Viral

Hemorrhagic Fever -
Dengue Fever

Presented by Guided by
Jega Subramaniam, AP. Dr Durgadas,
Student
IMS MSU
 Todays Topics

Dengue
Arboviru Fever
MCQS
ses And
and Case
General Dengue
Hemorrhagi Studies
Concept
c Fever
 Arboviruses
General Concept
viruses that are transmitted by
arthropods (mosquitoes, ticks)
Dengue Fever
 Outline
Introduction
Epidemiology
Vector
Viral Morphology
Mode of Transmission
Pathogenesis
Immune Response
Clinical Manifestations
Complications
Lab Diagnosis
Control and Prevention
Case Studies
 Introduction

Mosquito borne infection

Caused by flavivirus

Characterized by Fever ,
muscle and join pain
Nausea and Vomiting , eye pain , rash

Severe and non-severe clinical

manifestations
Epidemiology
Important arthropod-borne viral disease in
terms of mortality and morbidity

Distributed worldwide in tropical and

subtropical regions
Mainly in Urban and Semi
Urban area
Dengue globaly
390 million dengue
infections per year

22,000 deaths, mostly

among children.

South America, South-East

Asia and Western Pacific
regions are the most
seriously affected.
Jun
2015
Dengue in Malaysia
Incidence rate highest ever in 2014, followed by 2015
 Dengue in Malaysia
201
5
3

1
4

2
Why the no. of cases keep increases worldwide ??

Uneffective
Increased air
mosquito
travel
control

Unreliable
drainage
Increasing
population
 Vector
Mosquitos

Aedes aegypti Principle vector

Aedes albopictus

Bites during day

Lays eggs in clean

& stagnant water

Female feeds on blood

Black &
white
bands
 Dude Seriously ???
I dont cause dengue please !!
 Virus
morphology

Small enveloped virus

(40-50nm) Spherical

Positive sense single

stranded RNA virus

3 Structural & 7 non-

structural proteins
Adherence and
virulence factor
Transmission
 True or False
Regarding dengue fever
A. Is spread by the vector aedes aegypti
B. Has an incubation period of 2-3 week
C. Has an incubation period of 3 to 14 days ,
normally 4 to 7 days
D. Is caused by a flavivirus
E. Is more likely to cause haemorrhage in
patients previously infected by a dengue
virus
F. Characterized by Fever , muscle and join
pain
 Caused by any
one of four
closely related
dengue viruses

DEN DEN DEN DEN

1 2 3 4
Immune Response

Primary Infection - host develops a

Life-long protective immunity to the
homologous (same) serotype

Secondary Infection (caused by other

3 serotype) - host shows only
partial and transient protection

risk of Dengue Hemorragic

Fever
 Pathogenesis 0F Primary Infection
Incubation period : 4-7 days (range 3-14
Primary Dengue Infection Self Limited
May also progress to severe dengue
(DHF/DSS) (normally children, elderly &
immunocompromised)
Pathogenesis Of Secondary Infection
Antibody dependent enhancement
mechanism
Facilitate
Productio
Infection entry of
n of non
by virus virus to
neutralizi
of monocyte
ng
another s through
antibodie
serotype Fc
s
Receptor
More Cytokines
Released

Acute increase Dengue

in vascular Hemorrhagi
permeability c Fever
ma (DHF)
y

Hypovolaemia or Dengue
Shock
shock or death
Syndrome
(DSS)
 TRUE OR FALSE

1. After the Primary Infection , the host develops

a Life-long protective immunity to the
homologous serotype
2. Secondary Infection has less chances of
Dengue Hemorrhagic Fever
3. Primary Dengue Infection is usually not self
limited
4. Production of neutralizing antibodies is the
key concept in Secondary Infection
5. Non Neutralizing antibodies Facilitate the entry
of virus into monocytes through Fc Receptor
and enables the virus to grow in the host cell
(monocyte)
 Clinical Manifestation
Seconda
ry
Dengue Virus Infection
Infection

Asymptomatic Symptomatic

Dengue
Undifferentiated Dengue fever s to hemorrhagic
fever gres fever
pro (plasma leakage)
(viral syndrome) y
ma

Mostly Without With unusual No shock Dengue shock

hemorrhage hemorrhage syndrome

Dengue fever
Severe Dengue

2014 GUIDELINES
Clinical Manifestation Summary Without or
without
haemorrha
ge

Classic Dengue FeverIn **Monitor

critica
l
phase
Warning
,
Might
Signs***
Dengue hemorrhagic Fever
( > chances in ? )
Migh
t

Dengue Shock
Syndrome
Warning Sings of Dengue
Raised HCT, with rapid fall in platelet
Fever to hypothermia
Mucosal Bleed
Liver Enlargement

