Dengue Fever
(Pronounced as Dhen Gey)
A comprehensive presentation
by
Dr.R.V.S.N.Sarma., M.D.,
Alternative Names
Onyong- Nyang Fever
 West Nile Fever
 Break Bone Fever
 Dengue like Disease
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Background
Propagation of viral illnesses
 Transmission of viral illnesses
 Various families of Arbor viruses
 Manifestations of Arborviral illnesses
 Dengue – A Flavivirus- EM- Cell culture
 Transmitted by mosquito
 Aedes aegypti
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Viral Illnesses - Propagation
Human
Zoonotic
Human
Accidental
Human
Arthropod
Virus
Rodent
Transmission of Viral Illnesses
Droplet infection as in case of
Measles, Influenza, Coryza etc.
 Blood to blood transmission- HIV, HBV
 Feco-oral – Rota, Polio
 Direct contact – Herpes simplex etc
 Arthropod borne –Dengue, JE, YF
 Tick borne – CEE, Colorado TF
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Arthropod borne Viral Diseases
Flavivirus – Mosquito borne – YF, DF,JE
 Flavivirus – Tick Borne –CEE, RSSE, KFD
 Buniyavirus – Mosquito- CE
 Plebovirus – Sandfly Fever
 Arinavirus – LCM virus
 Colivirus – Colorado Tick fever
 Vesiculovirus – Vesicular stomatitis
 Alphavirus – E/W/V equine encephalitides
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Manifestations of
Arborviral Illnesses
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Most Arboviral diseases are rural
Arboviral illnesses cause typical
manifestations – Often overlap
The following clinical syndromes occur
FM – Fever – Myalgia complex
2. AR – Arthritis – Rash complex
3. HF – Haemorrhagic Fever
4. E – Encephalitis
1.
Epidemiology of Dengue
The Dengue Virus
 The Vector
 Global distribution of Dengue
 Transmission cycle – host – vector
 Propagation of virus – I.P
 Natural History of Dengue
 Dengue Hemorrhagic fever –
Endemicity pattern
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Epidemiological Triangle
The Host
Interaction
The Virus
The Vector
The Agent
Dengue Virus
The Dengue Virus
Flavivirus
 Positive sense
 Single stranded RNA virus
 40 to 50 nanometers
 Four sero-sub types
 Type 1 to 4
 Arthropod borne
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Dengue Virus
Electron Micrograms
Dengue Virus
Cell Culture
Of Dengue
Virus
The Vector
Aedes aegypti
(Infected Female Mosquito)
(rarely Aedes albapticus)
Peculiarities of A.aegypti
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It is a day biting mosquito when normally
coils, repellents, nets etc are not used
It breads in fresh water around homes
Lays eggs preferentially in water jars, discarded containers, coconut shells, old tires etc.
Can transmit trans-ovarially the infection
Year round breeding 250 N to 250 S
Tropics and sub-tropics are its favorite zones. It
is an urban vector
Aedes aegypti
Dengue, YF, CGF
Aedes aegypti
Dengue
Yellow Fever
Chichungunya
Fever
Dengue on the Globe
Highly endemic
Recently acquired
Dengue Fever
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Caused by an arthropod borne virus
It is a zoonotic virus
Man is accidentally infected
Other vertebrates are the reservoirs
Dengue virus has 4 subtypes 1 to 4
Positive sense, single str RNA- 40nm
Vector mosquito is Aedes aegypti
Mechanism of Transmission
Vector is infected after ingestion of blood
meal from a viremic vertebrate
 Virus multiplies in the system of vector
for 2-3 weeks – extrinsic incubation pd.
