Dengue

Milanie F. Valenton
Medical Resident
The virus
 Family Flaviviridae
 Single-stranded RNA virus
 4 serotypes (DEN-1, DEN-2 to 4)
 Distinguished by serologic methods
 Infection in humans by one serotype
produces lifelong immunity against
reinfection by that same serotype, but
only partial and temporary immunity
against other serotypes
The Vectors
 Aedes aegypti – a tropical and subtropical
species of mosquito found around the globe
 Limited by altitude – usually not found above
1000m
 One of the most efficient mosquito vectors
 highly anthrophilic
 thrives in close proximity to humans
 lives indoors
The Vectors

 Ae. albopictus, Ae. polynesiensis, Ae.

scutellaris complex – dengue outbreaks
but each has its own geographical
distribution
 A factor complicating eradication of the
vector ⇒ Ae. aegypti eggs can withstand
long periods of desiccation, sometimes
more than a year
The Host

 In humans, each of the 4 dengue virus

serotypes has been associated with DF
and with DHF.
 DSS occurs with higher frequency in 2
immunologically defined groups
 Children who have experienced a previous
dengue infection
 Infants with waning levels of maternal
dengue antibody
The Host

 Following an incubation of 3-14 days, the

acute phase lasts about 5-7 days,
followed by and immune response.
 Transmission of dengue virus from
infected humans to feeding mosquitoes
is determined by the magnitude and
duration of viremia in the human host.
Pathogenesis

 2 main pathophysiological changes

occur in DHF/DSS
 ↑ vascular permeability
 Disorder in hemostasis
Pathogenesis

↑ vascular permeability

Loss of plasma from the vascular

compartment

Hemoconcentration, low pulse pressure,

and other signs of shock
Pathogenesis

 Disorder in hemostasis involves

 Vascular changes
 Thrombocytopenia
 Coagulopathy
Pathogenesis

 Activation of complement system, with

profound depression of C3 and C5
levels, is a constant.
 Platelet defects may be both qualitative
and quantitative.
Clinical Diagnosis

 Dengue virus infections may be

asymptomatic or may lead to
undifferentiated fever, DF or DHF with
plasma leakage that may lead to
hypovolemic shock (DSS)
Dengue Fever
 Clinical features of DF frequently depend on the
age of the patient.
 Infants and young children may have an
undifferentiated febrile disease, often with a
maculopapular rash.
 Older children and adults may have either a
mild febrile syndrome or the classic
incapacitating disease with high fever of abrupt
onset, sometimes with 2 peaks (saddle-
backed), severe headache, pain behind the
eyes, muscle and bone or joint pains, nausea
and vomiting, and rash.
Dengue Fever

 Skin hemorrhages (petechiae) are not

uncommon
 Leukopenia
 Thrombocytopenia
 Recovery may be associated with
prolonged fatigue and depression,
especially in adults
Dengue Fever

 In some epidemics, DF may be

accompanied by bleeding complications
– epistaxis, gingival bleeding, GI
bleeding, hematuria, menorrhagia
 Case-fatality rate of DF - <1%
 Diffentiate DF with unusual bleeding
from cases of DHF with ↑ vascular
permeability (hemoconcentration)
Dengue Hemorrhagic Fever

 Characterized by 4 major manifestations

 High fever
 Hemorrhagic phenomena
 Hepatomegaly
 Circulatory failure
Dengue Hemorrhagic Fever

 Moderate to marked thrombocytopenia

with concurrent hemoconcentration is a
distinctive clinical laboratory finding.
 Leakage of plasma
 Major pathophysiological change that
determines the severity of disease and
differentiate it from DF
 Manifested by ↑ hematocrit, a serous
effusion or hypoproteinemia
Dengue Hemorrhagic Fever
 Sudden rise in temperature accompanied by
facial flush and constitutional signs and
symptoms resembling DF
 Other findings
 Sore throat and injection of pharynx but rhinitis and
cough are infrequent
 Mild conjunctival injection
 Epigastric discomfort, tenderness at the right costal
margin and/or generalized abdominal pain
Dengue Hemorrhagic Fever

