MANAGEMENT

OF DENGUE
INFECTION
Dr Wan Syazween Lyana
Fakulti Perubatan & Sains Kesihatan
UPM
 LEARNING OUTCOMES

1) Clinical Manifestation and Pathophysiology of Dengue Infection

2) Clinical History of Suspected Dengue Fever

3) Clinical Examination of Suspected Dengue Fever

4) Investigations in Suspected Dengue Fever

5) Management in Dengue Fever

 WHAT IS
DENGUE
FEVER?
Swahili phrase
“Ka -dinga pepo”
➤ cramp-like seizure
caused by an evil
spirit
➤ Flavi-virus
➤ Transmitted by Aedes aegypti & Aedes
albopictus
➤ 4 serotypes : DENV-1, 2, 3 & 4
➤ 3 phases : FEBRILE > CRITICAL >
RECOVERY
➤ 2 classifications* :
i) DENGUE ± WARNING SIGNS
ii) SEVERE DENGUE
➤ 2 types :
i) PRIMARY INFECTION
ii) SECONDARY INFECTION

So, remember : 4 > 3 > 2.

*WHO CLASSIFICATION 2009

CLINICAL COURSE OF DENGUE
Viraemia :
headache, N&V,
flushing
myalgia and rash,
retro-orbital pain, mild
haemorrhage Recovery
Incubation period Febrile phase Critical Phase phase

DAYS
0 (range
Incubation period : 4 - 7 days 1 3 - 14
2 days)3 4 6 8
After the incubation period, the illness begins abruptly.
Febrile phase : 2 - 7 days. Commences at symptom onset
Critical phase : Usually after D3 of fever (maybe earlier). Commences around time of
defervescence*. Coincides with increase in capillary permeability. Lasts 24 - 48 hours.
* Definition : Body temperature <38 degrees & remains below this level.
Recovery phase : Reabsorption of extravascular fluid.
FEBRILE PHASE

FBC maybe normal (in D1/D2) or

progressive fall in TWC & Platelet
FBC maybe normal (in D1/D2) or
progressive fall in TWC & Platelet
CRITICAL PHASE (1)
➤ Acute increase in vascular permeability > leakage of plasma
into extravascular compartment > haemoconcentration >
hypovolaemia / shock
1. VASCULAR
PERMEABILITY 2. PLASMA LEAKAGE

RBC

RBC RBC

3. HAEMOCONCENTRATION

4. HYPOVOLAEMIA/
SHOCK
CRITICAL PHASE (2)
➤ Development of warning symptoms :
➤ Identify dengue patients already in shock
*Leukopenia @relative
with at risk of of developing shock.
lymphocytosis
*Haemoconcentration
*Thrombocytopenia
Clinical Warning Signs Prolonged APTT
AST > ALT
1. Severe abdominal pain
Hypoproteinaemia
2. Vomiting > 3x/day
Hypoalbuminaemia
3. Diarrhea > 3x/day
4. Mucosal bleed
* common laboratory findings
5. Lethargy, confusion, restlessness
*Leukopenia with relative lymphocytosis
6. Clinical fluid accumulation (pleural effusion/ascites)
*Haemoconcentration
7. Liver tenderness / enlargement >2cm
*Thrombocytopenia
Prolonged APTT
Laboratory
AST > ALTWarning Signs
Hypoproteinaemia
Increase in HCT concurrent with rapid drop in Platelet
Hypoalbuminaemia

* common laboratory findings

 RECOVERY
PHASE
➤General well being improves
➤ Vascular permeability reverts to
normal
➤ Gradual reabsorption of
Hct stabilises (Hct maybe lower d/t reabsorption of fluid)
extravascular
Increase in TWC fluid : 48 - 72 hours
Increase Platelet
➤ Risk of fluid overload
Hct stabilises (Hct maybe lower d/t reabsorption of fluid)
➤ Isles
Increase of white in a sea of red
in TWC
Increase Platelet
 CLINICAL COURSE OF DENGUE IN
SUMMARY
Days of illness 1 2 3 4 5 6 7 8
Phases of dengue Febrile Critical Recovery
Defervescence
40 Biphasic picture
Temperature 39
38

