Dengue

Dr. Sachin Verma is a young, diligent and dynamic physician. He did his graduation from IGMC Shimla and MD in Internal Medicine from GSVM Medical College Kanpur. Then he did his Fellowship in Intensive Care Medicine (FICM) from Apollo Hospital Delhi. He has done fellowship in infectious diseases by Infectious Disease Society of America (IDSA). He has also done FCCS course and is certified Advance Cardiac Life support (ACLS) and Basic Life Support (BLS) provider by American Heart Association. He has also done a course in Cardiology by American College of Cardiology and a course in Diabetology by International Diabetes Centre. He specializes in the management of Infections, Multiorgan Dysfunctions and Critically ill patients and has many publications and presentations in various national conferences under his belt. He is currently working in NABH Approved Ivy super-specialty Hospital Mohali as Consultant Intensivists and Physician.

1. Dr. Sachin Verma MD, FICM, FCCS, ICFCDr. Sachin Verma MD, FICM, FCCS, ICFC
Fellowship in Intensive Care MedicineFellowship in Intensive Care Medicine
Infection Control Fellows Course Infection Control Fellows Course
Consultant Internal Medicine and Critical CareConsultant Internal Medicine and Critical Care
Web:- Web:- http://www.medicinedoctorinchandigarh.comhttp://www.medicinedoctorinchandigarh.com
Mob:- [phone]Mob:- [phone]
References;References;
1.1.HarrisonHarrison´s´s principle of internal medicine -16 principle of internal medicine -16
thth
ed ed
2.2.ParkPark´s textbook of preventive and social medicine -17´s textbook of preventive and social medicine -17
thth
ed ed
3.3.www.cdc.orgwww.cdc.org

2. DENGUEDENGUE

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

4. Dengue VirusesDengue Viruses
Each serotype provides specific lifetime Each serotype provides specific lifetime
immunity, and short-term cross-immunityimmunity, and short-term cross-immunity
All serotypes can cause severe and fatal All serotypes can cause severe and fatal
diseasedisease
Genetic variation within serotypesGenetic 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 potentialepidemic potential

5. Aedes aegyptiAedes aegypti
Dengue transmitted by Dengue transmitted by
infected female mosquitoinfected female mosquito
Primarily a daytime feederPrimarily a daytime feeder
Lives around human Lives around human
habitationhabitation
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.

6. Aedes aegypti:
Distribution
throughout the world

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

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

9. Population increase onlyPopulation increase only
Population at Population at
risk (billions)risk (billions)
% of total % of total
populationpopulation
2050s2050s 3.23.2 3434
2080s2080s 3.53.5 3535
Population increase plus Population increase plus
climate change (HADCM2)climate change (HADCM2)
2050s2050s 4.14.1 4444
2080s2080s 5.25.2 5252

10. Replication and TransmissionReplication 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

11. Replication and TransmissionReplication and Transmission
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

12. Transmission of Dengue VirusTransmission of Dengue Virus
by by Aedes aegyptiAedes 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

13. Clinical Manifestations of Dengue and Clinical Manifestations of Dengue and
Dengue Hemorrhagic FeverDengue Hemorrhagic Fever
Undifferentiated feverUndifferentiated fever
Classic dengue feverClassic dengue fever
Dengue hemorrhagic feverDengue hemorrhagic fever
Dengue shock syndromeDengue shock syndrome

14. Undifferentiated FeverUndifferentiated Fever
May be the most common manifestation of May be the most common manifestation of
denguedengue
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
symptomaticsymptomatic
Other prospective studies including all age- Other prospective studies including all age-
groups also demonstrate silent transmission. groups also demonstrate silent transmission.

15. Clinical CharacteristicsClinical Characteristics
of Dengue Feverof Dengue Fever
FeverFever
HeadacheHeadache
Muscle and joint painMuscle and joint pain
Nausea/vomitingNausea/vomiting
RashRash
Hemorrhagic manifestationsHemorrhagic manifestations

16. Hemorrhagic ManifestationsHemorrhagic Manifestations
of Dengueof Dengue
Skin hemorrhages: petechiae, purpura, Skin hemorrhages: petechiae, purpura,
ecchymosesecchymoses
Gingival bleedingGingival bleeding
Nasal bleedingNasal bleeding
Gastro-intestinal bleeding: Gastro-intestinal bleeding:
hematemesis, melena, hematocheziahematemesis, melena, hematochezia
HematuriaHematuria
Increased menstrual flowIncreased menstrual flow

17. Signs and Symptoms ofSigns and Symptoms of
Encephalitis/EncephalopathyEncephalitis/Encephalopathy
Associated with Acute Dengue Associated with Acute Dengue
InfectionInfection
Decreased level of consciousness: Decreased level of consciousness:
lethargy, confusion, comalethargy, confusion, coma
SeizuresSeizures
Nuchal rigidityNuchal rigidity
ParesisParesis

