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

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

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

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

Manifestations of
Arborviral Illnesses

Most Arboviral diseases are rural

Arboviral illnesses cause typical
manifestations Often overlap
The following clinical syndromes occur
1.
2.
3.
4.

FM Fever Myalgia complex

AR Arthritis Rash complex
HF Haemorrhagic Fever
E Encephalitis

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

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

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

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

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 doesnt suffer
Virus is injected by the A.aegypti into man
After 2-7 days of IP, man develops FM,HF

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

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 virions surface
Fc receptor and focus the Dengue virus
on to the target cells macro/monocytes
T cell - cytokines, interferon, TNF alpha

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)

Hemorrhagic Manifestations

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

Other manifestations- DF
Anorexia. Nausea, vomiting
In apparent illness-to acute incapacitation
Illness is about 25 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

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

DHF Clinical Criteria

Criteria for DHF

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
Low albumin, pleural effusion

Criteria for DSS

The four criteria of DHF

Evidence of circulatory failure
1.
2.
3.
4.
5.

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

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 inch (6.25 cm)

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

DHF- Poor Prognostic Signs

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

Differential Diagnosis

FM complex
1.
2.
3.

Anicteric leptospirosis
Rickettsial fevers
Influenza, Measles, Rubella

DHF / DSS
1.
2.
3.
4.

Other hemorrhagic fevers

DIC due to septicemia
Complicated Malaria
Meningococcemia

Laboratory Diagnosis

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

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

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

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

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

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

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

Vector Control

Biological
1.
2.

Environmental
1.
2.

Largely experimental
Use of fish to feed on larvae
Elimination of larval habitat
Most likely successful strategy

Purpose of control

To reduce female vector density

Vector Control of Dengue

Mosquito control is expensive impossible

Destruction of breeding sites viable
Spraying insecticides for adult control- ?
Individual measures to avoid vector contact
1.
2.

Mosquito screens, repellents (DEET)

Permithrin impregnated clothing

Non degradable tires, long life plastics-avoid

Challenge

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.

Together We Learn Better

Each Patient is a Book

Each Day is a Learning Opportunity
CME has More Relevance
Now Than Ever

Reach Yours Sincerely @

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 !