Normal Male Hct 40.7 to 50.3%

Normal Female Hct: 36.1 to 44.3%
The normal number of platelets in the
blood is 150,000 to 400,000 platelets
per microliter (mcL).
Symptoms Dengue Fever
( Based on WHO )

Fever, Chills ,
headache
Myalgia
Arthralgia
Retro-orbital pain
Deep bone pain
break bone
fever
Rashes
Positive
Tourniquet Test
Symptoms Dengue Fever
( Based on WHO )

Fever, chills,
headache
Myalgia
Arthralgia
Retro-orbital pain
Deep bone pain
break bone
fever
Rashes
Positive
Tourniquet Test
Symptoms Dengue Fever
( Based on WHO )

Fever, chills,
headache
Myalgia
Arthralgia
Retro-orbital
pain
Deep bone
pain break
bone fever
Rashes
Positive
Tourniquet Test
 Symptoms Dengue Fever
( Based on WHO )

Rashes
Fever, chills,
headache
Myalgia
Arthralgia
Retro-orbital
pain
Deep bone
pain break
bone fever
Rashes
Positive
Tourniquet Test
 Symptoms Dengue Fever
Positive tourniquet test
Goal of the test :-
20 or
To asses fragility of capillary walls more
To identify thrombocytopenia petechiae
In DHF grade 1, a positive per 1
tourniquet test serves as the only square
indicator of haemorrhagic tendency
inch.
(MOH
MALAYSIA
2014)
 How to do ?
1. Take the patient's blood pressure and
record it, for example, 100/70.
2. Inflate the cuff to a point midway between
SBP and DBP and maintain for 5 minutes.
(100 + 70) 2 = 85 mm Hg
3. Reduce the pressure and wait 2 minutes.
4. Count petechiae below antecubital fossa.
See image at right.
5. A positive test is 20 or more petechiae per
1 square inch.
Now Lets Move on to
symptoms of Severe
Dengue (Dengue
Hemorrhagic Fever )
 First , what is the criterias of
dengue hemorrhagic
fever ???
The 4 WHO Criteria for DHF
Fever
Hemorrhagic
manifestations(Symptoms)
Low platelet count (100,000/mm 3 or
less
Elevated hematocrit ( >20% then
normal) or ( > 50% THEN BASELINE)
2014
GUIDELINESS
Symptoms - Dengue Hemorrhagic Fever (DHF)

petechiae
epistaxis(nose
bleed),
gingival bleeding
(gum bleed)
Microscopic
hematuria.
Symptoms - Dengue Hemorrhagic Fever (DHF)

petechiae
epistaxis(nose
bleed),
gingival bleeding
(gum bleed)
Microscopic
hematuria.
Symptoms - Dengue Hemorrhagic Fever (DHF)

petechiae
epistaxis(nose
bleed),
gingival bleeding
(gum bleed)
Microscopic
hematuria
Symptoms - Dengue Haemorrhagic Fever (DHF)

epistaxis(nose
bleed),
gingival bleeding
(gum bleed)
Microscopic
hematuria.
 TRUE OR FALSE
Regarding the WHO criteria for D H F
A. Fever
B. Hemorrhagic manifestations
C. Muscle and Join Pain
D. Low platelet count (100,000/mm 3
or less
E. Elevated hematocrit ( >20% then
normal)
F. Elevated Hematocrit ( > 50% then
baseline)
 Diagnosis

Histo Clinic
Lab
ry al

History tells us the endemic area, previous dengue

infection and etc
Clinical diagnosis are all the symptoms. We can make
only provisional diagnosis
Lab Diagnosis is the confirmatory
Lab Diagnosis Is the Confirmatory test

Tests include
1. Serological Test ELISA To
Detect Antibody
2. Non Structural Protein (NS1
antigen) Test
3. Virus isolation
4. RT-PCR
 Most widely used
Diagnostic Test
1. Non Structural Protein (NS1
antigen) Test- to detect NS1
antigen
2. Serological Test using ELISA To
Detect Antibody( Ig M and Ig G )

MOH Malaysia 2014 Guideline

1. Non Structural Protein (NS1 antigen) Test
Latest diagnostic tool for diagnosing dengue
Useful in the diagnosing in the early phase (3 to
4 of illness) Some times even from second
day of illness
But It is not useful after 5 days of illness .

Criteria for primary infection

Postive NS1 antigen

Criteria for secondary infection

Usually Negative NS1 antigen rarely Can
be Positive as well. MOH Malaysia
2014 Guideline
2. Serological Test by ELISA To Detect
Antibody (Ig and Ig G)
Criteria for primary infection
Positive IgM after 5 to 7 days of

illness
Ig G present after 7 days

Criteria for secondary infection

Positive Ig G after 5 to 7 days onwards
Usually Absence or slight increase in IgM
after 5 to 7 days onwards
MOH Malaysia 2014 Guideline
 Rapid Test Combo Kit
SD BIOLINE Dengue
Duo
(To detect Dengue NS1 Ag
and IgG/IgM in a single
test )
 Can we rule out dengue fever if NS1 Antigen
is negative?

