Pathogenesis of Dengue Hemorrhagic Fever and How to Diagnose based on

CME Faculty of Medicine University of Trisakti 2012
Pathogenesis of Dengue Hemorrhagic Fever
and How to Diagnose based on
WHO Guidelines?
Hendarto Natadidjaja
Department of Internal Medicine
Faculty of Medicine University of Trisakti
AGENDA
The Epidemiology of Dengue Hemorrhagic
Fever
The General Pathogenesis of Dengue
Hemorrhagic Fever
Dengue Hemorrhagic Fever Diagnostic Criteria :
The Comparison among 1997,2009,2011
Dengue Laboratory Diagnostic Test
Fluid Management in Dengue Hemorrhagic
Fever
Conclusion
The Epidemiology of
Dengue Hemorrhagic Fever
CME Faculty of Medicine University of Trisakti 2012
Global Impact of Dengue
2.5 billion people (2/5ths of world population)
are at risk for dengue
50 million to 100 million dengue cases
worldwide every year (WHO)
500,000 cases require hospitalization (90% are
pediatric cases)
Leading cause of childhood death and
hospitalization in >8 southeast Asian countries.
25,000 fatalities annually
Source: Ron Rosenberg, CDC Forth Collin, 2008
CME Faculty of Medicine University of Trisakti 2012
Worldwide Extension of Dengue Transmission, 2000 - 2006
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IR is high in Jakarta (303.5), East Kalimantan (174.6)&
Bali(170.1)
MOH 2009
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Serology and Diagnosis
Pediatric Ward – Cipto Mangunkusumo Hospital
2007
Dengue
Fever
Dengue
Hemorrha
gic Fever
Primary
infection
2008
2009
2
5(14.71%) 9(56.25%)
(16.67%)
Secondary
infection
10(83.33
%)
29(85.29
%)
7(43.75%)
Primary
infection
12(14.46
%)
9(7.38%)
7(20%)
Secondary
infection
71(85.54
%)
113(92.62
%)
28(80%)
CME Faculty of Medicine University of Trisakti 2012
SEROTYPE OF DENGUE
IN CIPTO MANGUNKUSUMO HOSPITAL
DENV-1
2006
141
cases
15
2007
97
cases
1
2009
52
cases
5
DENV-2
43
20
4
DENV-3
25
20
11
DENV-4
4
1
2
Dengue Shock Syndrome was mostly caused
by DENV-3 serotype (54,54%).
Sudiro, MT, et al. Department of Microbiology, Faculty of
Medicine, University of Indonesia, 2009
The General Pathogenesis of
Dengue Hemorrhagic Fever
KONAS PETRI-ACEH.2012
CME Faculty of Medicine University of Trisakti 2012
Dengue Virus Characteristics
1. Single Stranded RNA Virus
2. Core dan Capsid
3. Late replication in target cells, starting
within 15 hours post infection
Noisakran S, Guey CP. Alternate hypothesis on the pathogenesis of Dengue Hemorrhagic Fever (DHF)/ De
ngue Shock Syndrome (DSS) in Dengue Virus Infection. Exp Biol Med 2008;233:401-8.
KONAS PETRI-ACEH.2012
CME Faculty of Medicine University of Trisakti 2012
Dengue Target Cells
Noisakran S, Guey CP. Alternate hypothesis on the pathogenesis of Dengue Hemorrhagic Fever (DHF)/ Dengue
Shock Syndrome (DSS) in Dengue Virus Infection. Exp Biol Med 2008;233:401-8.
KONAS PETRI-ACEH.2012
CME Faculty of Medicine University of Trisakti 2012
Dengue Target Cells :
1. Langerhans cells
2. Dendritic cells
3. Lymphocyte, Monocyte
4. Hepatocyte
5. Macrophage
6. Endothelium
CME Faculty of Medicine University of Trisakti 2012
DENGUE SPECIALITIES
LEUCOPENIA
SUPRESION
ROLLING
APOTOSIS
Decreasing of
Platelets
SUPRESION
ADHESION
ANTIBODY
BLEEDING
ENDOTEL DISFUNC.