Subnormal temperature
Potential clinical Reabsorption/fluid overload
issues Shock
Dehydration
Bleeding
Platelet Organ impairment
Laboratory changes
WBC
TWC
Platelet
HCT HCT
Viraemia IgM/IgG

Virology & Serology

CLASSIFICATION OF DENGUE
INFECTION
2009 WHO Dengue Classification & Level of Severity

DENGUE ± WARNING SIGNS SEVERE DENGUE

1) Severe plasma leakage :

➤ Shock
➤ Fluid accumulation +

with warning signs Respiratory distress

2) Severe bleeding

without
3) Severe organ involvement
➤ Liver : AST or ALT > 1000
➤ CNS : impaired GCS
➤ Heart or other organs
TYPES OF DENGUE
1. Primary infection
2. Secondary infection
➤ Previous history of dengue infection
➤ Antibody-dependent enhancement :
After a person is infected with one serotype of dengue ie DEN-1, specific antibodies to
DEN 1 developed.
If other serotype (DEN-2, 3 @ 4) infects the person, the virus will activate the immune
system to attack it thinking it was the DEN-1.
The antibodies bind to the surface proteins but are unable to inactivate the virus.
The immune response attracts numerous macrophages, which the virus proceeds to
infect because it has not been inactivated.
The secondary dengue infection becomes much more acute.
CLINICAL HISTORY OF SUSPECTED
DENGUE
➤
(1)
Date of onset of fever

➤ Assess warning signs

➤ Oral intake : quantity and quality ?

➤ Urine output : frequency, volume & time of most recent voiding?

➤ What activities could do patient do during the febrile illness ?

➤ Change in mental state/seizure/dizziness

CLINICAL HISTORY OF SUSPECTED
DENGUE
➤ (2) histories :
Other important relevant

Family or neighbourhood history of dengue or travel to dengue endemic area

Jungle trekking and swimming in waterfall ( DD : leptospirosis/malaria/typhus)

Recent unprotected sexual or IVDU (DD : acute HIV seroconversion illness)

Co-morbidities (DD : sepsis particularly in diabetes mellitus)

Medications : OTC/traditional meds/NSAIDS/IM injections/anti-HPT/all meds with last

time taken

Risk factors : pregnancy, obesity, diabetes mellitus, hypertension

CLINICAL EXAMINATION OF
SUSPECTED DENGUE
1. Assess mental state and GCS score INFECTION (1)
➤ Altered conscious level may indicate :
i) Shock
ii) Intracranial bleeding
iii) Encephalopathy/encephalitis
CLINICAL EXAMINATION OF
SUSPECTED
2. Assess hydration status. DENGUE INFECTION (2)
➤ Dry tongue
➤ Dry mucous membranes in mouth
➤ Reduced skin turgor
➤ Sunken eyes
➤ Dry tongue

Wet tongue Dry tongue

➤ Dry mucous membrane in mouth
Palate
Floor of mouth
Gums
Lips

Dry lips Wet lips

➤ Reduced skin turgor
➤ Sunken eyes

Normal eyes Sunken eyes

3. Assess haemodynamic status
➤ CCTVR

C : skin Colour

C : Capillary refill time < 2 seconds

T : Temperature (cold/warm extremities)

V : pulse Volume - good / weak @ thready / feeble @ absent

R : Rate

➤ Blood pressure
➤ Pulse pressure (difference between systolic & diastolic pressure : If 120/80, pulse pressure
40mmHg. If narrowing, indicates shock)
➤ Urine output : > 0.5 ml/kg/hour , concentrated @ diluted
➤ Urine output
Normal : 0.5 - 1ml/kg/hour
Inspect colour of urine
4. Look for tachypnoea / acidotic breathing / pleural effusion
5. Check for abdominal tenderness / hepatomegaly / ascites
6. Examine for bleeding tendency
➤ Petechiae
➤ Purpura and ecchymoses
➤ Malaena
➤ Bleeding gingiva
➤ Epistaxis
 Petechiae Purpura Ecchymoses

Small, purpuric lesions up to Discolouration of the skin or Larger extravasations of

