dengue-130319003111-phpapp01.pdf

Dr. Sachin Verma MD, FICM, FCCS, ICFC
Dr. Sachin Verma MD, FICM, FCCS, ICFC
Fellowship in Intensive Care Medicine
Fellowship in Intensive Care Medicine
Infection Control Fellows Course
Infection Control Fellows Course
Consultant Internal Medicine and Critical Care
Consultant Internal Medicine and Critical Care
Web:-
Web:- http://www.medicinedoctorinchandigarh.com
http://www.medicinedoctorinchandigarh.com
Mob:- +91-7508677495
Mob:- +91-7508677495
References;
References;
1.
1. Harrison
Harrison´s
´s principle of internal medicine -16
principle of internal medicine -16th
th
ed
ed
2.
2. Park
Park´s textbook of preventive and social medicine -17
´s textbook of preventive and social medicine -17th
th
ed
ed
3.
3. www.cdc.org
www.cdc.org

Virus vector and transmission
Virus vector and transmission
Dengue Virus
Dengue Virus
Causes dengue and dengue hemorrhagic fever
Causes dengue and dengue hemorrhagic fever
Is an arbovirus
Is an arbovirus
Transmitted by mosquitoes
Transmitted by mosquitoes
Composed of single-stranded RNA
Composed of single-stranded RNA
Has 4 serotypes (DEN-1, 2, 3, 4)
Has 4 serotypes (DEN-1, 2, 3, 4)

Dengue Viruses
Dengue Viruses
Each serotype provides specific lifetime
Each serotype provides specific lifetime
immunity, and short-term cross-immunity
immunity, and short-term cross-immunity
All serotypes can cause severe and fatal
All serotypes can cause severe and fatal
disease
disease
Genetic variation within serotypes
Genetic variation within serotypes
Some genetic variants within each serotype
Some genetic variants within each serotype
appear to be more virulent or have greater
appear to be more virulent or have greater
epidemic potential
epidemic potential

Aedes aegypti
Aedes aegypti
Dengue transmitted by
Dengue transmitted by
infected female mosquito
infected female mosquito
Primarily a daytime feeder
Primarily a daytime feeder
Lives around human
Lives around human
habitation
habitation
Lays eggs and produces
Lays eggs and produces
larvae preferentially in
larvae preferentially in
artificial containers.
artificial containers.
Diseases- yellow fever, filaria
Diseases- yellow fever, filaria
dengue, chikungunya fever,
dengue, chikungunya fever,
rift valley fever.
rift valley fever.

Aedes aegypti:
Distribution
throughout the world

Model of baseline transmission
Model of baseline transmission
potential (1961-1990 climate)
potential (1961-1990 climate)

Model of future transmission
Model of future transmission
potential (2080s climate)
potential (2080s climate)

Population increase only
Population increase only
Population at
Population at
risk (billions)
risk (billions)
% of total
% of total
population
population
2050s
2050s 3.2
3.2 34
34
2080s
2080s 3.5
3.5 35
35
Population increase plus
Population increase plus
climate change (HADCM2)
climate change (HADCM2)
2050s
2050s 4.1
4.1 44
44
2080s
2080s 5.2
5.2 52
52

Replication and Transmission
of Dengue Virus
of Dengue Virus
1. Virus transmitted
to human in mosquito
saliva
2. Virus replicates
in target organs
3. Virus infects white
blood cells and
lymphatic tissues
4. Virus released and
circulates in blood
3
4
1
2

of Dengue Virus
of Dengue Virus
5. Second mosquito
ingests virus with blood
6. Virus replicates
in mosquito midgut
and other organs,
infects salivary
glands
7. Virus replicates
in salivary glands
6
7
5

Transmission of Dengue Virus
Transmission of Dengue Virus
by
by Aedes aegypti
Aedes aegypti
Viremia Viremia
Extrinsic
incubation
period
DAYS
0 5 8 12 16 20 24 28
Human #1 Human #2
Illness
Mosquito feeds /
acquires virus
Mosquito refeeds /
transmits virus
Intrinsic
incubation
period
Illness

