Dengue is the most common and important arthropod-borne viral (arboviral) illness in humans. It is transmitted by mosquitoes of the genus Aedes, which are widely distributed in subtropical and tropical areas of the world (see the image below). [1, 2, 3, 4] The incidence of dengue has increased dramatically in recent decades, with estimates of 40-50% of the world’s population at risk for the disease in tropical, subtropical, and, most recently, more temperate areas.

 

A small percentage of persons who have previously been infected by one dengue serotype develop bleeding and endothelial leak upon infection with another dengue serotype. This syndrome is termed severe dengue (also known as dengue hemorrhagic fever and dengue shock syndrome).

 

Dengue fever typically is a self-limited disease with a mortality rate of less than 1% when detected early and with access to proper medical care. When treated, severe dengue has a mortality rate of 2-5%, but, when left untreated, the mortality rate is as high as 20%.

 

See 7 Bug Bites You Need to Know This Summer, a Critical Images slideshow, for helpful images and information on various bug bites.

 

Signs and symptoms

On average, dengue becomes symptomatic after a 4- to 10-day incubation period (range, 3-14 days). Dengue symptoms usually last 2-7 days.

Many individuals with dengue may be asymptomatic. Many patients with dengue experience a prodrome of chills; rash, including erythematous mottling of the skin; and facial flushing, which may last 2-3 days. Children younger than 15 years who have dengue usually have a nonspecific febrile syndrome, which a maculopapular rash may accompany. Dengue should be suspected in individuals who present with high fever (104°F/40°C), retro-orbital headache, muscle and joint pain, nausea, lymphadenopathy, vomiting, and rash and who have traveled within 2 weeks of symptom onset to an area where appropriate vectors are present and dengue transmission may be occurring.

Accompanying symptoms in patients with dengue may include any of the following:

• Fever
• Headache
• Retro-orbital pain
• Severe myalgias: Especially of the lower back, arms, and legs
• Arthralgias: Usually of the knees and shoulders
• Nausea and vomiting (diarrhea is rare)
• Rash: A maculopapular or macular confluent rash over the face, thorax, and flexor surfaces, with islands of skin-sparing
• Weakness, malaise, and lethargy
• Altered taste sensation
• Anorexia
• Sore throat
• Mild hemorrhagic manifestations (eg, petechiae, bleeding gums, epistaxis, menorrhagia, hematuria)
• Lymphadenopathy

 

Severe dengue (dengue hemorrhagic fever and dengue shock syndrome)

The initial phase of severe dengue is similar to that of dengue fever and other febrile viral illnesses. Shortly after the fever breaks (3-7 days after symptom onset or sometimes within 24 hours before), signs of plasma leakage appear, along with the development of hemorrhagic symptoms such as bleeding from sites of trauma, gastrointestinal bleeding, and hematuria. Patients may also present with severe abdominal pain, persistent vomiting that may contain blood, fatigue, and febrile seizures (in children).

The subsequent 24 hours frequently prove critical. If left untreated, hemorrhagic fever most likely progresses to shock. Common symptoms of impending shock include abdominal pain, vomiting, and restlessness. Patients also may have symptoms related to circulatory failure, such as pallor, tachypnea, tachycardia, dizziness/lightheadedness, and a decreased level of consciousness.

Diagnosis

Laboratory criteria for the diagnosis of dengue include one or more of the following, which are used to detect the virus, viral nucleic acid, antibodies or antigens, or a combination thereof:

• Demonstration of a fourfold or greater change in reciprocal immunoglobulin G (IgG) or IgM antibody titers to 1 or more dengue virus antigens in paired serum samples
• Demonstration of dengue virus antigen in autopsy tissue via immunohistochemistry or immunofluorescence or in serum samples via enzyme immunoassay (MAC-ELISA, IgG ELISA, nonstructural protein 1 [NS1] ELISA, EIA)
• Detection of viral genomic sequences in autopsy tissue, serum, or cerebral spinal fluid (CSF) samples via reverse-transcriptase polymerase chain reaction (RT-PCR) assay: RT-PCR provides an earlier and more specific diagnosis.
• Less frequently, isolation of the dengue virus from serum, plasma, leukocytes, or autopsy samples

During the early phase of the disease (first 4-5 days), the virus can be detected in serum, plasma, circulating blood cells, and tissues. Virus isolation, nucleic acid detection, and antigen detection are more useful to diagnose infection. At the end of the acute phase of illness, serology becomes the method of choice.

The following laboratory tests should also be performed in the workup of patients with possible dengue:

• Complete blood cell (CBC) count
• Metabolic panel
• Serum protein and albumin levels
• Liver panel
• Coagulation panel with or without disseminated intravascular coagulation (DIC) panel

Characteristic laboratory findings in dengue are as follows:

• Thrombocytopenia (platelet count < 100 x 109/L)
• Leukopenia
• Mild to moderate elevation of aspartate aminotransferase and alanine aminotransferase values

In patients with severe dengue, the following may be present:

• Increased hematocrit level secondary to plasma extravasation and/or third-space fluid loss
• Hypoproteinemia
• Prolonged prothrombin time
• Prolonged activated partial thromboplastin time
• Decreased fibrinogen
• Increased amount of fibrin split products

Guaiac testing for occult blood in the stool should be performed on all patients in whom dengue virus infection is suspected. Urinalysis identifies hematuria.

Imaging studies include the following:

• Chest radiography
• Head computed tomography (CT) scanning without contrast: To detect intracranial bleeding or cerebral edema due to severe dengue
• Ultrasonography: To detect fluid in the chest and abdominal cavities, pericardial effusion, and a thickened gallbladder wall in patients with severe dengue

Management

Oral rehydration therapy is recommended for patients with moderate dehydration caused by high fever and vomiting.

Patients who develop signs of severe dengue warrant closer observation. Admission for close volume status monitoring and intravenous fluid administration is indicated for patients who develop signs of dehydration, such as the following:

• Tachycardia
• Prolonged capillary refill time
• Cool or mottled skin
• Diminished pulse amplitude
• Altered mental status
• Decreased urine output
• Rising hematocrit
• Narrowed pulse pressure
• Hypotension

Patients with internal or gastrointestinal bleeding may require transfusion, and patients with coagulopathy may require fresh frozen plasma.

 

 

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