18. Clinical Case Definition forClinical Case Definition for
Dengue Hemorrhagic FeverDengue Hemorrhagic Fever
Fever, or recent history of acute feverFever, or recent history of acute fever
Hemorrhagic manifestationsHemorrhagic manifestations
Low platelet count (100,000/mmLow platelet count (100,000/mm
33
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 albuminlow albumin
–pleural or other effusionspleural or other effusions
4 Necessary Criteria:4 Necessary Criteria:

19. Four Grades of DHFFour Grades of DHF
Grade 1Grade 1
–Fever and nonspecific constitutional symptomsFever and nonspecific constitutional symptoms
–Positive tourniquet test is only hemorrhagic Positive tourniquet test is only hemorrhagic
manifestationmanifestation
Grade 2Grade 2
–Grade 1 manifestations + spontaneous bleedingGrade 1 manifestations + spontaneous bleeding
Grade 3Grade 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 4Grade 4
–Profound shock (undetectable pulse and BP)Profound shock (undetectable pulse and BP)

20. Danger Signs inDanger Signs in
Dengue Hemorrhagic FeverDengue Hemorrhagic Fever
Abdominal pain - intense and sustainedAbdominal pain - intense and sustained
Persistent vomitingPersistent vomiting
Abrupt change from fever to Abrupt change from fever to
hypothermia, with sweating and hypothermia, with sweating and
prostrationprostration
Restlessness or somnolenceRestlessness or somnolence

21. Clinical Case Definition for Dengue Clinical Case Definition for Dengue
Shock SyndromeShock Syndrome
4 criteria for DHF4 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 pulseRapid and weak pulse
–Narrow pulse pressure (Narrow pulse pressure (£ 20 mm Hg) 20 mm Hg) OR OR
hypotension for agehypotension for age
–Cold, clammy skin and altered mental Cold, clammy skin and altered mental
statusstatus
Frank shock is direct evidence of circulatory Frank shock is direct evidence of circulatory
failurefailure

22. Risk Factors Reported for DHFRisk 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-1by DEN-3, DEN-4 and DEN-1
Pre-existing anti-dengue antibodyPre-existing anti-dengue antibody
–previous infectionprevious infection
–maternal antibodies in infantsmaternal antibodies in infants
Host genetics-females more affected, Host genetics-females more affected,
malnutrition protective.malnutrition protective.
Age(<12)Age(<12)

23. Unusual PresentationsUnusual Presentations
of Severe Dengue Feverof Severe Dengue Fever
EncephalopathyEncephalopathy
Hepatic damageHepatic damage
CardiomyopathyCardiomyopathy
Severe gastrointestinal hemorrhageSevere gastrointestinal hemorrhage

24. Increased Probability of DHFIncreased 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

25. Neutralizing antibody to Dengue 1 virus
1
1
Dengue 1 virus
1
Pathogenesis of DHFPathogenesis 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

26. 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 serotypewith second serotype
Complex formed by non-neutralizing antibody
and virus
2

27. 2
2
2
2
2
2
2
2
2
2
STEP3 - Heterologous Complexes Enter More STEP3 - Heterologous Complexes Enter More
Monocytes, Where Virus ReplicatesMonocytes, Where Virus Replicates
Non-neutralizing antibody
Dengue 2 virus
2
Complex formed by non-neutralizing
antibody and Dengue 2 virus
2

28. STEP4 –DHF pathogenesisSTEP4 –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 DSSthat characterize DHF and DSS

29. Clinical Evaluation in Dengue FeverClinical Evaluation in Dengue Fever
Blood pressureBlood pressure
Evidence of bleeding in skin or other sitesEvidence of bleeding in skin or other sites
Hydration statusHydration status
Evidence of increased vascular Evidence of increased vascular
permeability-- pleural effusions, ascitespermeability-- pleural effusions, ascites
Tourniquet testTourniquet test

30. PetechiaePetechiae

31. Tourniquet TestTourniquet 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
minutesminutes
Positive test: 20 or more Positive test: 20 or more
petechiae per 1 inchpetechiae per 1 inch
2 2
(6.25 cm(6.25 cm
22
))

32. Laboratory TestsLaboratory Tests
in Dengue Feverin Dengue Fever
Clinical laboratory testsClinical laboratory tests
–CBC--WBC, platelets, hematocritCBC--WBC, platelets, hematocrit
–AlbuminAlbumin
–Liver function testsLiver function tests
–Urine--check for microscopic hematuriaUrine--check for microscopic hematuria
Dengue-specific testsDengue-specific tests
–Virus isolationVirus isolation
–SerologySerology