Clinical Manifestations of Dengue and
Clinical Manifestations of Dengue and
Dengue Hemorrhagic Fever
Undifferentiated fever
Undifferentiated fever
Classic dengue fever
Classic dengue fever
Dengue hemorrhagic fever
Dengue hemorrhagic fever
Dengue shock syndrome
Dengue shock syndrome

Undifferentiated Fever
Undifferentiated Fever
May be the most common manifestation of
May be the most common manifestation of
dengue
dengue
Prospective study found that 87% of patients
Prospective study found that 87% of patients
infected were either asymptomatic or only mildly
infected were either asymptomatic or only mildly
symptomatic
symptomatic
Other prospective studies including all age-
Other prospective studies including all age-
groups also demonstrate silent transmission.
groups also demonstrate silent transmission.

Clinical Characteristics
Clinical Characteristics
of Dengue Fever
of Dengue Fever
Fever
Fever
Headache
Headache
Muscle and joint pain
Muscle and joint pain
Nausea/vomiting
Nausea/vomiting
Rash
Rash
Hemorrhagic manifestations

Hemorrhagic Manifestations
Hemorrhagic Manifestations
of Dengue
of Dengue
Skin hemorrhages: petechiae, purpura,
Skin hemorrhages: petechiae, purpura,
ecchymoses
ecchymoses
Gingival bleeding
Gingival bleeding
Nasal bleeding
Nasal bleeding
Gastro-intestinal bleeding:
Gastro-intestinal bleeding:
hematemesis, melena, hematochezia
hematemesis, melena, hematochezia
Hematuria
Hematuria
Increased menstrual flow
Increased menstrual flow

Signs and Symptoms of
Signs and Symptoms of
Encephalitis/Encephalopathy
Encephalitis/Encephalopathy
Associated with Acute Dengue
Associated with Acute Dengue
Infection
Infection
Decreased level of consciousness:
Decreased level of consciousness:
lethargy, confusion, coma
lethargy, confusion, coma
Seizures
Seizures
Nuchal rigidity
Nuchal rigidity
Paresis
Paresis

Clinical Case Definition for
Clinical Case Definition for
Fever, or recent history of acute fever
Fever, or recent history of acute fever
Low platelet count (100,000/mm
Low platelet count (100,000/mm3
3
or less)
or less)
Objective evidence of “leaky capillaries:”
Objective evidence of “leaky capillaries:”
– elevated hematocrit (20% or more over
elevated hematocrit (20% or more over
baseline)
baseline)
– low albumin
low albumin
– pleural or other effusions
pleural or other effusions
4 Necessary Criteria:
4 Necessary Criteria:

Four Grades of DHF
Four Grades of DHF
Grade 1
Grade 1
– Fever and nonspecific constitutional symptoms
Fever and nonspecific constitutional symptoms
– Positive tourniquet test is only hemorrhagic
Positive tourniquet test is only hemorrhagic
manifestation
manifestation
Grade 2
Grade 2
– Grade 1 manifestations + spontaneous bleeding
Grade 1 manifestations + spontaneous bleeding
Grade 3
Grade 3
– Signs of circulatory failure (rapid/weak pulse, narrow
Signs of circulatory failure (rapid/weak pulse, narrow
pulse pressure, hypotension, cold/clammy skin)
pulse pressure, hypotension, cold/clammy skin)
Grade 4
Grade 4
– Profound shock (undetectable pulse and BP)
Profound shock (undetectable pulse and BP)

Danger Signs in
Danger Signs in
Abdominal pain - intense and sustained
Abdominal pain - intense and sustained
Persistent vomiting
Persistent vomiting
Abrupt change from fever to
Abrupt change from fever to
hypothermia, with sweating and
hypothermia, with sweating and
prostration
prostration
Restlessness or somnolence
Restlessness or somnolence

