DENGUE

Virus vector and transmission

Dengue Virus
Causes dengue and dengue hemorrhagic fever
Is an arbovirus
Transmitted by mosquitoes
Composed of single-stranded RNA
Has 4 serotypes (DEN-1, 2, 3, 4)
 Aedes aegypti
Dengue transmitted by
infected female mosquito
Primarily a daytime
feeder
Lives around human
habitation
Lays eggs and produces
larvae preferentially in
artificial containers.
Diseases- yellow fever, filaria
dengue, chikungunya fever,
rift valley fever.
 Replication and Transmission
of Dengue Virus
1. Virus transmitted 1
to human in mosquito
saliva
2
2. Virus replicates 4
in target
organs 3
3. Virus infects white
blood cells and
lymphatic tissues
4. Virus released and
circulates in
 Replication and Transmission
of Dengue Virus

5. Second mosquito 6
ingests virus with blood

6. Virus replicates
in mosquito midgut
and other organs,
7
infects salivary
glands
5
7. Virus replicates
in salivary glands
 Transmission of Dengue Virus
by Aedes aegypti

Mosquito feeds / Mosquito refeeds /

acquires virus transmits virus

Extrinsic Intrinsic
incubation incubation
period period
Viremia Viremia
0 5 8 12 16 20 24 28
DAYS
Illness Illness
Human #1 Human
#2
Clinical Manifestations of Dengueand
Dengue Hemorrhagic Fever

Undifferentiated fever
Classic dengue fever
Dengue hemorrhagic fever
Dengue shock syndrome
 Clinical Characteristics
of Dengue Fever
Fever
Headache
Muscle and joint pain
Nausea/vomiting
Rash
Hemorrhagic
manifestations
 Hemorrhagic Manifestations
of Dengue
Skin hemorrhages: petechiae, purpura,
ecchymoses
Gingival bleeding
Nasal bleeding
Gastro-intestinal bleeding:
hematemesis, melena, hematochezia
Hematuria
Increased menstrual flow
 Signs and Symptoms of
Encephalitis/Encephalopathy
Associated with Acute
Dengue Infection
Decreased level of consciousness:
lethargy, confusion, coma
Seizures
Nuchal rigidity
Paresis
Clinical Case Definition for
Dengue Hemorrhagic
Fever4 Necessary Criteria:
Fever, or recent history of acute fever
Hemorrhagic manifestations
Low platelet count (100,000/mm3 or less)
Objective evidence of “leaky
capillaries:”
– elevated hematocrit (20% or more over
baseline)
– low albumin
 Four Grades of DHF
Grade 1
– Fever and nonspecific constitutional symptoms
– Positive tourniquet test is only hemorrhagic
manifestation
Grade 2
– Grade 1 manifestations + spontaneous
bleeding
Grade 3
– Signs of circulatory failure (rapid/weak pulse, narrow
pulse pressure, hypotension, cold/clammy skin)
Grade 4
 Danger Signs in
Dengue Hemorrhagic Fever
Abdominal pain - intense and sustained
Persistent vomiting
Abrupt change from fever to
hypothermia, with sweating and
prostration
Restlessness or somnolence
Clinical Case Definition for Dengue
Shock Syndrome
4 criteria for DHF
Evidence of circulatory failure manifested
indirectly by all of the following:
– Rapid and weak pulse
– Narrow pulse pressure ( 20 mm Hg)
OR
hypotension for age
– Cold, clammy skin and altered mental
status
Frank shock is direct evidence of circulatory
failure
 Risk Factors Reported for DHF
Virus strain :DHF risk is greatest for DEN-2, followed
by DEN-3, DEN-4 and DEN-1
Pre-existing anti-dengue antibody
– previous infection
– maternal antibodies in infants
Host genetics-females more affected,
malnutrition protective.
Age(<12)
 Unusual Presentations
of Severe Dengue Fever

Encephalopathy
Hepatic
damage
Cardiomyopathy
Severe
gastrointestinal
hemorrhage
 Increased Probability of DHF
Hyperendemicity

Increased circulation Increased probability

of viruses of secondary infection

Increased probability of Increased probability of

occurrence of virulent strains immune enhancement

Increased probability of DHF

 Pathogenesis of DHF
STEP 1- Homologous Antibodies Form Non-
infectious Complexes

1
1

1
1
Dengue 1 virus
Neutralizing antibody to Dengue 1 virus
Non-neutralizing antibody
1 Complex formed by neutralizing antibody and virus
 STEP2- Heterologous Antibodies of first
serotype infection form Infectious Complexes
with second serotype

2 2
2

2
Dengue 2 virus
Non-neutralizing antibody to Dengue 1 virus
2
Complex formed by non-neutralizing antibody
and virus
STEP3 - Heterologous Complexes Enter More
Monocytes, Where Virus Replicates

2
2
2
2
2
2 2
2
2

2 Dengue 2 virus

Non-neutralizing antibody
2 Complex formed by non-neutralizing
antibody and Dengue 2 virus
STEP4 –DHF pathogenesis

Infected monocytes release vasoactive

mediators, resulting in increased vascular
permeability and hemorrhagic manifestations
that characterize DHF and DSS
Clinical Evaluation in Dengue Fever

Blood pressure
Evidence of bleeding in skin or other sites
Hydration status
Evidence of increased vascular
permeability-- pleural effusions, ascites
Tourniquet test
Petechiae
 Tourniquet Test
Inflate blood pressure
cuff to a point midway
between systolic and
diastolic pressure for 5
minutes
Positive test: 20 or more
petechiae per 1 inch2
(6.25 cm2)
 Laboratory Tests
in Dengue
Fevertests
Clinical laboratory
– CBC--WBC, platelets, hematocrit
– Albumin
– Liver function tests
– Urine--check for microscopic hematuria
Dengue-specific tests
– Virus isolation
– Serology
Laboratory Methods for Dengue Diagnosis-

Virus isolation to determine serotype of

the infecting virus
IgM ELISA test for serologic diagnosis
Virus isolation: cell culture, mosquito inoculation&
fluroscent antibody test
ELISA Plate
 Collection and Processing of
Samples for Laboratory
Diagnosis
Type of Time of Type of
Specimen Collection Analysis
Acute-phase When patient presents; Virus isolation
blood collect second sample and/or serology
(0-5 days after during convalescence
onset)
Convalescent-phase Between days 6 and 21 Serology
blood after onset
( 6 days after
onset)
 Temperature, Virus Positivity
and Anti-Dengue IgM , by
Fever Day
Temperature (degrees Celsius)

100

Dengue IgM (EIA units)

300
39.5
Percent Virus Positive

80
39.0 225
38.5 60
150
38.0 40
37.5 20 75

37.0
0 0
-4 -3 -2 0 1 2 3 4 5 6
-1 Fever Day
Mean Max. Temperature Virus Dengue IgM
 Warning Signs for Dengue Shock
Four Criteria for DHF:
• Fever
• Hemorrhagic manifestations
• Excessive capillary permeability
•  100,000/mm3 platelets
Initial Warning Signals:
• Disappearance of fever
• Drop in platelets
• Increase in hematocrit
Alarm Signals:
• Severe abdominal pain
• Prolonged vomiting
• Abrupt change from fever
to
hypothermia
• Change in level of
When Patients Develop DSS:
consciousness (irritability
• 3 to 6 days after onset of

or
symptoms
somnolence)