Answer : WE CAN NOT Rule out dengue

fever if NS1 antigen is negative

State your reasons

1. Its only useful in the diagnosing in the early phase

as it is detectable in the blood from 3 to 4 of illness .
Some times even from second day of illness. But
It is not detectable after 5 days of illness as its
level will decline

2. Usually Negative NS1 antigen in secondary

dengue infection
 Scenario 1
Day of illness = 4

Ig M - Positive
Ig G - Negative
NS1 - Antigen Positive

Diagnosis ?
 Scenario 2
Day of illness = 4
Ig M Negative
Ig G Positive
NS1 Negative

Diagnosis - ?
 Scenario 3
Day of illness = 3

Ig M Negative
Ig G Negative
NS1 Positive

Diagnosis - ?
 OTHER TEST

Virus Isolation performed in the lab

equipped with tissue culture and other
virus isolation facilities. blood should be
collected before day 5 of illness -
before the formation of neutralizing
antibodies.
It may take up to two weeks to
complete the test and it is expensive.

PCR can be used as a diagnostic tool in

early dengue infection . It is not
recommended as a routine diagnostic
 Lab Test for Provisional Diagnosis/ Screening
Criteria and disease monitoring purpose

Full Blood Count (FBC)

White cell count (WCC) shows -
1 Leucopaenia
2. ThrombocytopaeniaRefer the
3. Normal or rised HCT note

DISEASE MONITORING purpose FBC have to be taken each

and everyday once the patient is admitted .
Platelet count should be closely monitored as it shows us
the severity of the disease . ( Recall !! Rise in Hct and Fall
in Platelet = Patient is going from Dengue fever to
.. ? ) . While if the platelet drop is minimal , then patient
is in recovery stage
Complications
1- Febrile phase - Dehydration

2- Critical phase - Shock from

plasma leakage: severe haemorrhage;
organ impairment
= Dengue Shock Syndrome

3- Recovery phase - Hypervolaemia

Control and Prevention

Vector Control
Individual Measures
Immunization
Control and Prevention

Vector Control
Preventive Measures
Immunization
Control and Prevention
Vector Control
Individual Measures
Immunization

Sanofi Dengvaxia
All four dengue
types
9-45 years of age
living in endemic
areas.
Treatment
No specific treatment , only Supportive
therapy

No antiviral agents are of proven value

Fluid replacement and Monitor the Ht and

Platelet Count
*Only* for severe cases ( DHF and
DSS )
Close monitoring of
hypotension/shock
IV. Infusion of crystalloids/colloids
Oxygen administration
Platelet transfusion
Clotting factors replacement
 True or False
A. Dengue Fever has no specific treatment , only
supportive care is provided
B. The Supportive care in dengue includes fluid
replacement and close monitoring of platelet and Hct
C. Dengue fever can be cured by antiviral
D. Platelet transfusion is given in Dengue Fever
E. Dengue vaccine is used in all the endemic countries
currently
F. Dengue vaccine is given to new born babies as
preventive method
G. We can advice the people above 45 years old to take
dengue vaccine
 Simplified
case studies
 1 A. What is your provisional
diagnosis ? State your reasons ?
Fever, Platelet : 90 000 / mm3
chills,
Hematocrit : 75%
headache
Myalgia Low WBC Count
Arthralgia
Nose Normal
HCT Male: 40.7 to
Bleeding 50.3%
Female: 36.1 to
44.3%

Platelets 150,000 to
B. Which Lab test you will order to
confirm your diagnosis ?
1
2

C. Interpret your Lab findings if

your result is positive for Dengue
?

1
2
 2 A. What is your provisional
diagnosis ? State your reasons ?
Fever,
Platelet : 90 000 / mm3
chills,
headache Hematocrit : 50%
Myalgia
Arthralgia Slightly Low WBC Count
No signs of
bleeding Normal
HCT Male: 40.7 to
50.3%
Female: 36.1 to
44.3%

Platelets 150,000 to
 B. Cntd . Which Lab test you will
order to confirm your diagnosis ?
1
2

C. Interpret your Lab findings if

your result is positive for dengue
?

1
2
 Reference
Mentor : AP. DR. Durgadas , IMS MSU
Book : Lange Microbiology 14th edition
Guidelines : MOH Malaysia 2014 and
WHO 2014
Journal : International Medical Journal
Malaysia ( IMJM)
Official Portal : Selangor Health
Department
Online web site : Medscape
Picture Source : Flicker , Google Images
Thank You
for your
attention