Clinical Case Definition for Dengue
Clinical Case Definition for Dengue
Shock Syndrome
Shock Syndrome
4 criteria for DHF
4 criteria for DHF
Evidence of circulatory failure manifested
Evidence of circulatory failure manifested
indirectly by all of the following:
indirectly by all of the following:
– Rapid and weak pulse
Rapid and weak pulse
– Narrow pulse pressure (
Narrow pulse pressure (≤ 20 mm Hg)
20 mm Hg) OR
OR
hypotension for age
hypotension for age
– Cold, clammy skin and altered mental
Cold, clammy skin and altered mental
status
status
Frank shock is direct evidence of circulatory
Frank shock is direct evidence of circulatory
failure
failure

Risk Factors Reported for DHF
Risk Factors Reported for DHF
Virus strain :
Virus strain :DHF risk is greatest for DEN-2, followed
DHF risk is greatest for DEN-2, followed
by DEN-3, DEN-4 and DEN-1
by DEN-3, DEN-4 and DEN-1
Pre-existing anti-dengue antibody
Pre-existing anti-dengue antibody
– previous infection
previous infection
– maternal antibodies in infants
maternal antibodies in infants
Host genetics-females more affected,
Host genetics-females more affected,
malnutrition protective.
malnutrition protective.
Age(<12)
Age(<12)

Unusual Presentations
Unusual Presentations
of Severe Dengue Fever
of Severe Dengue Fever
Encephalopathy
Encephalopathy
Hepatic damage
Hepatic damage
Cardiomyopathy
Cardiomyopathy
Severe gastrointestinal hemorrhage
Severe gastrointestinal hemorrhage

Increased Probability of DHF
Increased Probability of DHF
Hyperendemicity
Increased circulation
of viruses
Increased probability
of secondary infection
Increased probability of
occurrence of virulent strains
Increased probability of
immune enhancement
Increased probability of DHF

Neutralizing antibody to Dengue 1 virus
1
1
Dengue 1 virus
1
Pathogenesis of DHF
Pathogenesis of DHF
STEP 1- Homologous Antibodies Form Non-
STEP 1- Homologous Antibodies Form Non-
infectious Complexes
infectious Complexes
Non-neutralizing antibody
1
1 Complex formed by neutralizing antibody and virus

Non-neutralizing antibody to Dengue 1 virus
Dengue 2 virus
2 2
2
2
2
STEP2- Heterologous Antibodies of first
STEP2- Heterologous Antibodies of first
serotype infection form Infectious Complexes
serotype infection form Infectious Complexes
with second serotype
with second serotype
Complex formed by non-neutralizing antibody
and virus
2

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

STEP4 –DHF pathogenesis
STEP4 –DHF pathogenesis
Infected monocytes release vasoactive
Infected monocytes release vasoactive
mediators, resulting in increased vascular
mediators, resulting in increased vascular
permeability and hemorrhagic manifestations
permeability and hemorrhagic manifestations
that characterize DHF and DSS
that characterize DHF and DSS

Clinical Evaluation in Dengue Fever
Clinical Evaluation in Dengue Fever
Blood pressure
Blood pressure
Evidence of bleeding in skin or other sites
Evidence of bleeding in skin or other sites
Hydration status
Hydration status
Evidence of increased vascular
Evidence of increased vascular
permeability-- pleural effusions, ascites
permeability-- pleural effusions, ascites
Tourniquet test
Tourniquet test

Tourniquet Test
Tourniquet Test
Inflate blood pressure
Inflate blood pressure
cuff to a point midway
cuff to a point midway
between systolic and
between systolic and
diastolic pressure for 5
diastolic pressure for 5
minutes
minutes
Positive test: 20 or more
Positive test: 20 or more
petechiae per 1 inch
petechiae per 1 inch2
2
(6.25 cm
(6.25 cm2
2
)
)

Laboratory Tests
Laboratory Tests
in Dengue Fever
in Dengue Fever
Clinical laboratory tests
Clinical laboratory tests
– CBC--WBC, platelets, hematocrit
CBC--WBC, platelets, hematocrit
– Albumin
Albumin
– Liver function tests
Liver function tests
– Urine--check for microscopic hematuria
Urine--check for microscopic hematuria
Dengue-specific tests
Dengue-specific tests
– Virus isolation
Virus isolation
– Serology
Serology

