My Presentation in College. Hope its useful for you rather than sleeping in my desktop. Sorry if there is any mistakes. The presentation is about Dengue fever. First starting with the basic information like Introduction , Epidemiology ,Vector , Viral Morphology ,Mode of Transmission. Then little bit on Pathogenesis and Immune Response. Extra focus given to the Clinical Manifestations, symptoms and Lab Diagnosis with few simplified case studies. Control and prevention and treatment also included.

2. Viral
Hemorrhagic Fever -
Dengue Fever
Presented by
Jega Subramaniam,
Student
Guided by
AP. Dr Durgadas,
IMS –MSU

3. Today’s Topics
Arboviruses
– General
Concept
Dengue Fever
And
Dengue
Hemorrhagic
Fever
MCQ’S and
Case
Studies

4. viruses that are transmitted by arthropods
(mosquitoes, ticks)
Arboviruses – General Concept

5. Dengue Fever

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

7. 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

8. Epidemiology
Important arthropod-borne viral disease in terms of
mortality and morbidity
Distributed worldwide in tropical and subtropical
regions

9. Mainly in
Urban and
Semi Urban
area

10. 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.

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

12. Dengue in Malaysia
2015
1
2
3
4

14. Why the no. of cases keep increases worldwide ??
Increased air travel
Uneffective mosquito
control
Unreliable
drainage systems
Increasing
population

15. Vector
Mosquitos
Aedes aegypti – Principle vector
 Aedes albopictus
Bites during day
Lays eggs in clean
& stagnant water
Female feeds on blood

16. Black &
white
bands

17. Dude Seriously ???
I don’t cause dengue please !!

18. Virus morphology
Small enveloped virus
(40-50nm) – Spherical
Positive sense single
stranded RNA virus
3 Structural & 7 non-
structural proteins –
Adherence and
virulence factor

19. Transmission

20. 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

21. DEN 1 DEN 2 DEN 3 DEN 4
Caused by any one of
four closely related
dengue viruses

22. 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

23. 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
Infection by
virus of
another
serotype
Production
of non
neutralizing
antibodies
Facilitate
entry of virus
to
monocytes
through Fc
Receptor
“Antibody dependent enhancement mechanism”

24. More
Cytokines
Released
Acute increase
in vascular
permeability
Hypovolaemia
or shock or
death
may
Dengue
Hemorrhagic
Fever (DHF)
Dengue Shock
Syndrome
(DSS)

25. 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)
6. In secondary infection the immune response is destructive
rather then protective – Its due to “Antibody dependent
enhancement mechanism”

26. Clinical Manifestation
Dengue Virus Infection
Asymptomatic Symptomatic
Undifferentiated
fever
(viral syndrome)
Dengue fever
Mostly Without
hemorrhage
With unusual
hemorrhage
Dengue hemorrhagic
fever
(plasma leakage)
No shock Dengue shock
syndrome
Dengue fever
Severe Dengue
2014 GUIDELINES
Secondary
Infection

27. 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

28. 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).

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

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

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

32. 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

33. Symptoms – Dengue Fever
Positive tourniquet test
Goal of the test :-
 To asses fragility of capillary walls
 To 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)

34. 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.

35. Now Lets Move on to
symptoms of Severe
Dengue (Dengue
Hemorrhagic Fever )

36. 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)
First , what is the criteria’s of dengue
hemorrhagic fever ???
2014 GUIDELINESS

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

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

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

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

41. 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)

42. Diagnosis
History Clinical Lab
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

43. 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
MOH Malaysia 2014 Guideline

44. 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

45. 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

46. 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

47. Rapid Test Combo Kit
• SD BIOLINE Dengue Duo
(To detect Dengue NS1 Ag and IgG/IgM
in a single test )

49. 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

50. Scenario 1
Day of illness = 4
Ig M - Positive
Ig G - Negative
NS1 - Antigen Positive
Diagnosis – ?

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

52. Scenario 3
Day of illness = 3
Ig M Negative
Ig G Negative
NS1 Positive
Diagnosis - ?

53. 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.

54. 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

55. Complications
1- Febrile phase - Dehydration
2- Critical phase - Shock from plasma
leakage: severe haemorrhage; organ impairment
= Dengue Shock Syndrome
3- Recovery phase - Hypervolaemia

56. Control and Prevention
Vector Control
Individual Measures
Immunization

57. Vector Control
Preventive Measures
Immunization
Control and Prevention

58. Vector Control
Individual Measures
Immunization
• Sanofi Dengvaxia
• All four dengue
types
• 9-45 years of age
living in endemic
areas.
Control and Prevention

59. Treatment
No specific treatment , only Supportive therapy
No antiviral agents are of proven value
Fluid replacement and Monitor the Ht and Platelet
Count

60. *Only* for severe cases ( DHF and DSS )
• Close monitoring of hypotension/shock
• IV. Infusion of crystalloids/colloids
• Oxygen administration
• Platelet transfusion
• Clotting factors replacement

61. 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

62. Simplified case
studies

63. 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

64. 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

65. 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

66. 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

68. 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

69. Thank You
for your
attention