 Natural vertebrate partner has only
transient viremia and doesn’t suffer
 Virus is injected by the A.aegypti into man
 After 2-7 days of IP, man develops FM,HF
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Dengue Transmission Cycle
Dengue Transmission
Dengue Illnesses - Propagation
Natural History of Dengue
In apparent
30%
Human Inf
DFM
Re infection
69%
10%
Secondary
Primary
DHF/DSS
DHF/DSS
01%
100% Recovery
95%
Death
5%
DHF Endemicity
Pathogenesis of DHF
Immuno-pathogenic
Cascade
Hypotheses on DHF - DSS
Neutralizing Ab are type specific
nutralize the homologous sub type
 Subsequent infection with heterologous
sub type causes immune complexes
 These Immune Complexes target the
mononuclear lineage foe enhanced viral
replication
 Infected monocytes release vasoactive
mediators causing vascular damage
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Initial Immunogenecity
Immune Complexes
Attack on Host Immune Cells
Immunopathogenic
Cascade of DHF/DSS
Macrophage – monocyte infection
 Previous infection with heterologous
Dengue serotype results in production
of non protective antiviral antibodies
 These Ab bind to the virion’s surface
Fc receptor and focus the Dengue virus
on to the target cells – macro/monocytes
 T cell - cytokines, interferon, TNF alpha
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The Disease
Clinical Features
Dengue Presentations
Undifferentiated fever
 Dengue Fever (DF) with the FeverMyalgia (FM) presentation (classical)
 Dengue Hemorrhagic Fever (DHF)
 Dengue Shock Syndrome (DSS)
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Hemorrhagic Manifestations
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Skin hemorrhages:
petechiae, purpura, ecchymoses
Gingival bleeding
Nasal bleeding
Gastro-intestinal bleeding:
hematemesis, melena, hematochezia
Haematuria
Increased menstrual flow
Clinical Manifestations- DF
IP of 2 – 7 days - typical patient develops
 Sudden onset of fever, chills, headache
 Back pain with severe myalgia, arthralgia
 Retro-orbital pain – break bone fever
 Macular rash – in axillary area
 Adenopathy, palatal vesicles, scleral inj.
 Maculo-papular rash on trunk –
extremities
 Epistaxis and scattered petechiae
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Other manifestations- DF
Anorexia. Nausea, vomiting
 In apparent illness-to acute incapacitation
 Illness is about 2–5 days, biphasic course
 Pain on eye movements
 Pain on palpating abdominal muscles
 Primarily not a respiratory illness
 Rare - aseptic meningitis
 Complete recovery is the rule - asthenia
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Petechiae
Dengue Haemorrhagic Fever (DHF)
Vascular instability
 Decreased vascular integrity
 Assault on macro vasculature
 Decreased platelet function
 Increased vascular permeability
 Vascular disruption and local bleeds
 Hypotension, hemoconcentration- shock
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DHF – Clinical Criteria
Criteria for DHF
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Fever, or recent history of acute fever
Hemorrhagic manifestations
Low platelet count (100,000/mm 3 or
less)
Objective evidence of “leaky capillaries:”
Elevated hematocrit -20% or more
more over baseline or  50%
Low albumin, pleural effusion
Criteria for DSS
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The four criteria of DHF
Evidence of circulatory failure
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Rapid and weak pulse
Narrow pulse pressue (less than 20mm)
Hypotension for the age
Cold clammy skin
Altered mental status
Four Grades of DHF/DSS
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Grade 1
Fever, Const. Symptoms, +ve tourniquet test
Grade 2
Grade 1 + Spontaneous bleeding
Grade 3
Signs of circulatory failure
Grade 4
Profound shock - B.P. Pulse not recordable
Ecchymosis – Periorbital Edema
Large Subcutaneous Bleed
Capillary Damage
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)
Tourniquet Test
Pleural Effusion
PEI = A / B x 100
Clinical tests for DHF
Petechiae after tourniquet test
 Overt bleed from previous GI lesions
 Platelet count less than 100,000/ul
 Low pulse pressure, cyanosis, effusions
 Hypotension, Shock
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DHF- Poor Prognostic Signs
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Girl children under 12 with DHF/DSS
Severe hypotension and shock
Multifocal bleeding – abdominal pain
CNS encepahlopathy, fits, coma
Watch for preorbital edema, proteinuria
postural or otherwise hypotension
Serotype 2 infection after type 4
Malnutrition is protective
Unusual Presentations of Dengue
Encephalopathy
 Hepatic damage
 Cardiomyopathy
 Severe GI bleeding
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Differential Diagnosis
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FM complex
Anicteric leptospirosis
2. Rickettsial fevers
3. Influenza, Measles, Rubella
1.
