AETIOLOGY,PATHOPHYSIOLOGY AND AETIOLOGY,PATHOPHYSIOLOGY AND DIAGNOSIS OF DENGUE INFECTIONDIAGNOSIS OF DENGUE INFECTION

DR LEE OI WAHDR LEE OI WAH

PEG. PERUBATAN UD54PEG. PERUBATAN UD54

Dengue VirusDengue Virus

Causes dengue and dengue hemorrhagic feverCauses dengue and dengue hemorrhagic fever Is an arbovirusIs an arbovirus Transmitted by mosquitoesTransmitted by mosquitoes Composed of single-stranded RNAComposed of single-stranded RNA Has 4 serotypes (DEN-1, 2, 3, 4)Has 4 serotypes (DEN-1, 2, 3, 4)

Dengue VirusesDengue Viruses

Each serotype provides specific lifetime Each serotype provides specific lifetime immunity, and short-term cross-immunityimmunity, and short-term cross-immunity

All serotypes can cause severe and fatal All serotypes can cause severe and fatal diseasedisease

Genetic variation within serotypesGenetic variation within serotypes Some genetic variants within each serotype Some genetic variants within each serotype

appear to be more virulent or have greater appear to be more virulent or have greater epidemic potentialepidemic potential

4

1

Circulating Dengue Virus Serotype : 1992-2007

0

10

20

30

40

50

60

70

80

90

100

DEN 1 DEN 2 DEN 3 DEN 4

DEN 1 3.7 0 4.8 14.7 48.7 63.5 44.4 28.2 9.3 5.4 29.8 46.9 73.4 58.6 33 30

DEN 2 8.6 4.1 9.5 29.5 48.7 33.4 51.9 69.2 58.1 39.2 23.8 20.6 7.4 8.4 36.4 53

DEN 3 83.7 93.1 84.1 54.6 2.6 2.1 3.7 2.7 32.6 50 33.3 27.8 14.6 17.1 19.3 11

DEN 4 4 2.8 1.6 1.2 0 0 0 0 0 5.4 13.1 4.7 4.6 1.2 4.5 6

1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007

Serotype Surveilan Di Ng Perak 2002 - 2007

YearYear No of No of Samples Samples Type 1Type 1 Type 2Type 2 Type 3Type 3 Type 4Type 4

20022002 113113 00 11 11 22

20032003 2222 00 00 00 00

20042004 88 00 11 00 00

20052005 250250 44 11 33 22

20062006 160160 44 00 44 11

20072007 243243 99 1919 77 00

TotalTotal 796796 1717 2222 1515 55

DENGUE VECTORS

Aedes aegypti Aedes albopictus

Larva

Pupa

1 - 2 Days

1 - 3 Days

6 - 8 Days

2 - 3 Days

Water

LIFE CYCLE OF THE AEDESLIFE CYCLE OF THE AEDES

Adult

Eggs Hatch 1- 48 hrs

Complete cycle 9 – 10 days

DENGUE TRANSMISSIONDENGUE TRANSMISSION

Infected Person Susceptible Person

Mosquito BiteInfected

Mosquito

Infected Mosquito

Bites next person

Becomes Sick

Mosquito Bite Infected

Mosquito

3 – 14 days laterRemains viremic

2 to 10 Days 8 – 12 DAYS

Manifestations of the dengue Manifestations of the dengue syndromesyndrome

Asymptomatic

Undifferentiatedfever

No h'rage Unusualhemorrhage

Dengue Fever

DHF I & II DSS

Dengue Hemorrhagic Fever(plasma leakage)

Symptomatic

Dengue virusInfection

Fever lasting 2-7 days, occasionally biphasic

Bleeding tendencies

Thrombocytopenia (100,000/mm3 or less)

Evidence of plasma leakage: Haemoconcentration (20% above baseline)

A drop in haematocrit following fluid replacement Pleural effusion, ascites (not obvious in early stage of critical phase), circulatory disturbances.

Hypovolemic shock

Dengue Haemorrhagic Fever (WHO 1997)

Dengue Shock Syndrome (WHO 1997)

All the above 4 criteria for DHF, plus evidence of circulatory failure:

rapid and weak pulsenarrow pulse pressure less than 20mmHgor hypotension for agecold clammy skin and restlessness

WHO grading of DHF/DSS (WHO WHO grading of DHF/DSS (WHO 19971997))

Grade 1In the presence of haemoconcentration, fever and symptoms, a positive TTGrade 2spontaneous bleeding in addition to the manifestation from Grade 2Grade 3*circulatory failure, pulse pressure less than 20 mmHg but systolic pressure normalGrade 4*profound shock, hypotension or unrecordable blood pressure.

