DENGUE FEVER by Prof M Ali Khan

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DENGUE FEVER

Prof. Dr. Muhammad Ali Khan


MBBS, DCH, MRCP (UK)

Secretary DEAG Punjab

Ex Head Department of Pediatrics


SIMS/Services Hospital Lahore
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Dengue Virus
 Family : Flaviviridae
 Genus : Flavivirus
 Serotypes : DV1, DV2, DV3, DV4

 Enveloped virus
 3 major proteins
 SS positive sense RNA

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

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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

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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)
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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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