Dengue

Last updated: August 26, 2024

Summary

Dengue is a viral disease transmitted by mosquitoes (especially Aedes aegypti) and is widely distributed throughout the tropics and subtropics. Dengue classically presents with high fever, headache, body aches, exanthem, and generalized lymphadenopathy. Symptoms usually subside within one week. Some cases progress to the more severe dengue hemorrhagic fever (DHF) with thrombocytopenia, spontaneous bleeding, and potentially shock (dengue shock syndrome). Treatment is supportive. A vaccination is available for use in children, living in endemic areas, with confirmed prior dengue virus infection.

Epidemiology

Distribution: tropical regions worldwide, particularly Asia (e.g., Thailand)
Incidence
- Most common viral disease affecting tourists in tropical regions
- ∼ 400 million infections per year worldwide

Geographic distribution of dengue virus infections Chalk Talk: Travel medicine

References:^[1]

Epidemiological data refers to the US, unless otherwise specified.

Etiology

Pathogen
- Dengue virus (Serotype: DENV 1–4)
- RNA virus of the genus Flavivirus
Transmission route ^[2]
- Vector-borne; : mosquitoes most commonly from the species Aedes aegypti

Mosquito (Aedes aegypti)

References:^[3]

Clinical features

Clinical featues of Dengue fever
		Course	Clinical features
Dengue fever	Dengue without warning signs ^[3]^[4]	Incubation period: 4–10 days after mosquito bite Duration of febrile phase of dengue fever: usually 2–7 days	High fever (40°C) PLUS 2 of the following symptoms during the febrile phase indicate dengue Severe headache Retro-orbital pain Severe arthralgia and myalgia (often referred to as “break-bone fever”) Maculopapular, measles-like exanthem (typically appears 2–5 days after fever onset) Generalized lymphadenopathy Positive capillary fragility test ^[5] Children are usually asymptomatic
Dengue fever	Dengue with warning signs ^[3]^[4]	Critical phase: increased risk of clinical deterioration that occurs 3–7 days after symptom onset (coincides with fever abatement) At risk population Individuals with a history of previous dengue infection Infants < 1 year of age Patients with severe comorbidities	Abdominal pain Persistent vomiting Lethargy or restlessness Enlarged liver (> 2 cm) Signs of fluid accumulation e.g., pleural effusion and/or ascites Hemorrhagic manifestations: petechiae, epistaxis, gingival bleeding
Severe dengue (Formally called dengue hemorrhagic fever or DHF) ^[3]^[4]		DHF typically occurs as a result of an antibody-dependent reaction in patients who are reinfected with a different serotype Generally develops as the initial fever subsides (∼ 1 week after onset) Severe dengue occurs in 1–2% of cases.	Temperature change: ranges from hypothermia to a second spike in fever Severe hemorrhagic manifestations (e.g., petechiae, ecchymoses, purpura, hematemesis, melena) due to thrombocytopenia (< 100,000/mm3) Severe organ involvement Hepatomegaly, liver failure Changes in mental status (e.g., confusion) Severely increased vascular permeability Pleural effusion, respiratory distress Ascites, abdominal pain Severe ↑ or ↓ Hct Positive capillary fragility test ^[5]
Dengue shock syndrome (DSS)		Develops due to further deterioration of severe dengue	Presence of both symptoms of severe dengue and circulatory collapse and shock due to plasma leakage

If symptoms appear more than 2 weeks after returning from a dengue-endemic region, it is very unlikely that dengue is the cause.

Severe dengue is more frequent in individuals who experience a repeat infection with a second serotype, especially serotype 2.

Exanthem in dengue fever

Diagnosis

Laboratory tests

Leukopenia
Neutropenia
Thrombocytopenia
↑ AST
Hct significantly increased or decreased in DHF (due to plasma leakage)

Confirmation of diagnosis ^[6]

Acute phase (≤ 7 days after symptom onset)

Serologic tests: MAC-ELISA to detect IgM
Molecular Tests (NAAT) to detect viral RNA
NS1 antigen test: detection of the Dengue NS1 antigen (Dengue non-structural protein 1) via ELISA ^[7]
- Allows early detection of the viral antigen in the serum
- A positive test confirms the diagnosis (without identifying the dengue serotype)
- A negative test does not rule out dengue infection; IgM testing should be performed
- Not recommended after day 7 of symptomatic infection (low sensitivity)
Tissue tests (IHC)

Convalescent phase (i.e., > 7 days after symptom onset)

Serologic tests (IgM, IgG)
Molecular Tests (NAAT)
Tissue tests (IHC)

Differential diagnoses

Chikungunya fever and other viral hemorrhagic fevers
Malaria
Zika virus infection
Oropouche virus disease

Severe hemorrhagic manifestations with shock and death as well as decreased neutrophil and platelet counts are more indicative of Dengue fever than Chikungunya fever.

The differential diagnoses listed here are not exhaustive.

Treatment

Symptomatic treatment
- Fluid administration to avoid dehydration
- Acetaminophen
Dengue with warning signs and severe dengue
- Blood transfusions in case of significant internal bleeding (e.g., epistaxis, gastrointestinal bleeding, or menorrhagia)
- Urgent resuscitation with IV fluids

Prevention

Avoid exposure, use of mosquito repellent (see also → mosquito bite prevention)
Dengue vaccine: a tetravalent attenuated live vaccine (CYD) ^[8]^[9]
- Recombinant yellow fever virus in which genetic material coding for the Dengue virus envelope and premembrane proteins has been inserted
- Has been approved for use in children between 9–16 years of age who live in endemic areas and have a laboratory confirmed prior dengue virus infection.
- See “ACIP immunization schedule” for details on dosing.

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