Dengue Fever by Prof M Ali Khan

DENGUE FEVER
Prof. Dr. Muhammad Ali Khan

MBBS, DCH, MRCP (UK)
Secretary DEAG Punjab
Ex Head Department of Pediatrics

SIMS/Services Hospital Lahore
2
Dengue Virus
 Family : Flaviviridae
 Genus : Flavivirus
 Serotypes : DV1, DV2, DV3, DV4
 Enveloped virus
 3 major proteins
 SS positive sense RNA
3
Dr. S Guanasena
Viral Serotypes
 DV1
 DV2
 DV3
 DV4
 Subgroups and clades
 One or more virus types in circulation during an
epidemic
4
Spectrum of Disease
Asymptomatic Mild viral DF DHF

syndrome
95% 5%
Clinical course of Dengue
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%)
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
DHF
or
DLF
SHOCK
A complex clinical syndrome of
decreased blood flow
to body tissues
resulting in
cellular dysfunction and
eventual
organ failure
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
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
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

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

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

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

Clinical course of
DHF
 Both the DF and DHF can have bleeding tendencies

therefore:
Bleeding is not the differentiating point between the two
Clinical course of
DHF
 Clinical course can be divided into three stages
1. Febrile Phase
2. Critical Phase
3. Recovery Phase
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

Clinical course of
DHF
Critical Phase
 Starts with the resolution of fever

 Occurs in a few people
 Lasts for just 24-48 hours or so
 Is associated with plasma leak – volume depletion & shock
This is the phase where management is critical

Clinical course of
DHF
 DHF is classically associated with
 Plasma leak into the 3rd compartment

 And circulatory compromise
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
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

Highly Suggestive of DHF Confirmed DHF**
 Disproportionate tachycardia  Ascites on U/S
 Narrowing of pulse pressure < 20  Pleural effusions (CXR Right lateral
mm decubitus or chest U/S to detect
 CRFT > 2 secs minimal effusion)
 Tender hepatomegaly (DHF likely) ** Definitive evidence of plasma leakage
 Haemoconcentration
HCT 20% rise from baseline or rise
approaching 20% if patient already
on IV fluids
 Biochemistry
o 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
25
Rate of Fluid loss and intake
(Critical Phase)
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
Lab Diagnosis
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)
29
Dr. S Guanasena
Investigations
 CBC and platelet count
 First 5 days
 NS 1
 PCR
 >5 days
 IgM
 IgG
Update on vaccine
 Chimera vaccine  Attenuated vaccine
 Yellow fever & dengue  6-8 cycles in DKC
 Launched 2016 (Dog kidney cells)
 Partial immunity
 Risk of secondary infection
HAVE WE DONE ENOUGH?
Asia pacific strategic plan for

control of Dengue (2010-2015)
 Decrease prevalence by 10% per

year
What are our Goals?????
 Keep DHF mortality below 1%
Current situation in Punjab
Lahore 2011 Rawalpindi 2015
 DEN 2  DEN 1,2,3,4
 Innumerable  2349 cases (uptill 27-10-2015)
 > 300 cases of DHF and DSS
 Few DHF  10 deaths
DEAG TRINED MEDICS

AND PARAMEDICS = 13000
Current situation in Punjab
Lahore, 2016 Rawalpindi, 2016
 DEN 1  DEN 1,2,3
 109  299
 Few DHF  18
 No death  03 deaths
DEAG TRINED MEDICS

AND PARAMEDICS = 3165
Take Home message
 We can prevent quite a few deaths ---- if we can
1. Differentiate DF from DHF

2. Diagnose the onset of critical phase (phase of
leaking)
3. Give appropriate fluids

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Dengue Fever by Prof M Ali Khan

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DENGUE FEVER

Prof. Dr. Muhammad Ali Khan

Secretary DEAG Punjab

Ex Head Department of Pediatrics

Asymptomatic Mild viral DF DHF

Clinically significant Dengue infection may be

1. Simple dengue fever (DF)

2. Dengue hemorrhagic fever (DHF)

3. Dengue Shock Syndrome (DSS)

 Increased viremia increased TNF, interferon,

 Circulatory volume collapses – SHOCK

 Sympathetic over activity

 Blood becomes thick due to loss of fluid

 Compromised renal and hepatic perfusion –

 But there is one important consideration:

fluid over load during the recovery phase

 People do not die of hemorrhage in DHF

 Two organ Failure - mortality = 80%

 Three organ failure - mortality = >99%

 8 died of profound shock and associated end organ failure

 Only one had suspected CVA as a cause of death

 Course of simple Dengue fever is generally

 Whereas DHF can be life-threatening

Differentiating DF from DHF is critical

 Both the DF and DHF can have bleeding tendencies

 Clinical course can be divided into three stages

People generally don’t die during this stage

 Starts with the resolution of fever

This is the phase where management is critical

 DHF is classically associated with

 Plasma leak into the 3rd compartment

 Low urine output

 Delayed capillary filling

Warning signs (lab reports)

 Edema of the gall bladder, ascites or pleural effusion

 Acute fall in platelet count

 Volume gets resorbed

IgM antibody to the

Following primary infection –

Asia pacific strategic plan for

 Decrease prevalence by 10% per

 DEN 2  DEN 1,2,3,4

 Innumerable  2349 cases (uptill 27-10-2015)

 > 300 cases of DHF and DSS

 Few DHF  10 deaths

DEAG TRINED MEDICS

 DEN 1  DEN 1,2,3

DEAG TRINED MEDICS

 We can prevent quite a few deaths ---- if we can

1. Differentiate DF from DHF

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