Dengue hemorrhagic fever (DHF) is a severe illness caused by the mosquito-borne dengue virus. DHF is characterized by high fever, hemorrhagic phenomena, and plasma leakage. Loss of a large volume of plasma may result in potentially fatal hypovolemic shock, known as dengue shock syndrome (DSS).
DHF is caused by a flavivirus that can be categorized into the four serotypes DENV-1 through DENV-4. Aedes mosquitoes, which are widely distributed in subtropical and tropical areas of the world, become infected with the dengue virus upon biting an infected human, and, after an incubation period, transmit the virus to new hosts during a subsequent blood meal. Dengue virus infection usually causes dengue fever (DF), a self-limiting flulike illness characterized by fever, joint and muscle pain, and rash (see Quick Lesson About … Dengue Fever). In its beginning stages, the clinical presentation of DHF mimics DF, making close monitoring of the patient for signs of disease progression critical. DHF pathogenesis is poorly understood, but involves increased vascular permeability that leads to leakage of plasma, resulting in hemoconcentration, low blood pressure, and signs of shock. Left untreated, DSS can cause tissue anoxia, metabolic acidosis, and death.
It has been theorized that DHF occurs at a greater rate in secondary infections due to antibody-dependent viral replication. Emerging data from studies on travelers to endemic regions who develop DHF as a primary infection, however, indicate that DHF occurs at similar rates among individuals with primary and secondary infections. This data challenges the traditionally accepted theory that DHF is caused by antibody-dependent viral replication. Further research on the cause of DHF is needed.
Isolation of dengue virus from patient samples, or demonstration of infection by serological tests showing dengue-specific antibodies, provides a definitive diagnosis of dengue virus infection. Because no dengue-specific medications exist, treatment involves intensive supportive care and monitoring, as well as prompt replacement of lost fluid volume.
Facts and Figures
Dengue viral infection is endemic in most tropical and subtropical areas of the world. DHF is the leading cause of hospitalization and death in children in many Southeast Asian countries. Adult DHF is more frequent in patients with asthma, diabetes mellitus, hypertension, and sickle cell anemia. Globally, more than 2.5billion people are at risk for DHF. Each year, an estimated 50-100 million cases of Dengue infection occur worldwide. In 2013, there were more than 2.35 million reported cases of dengue in the Americas, of which more than 37,000 cases were DHF (World Health Organization, 2014).
Dengue is becoming increasingly widespread; factors leading to the spread of the virus include the increased worldwide distribution of Aedes mosquitoes; frequent air travel, which allows people to carry the virus to distant locations; and the increasing proportion of the world’s population living in urban settings.
In patients experiencing their first dengue viral infection, the risk for developing DHF is approximately 0.2%; subsequent infection with a second serotype increases that risk to 2%. Without proper treatment, DHF may be fatal in approximately 20% of patients; with appropriate supportive care, the mortality rate is < 1%. In patients who progress to DSS, the fatality rate is approximately 10%.
Risk Factors
DHF is rarely seen in persons older than 15 years of age. Other risk factors for development of DHF include having a history of dengue infection; the presence of antibodies to a different dengue serotype is thought to enhance viral replication, increasing the severity of the disease. Susceptibility to DHF may vary by race; although all four dengue serotypes are seen in Africa, DHF is very rare. Studies have suggested that certain HLA alleles may confer protection against DHF, while others seem to increase the risk.
Signs and Symptoms/Clinical Presentation
Initial symptoms of DHF mimic those seen in patients with DF, including rapid-onset fever, headache, retro-orbital pain, severe muscle and/or joint pain, anorexia, and upper respiratory symptoms. Some patients complain of severe backache, lethargy, hepatomegaly, sore throat, or abdominal pain, or may develop a maculopapular rash. Around the time the fever begins to drop, DHF patients become restless, diaphoretic, show signs of circulatory failure, and exhibit hemorrhagic phenomena, including skin hemorrhages, bleeding gums, hematemesis, and melena. DHF-associated hemorrhage most commonly involves the skin, gastrointestinal tract, heart, and liver.
Assessment
Laboratory Tests That May Be Ordered
Isolation and culture of the dengue virus provide a definitive diagnosis of dengue viral infection
Serologic tests—including the hemagglutination-inhibition test, complement fixation test, neutralization test, and enzyme-linked immunosorbent assay (ELISA)—will identify the presence of antibodies to the dengue virus; a 4-fold or greater increase in antibody titer in paired sera is diagnostic for dengue infection
Hematological testing may show low platelet counts (≤ 100,000 cells/mm3) and elevated Hct levels (≥ 20%), as well as leukopenia and elevated liver enzymes
PT and aPTT, is prolonged, fibrinogen level is decreased and fibrinogen degradation product (FDP) level is elevated in patients with severe hemorrhagic manifestations
Detection of dengue-virus RNA by reverse transcriptase-polymerase chain reaction (RT-PCR) test or nucleic acid hybridization test demonstrates active infection
Other Diagnostic Tests/Studies
Chest X-ray may show signs of pleural effusion or bronchopneumonia
Ultrasonography of the abdomen may show peritoneal fluid accumulation
Treatment Goals
Relieve Symptoms and Promote Optimal Physiologic Function
Assess for pain and administer prescribed analgesics for relief. Acetaminophen is usually the preferred analgesic; aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) should be avoided due to risk for hemorrhage
Administer sedatives, such as chloral hydrate, if needed, to calm an agitated patient
Replace lost fluid volume with plasma expander or fluid and electrolyte solution
Administer hydration to combat dehydration due to fever, anorexia, and vomiting
Administer blood transfusion as ordered for severe bleeding; a drop in Hct that is not corrected by adequate fluid administration is a sign of internal hemorrhage
Closely monitor for shock, including frequent assessment of pulse, blood pressure, respiration, fluid balance, and for signs of bleeding
Shock is a medical emergency for which immediate treatment to maintain blood volume and blood pressure is critical
Decreased platelet count accompanied by rising Hct may indicate the onset of DSS; narrowing of pulse pressure (≤ 20 mm Hg) and hypotension are signs of shock. Other warning signs of shock include restlessness, lethargy, acute abdominal pain, cold extremities, skin congestion, and decreased urine output
If shock is present, follow facility protocols or clinician orders for administration of supplemental oxygen, fluid/electrolyte replacement, and blood transfusion
Support Emotional Well-Being of Patient and Family, and Educate
Assess patient and family anxiety level and coping ability; educate and encourage discussion about DHF, potential complications, prevention strategies (e.g., mosquito avoidance), treatment risks and benefits, and individualized prognosis
Food for Thought
Development of a dengue vaccine has been complicated by several factors, including the lack of a clear understanding of disease pathology, lack of an appropriate animal model of dengue infection, and by the possibility that the immune system is involved in disease pathogenesis and may not respond appropriately to a vaccine
Red Flags
Red Flags Mortality rate is highest when the difference between the systolic and diastolic blood pressure is < 10 mm Hg
Red Flags Indicators of poor prognosis in patients with DSS include profound or recurrent shock, respiratory failure, and high-level leukocytosis without evidence of a secondary bacterial infection
What Do I Need to Tell the Patient/Patient’s Family?
Advise that DHF cannot be directly transmitted between humans
Educate patient/family about ways to decrease the risk for contracting dengue while in endemic areas; these include use of insect repellent, mosquito netting, and protective clothing; avoid traveling to endemic areas during peak mosquito activity