1. Dengue Fever

2. Alternative Names Onyong- Nyang Fever West Nile Fever Break Bone Fever
Dengue like Disease

3. 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

4. Viral Illnesses - Propagation
Human
Human
Accidental
Zoonotic
Human
Arthropod
Virus
Rodent

5. 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

6. 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

7. Manifestations of Arborviral Illnesses
Most Arboviral diseases are rural
Arboviral illnesses cause typical
manifestations – Often overlap
The following clinical syndromes occur
FM – Fever – Myalgia complex
AR – Arthritis – Rash complex
HF – Haemorrhagic Fever
E – Encephalitis

8. 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

9. Epidemiological Triangle
The Host
Interaction
The Virus
The Vector

10. The Agent
Dengue Virus

11. The Dengue Virus Flavivirus Positive sense Single stranded RNA virus
40 to 50 nanometers
Four sero-sub types
Type 1 to 4
Arthropod borne

12. Dengue Virus
Electron Micrograms

13. Dengue Virus
Cell Culture
Of Dengue
Virus

14. Aedes aegypti The Vector (Infected Female Mosquito)
(rarely Aedes albapticus)

15. 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, discar- ded 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

16. Aedes aegypti
Dengue, YF, CGF

17. Aedes aegypti
Dengue
Yellow Fever
Chichungunya
Fever

18. Dengue on the Globe
Highly endemic
Recently acquired

19. 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

20. 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 doesn’t suffer
Virus is injected by the A.aegypti into man
After 2-7 days of IP, man develops FM,HF

21. Dengue Transmission Cycle

22. Dengue Transmission

23. Dengue Illnesses - Propagation

24. Natural History of Dengue
In apparent
Human Inf
30%
100%
Recovery
DFM
Re infection
69%
95%
10%
Death
Primary
DHF/DSS
Secondary
DHF/DSS 5%
01%

25. DHF Endemicity

26. Pathogenesis of DHF
Immuno-pathogenic
Cascade

27. 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

28. Initial Immunogenecity

29. Immune Complexes

30. Attack on Host Immune Cells

31. 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 virion’s surface
Fc receptor and focus the Dengue virus
on to the target cells – macro/monocytes
T cell - cytokines, interferon, TNF alpha

32. The Disease
Clinical Features

33. Dengue Presentations Undifferentiated fever
Dengue Fever (DF) with the Fever- Myalgia (FM) presentation (classical)
Dengue Hemorrhagic Fever (DHF)
Dengue Shock Syndrome (DSS)

34. Hemorrhagic Manifestations
Skin hemorrhages: petechiae, purpura, ecchymoses
Gingival bleeding
Nasal bleeding
Gastro-intestinal bleeding: hematemesis, melena, hematochezia
Haematuria
Increased menstrual flow

35. 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

36. Other manifestations- DF
Anorexia. Nausea, vomiting
In apparent illness-to acute incapacitation
Illness is about 2–5 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

37. Petechiae

38. 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

39. DHF – Clinical Criteria

40. 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  50%
Low albumin, pleural effusion

41. Criteria for DSS The four criteria of DHF
Evidence of circulatory failure
Rapid and weak pulse
Narrow pulse pressue (less than 20mm)
Hypotension for the age
Cold clammy skin
Altered mental status

42. 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

43. Ecchymosis – Periorbital Edema

44. Large Subcutaneous Bleed

45. Capillary Damage

46. 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 inch² (6.25 cm²)

47. Tourniquet Test

48. Pleural Effusion
PEI = A / B x 100

49. 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

50. 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

51. Unusual Presentations of Dengue
Encephalopathy
Hepatic damage
Cardiomyopathy
Severe GI bleeding

52. Differential Diagnosis
FM complex
Anicteric leptospirosis
Rickettsial fevers
Influenza, Measles, Rubella
DHF / DSS
Other hemorrhagic fevers
DIC due to septicemia
Complicated Malaria
Meningococcemia

53. Laboratory Diagnosis Complete Blood Counts Hematocrit Platelet Count
Serum GOT, GPT
Serum Albumin
Proteinuria, hematuria
Immunological Tests
Chest Skiagram

54. 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

55. Immuno Detection Tests
ELISA Plate
IgM-capture ELISA

56. 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

57. DHF / DSS Intensive Care Oxygen Rehydration Barrier Nursing
Mosquito Screen

58. 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

59. 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

60. 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

61. 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. { x (60-20)} x 2
= { (2x 40)} x 2 = ( ) x 2
= 2300 x 2 = 4600 ml = 10 pints

62. 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

63. Vector Control Biological Environmental Purpose of control
Largely experimental
Use of fish to feed on larvae
Environmental
Elimination of larval habitat
Most likely successful strategy
Purpose of control
To reduce female vector density

64. 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
Mosquito screens, repellents (DEET)
Permithrin impregnated clothing
Non degradable tires, long life plastics-avoid

65. Challenge Achieve active community involvement
Solicit input from the earliest program planning stages
Encourage community ownership
True community participation is key
          

66. 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.

67. Thank You !