There are an estimated 50 million infections per year with the dengue virus, which is transmitted primarily by urban adapted Aedes aegypti mosquitoes. The latest review in our Current Concepts series summarizes pathophysiology and treatment as well as prospects for a vaccine and for vector-control approaches.
Dengue is a self-limited, systemic viral infection transmitted between humans by mosquitoes. The rapidly expanding global footprint of dengue is a public health challenge with an economic burden that is currently unmet by licensed vaccines, specific therapeutic agents, or efficient vector-control strategies.
• What are the clinical manifestations of the initial (febrile) phase of dengue?
After an incubation period of 3 to 7 days, symptoms start suddenly. The initial febrile phase is typically characterized by high fever accompanied by headache, vomiting, myalgias, and joint pain, sometimes with a transient macular rash. Children have high fever but are generally less symptomatic than adults during this phase of the illness. Mild hemorrhagic manifestations such as petechiae and bruising, particularly at venipuncture sites, and a palpable liver are commonly noted. Laboratory findings include mild-to-moderate thrombocytopenia and leukopenia, often with a moderate elevation of hepatic aminotransferase levels. This phase lasts for 3 to 7 days, after which most patients recover without complications.
• What are the manifestations of the critical phase of dengue?
In a small proportion of patients, typically in children and young adults, a systemic vascular leak syndrome becomes apparent around the time of defervescence, evidenced by increasing hemoconcentration, hypoproteinemia, pleural effusions, and ascites. Once hypotension develops, systolic pressure decreases rapidly and irreversible shock and death may follow despite aggressive attempts at resuscitation. Signs of impending deterioration include persistent vomiting, increasingly severe abdominal pain, tender hepatomegaly, a high or increasing hematocrit level that is concurrent with a rapid decrease in the platelet count, serosal effusions, mucosal bleeding, and lethargy or restlessness. Hemorrhagic manifestations are most common during this critical period. Major skin bleeding, mucosal bleeding (gastrointestinal or vaginal), or both may occur in adults with no obvious precipitating factors and only minor plasma leakage. Moderate-to-severe thrombocytopenia is common, and a transient increase in the activated partial- thromboplastin time and a decrease in fibrinogen levels are also frequently noted.
Morning Report Questions
Q: How is dengue diagnosed?
A: Laboratory diagnosis of dengue is established directly by detection of viral components in serum or indirectly by serologic means. During the febrile phase, detection of viral nucleic acid in serum by means of reverse-transcriptase- olymerase-chain-reaction assay or detection of the virus-expressed soluble nonstructural protein 1 (NS1) is sufficient for a confirmatory diagnosis. For primary infections in persons who have not received treatment previously (which is typical in the case of most travelers), the diagnostic sensitivity of NS1 detection in the febrile phase can exceed 90%, and antigenemia may persist for several days after the resolution of fever. The sensitivity of NS1 detection in the febrile phase is lower in secondary infections (60 to 80%). Serologic diagnosis of dengue relies on the detection of high levels of serum IgM that bind dengue virus antigens; IgM can be detected as early as 4 days after the onset of fever.
Q: What treatment options are available?
A: Currently, no effective antiviral agents to treat dengue infection are available, and treatment remains supportive, with particular emphasis on careful fluid management. Development of any warning sign indicates the need for hospitalization and close observation, with judicious use of parenteral fluids in patients with inadequate oral intake or a rapidly increasing hematocrit. If the condition progresses to the dengue shock syndrome, prompt fluid resuscitation to restore plasma volume is imperative, followed by ongoing fluid therapy to support the circulation at a level just sufficient to maintain critical organ perfusion. Blood transfusion can be lifesaving for patients with severe bleeding that compromises cardiovascular function, but it should be undertaken with care because of the risk of fluid overload.