Simplification:Grade 1 & 2: Non-shock DHFGrade 3: COMPENSATED shockGrade 4: DECOMPENSATED shock #

Dengue Case ClassificationDengue Case Classification

13Dengue Perak 5/2010

PATHOPHYSIOLOGY OF DENGUE PATHOPHYSIOLOGY OF DENGUE INFECTIONINFECTION

Deferversence

24-48 hours

Recognition of onset of reabsorption Recognition of onset of reabsorption phase is also important because i.v fluid phase is also important because i.v fluid regime needs to be progressively reduced/ regime needs to be progressively reduced/ discontinued at this stage.discontinued at this stage.

Thrombocytopenia

12011010090807060

Blood pressure, pulse pressure, heart rate in hypovolemic shock

Time LCS Lum

Compensated shock Decompensated shock

First sign of shock is tachycardiaFollowed by increasing diastolic BP

Drop is systolic BP is relatively late event

PR

DIAGNOSIS OF DF OR DHFDIAGNOSIS OF DF OR DHF

Important points to evaluate:Important points to evaluate:

History:History:date of onset of fever/ illnessdate of onset of fever/ illnessnausea, vomiting, abdominal pain, diarrhoea nausea, vomiting, abdominal pain, diarrhoea bleeding tendencybleeding tendencychange in mental state/seizure/dizzinesschange in mental state/seizure/dizzinessurine output (frequency, volume and time of last voiding)urine output (frequency, volume and time of last voiding)other important relevant histories:other important relevant histories:

family or neighbourhood history of denguefamily or neighbourhood history of denguejungle trekking and swimming in waterfall (consider leptospirosis, jungle trekking and swimming in waterfall (consider leptospirosis,

typhus, malaria)typhus, malaria)travellingtravellingrecent unprotected sexual or drug use behaviour (consider acute recent unprotected sexual or drug use behaviour (consider acute

HIV seroconversion illness)HIV seroconversion illness)

co-morbidities (consider sepsis in patients with diabetesco-morbidities (consider sepsis in patients with diabetes mellitus) mellitus)

Physical examination: Physical examination:

Assess mental state and GCS scoreAssess mental state and GCS score Assess haemodynamic status Assess haemodynamic status

Cold/ warm extremitiesCold/ warm extremities

Capillary filling time (normal < 2 seconds); Capillary filling time (normal < 2 seconds);

Pulse rate and Pulse volumePulse rate and Pulse volume

Blood pressure and Pulse pressureBlood pressure and Pulse pressure

Look out for tachypnoea/ acidotic breathing/ pleural effusionLook out for tachypnoea/ acidotic breathing/ pleural effusion Check for abdominal tenderness/ hepatomegaly/ ascitesCheck for abdominal tenderness/ hepatomegaly/ ascites Examine for bleeding manifestationExamine for bleeding manifestation Tourniquet test (repeat if previously negative or if there is Tourniquet test (repeat if previously negative or if there is

no bleeding manifestation) no bleeding manifestation)

Investigations:Investigations:

FBC & HCT FBC & HCT Renal and liver function testsRenal and liver function tests INR & APTTINR & APTT Dengue serologyDengue serology BFMPBFMP Other relevent tests Other relevent tests

After clinical assessmentAfter clinical assessment1.1. Day…….feverDay…….fever2.2. Temp chart – Febrile phase / Temp chart – Febrile phase / Critical phaseCritical phase

Hours of defervescenceHours of defervescence3.3. Alarm signalsAlarm signals – Yes/No – Yes/No

Abdominal pain and vomiting / Restlessness / Cold and Abdominal pain and vomiting / Restlessness / Cold and clammy extrimities / Altered conscious level / A sudden clammy extrimities / Altered conscious level / A sudden change from fever to hypothermiachange from fever to hypothermia

4.4. Bleeding tendencyBleeding tendency – Yes/No – Yes/No5.5. Evidence of plasma leakageEvidence of plasma leakage – Yes/No – Yes/No

Pleural effusion / AscitesPleural effusion / Ascites Hemodynamic instability - INCLUDING Hemodynamic instability - INCLUDING

TACHYCARDIA (PR>90)TACHYCARDIA (PR>90) Increase in HCTIncrease in HCT

Diagnosis :Diagnosis :

Dengue Haemorrhagic FeverDengue Haemorrhagic Fever D6 illnessD6 illness Deferversence 12 hoursDeferversence 12 hours With right pleural effusion and ascitesWith right pleural effusion and ascites Clinically no alarming signs / bleedingClinically no alarming signs / bleeding

(EXAMPLE)(EXAMPLE)