory distress, confusion... read more , Zika virus infection Zika Virus (ZV) Infections The Zika virus is a mosquito-borne flavivirus that is antigenically and structurally similar to the viruses that cause dengue, yellow fever, and West Nile virus. Zika virus infection is typically... read more , chikungunya disease Chikungunya Disease Chikungunya disease is transmitted by the Aedes mosquito. Chikungunya disease usually presents with acute fever. Chronic polyarthritis can persist and be disabling. Diagnosis is confirmed... read more and leptospirosis Leptospirosis Leptospirosis is an infection caused by one of several pathogenic serotypes of the spirochete Leptospira. Symptoms are biphasic. Both phases involve acute febrile episodes; the second... read more .
Diagnostic studies include acute and convalescent serologic testing, antigen detection, and virus genome detection by polymerase chain reaction (PCR) of blood (1 Diagnosis reference 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... read more ). 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.
Treatment of Dengue
Treatment of dengue is symptomatic. Acetaminophen can be used, but NSAIDs (nonsteroidal anti-inflammatory drugs), including aspirin, should be avoided because bleeding is a risk. Aspirin increases the risk of Reye syndrome Reye Syndrome Reye syndrome is a rare form of acute encephalopathy and fatty infiltration of the liver that occurs almost exclusively in children The cause of Reye syndrome is unknown, but many cases seem... read more 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 Prevention references 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... read more ). 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 Prevention references 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... read more ) 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).
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.
Drugs Mentioned In This Article
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