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DHF / DSS
Other hemorrhagic fevers
2. DIC due to septicemia
3. Complicated Malaria
4. Meningococcemia
1.
Laboratory Diagnosis
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Complete Blood Counts
Hematocrit
Platelet Count
Serum GOT, GPT
Serum Albumin
Proteinuria, hematuria
Immunological Tests
Chest Skiagram
Laboratory Diagnosis
Leucopenia. Thrombocytopenia
 Increased SGOT, SGPT
 Rising Ab titre in paired sera
 Antigen detection ELISA
 IgM-capture ELISA within few hours
 Reverse transcription PCR confirmatory
 IgG ELISA significant of past infection
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Immuno Detection Tests
ELISA Plate
IgM-capture ELISA
Treatment of DF
Supportive measures - Vector barrier
 Avoid Aspirin and if possible NSAIDs
 Steroids should not be used
 Fluid replacement to avoid hemoconc.
 Children below 12 require careful watch
for DHF / DSS
 No antiviral agents are of proven value
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DHF / DSS
Intensive Care
Oxygen
Rehydration
Barrier Nursing
Mosquito Screen
Common Misconceptions- DHF
Dengue + bleeding = DHF
 DHF is fatal only due to hemorrhage
No Majority of deaths are due to shock
 Poorly managed DF turns into DHF
 Positive tourniquet = DHF
it is not specific for DHF,
it indicates capillary fragility of any origin
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More Common Misconceptions
DHF is only a pediatric illness –
No, All ages may be involved
 DHF is a problem of poor families –
No, in fact they may not have
immune complexes to required level
 Tourists will get DHF –
No, in fact they are at low risk
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Management of DHF/DSS
Close monitoring of hypotension/shock
 Oxygen administration
 IV. Infusion of crystalloids/colloids
 Platelet transfusion
 Clotting factors replacement
 Case fatality is 5% in good centers
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Fluid Balance
Continue monitoring after defervescence
 Serial hematocrits, BP, Urine output
 Fluid replacement is twice the requirement
 1500 ml + 2 x (weight-20) – for 60 kg wt.
Eg. {1500 + 2 x (60-20)} x 2
= {1500 + (2x 40)} x 2 = (1500 + 800) x 2
= 2300 x 2 = 4600 ml = 10 pints
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Immunization
Each serotype produces life long immunity
 There is not efficacious vaccine available
 Vaccine needs to be tetravalent
 Live attenuated vaccines possible
 Several candidate vaccines are on trials
 It may be harmful to vaccinate in view
of the pathogenesis of DHF/DSS
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Vector Control
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Biological
Largely experimental
2. Use of fish to feed on larvae
1.
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Environmental
Elimination of larval habitat
2. Most likely successful strategy
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Purpose of control
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To reduce female vector density
Vector Control of Dengue
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Mosquito control is expensive –impossible
Destruction of breeding sites – viable
Spraying insecticides for adult control- ?
Individual measures to avoid vector contact
Mosquito screens, repellents (DEET)
2. Permithrin impregnated clothing
1.
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Non degradable tires, long life plastics-avoid
Challenge
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Achieve active community involvement
Solicit input from the earliest program
planning stages
Encourage community ownership
True community participation is key
Bibliography
World Health Organization Reports
 Pan American Health Organization
 Center for Diseases Control, Atlanta
 National Institute of Communicable
Diseases, New Delhi
 Bangladesh Center for Dengue
 Harrison's Principles of Internal
Medicine, 15 ed.
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Together We Learn Better
Each Patient is a Book
 Each Day is a Learning Opportunity
 CME has More Relevance
Now Than Ever
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Reach Yours Sincerely @
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Dr.SARMA RVSN
Voice : +91-4116-2309226, 260593
Mobile : +91- 93805 21221
E-mail : sarma.rvsn@gmail.com
Web site : www.drsarma.in
Snail mail :
3, Jayanagar, Tiruvallur
Tamilnadu, INDIA
Pin : 602 001
Thank You !