 Temperature is usually high (>39) and

remains so for 2-7 days.
 Most common hemorrhagic
phenomenon
 (+) tourniquet test
 Easy bruising
 Bleeding at venipuncture sites
Dengue Hemorrhagic Fever

 Discrete fine petechiae scattered on the

extremities, axillae, face and soft palate
are usually seen during the early febrile
phase.
 Epistaxis and gum bleeding occur
infrequently
Dengue Hemorrhagic Fever
 Liver is usually palpable early in the febrile
phase and varies in size from just palpable to 2-
4 cm below the costal margin
 Liver size is not usually
 The critical stage of the disease course is
reached at the end of the febrile phase . After 2-
7 days of fever, a rapid fall in temperature is
often accompanied by signs of circulatory
disturbance of varying severity
Dengue Hemorrhagic Fever
 Many patients recover spontaneously, or after a
short period of fluid and electrolyte therapy.
 In severe cases, shock ensues and can rapidly
progress to profound shock and death if not
properly treated.
 The severity of the disease can be modified by
early diagnosis and replacement of plasma
loss.
 Thrombocytopenia and hemoconcentration are
usually detectable before the subsidence of
fever and the onset of shock.
Dengue Shock Syndrome

 Patients who progress to shock suddenly

deteriorates after a fever of 2-7 days.
 Characterized by a rapid, weak pulse
with narrowing of pulse pressure,
regardless of pressure level or
hypotension with cold, clammy skin and
restlessness
Dengue Shock Syndrome
 Most remain conscious
 Duration of shock is short: typically
patient dies within 12-24 hours, or
recover rapidly following appropriate
volume-replacement therapy.
 Once shock is overcome, patients
recover within 2-3 days.
 Good prognostic signs- good urine
output, return of appetite
Case Definition: Dengue Fever
 Probable – an acute febrile illness with 2 or more of the
following manifestations
 Headache
 Retro-orbital pain
 Myalgia
 Arthralgia
 Rash
 Hemorrhagic manifestations
 Leukopenia, and
 Supportive serology titer or a (+) IgM antibody test on
late acute or convalescent-phase serum
Or
- Occurrence at the same location and time as other
confirmed cases of DF
Case Definition: Dengue Fever

 Confirmed – a case confirmed by

laboratory criteria
 Reportable – any probable or confirmed
case should be reported
Case Definition: Dengue Fever
 Laboratory criteria
 Isolation of dengue virus from serum or autopsy
samples
 Demonstration of a 4-fold or greater change in
reciprocal IgG or IgM antibody titers to one or
more dengue virus antigens
 Demonstration of dengue virus antigen in autopsy
tissue, serum or CSF by immunohistochemistry,
immunofluorescence, or ELISA
 Detection of dengue virus genomic sequences in
autopsy tissue, serum or CSF by PCR
Case Definition: DHF
 The following must all be present
 Fever, or history of fever, lasting for 2-7 days,
occasionally, biphasic
 Hemorrhagic tendencies
 Thrombocytopenia (≤ 100,000/ mm3)
 Evidence of plasma leakage due to the ↑ vascular
permeability
 Hemoconcentration

 Drop in hematocrit following volume-replacement

treatment ≥ 20% of baseline
 Pleural effusion, ascites, hypoproteinemia
Case Definition: DSS

 All 4 criteria of DHF + evidence of

circulatory failure
 Rapid, weak pulse, and
 Narrow pulse pressure
or
 Hypotension for age, and
 Cold clammy skin and restlessness
Grading Severity of DHF

 Grade I: fever with non-specific s/sx;

only hemorrhagic manifestation is (+) TT
and/or easy bruising
 Grade II: all of Grade I + spontaneous
bleeding
 Grade III: (+) circulatory failure
 Grade IV: profound shock with
undetectable BP or pulse
Treatment

 Supportive
 Hydration
 Correction of electrolyte and metabolic
disturbances
 Sedation
 Oxygen therapy
 Blood transfusion