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

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

35. ELISA PlateELISA Plate

36. Collection and Processing of Collection and Processing of
Samples for Laboratory Samples for Laboratory
DiagnosisDiagnosis
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
(³ 6 days after onset)
Between days 6 and 21
after onset
Serology

37. Temperature, Virus Positivity Temperature, Virus Positivity
and Anti-Dengue IgM , by and Anti-Dengue IgM , by
Fever DayFever Day
Dengue IgMMean Max. Temperature Virus
Fever Day
0
20
40
60
80
100
P
e
r
c
e
n
t

V
i
r
u
s

P
o
s
i
t
i
v
e
-4-3-2-10 1 2 3 4 5 6
39.5
39.0
38.5
38.0
37.5
37.0
T
e
m
p
e
r
a
t
u
r
e
(
d
e
g
r
e
e
s

C
e
l
s
i
u
s
)
D
e
n
g
u
e

I
g
M

(
E
I
A

u
n
i
t
s
)
300
150
0
75
225

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

39. Warning Signs for Dengue ShockWarning 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
somnolence)
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/mm
3
platelets
Four Criteria for DHF:
• Fever
• Hemorrhagic manifestations
• Excessive capillary permeability
• £ 100,000/mm
3
platelets

40. Treatment of Dengue FeverTreatment of Dengue Fever
FluidsFluids
RestRest
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 consciousnessplatelet count, level of consciousness

41. Treatment of Dengue FeverTreatment of Dengue Fever
Continue monitoring after defervescenceContinue 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
outputoutput
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)

42. Rehydrating Patients Over 40 kgRehydrating Patients Over 40 kg
Volume required for rehydration is Volume required for rehydration is twicetwice the the
recommended maintenance requirementrecommended 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 mlpatient 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.

43. Treatment of Dengue FeverTreatment of Dengue Fever
Avoid invasive procedures when Avoid invasive procedures when
possiblepossible
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 effectivethrombocytopenia is effective
Patients in shock may require treatment Patients in shock may require treatment
in an intensive care unitin an intensive care unit

44. Indications for Hospital Indications for Hospital
DischargeDischarge
Absence of fever for 24 hours (without Absence of fever for 24 hours (without
anti-fever therapy) and return of appetiteanti-fever therapy) and return of appetite
Visible improvement in clinical pictureVisible improvement in clinical picture
Stable hematocritStable hematocrit
3 days after recovery from shock3 days after recovery from shock
Platelets Platelets ³ 50,000/mm 50,000/mm
33
No respiratory distress from pleural No respiratory distress from pleural
effusions/asciteseffusions/ascites

45. Common Misconceptions aboutCommon Misconceptions about
Dengue Hemorrhagic FeverDengue Hemorrhagic Fever
Dengue + bleeding = DHFDengue + bleeding = DHF
Need 4 WHO criteria, capillary permeabilityNeed 4 WHO criteria, capillary permeability
DHF kills only by hemorrhageDHF kills only by hemorrhage
Patient dies as a result of shockPatient dies as a result of shock
Poor management turns dengue into DHFPoor management turns dengue into DHF
Poorly managed dengue can be more severe, Poorly managed dengue can be more severe, butbut DHF is a DHF is a
distinct condition, which even well-treated patients may distinct condition, which even well-treated patients may
developdevelop
Positive tourniquet test = DHFPositive tourniquet test = DHF
Tourniquet test is a nonspecific indicator of capillary Tourniquet test is a nonspecific indicator of capillary
fragilityfragility

46. DHF is a pediatric diseaseDHF is a pediatric disease
All age groups are involved in the All age groups are involved in the
AmericasAmericas
DHF is a problem of low income DHF is a problem of low income
familiesfamilies
All socioeconomic groups are affectedAll socioeconomic groups are affected
Tourists will certainly get DHF with a Tourists will certainly get DHF with a
second infectionsecond infection
Tourists are at low risk to acquire DHFTourists are at low risk to acquire DHF

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

48. Vector Control Methods:Vector Control Methods:
Biological and Environmental Biological and Environmental
ControlControl
Biological controlBiological control
–Largely experimentalLargely experimental
–Option: place fish in containers to eat Option: place fish in containers to eat
larvaelarvae
Environmental controlEnvironmental control
–Elimination of larval habitatsElimination of larval habitats
–Most likely method to be effective in the Most likely method to be effective in the
long termlong term

49. Purpose of ControlPurpose 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 occurtransmission 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 vectorenvironment will control the vector
The minimum vector density to prevent The minimum vector density to prevent
epidemic transmission is unknownepidemic transmission is unknown