What are the key facts about dengue fever? How does dengue fever present clinically? What are the warning signs of severe dengue? What are the different phases of dengue fever?

Key Facts About Dengue Fever

Dengue fever is a viral infection that can range from asymptomatic to severe, life-threatening disease. An estimated one in four dengue virus infections are symptomatic, with the most common presentation being a mild to moderate, nonspecific, acute febrile illness. Infection with one of the four dengue viruses will induce long-lasting immunity for that specific virus, but people can be infected with DENV multiple times in their life. Approximately one in 20 patients with dengue virus disease progress to develop severe, life-threatening severe dengue, with the second infection with DENV being a risk factor for this more severe form.

Clinical Presentation of Dengue Fever

The early clinical findings of dengue fever are nonspecific, but require a high index of suspicion as recognizing the early signs of shock and promptly initiating intensive supportive therapy can reduce the risk of death among patients with severe dengue to less than 0.5%. The World Health Organization (WHO) guidelines for classifying dengue define dengue as a combination of at least two clinical findings in a febrile person who traveled to or lives in a dengue-endemic area, including 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.

Severe Dengue and Warning Signs

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. The presence of a warning sign may predict the progression to severe dengue in a patient.

The Three Phases of Dengue Fever

Dengue fever follows three distinct phases: the febrile phase, the critical phase, and the convalescent phase. The febrile phase typically lasts 2-7 days and can be biphasic, with symptoms including severe headache, retro-orbital eye pain, muscle, joint, and bone pain, macular or maculopapular rash, and minor hemorrhagic manifestations. The critical phase begins at defervescence and typically lasts 24-48 hours, during which time most patients clinically improve, but those with substantial plasma leakage can develop severe dengue as a result of a marked increase in vascular permeability. The convalescent phase follows the critical phase, during which time the patient’s condition typically improves.

Recognizing the Warning Signs of Severe Dengue

The 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). Recognizing these warning signs early and promptly initiating intensive supportive therapy can significantly reduce the risk of death among patients with severe dengue.

The Importance of Early Recognition and Intervention

Early clinical findings in dengue fever are often nonspecific, but require a high index of suspicion as recognizing the early signs of shock and promptly initiating intensive supportive therapy can reduce the risk of death among patients with severe dengue to less than 0.5%. Clinicians should be vigilant in monitoring for the warning signs of progression to severe dengue, which occur in the late febrile phase around the time of defervescence, and be prepared to provide timely and appropriate supportive care to those patients at risk of developing life-threatening complications.

The Evolution of Dengue Case Definitions

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). However, the case definition was changed to the 2009 clinical classification after reports that the previous definition 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. Additionally, the new guidelines have been criticized for not defining 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.