Dengue Fever

Introduction
A. Background
Dengue has been called the most important mosquito-transmitted viral disease in terms of morbidity and
mortality. 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). Secondary infection by a different
dengue virus serotype has been confirmed as an important risk factor for the development of DHF. In 20-30% of
DHF cases, the patient develops shock, known as the dengue shock syndrome (DSS). Worldwide, children
younger than 15 years comprise 90% of DHF subjects;however, in the Americas, DHF occurs in both adults and
children.
Dengue is a homonym for the African ki denga pepo, which appeared in English literature during an
1827-28 Caribbean outbreak. The first definite clinical report of dengue is attributed to Benjamin Rush in 1789,
but the viral etiology and its mode of transmission via mosquitos were not established until the early 20th
century.

Causes
Dengue virus types 1-4
o Aedes aegypti mosquito vector
o Human-mosquito-human cycle
o Found in tropical regions, especially Southeast Asia

B. Pathophysiology
Dengue viral infections frequently are not apparent. Classic dengue primarily occurs in nonimmune,
nonindigenous adults and children. Symptoms begin after a 5- to 10-day incubation period. DHF/DSS usually
occurs during a second dengue infection in persons with preexisting actively or passively (maternally) acquired
immunity to a heterologous dengue virus serotype. Illness begins abruptly with a minor stage of 2-4 days'
duration followed by rapid deterioration. Increased vascular permeability, bleeding, and possible DIC may be
mediated by circulating dengue antigen-antibody complexes, activation of complement, and release of
vasoactive amines. In the process of immune elimination of infected cells, proteases and lymphokines may be
released and activate complement coagulation cascades and vascular permeability factors.

C. Frequency
International
Dengue virus causes about 100 million cases of acute febrile disease annually, including more than
500,000 reported cases of DHF/DSS.1,2 Currently, dengue is endemic in 112 countries. The world's largest
known epidemic of DHF/DSS occurred in Cuba in 1981, with more than 116,000 persons hospitalized and as
many as 11,000 cases reported in a single day.

D. Mortality/Morbidity
Treated DHF/DSS is associated with a 3% mortality rate.
Untreated DHF/DSS is associated with a 50% mortality rate.

E. Race
Ethnicity is nonspecific, but the disease's distribution is geographically determined. Fewer cases have
been reported in the black population than in other races.

F. Sex
No predilection is known; however, fewer cases of DHF/DSS have been reported in men than in women.
G. Age
All ages are susceptible. In endemic areas, a high prevalence of immunity in adults may limit outbreaks
to children.
Clinical
A. History
Fever
o Abrupt onset, rising to 39.5-41.4C
o Accompanied by frontal or retro-orbital headache
o Lasts 1-7 days, then defervesces for 1-2 days
o Biphasic, recurring with second rash but not as high
Rash
o Initial rash transient, generalized, macular, and blanching; occurs in first 1-2 days of fever
o Second rash occurring within 1-2 days of defervescence, lasting 1-5 days
o Second rash morbilliform, maculopapular, sparing palms and soles
o Occasionally desquamates
Bone pain
o Absent in dengue hemorrhagic fever (DHF)/dengue shock syndrome (DSS)
o After onset of fever
o Increases in severity
o Not associated with fractures
o May last several weeks
o Most common in legs, joints, and lumbar spine
Miscellaneous symptoms
o Nausea and vomiting
o Cutaneous hyperesthesia
o Taste aberrations
o Anorexia
o Abdominal pain (severe in DHF/DSS)
B. Physical
Fever
Signs of intravascular volume depletion
o Hypotension with narrowed pulse pressure
o Delayed capillary refill
Delayed capillary refill may be the first sign of intravascular volume depletion.
Hypotension usually is a late sign in children. This child's capillary refill at 6 seconds was
delayed well beyond a normal duration of 2 seconds.
Hemorrhagic manifestations
o Positive tourniquet test
o Petechiae, purpura, epistaxis, gum bleeding, GI bleeding, menorrhagia
Rash
Hepatomegaly (inconsistent)
Generalized lymphadenopathy

Workup

A. Laboratory Studies
Isolation of virus in serum and detection of immunoglobulins (IgM and IgG) by enzyme-linked
immunosorbent assay (ELISA) antibody capture, monoclonal antibody, or hemagglutination
 Complete blood count
o Hemoconcentration (hematocrit increased 20%)
o Thrombocytopenia (platelet count <100 x 109/L)
o Leukopenia
Chemistry panel
o Electrolyte imbalances
o Acidemia
o Elevated BUN
Liver function tests
o Elevated transaminases
o Hypoproteinemia
Guaiac test for occult blood in stool
DIC panel, as indicated
B. Imaging Studies
Chest radiography
o Bronchopneumonia
o Pleural effusion
Head CT scan without contrast
o For altered level of consciousness
o Intracranial bleeding
o Cerebral edema
C. Other Tests
Electrocardiography
o Nonspecific changes may be effects of fever, electrolyte disturbances, tachycardia, or
medications.
o Usefulness of these changes as a marker of cardiac involvement is unclear.

Treatment
A.Prehospital Care
Initiate supportive therapy
o Intravenous (IV) crystalloids, as needed to keep systolic blood pressure above 90 mm Hg
o O2, empirically
B.Emergency Department Care
Supportive therapy
o IV access, O2, and monitoring are helpful.
o IV crystalloids may be necessary for hypotension; central line may be needed.
o Correct electrolyte abnormalities and acidemia.
Implement therapy for DIC if indicated.
Corticosteroids are not helpful.
No antiviral therapy is available.
C.Medication
No specific medications are indicated for direct treatment of the dengue virus infection.
D. Consultations
Infectious disease
Travel clinic, if available
Follow-up
A.Further Inpatient Care
Admit to ICU if hypotensive or in DIC, otherwise admit to medicine ward.
o Patient may require a central line.
o Patient may require an arterial line.
o Patient may require blood components.
B.Deterrence/Prevention

Reduce A aegypti vector populations.3

Reduce exposure to A aegypti.
o Use insect repellent.
o Sleep under a mosquito net in affected areas.
o Wear protective clothing.

Vaccines against all 4 serotypes are currently under development. While this is challenging due to the
complex immune response, vaccines may ultimately be the most effective control strategy, since vector
control programs have been largely unsuccessful and of only short-term local benefit.4,5
Complications
Complications are rare but may include the following:
o Brain damage from prolonged shock or intracranial hemorrhage
o Myocarditis
o Encephalopathy
o Liver failure
Prognosis

Morens states that 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.6

Convalescence may be prolonged, with weakness and mental depression.

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

Survival is related directly to early hospitalization and aggressive supportive care.

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

Miscellaneous
Medicolegal Pitfalls
Failure to admit patients for aggressive supportive therapy
Failure to rule out other possible illnesses and specific therapies
Special Concerns
Pediatric deaths associated with dengue viral infection most commonly occur in infants younger than 1
year