2mm mucous membranes due to blood
haemorrhage from small
blood vessels.
INVESTIGATIONS OF SUSPECTED
DENGUE INFECTION (1)

DISEASE
DIAGNOSTIC
MONITORING
TESTS
TESTS

➤ FBC (TWC, Hb, HCT, ➤ Rapid Combo Test

Platelet)
➤ Dengue Antigen &
➤ RP, LFT Serology Test by ELISA
i) NS1 Antigen
➤ Coagulation Profile ii) Dengue IgM test
iii) Dengue IgG test
➤ ABG/VBG/lactate
➤ Dengue PCR
➤ CK / Troponin
 INVESTIGATIONS OF SUSPECTED
DENGUE
Disease MonitoringINFECTION
Test (2)
1. Identify different phase of dengue : TWC, HCT, Platelet
2. Marker of plasma leakage & hypovolaemia : HCT , blood gas , lactate
3. Monitor complications :
➤ bleeding : Hb , blood gas , lactate
➤ hepatitis : AST , ALT
➤ myocarditis : CK , Troponin , ECG , ECHO
➤ myositis : CK
➤ acute renal failure : RP , blood gas
➤ neurological (encephalopathy/encephalitis) : CT brain , Lumbar puncture
➤ Pleural effusion : CXR, US thorax
➤ Ascites / gallbladder wall edema : US Abdomen
LEVEL OF HAEMOCONCENTRATION

HAEMATOCRIT

MARKER OF PLASMA LEAKAGE

MALE FEMALE

≤ 60 YEARS > 60 YEARS ALL AGE GROUPS

46% 42% 40%

INVESTIGATIONS OF SUSPECTED
DENGUE INFECTION (3)
Diagnosis
I) Rapid combo test - check presence of virus (NS-1 antigen) and antibodies (IgM & IgG)
simultaneously
II) Dengue Antigen and Serology Test by ELISA
- NS1 Antigen : sensitivity drop day 4-5. In defervescence,
usually non-detectable. If present >D5, predict severe
dengue.
- IgM : >D5 of illness, peaks about 2/52 then wanes
down over 1 hour.
- IgG : after Day 7
- check titre. If 1 : 2560, indicate of secondary dengue
III) Dengue Viral RNA Detection (Real time RT PCR)
- determine Dengue serotype
IV) Virus Isolation
FLUID MANAGEMENT OF DENGUE
INFECTION
1. Is the haemodynamic status stable or compromised?
2. Which phase of disease?
3. Can the patient tolerate orally well?
4. Is there a warning sign?
5. What is the aim for fluid therapy?
MANAGEMENT OF DENGUE INFECTION
1. Is the haemodynamic status stable or compromised?
HAEMODYNAMIC ASSESSMENT - CLINICAL PARAMETERS

PARAMETERS

Conscious level 3a. Organ perfusion (Brain)

Capillary refill time

Extremities (colour, temp) 1. Peripheral perfusion

Peripheral pulse volume

Heart rate

Pulse pressure
2. Cardiac output

Blood pressure
4. Respiratory compensation for metabolic acidosis d/t
Respiratory rate tissue hypoxia
Urine output
3b. Organ perfusion (renal)
MANAGEMENT OF DENGUE INFECTION

PARAMETERS STABLE

Conscious level Clear and lucid

Capillary refill time

Brisk <2 seconds

Extremities (colour, temp) Warm and pink

Peripheral pulse volume Good volume

Heart rate
SBP - DBP
Pulse pressure

Blood pressure

Respiratory rate 12 - 20 breathing/min

Urine output 0.5 - 1ml/kg/hr

MANAGEMENT OF DENGUE INFECTION
COMPENSATED SHOCK

PARAMETERS STABLE COMPENSATED SHOCK

Conscious level Clear and lucid Clear and lucid

Capillary refill time

Brisk <2 seconds Prolonged > 2 seconds

Extremities (colour, temp) Warm and pink Cool peripheries

Peripheral pulse volume Good volume Weak and thready

Heart rate Normal Tachycardia

Normal SBP, rising DBP

Pulse pressure Normal
- reducing pulse pressure

Blood pressure Normal Postural hypotension

Respiratory rate 12 - 20 breathing/min Quiet tachypneoa

Urine output 0.5 - 1ml/kg/hr Reducing trend

MANAGEMENT OF DENGUE INFECTION
COMPENSATED SHOCK
Blood Pressure
Increasing tachycardia
120

