Severe Dengue Infection

Updated: May 03, 2019
  • Author: Sukhveer (Sukhi) Bains, MD, MA; Chief Editor: Barry E Brenner, MD, PhD, FACEP  more...
  • Print


Dengue has been called the most important mosquito-transmitted viral disease in terms of morbidity and mortality. [1] It is the most prevalent viral mosquito-borne disease, with over 2.5 billion humans at risk of exposure given it endemicity in more than 100 countries. [2, 3]

Dengue fever is a benign, acute febrile syndrome occurring in tropical regions. In a small proportion of cases, the virus causes increased vascular permeability that leads to a bleeding diathesis or disseminated intravascular coagulation (DIC) known as dengue hemorrhagic fever (DHF). [4]

The WHO estimates that 50-100 million cases of dengue infection occur annually, with approximately 500,000 of those cases resulting in dengue hemorrhagic fever (DHF), with an estimated 22,000 deaths per year, mostly in children. [3] Secondary infection by a different dengue virus serotype has been confirmed as an important risk factor for the development of DHF. [5, 6, 7]

In 20-30% of DHF cases, the patient develops shock, known as the dengue shock syndrome (DSS).

Worldwide, children younger than 15 years make up 90% of DHF cases. [8] In the Americas, however, DHF occurs in adults and children.

Dengue fever is not contagious through person-to-person contact.


Complications are rare but may include the following: [9]

  • CNS dysfunction due to prolonged shock or intracranial hemorrhage
  • Myocarditis
  • Encephalopathy
  • Liver failure

Go to Dengue and Dermatologic Manifestations of Dengue for complete information on these topics.


Emergency Department Care

WHO guidelines recommend obtaining a baseline hematocrit measurement. Thrombocytopenia and hemoconcentration are consistent findings in dengue infection. [10] When the plasma leakage phase starts to resolve, the hematocrit level begins to fall, making identification of significant occult hemorrhage difficult. Administer blood transfusion if significant hemorrhage ensues (GI bleeding may be profound). Administer fresh frozen plasma or platelets if DIC is extensive and the patient is hemodynamically unstable. Prophylactic platelet transfusions in a stable thrombocytopenic patient are not needed.

There is no specific pharmacologic treatment for dengue infection. Initiate early supportive care by administering isotonic NS solution intravenously, as clinically indicated, to maintain adequate blood pressure and adequate urine output of 0.5-1 mL/kg/hour. The plasma leakage period is short (24-48 hours), and intravenous fluids may be reduced based on clinical response.

Administer acetaminophen for fever control (not salicylates or ibuprofen, which can further hinder platelet function and increase bleeding complications). Glucocorticoids are not indicated.

Corticosteroids are not helpful.

No antiviral therapy is available.

Patients with suspected dengue infection who are maintaining adequate hydration orally and have no warning signs/symptoms may be treated on an outpatient basis with appropriate anticipatory guidance and outpatient follow-up within 24 hours for reassessment.



Dengue vaccine was approved by the FDA in 2019 for prevention of dengue disease caused by dengue virus serotypes 1, 2, 3, and 4 in individuals aged 9-16 years with laboratory-confirmed previous dengue infection who live in endemic areas. It is approved only in individuals previously infected by any dengue virus serotype or in whom this information is unknown. Persons not previously infected are at an increased risk of severe dengue disease when vaccinated and subsequently infected with dengue virus.

The approval was based on data from 2 placebo-controlled studies in patients (n > 35,000) living in dengue-endemic areas. Patients were randomized 2:1 to receive either the vaccine or saline placebo and monitored for symptomatic virologically confirmed dengue (VCD) starting at day 0. Vaccine efficacy was assessed beginning 28 days after the third vaccination for 12 months. The vaccine was approximately 76% effective in preventing symptomatic VCD disease among patients aged 9-16 years who were seropositive for dengue at baseline. [11]


Inpatient Care

Admit the patient to the intensive care unit (ICU) in the setting of severe dengue infection (DHF or DSS); otherwise, admit to medicine ward for appropriate hydration, supportive care, and close reassessment. [12, 13, 2]

Admit patients with suspected dengue without warning signs who have concerning comorbid conditions that could affect their immune system and who are unable to follow up as an outpatient for daily reassessment. [2]



Dengue is generally a self-limited viral infection; however, in patients who develop the potentially catastrophic complications of DHF and DSS, survival is directly dependent on the hemodynamic support of patient through the disease manifestations. [10]

The rapid clinical response to aggressive fluids and electrolytes in even moribund children with DHF/DSS "is among the most dramatic events in clinical medicine." Treated promptly, children in shock and coma can wake up and return to near normalcy within hours. [14]

Convalescence may be prolonged, with weakness and mental depression.

Continued bone pain, bradycardia, and premature ventricular contractions (PVCs) are common.

Pediatric deaths associated with dengue viral infection most commonly occur in infants younger than 1 year.



Dengue virus is a flavivirus (single-stranded RNA) transmitted by various mosquitoes. Person-to-person transmission does not occur. There are four subtypes of the dengue virus, named DENV1 through DENV4, which are antigenically distinct. This characteristic drives the predominant hypothesis of how clinically severe dengue infection develops since most individuals who develop DHF or DSS have had a prior infection with a nonhomologous dengue virus. DHF and DSS may evolve based on antibody-dependent enhancement through a secondary infection. It is believed that secondary dengue virus infections greatly increase the risk of developing elevated levels of cytokines known to drive the clinical manifestations of DHF and DSS through endothelial damage, vascular leakage, and hemorrhage. [2]

Dengue infection has three phases: (1) the febrile phase, (2) the critical phase, and (3) the recovery phase. The entire course of the illness is typically 7-10 days with each phase lasting approximately 48-72 hours. The febrile phase (the initial phase) coincides with the peak of viremia during the illness and rapidly resolves after the first three days. It is associated with nonspecific signs and symptoms. The critical phase is marked by vascular permeability and its resultant complications. It is during this time that the clinician must be vigilant in monitoring for warning signs of severe dengue. The recovery phase includes diuresis and resolution of the symptoms that mark the critical phase of the illness. [2]



Dengue virus infection is largely a clinical diagnosis. The WHO-TDR has developed a simplified and binary system of classification for dengue infection. They classify infection as either (1) dengue infection with or without warning signs or (2) severe dengue infection. [2, 15] Clinicians should suspect dengue infection in patients with possible exposure (travel or endemic) and fever and two of the following characteristics: [2, 15]

  • Nausea/vomiting
  • Rash
  • Aches and pains
  • Positive tourniquet test result
  • Leukopenia
  • Any warning sign

Warning signs for dengue include the following [2, 15]

  • Abdominal pain or tenderness
  • Persistent vomiting
  • Clinical fluid accumulation
  • Mucosal bleeding
  • Lethargy, restlessness
  • Liver enlargement of more than 2 cm
  • Laboratory: Increased hematocrit coupled with rapid decrease in platelet count

Severe dengue infection diagnosis criteria include the following: [2, 15]

  • Severe plasma leakage leading to shock and/or fluid accumulation with respiratory distress
  • Severe hemorrhage
  • Severe organ impairment

RNA PCR testing is available for DENV1-4 through the CDC for diagnosis during the first 5 days of infection (after this period, IgM ELISA testing is preferred), although this is unlikely to assist directly in emergency department management. [2] Information on how to obtain PCR testing in suspected cases can be found at