Module 1
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Pathophysiology
Clinical course
WHO classification & limitation
Other manifestations
Dr Suresh Kumar
Infectious Diseases Unit
Hospital Sungai Buloh
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• Dengue virus – Flavivirus
• Transmitted by Aedes aegypti and Aedes
albopictus
• 4 distinct serotypes
– DEN-1, 2, 3 and 4
• Each episode
– Induces life long immunity to homologous serotype
– Only partial or transient protection to other serotypes
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Manifestations of the dengue syndrome
• Incubation period: 4-7 days (range 3-14)
• Spectrum of illness:
Dengue virus
Infection
Asymptomatic
Symptomatic
Undifferentiated
fever
Dengue Fever
No
hemorrhage
Unusual
hemorrhage
Dengue Hemorrhagic Fever
(plasma leakage)
DHF 1& 2
DHF 3&4
DSS
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Risk factors for DHF
• Secondary infection
– Due to antibody-dependent enhancement
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Viral virulence
Viral load
Host genetic background
T-cell activation
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Pathophysiology of DHF - 1
• Primary pathophysiological abnormality in
DHF and DSS is an acute increase in
vascular permeability
• Plasma leakage results in hemoconcentration
and hypovolemia or shock
• Hypovolemia leads to reflex tachycardia and
generalised vasoconstriction
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Pathophysiology of DHF - 2
Clinical manifestations of vasoconstriction in
various systems are;
– Skin
• coolness, pallor and delayed capillary refill time
– Cardiovascular system
• raised diastolic blood pressure and a narrowing pulse pressure
– Renal system
• reducing urine output
– Gastrointestinal system
• vomiting and abdominal pain
– Central nervous system
• lethargy, restlessness, apprehension, reduced level of consciousness
– Respiratory system
• tachypnoea (respiratory rate >20/min)
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Clinical course of dengue infection - Overview
Febrile
Phase
Lasts for 2 – 7 days
Clinical features are indistinguishable between DF and DHF
Critical
Phase
Happens often after the 3rd day of fever
Clinical presentation depends on the presence and degree of
plasma leakage
Lasts for about 24-48 hours
Recovery
Phase
In DHF patients – plasma leakage stops and is followed by
reabsorption of extravascular fluid
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Febrile Phase
• Usually lasts for 2 – 7 days
• Fever is often accompanied by
– Facial flushing, skin erythema, generalised body ache,
myalgia, arthalgia and headache
– Anorexia, nausea and vomiting are common
• Mild hemorrhagic manifestations may be seen
– This may include positive tourniquet test, petechiae or
mucosal bleeding
• Earliest abnormality in FBC is a progressive
decrease in total WBC count
• These features are indistinguishable between DF
and DHF
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Critical Phase - 1
• Occurs either
– Towards the late febrile phase
• Often after 3rd day of fever
or
– Around defervescence
• Usually between 3rd day to 5th day of fever; but
may go up to the 7th day of fever.
• This phase lasts for 24- 48 hours
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Critical Phase - 2
During this phase if,
• Minimal or no plasma
leakage occurs
– Patient feels better as the
temperature subsides
• Dengue fever
• Critical volume of plasma
leakage occurs
– Patient develops DHF
– Varying degrees of
circulatory disturbances
occur depending on the
degree of plasma leakage
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Critical Phase -3
• In more severe form of plasma leakage
– Patients may sweat, become restless, have
cool extremities and prolonged capillary filling
time
– The pulse rate increases, diastolic BP
increases and the pulse pressure narrows
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Blood pressure, pulse pressure, heart rate in
hypovolemic shock
120
110
100
90
80
70
60
Compensated shock Decompensated shock
Time
LCS Lum
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Critical Phase - 3
Clinical warning signs of severe dengue or
high possibility of rapid progression to shock
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Critical phase - 4
• Thrombocytopenia and hemoconcentration
are usually detectable before the onset of
shock
• HCT level correlates well with plasma
volume loss and disease severity.
• However HCT values may be equivocal and
hence unhelpful when there is frank
hemorrhage or with untimely HCT
determinations
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Recovery Phase
• Plasma leakage stops after 24-48 hours of
defervescence
• This followed by reabsorption of extravascular
fluid
• Patients’ general well being improves, appetite
returns, gastrointestinal symptoms abate,
hemodynamic status stabilises and diuresis
ensues.
• Recovery of platelet count is typically preceded
by the recovery of WCC count
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WHO classification - DHF
• Grade 1
In the presence of haemoconcentration, fever and symptoms, a
positive TT and/or easy bruising
• Grade 2
spontaneous bleeding in addition to the manifestation from Grade 1
• Grade 3*
circulatory failure – rapid, week pulse and narrowing of pulse
pressure or hypotension with the presence of cold, clammy skin
and restlessness.
• Grade 4*
profound shock – with undetectable blood pressure or pulse.
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WHO classification - DHF
• Grade 1 & 2 – Non-shock DHF
• Grade 3 & 4 – DSS
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Limitations of WHO classification
1. Patients may present with severe
dengue with shock without fulfilling all the
4 criteria for DHF
2. The existing guideline does not account
for severe dengue primarily due to organ
dysfunction such as liver, respiratory,
brain and cardiac dysfunction.
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Limitations of WHO classification
3. Diagnosing plasma leakage in DHF
based on HCT
– Very often we do not have patient’s baseline
HCT
– Early fluid therapy and bleeding affects HCT
value
4. Often not useful for disease
management since correct diagnosis can
only made retrospectively
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Other important manifestations
• Acute abdomen
– Causes include hepatitis, acalculous
cholecystitis and shock
– Need to differentiate from surgical causes
• Fever before abdominal pain
• Leucopenia, thrombocytopenia, prolonged APTT
with normal PT
• Improvement of pain with fluid resuscitation
– Most recover within 48-72 hours with
conservative treatment
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Other important manifestations
• Hepatitis
– May be mild or severe regardless of the
degree of plasma leakage
– Patients with liver failure have a high
propensity to bleed esp. GIT bleeding
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Other important manifestations
Neurological manifestations: mainly
encephalitis or encephalopathy.
• Encephalopathy is usually secondary to liver
failure.
• These manifestations may coincide with onset of
clinical features of DHF or may present on
admission with no other features suggestive of
dengue.
• Rarer neurological manifestations include
myelitis and GBS
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Thank you