Clinical Presentation

Key Facts

Dengue can range from asymptomatic infection or mild illness to severe disease.
An estimated 1 in 4 dengue virus infections are symptomatic. Symptomatic dengue virus infection most commonly presents as a mild to moderate, nonspecific, acute febrile illness.
Infection with one of the four dengue viruses will induce long-lived immunity for that specific virus.
Because there are four dengue viruses, people can be infected with DENV multiple times in their life.
Approximately 1 in 20 patients with dengue virus disease progress to develop severe, life-threatening disease called severe dengue.
- The second infection with DENV is a risk factor for severe dengue.
Early clinical findings are nonspecific but require a high index of suspicion because recognizing early signs of shock and promptly initiating intensive supportive therapy can reduce risk of death among patients with severe dengue to <0.5%.
See Box 3-01 for information regarding the World Health Organization (WHO) guidelines for classifying dengue.

Box 3-01. Guidelines for classifying dengue

In November 2009, WHO issued a new guideline that classifies symptomatic cases as dengue or severe dengue.

Dengue is defined by a combination of ≥2 clinical findings in a febrile person who traveled to or lives in a dengue-endemic area. Clinical findings include nausea, vomiting, rash, aches and pains, a positive tourniquet test, leukopenia, and the following warning signs: abdominal pain or tenderness, persistent vomiting, clinical fluid accumulation, mucosal bleeding, lethargy, restlessness, and liver enlargement. The presence of a warning sign may predict severe dengue in a patient.

Severe dengue is defined by dengue with any of the following symptoms: severe plasma leakage leading to shock or fluid accumulation with respiratory distress; severe bleeding; or severe organ impairment such as elevated transaminases ≥1,000 IU/L, impaired consciousness, or heart impairment.

From 1975 through 2009, symptomatic dengue virus infections were classified according to the WHO guidelines as dengue fever, dengue hemorrhagic fever (DHF), and dengue shock syndrome (the most severe form of DHF). The case definition was changed to the 2009 clinical classification after reports that the case definition of DHF was both too difficult to apply in resource-limited settings and too specific, as it failed to identify a substantial proportion of severe dengue cases, including cases of hepatic failure and encephalitis. The 2009 clinical classification has been criticized for being overly inclusive, as it allows several different ways to qualify for severe dengue, and nonspecific warning signs are used as diagnostic criteria for dengue. Lastly, the new guidelines have been criticized because they do not define the clinical criteria for establishing severe dengue (with the exception of providing laboratory cutoff values for transaminase levels), thereby leaving severity determination up to individual clinical judgment.

Dengue begins abruptly after a typical incubation period of 5–7 days, and the course follows 3 phases: febrile, critical, and convalescent.

Febrile Phase

Fever typically lasts 2–7 days and can be biphasic.
Other signs and symptoms may include severe headache; retro-orbital eye pain; muscle, joint, and bone pain; macular or maculopapular rash; and minor hemorrhagic manifestations including petechia, ecchymosis, purpura, epistaxis, bleeding gums, hematuria, or a positive tourniquet test result.
Some patients have injected oropharynx and facial erythema in the first 24–48 hours after onset.

Emergency room sign outside of a hospital

Warning Signs

Warning signs of progression to severe dengue occur in the late febrile phase around the time of defervescence, and include persistent vomiting, severe abdominal pain, fluid accumulation, mucosal bleeding, difficulty breathing, lethargy/restlessness, postural hypotension, liver enlargement, and progressive increase in hematocrit (i.e., hemoconcentration).

Critical Phase

The critical phase of dengue begins at defervescence and typically lasts 24–48 hours.
Most patients clinically improve during this phase, but those with substantial plasma leakage can, within a few hours, develop severe dengue as a result of a marked increase in vascular permeability.
Initially, physiologic compensatory mechanisms maintain adequate circulation, which narrows pulse pressure as diastolic blood pressure increases.
Patients with severe plasma leakage may have pleural effusions, ascites, hypoproteinemia, or hemoconcentration.
Patients may appear to be well despite early signs of shock. However, once hypotension develops, systolic blood pressure rapidly declines, and irreversible shock and death may ensue despite resuscitation.
Patients can also develop severe hemorrhagic manifestations, including hematemesis, bloody stool, or menorrhagia, especially if they have been in prolonged shock. Uncommon manifestations include hepatitis, myocarditis, pancreatitis, and encephalitis.

Convalescent Phase

As plasma leakage subsides, the patient enters the convalescent phase and begins to reabsorb extravasated intravenous fluids and pleural and abdominal effusions.
As a patient’s well-being improves, hemodynamic status stabilizes (although he or she may manifest bradycardia), and diuresis ensues. The patient’s hematocrit stabilizes or may fall because of the dilutional effect of the reabsorbed fluid, and the white cell count usually starts to rise, followed by a recovery of platelet count.
The convalescent-phase rash may desquamate and be pruritic.

Laboratory findings commonly include leukopenia, thrombocytopenia, hyponatremia, elevated aspartate aminotransferase and alanine aminotransferase, and a normal erythrocyte sedimentation rate.

Dengue During Pregnancy

Data are limited on health outcomes of dengue in pregnancy and effects of maternal infection on the developing fetus.
Perinatal transmission can occur, and peripartum maternal infection may increase the likelihood of symptomatic infection in the newborn.
Of 41 perinatal transmission cases described in the literature, all developed thrombocytopenia, most had evidence of plasma leakage evidenced by ascites or pleural effusions, and fever was absent in only two cases. Nearly 40% had a hemorrhagic manifestation, and 1 in 4 had hypotension.
Perinatally infected neonates typically become ill during the first week of life.
Placental transfer of maternal IgG against dengue virus (from a previous maternal infection) may increase risk for severe dengue among infants infected at 6–12 months of age, when the protective effect of these antibodies wanes.