Download - 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