Laboratory Methods for Dengue Diagnosis-
Laboratory Methods for Dengue Diagnosis-
Virus isolation to determine serotype of
Virus isolation to determine serotype of
the infecting virus
the infecting virus
IgM ELISA test for serologic diagnosis
IgM ELISA test for serologic diagnosis

Virus isolation: cell culture, mosquito inoculation&
Virus isolation: cell culture, mosquito inoculation&
fluroscent antibody test
fluroscent antibody test

Collection and Processing of
Collection and Processing of
Samples for Laboratory
Samples for Laboratory
Diagnosis
Diagnosis
Type of
Specimen
Time of
Collection
Type of
Analysis
Acute-phase
blood
(0-5 days after onset)
When patient presents;
collect second sample
during convalescence
Virus isolation
and/or serology
Convalescent-phase
blood
(≥ 6 days after onset)
Between days 6 and 21
after onset
Serology

Temperature, Virus Positivity
Temperature, Virus Positivity
and Anti-Dengue IgM , by
and Anti-Dengue IgM , by
Fever Day
Fever Day
Dengue IgM
Mean Max. Temperature Virus
Fever Day
0
20
40
60
80
100
Percent
Virus
Positive
-4 -3 -2 -1 0 1 2 3 4 5 6
39.5
39.0
38.5
38.0
37.5
37.0
Temperature
(degrees
Celsius)
Dengue
IgM
(EIA
units)
300
150
0
75
225

Management of dengue fever
Management of dengue fever
Outpatient Triage
Outpatient Triage
No hemorrhagic manifestations and patient is
No hemorrhagic manifestations and patient is
well-hydrated:
well-hydrated: home treatment
home treatment
Hemorrhagic manifestations or hydration
Hemorrhagic manifestations or hydration
borderline:
borderline: outpatient observation center or
outpatient observation center or
hospitalization
hospitalization
Warning signs (even without profound shock) or
Warning signs (even without profound shock) or
DSS:
DSS: hospitalize
hospitalize

Warning Signs for Dengue Shock
Warning Signs for Dengue Shock
When Patients Develop DSS:
• 3 to 6 days after onset of
symptoms
When Patients Develop DSS:
• 3 to 6 days after onset of
symptoms
Initial Warning Signals:
• Disappearance of fever
• Drop in platelets
• Increase in hematocrit
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
consciousness (irritability
or
Alarm Signals:
• Severe abdominal pain
• Prolonged vomiting
• Abrupt change from fever
to
hypothermia
• Change in level of
consciousness (irritability
or
somnolence)
Four Criteria for DHF:
• Fever
• Hemorrhagic manifestations
• Excessive capillary permeability
• ≤ 100,000/mm3
platelets
Four Criteria for DHF:
• Fever
• Hemorrhagic manifestations
• Excessive capillary permeability
• ≤ 100,000/mm3
platelets

Treatment of Dengue Fever
Fluids
Fluids
Rest
Rest
Antipyretics (avoid aspirin and non-
Antipyretics (avoid aspirin and non-
steroidal anti-inflammatory drugs)
steroidal anti-inflammatory drugs)
Monitor blood pressure, hematocrit,
Monitor blood pressure, hematocrit,
platelet count, level of consciousness
platelet count, level of consciousness

Continue monitoring after defervescence
Continue monitoring after defervescence
If any doubt, provide intravenous fluids, guided
If any doubt, provide intravenous fluids, guided
by serial hematocrits, blood pressure, and urine
by serial hematocrits, blood pressure, and urine
output
output
The volume of fluid needed is similar to the
The volume of fluid needed is similar to the
treatment of diarrhea with mild to moderate
treatment of diarrhea with mild to moderate
isotonic dehydration (5%-8% deficit)
isotonic dehydration (5%-8% deficit)

Rehydrating Patients Over 40 kg
Rehydrating Patients Over 40 kg
Volume required for rehydration is
Volume required for rehydration is twice
twice the
the
recommended maintenance requirement
recommended maintenance requirement
Formula for calculating maintenance volume:
Formula for calculating maintenance volume:
1500 + 20 x (weight in kg - 20)
1500 + 20 x (weight in kg - 20)
For example, maintenance volume for 55 kg
For example, maintenance volume for 55 kg
patient is: 1500 + 20 x (55-20) = 2200 ml
patient is: 1500 + 20 x (55-20) = 2200 ml
For this patient, the rehydration volume would
For this patient, the rehydration volume would
be 2 x 2200, or 4400 ml.
be 2 x 2200, or 4400 ml.