110
Normal SBP, rising DBP
100

90
Narrowing pulse pressure
80

70

60

Time
MANAGEMENT OF DENGUE INFECTION
DECOMPENSATED SHOCK
DECOMPENSATED
PARAMETERS STABLE COMPENSATED SHOCK
SHOCK

Conscious level Clear and lucid Clear and lucid Restless, combative

Capillary refill time Very prolonged, mottled

Brisk <2 seconds Prolonged > 2 seconds
skin

Extremities (colour, temp) Warm and pink Cool peripheries Cold, clammy

Peripheral pulse volume Good volume Weak and thready Feeble or absent

Severe tachycardia or
Heart rate Normal Tachycardia
bradycardia in late shock
Normal SBP, rising DBP Narrowed pulse pressure
Pulse pressure Normal
- reducing pulse pressure ≤20 mmHg
Hypotension or
Blood pressure Normal Postural hypotension
unrecordable BP

Respiratory rate 12 - 20 breathing/min Quiet tachypneoa Kussmaul breathing

Urine output 0.5 - 1ml/kg/hr Reducing trend Oliguria or anuria

MANAGEMENT OF DENGUE INFECTION
COMPENSATED SHOCK DECOMPENSATED SHOCK
Blood Pressure

120 More increasing tachycardia

110

100

90
Reducing SBP and DBP
80

70 Normal SBP, rising DBP Narrowed pulse pressure

60
Narrowing pulse pressure

Increasing tachycardia

Time
FLUID MANAGEMENT OF DENGUE
INFECTION
1. Is the haemodynamic status stable or compromised?
2. Which phase of disease?
3. Can the patient tolerate orally well?
4. Is there a warning sign?
5. What is the aim for fluid therapy?
MANAGEMENT OF DENGUE INFECTION
WHICH PHASE OF DISEASE?

FEBRILE RECOVERY
PHASE CRITICAL
PHASE
PHASE
➤ Limit IV fluids
➤ Should stop IVD for
➤ Early IVD may lead ➤ IVD maybe needed
reabsorption of
to fluid overload for 24 - 48 hours
extravasated fluid
later
FLUID MANAGEMENT OF DENGUE
INFECTION
1. Is the haemodynamic status stable or compromised?
2. Which phase of disease?
3. Can the patient tolerate orally well?
4. Is there a warning sign?
5. What is the aim for fluid therapy?
MANAGEMENT OF DENGUE INFECTION
IVD is indicated if :
➤ Increasing HCT with evidence of ongoing plasma leakage
despite increased oral intake
➤ Vomiting
➤ Severe diarrhoea
➤ Not tolerating orally

If can tolerate orally, encourage orally 2 - 3L per day

If cant, give IVD maintenance
MANAGEMENT OF DENGUE INFECTION
Calculations for IVD maintenance
FLUID MANAGEMENT OF DENGUE
INFECTION
1. Is the haemodynamic status stable or compromised?
2. Which phase of disease?
3. Can the patient tolerate orally well?
4. Is there a warning sign?
5. What is the aim for fluid therapy?
MANAGEMENT OF DENGUE INFECTION
➤ In patients with persistent warning signs with increasing or
persistently high HCT,initiate graded fluid bolus.
FLUID MANAGEMENT OF DENGUE
INFECTION
1. Is the haemodynamic status stable or compromised?
2. Which phase of disease?
3. Can the patient tolerate orally well?
4. Is there a warning sign?
5. What is the aim for fluid therapy?
MANAGEMENT OF DENGUE INFECTION
Fluid responsiveness parameters :
RECOVERY PHASE OF DENGUE
1. Improved general well being
2. Rising TWC followed by Platelet count
3. Stable or reducing haematocrit (reabsorption of extravasated
fluid)
4. Resolution/recovery of organ dysfunction