1. DENGUE FEVER Prof. Dr. Muhammad Ali Khan MBBS, DCH, MRCP (UK)
Secretary DEAG Punjab
Ex Head Department of Pediatrics
SIMS/Services Hospital Lahore

3. Dengue Virus Family : Flaviviridae Genus : Flavivirus
Serotypes : DV1, DV2, DV3, DV4
Enveloped virus
3 major proteins
SS positive sense RNA
Dr. S Guanasena

4. Viral Serotypes DV1 DV2 DV3 DV4 Subgroups and clades
One or more virus types in circulation during an epidemic

5. Spectrum of Disease
Asymptomatic
Mild viral syndrome DF
DHF
95% 5%

6. Clinical course of Dengue

7. Dengue Infection Clinically significant Dengue infection may be
1. Simple dengue fever (DF)
2. Dengue hemorrhagic fever (DHF)
(plasma leak <5%)
3. Dengue Shock Syndrome (DSS)
(plasma leak >5%)

8. Clinical Features – DF
Fever > 2 and < 10 days (essential criterion)
Headache
Retro orbital pain
Myalgia
Arthralgia/ severe backache/ bone pains
Rash
Bleeding manifestations (epistaxis, hematemesis, bloody stools, menorrhagia, hemoptysis)
Abdominal pain
Decreased urinary output despite adequate fluid intake
Irritability in infants

9. DHF or
DLF

10. cellular dysfunction and
SHOCK
A complex clinical syndrome of decreased blood flow
to body tissues
resulting in
cellular dysfunction and
eventual
organ failure

11. Plasma leaks - Pathophysiology
Host response
Subsequent infection
Previous IgG
Neutralizing (protective)
non neutralizing (replication enhancing)
Increased viremia increased TNF, interferon, interleukin-2 and hypocomplementemia endothelial injury and increased leakage
Viral response

12. Pathophysiology of DHF
Increased capillary permeability
Protein rich fluid exudes into the interstitial space - Pleural effusion , Ascites etc.
Circulatory volume collapses – SHOCK
Sympathetic over activity
Vasoconstriction, tachycardia
Loss of volume
Reduces pulse pressure
Blood becomes thick due to loss of fluid
Rising hematocrit and delayed capillary filling
Compromised renal and hepatic perfusion –
Reduced urine output and tender hepatomegaly

13. Patho-physiology of DHF
Management of DHF during the critical stage is that of Shock
But there is one important consideration:
Fluid is not being lost out but it is going to 3rd space and will be resorbed back so
Over-enthusiastic fluid replacement
during the critical phase – when the fluid is oozing out - would result in
fluid over load during the recovery phase

14. Patho-physiology of DHF
People do not die of hemorrhage in DHF
They die
Either due to shock and 20 organ failure
Or due to Pulmonary edema & fluid over load during the recovery phase

15. End organ failure in DHF
Approximate outcomes
Single organ failure - mortality = 40%
Two organ Failure - mortality = 80%
Three organ failure - mortality = >99%

16. Case review ( of 9 deaths at Services Hospital )
8 died of profound shock and associated end organ failure
Only one had suspected CVA as a cause of death

17. Clinical course of DHF
Course of simple Dengue fever is generally uneventful and non-fatal
Whereas DHF can be life-threatening
Differentiating DF from DHF is critical

18. Clinical course of DHF
Both the DF and DHF can have bleeding tendencies therefore:
Bleeding is not the differentiating point between the two

19. Clinical course of DHF
Clinical course can be divided into three stages
Febrile Phase
Critical Phase
Recovery Phase

20. Clinical course of DHF Febrile Phase High fever
Some petechial hemorrhages
With generalized aches & pains and headache;
this usually lasts two to seven days
People generally don’t die during this stage

21. Clinical course of DHF Critical Phase
Starts with the resolution of fever
Occurs in a few people
Lasts for just hours or so
Is associated with plasma leak – volume depletion & shock
This is the phase where management is critical

22. Clinical course of DHF DHF is classically associated with
Plasma leak into the 3rd compartment
And circulatory compromise

23. Signs of plasma leak in DHF
Patient is not feeling well with resolution of fever
Warning signs
Low pulse pressure <20 mm
Low urine output
Delayed capillary filling
Tender hepatomegaly

24. Signs of impending DHF Warning signs (lab reports)
Increasing hematocrit
Edema of the gall bladder, ascites or pleural effusion
Low albumin
Low cholesterol
Acute fall in platelet count

25. Highly Suggestive of DHF Confirmed DHF**
Disproportionate tachycardia
Narrowing of pulse pressure < 20 mm
CRFT > 2 secs
Tender hepatomegaly (DHF likely)
Haemoconcentration
HCT 20% rise from baseline or rise approaching 20% if patient already on IV fluids
Biochemistry
Serum albumin < 3.5 g/dl or 0.5 gm/dl fall during illness
Non fasting serum cholesterol < 100 mg/dl or 20mg/dl fall during illness
Oedematous gall bladder wall on U/S
Ascites on U/S
Pleural effusions (CXR Right lateral decubitus or chest U/S to detect minimal effusion)
** Definitive evidence of plasma leakage

26. Rate of Fluid loss and intake (Critical Phase)

27. Clinical course of DHF Recovery Phase Volume gets resorbed
Volume over-load may occur
This is the phase where people die because of the problems faced during the critical stage

28. Lab Diagnosis

29. IgM antibody to the secondary infecting DV serotype
IgG antibody - specific to the initial infecting DV serotype + cross reacting antibody
IgM antibody to the secondary infecting DV serotype
Following primary infection –
Specific antibody response + CMI (memory T cells)
Cross reactive antibody response + CMI (memory T cells)
Dr. S Guanasena

30. Investigations CBC and platelet count First 5 days >5 days NS 1 PCR
IgM
IgG

31. Update on vaccine Chimera vaccine Attenuated vaccine
Yellow fever & dengue
Launched 2016
Partial immunity
Risk of secondary infection
Attenuated vaccine
6-8 cycles in DKC (Dog kidney cells)

32. HAVE WE DONE ENOUGH?
Asia pacific strategic plan for control of Dengue ( )
Decrease prevalence by 10% per year
Keep DHF mortality below 1%
What are our Goals?????

33. Current situation in Punjab
Lahore 2011
Rawalpindi 2015
DEN 2
Innumerable
Few DHF
DEAG TRINED MEDICS AND PARAMEDICS = 13000
DEN 1,2,3,4
2349 cases (uptill )
> 300 cases of DHF and DSS
10 deaths

34. Current situation in Punjab
Lahore, 2016
Rawalpindi, 2016
DEN 1
109
Few DHF
No death
DEAG TRINED MEDICS AND PARAMEDICS = 3165
DEN 1,2,3
299 18
03 deaths

35. Take Home message We can prevent quite a few deaths ---- if we can
Differentiate DF from DHF
Diagnose the onset of critical phase (phase of leaking)
Give appropriate fluids

36. Thank you