dengue and dengue hemorrhagic fever

Viral Hemorrhagic Fever -

Dengue Fever

Presented by Jega Subramaniam,

Student

Guided by AP. Dr Durgadas,

IMS –MSU

Today’s Topics

Arboviruses – General

Concept

Dengue FeverAnd

Dengue Hemorrhagic

Fever

MCQ’S and Case

Studies

viruses that are transmitted by arthropods (mosquitoes, ticks)

Arboviruses – General Concept

Dengue Fever

• Introduction • Epidemiology• Vector • Viral Morphology • Mode of Transmission • Pathogenesis • Immune Response• Clinical Manifestations • Complications • Lab Diagnosis • Control and Prevention • Case Studies

Outline

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

EpidemiologyImportant 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

Jun 2015

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.

Dengue in Malaysia• Incidence rate highest ever in 2014, followed by 2015

Dengue in Malaysia2015

1

2

3

4

Why the no. of cases keep increases worldwide ??

Increased air travel Uneffective mosquito control

Unreliable drainage systems

Increasing population

VectorMosquitos

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 don’t 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 aegyptiB. Has an incubation period of 2-3 weekC. Has an incubation period of 3 to 14 days ,

normally 4 to 7 days D. Is caused by a flavivirusE. Is more likely to cause haemorrhage in

patients previously infected by a dengue virusF. Characterized by Fever , muscle and join pain

DEN 1

DEN 2

DEN 3

DEN 4

Caused by any one of four closely related

dengue viruses

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 LimitedMay also progress to severe dengue (DHF/DSS)

(normally children, elderly & immunocompromised)

Pathogenesis Of Secondary Infection

Infection by virus of another

serotype

Production of non

neutralizing antibodies

Facilitate entry of virus to

monocytes through Fc Receptor

“Antibody dependent enhancement mechanism”

More Cytokines Released

Acute increase in vascular permeability

Hypovolaemia or shock or death

may

Dengue Hemorrhagic Fever (DHF)

Dengue Shock 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 limited4. 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)

6. In secondary infection the immune response is destructive rather then protective – Its due to “Antibody dependent enhancement mechanism”

Clinical Manifestation Dengue Virus Infection

Asymptomatic Symptomatic

Undifferentiated fever

(viral syndrome)

Dengue fever

Mostly Without

hemorrhage

With unusualhemorrhage

Dengue hemorrhagic

fever(plasma leakage)

No shock Dengue shocksyndrome

Dengue fever Severe Dengue

2014 GUIDELINES

Secondary Infection

may progress to

Classic Dengue Fever

Dengue hemorrhagic Fever ( > chances in ? )

Dengue Shock Syndrome

In critical phase , Might

Might

**Monitor Warning Signs***

Clinical Manifestation Summary Without or without haemorrhage

Warning Sings of Dengue

Raised HCT, with rapid fall in plateletFever to hypothermiaMucosal 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

• 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

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 FeverPositive tourniquet test

Goal of the test :-  To asses fragility of capillary wallsTo identify thrombocytopenia In DHF grade 1, a positive

tourniquet test serves as the only indicator of haemorrhagic tendency

• 20 or more petechiae per 1 square 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 )

The 4 WHO Criteria for DHFFever Hemorrhagic

manifestations(Symptoms)Low platelet count (100,000/mm 3 or

lessElevated hematocrit ( >20% then

normal) or ( > 50% THEN BASELINE)

First , what is the criteria’s of dengue hemorrhagic fever ???

2014 GUIDELINESS

Symptoms - Dengue Hemorrhagic Fever (DHF)

petechiaeepistaxis(nose bleed),

gingival bleeding (gum bleed)

Microscopic hematuria.

Symptoms - Dengue Hemorrhagic Fever (DHF)

petechiaeepistaxis(nose bleed),

gingival bleeding (gum bleed)

Microscopic hematuria.

Symptoms - Dengue Hemorrhagic Fever (DHF)

petechiaeepistaxis(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 manifestationsC. Muscle and Join Pain D.Low platelet count (100,000/mm 3

or lessE. Elevated hematocrit ( >20% then

normal)F. Elevated Hematocrit ( > 50% then

baseline)

Diagnosis

History

Clinical Lab

History tells us the endemic area, previous dengue infection and etcClinical 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

Antibody2. Non Structural Protein (NS1 antigen) Test3. Virus isolation 4. RT-PCR

MOH Malaysia 2014 Guideline

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

Most widely used Diagnostic Test

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 infectionPositive IgM after 5 to 7 days of illness Ig G present after 7 days

Criteria for secondary infectionPositive 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 = 4Ig M Negative Ig G Positive NS1 Negative

Diagnosis - ?

Scenario 3

Day of illness = 3

Ig M Negative Ig G NegativeNS1 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 test due to limited availability and cost.

Lab Test for Provisional Diagnosis/ Screening Criteria and disease monitoring purpose

• Full Blood Count (FBC) White cell count (WCC) shows - 1 Leucopaenia 2. Thrombocytopaenia 3. Normal or rised HCT

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

Refer the note

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

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.

Control and Prevention

TreatmentNo 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, chills, headache

• Myalgia• Arthralgia• Nose

Bleeding

• Platelet : 90 000 / mm3

• Hematocrit : 75%

• Low WBC Count

Normal HCT Male: 40.7 to 50.3% Female: 36.1 to 44.3%

Platelets 150,000 to 400,000 / mm3

B. Which Lab test you will order to confirm your diagnosis ?

12

C. Interpret your Lab findings if your result is positive for Dengue ?

12

2 A. What is your provisional diagnosis ? State your reasons ?

• Fever, chills, headache

• Myalgia• Arthralgia• No signs of

bleeding

• Platelet : 90 000 / mm3

• Hematocrit : 50%

• Slightly Low WBC Count

Normal HCT Male: 40.7 to 50.3% Female: 36.1 to 44.3%

Platelets 150,000 to 400,000 / mm3

B. Cntd . Which Lab test you will order to confirm your diagnosis ?

12

C. Interpret your Lab findings if your result is positive for dengue ?

12

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