Avoid invasive procedures when
Avoid invasive procedures when
possible
possible
Unknown if the use of steroids,
Unknown if the use of steroids,
intravenous immune globulin, or platelet
intravenous immune globulin, or platelet
transfusions to shorten the duration or
transfusions to shorten the duration or
decrease the severity of
decrease the severity of
thrombocytopenia is effective
thrombocytopenia is effective
Patients in shock may require treatment
Patients in shock may require treatment
in an intensive care unit
in an intensive care unit

Indications for Hospital
Indications for Hospital
Discharge
Discharge
Absence of fever for 24 hours (without
Absence of fever for 24 hours (without
anti-fever therapy) and return of appetite
anti-fever therapy) and return of appetite
Visible improvement in clinical picture
Visible improvement in clinical picture
Stable hematocrit
Stable hematocrit
3 days after recovery from shock
3 days after recovery from shock
Platelets
Platelets ≥ 50,000/mm
50,000/mm3
3
No respiratory distress from pleural
No respiratory distress from pleural
effusions/ascites
effusions/ascites

Common Misconceptions about
Common Misconceptions about
Dengue + bleeding = DHF
Dengue + bleeding = DHF
Need 4 WHO criteria, capillary permeability
Need 4 WHO criteria, capillary permeability
DHF kills only by hemorrhage
DHF kills only by hemorrhage
Patient dies as a result of shock
Patient dies as a result of shock
Poor management turns dengue into DHF
Poor management turns dengue into DHF
Poorly managed dengue can be more severe,
Poorly managed dengue can be more severe, but
but DHF is a
DHF is a
distinct condition, which even well-treated patients may
distinct condition, which even well-treated patients may
develop
develop
Positive tourniquet test = DHF
Positive tourniquet test = DHF
Tourniquet test is a nonspecific indicator of capillary
Tourniquet test is a nonspecific indicator of capillary
fragility
fragility

DHF is a pediatric disease
DHF is a pediatric disease
All age groups are involved in the
All age groups are involved in the
Americas
Americas
DHF is a problem of low income
DHF is a problem of low income
families
families
All socioeconomic groups are affected
All socioeconomic groups are affected
Tourists will certainly get DHF with a
Tourists will certainly get DHF with a
second infection
second infection
Tourists are at low risk to acquire DHF
Tourists are at low risk to acquire DHF

Vector Control Methods:
Chemical Control
Chemical Control
Larvicides (organophosphorus compounds –
Larvicides (organophosphorus compounds –
fenthion ,abate) may be used to kill immature
fenthion ,abate) may be used to kill immature
aquatic stages
aquatic stages
Ultra-low volume fumigation ineffective against
Ultra-low volume fumigation ineffective against
adult mosquitoes
adult mosquitoes
Mosquitoes may have resistance to commercial
Mosquitoes may have resistance to commercial
aerosol sprays
aerosol sprays

Biological and Environmental
Biological and Environmental
Control
Control
Biological control
Biological control
– Largely experimental
Largely experimental
– Option: place fish in containers to eat
Option: place fish in containers to eat
larvae
larvae
Environmental control
Environmental control
– Elimination of larval habitats
Elimination of larval habitats
– Most likely method to be effective in the
Most likely method to be effective in the
long term
long term

Purpose of Control
Purpose of Control
Reduce female vector density to a level
Reduce female vector density to a level
below which epidemic vector
below which epidemic vector
transmission will not occur
transmission will not occur
Based on the assumption that
Based on the assumption that
eliminating or reducing the number of
eliminating or reducing the number of
larval habitats in the domestic
larval habitats in the domestic
environment will control the vector
environment will control the vector
The minimum vector density to prevent
The minimum vector density to prevent
epidemic transmission is unknown
epidemic transmission is unknown

dengue-130319003111-phpapp01.pdf

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