SHEAR STRESS
DIC
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PLASMA LEAKAGE
•Cell anchored to extracellular matrix
•Present in tissues subject to shear or lateral stress
•Hemi=half
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Macromolecules Can Cross The Endothelial
Barrier in Three Ways:
1.Between the cells, through cell junctions
(paracellular)
2.Through the EC, via pores (diaphragms or
fused vesicles)
3.Transcellularly, via shuttling vesicles
(transcytosis) and specific receptors
(transcellular).
Dengue Hemorrhagic Fever
Diagnostic Criteria :
The Comparison among
1997,2009,2011
KONAS PETRI-ACEH.2012
CME Faculty of Medicine University of Trisakti 2012
Dengue Haemorrhagic Fever
Guidelines
WHO, 1997
WHO, 2009
WHO, 2011
KONAS PETRI-ACEH.2012
CME Faculty of Medicine University of Trisakti 2012
Diagnosis Classification
1997
2009
2011
Dengue fever
Dengue without warning
signs
Dengue fever
DHF grade I
Dengue with warning
signs
DHF grade I
DHF grade II
DHF grade III
DHF grade II
Severe dengue
( severe plasma leakage,
severe hemorrhage,
severe organ involvement)
DHF grade IV
DHF grade III
DHF grade IV
lExpanded dengue
syndrome
Adult management
Adult management
CME Faculty of Medicine University of Trisakti 2012
Criteria of Clinical Diagnosis DHF (WHO 1997)
Fever: acute onset, high and continuous, lasting 2 to 7 days.
Any of the following hemorrhagic manifestations (including at
least a positive tourniquet test: petechiae, purpura, echymosis,
epistaxis, gum bleeding, and hematemesis and/or melena).
Thrombocytopenia (100,000/mm3 or less)
Any of the following signs of plasma leakage:
– Increment of > 20% hematocrit compared to standard
age and sex
– Decrement of > 20% hematocrit after fluid therapy,
compared to previous hematocrit level
– Pleural effusion, ascites, Pericardial effusion or
hypoprotreinemia
WHO.1997
KONAS PETRI-ACEH.2012
CME Faculty of Medicine University of Trisakti 2012
Diagnostic Criteria 2009
2009
Dengue guidelines for diagnosis, treatment, prevention, and control. World Health Organization, UNICEF, UNDP.
New Edition 2009.
CME Faculty of Medicine University of Trisakti 2012
DENGUE HEMORRAGHIC FEVER PHASES (WHO 2009)
DENGUE. GUIDELINES FOR DIAGNOSIS, TREATMENT, PREVENTION AND CONTROL.
CME Faculty of Medicine University of Trisakti 2012
WHO
2009
Group A / Probable Dengue
Patients who may be sent home
Able to tolerate adequate volumes of oral
fluids
Pass urine at least once every six hours
Do not have any of the warning signs,
particularly when fever subsides.
CME Faculty of Medicine University of Trisakti 2012
WHO
2009
Group B
Should be referred for in-hospital
management
– patients with warning signs
– co-existing conditions that may make dengue or
its management more complicated (such as
pregnancy, infancy, old age, obesity, diabetes
mellitus, renal failure, chronic haemolytic
diseases)
– certain social circumstances (living alone, or living
far from a health facility without reliable means of
transport)
CME Faculty of Medicine University of Trisakti 2012
WHO
2009
Group C / Severe Dengue
Require emergency treatment and urgent
referral when they have severe dengue
– severe plasma leakage leading to dengue
shock and/or fluid accumulation with
respiratory distress;
– severe haemorrhages;
– severe organ impairment (hepatic damage,
renal impairment, cardiomyopathy,
encephalopathy or encephalitis).
Dengue Laboratory
Diagnostic Test
CME Faculty of Medicine University of Trisakti 2012
Concentration
Immunity Response Against DHF
Early symptoms
IgG cut off
Early symptoms
IgG
HAI 1:2500
Virus
Infection 1
IgM
Virus
Days
IgM
IgM cut off
Infection 2
WD Santoso,2009
CME Faculty of Medicine University of Trisakti 2012
Immunity Response Diagnostic
Onset of
symptoms
NS1 Ag
Bite
Antibody
DA
-7 -6 -5 -4 -3 -2 -1 1 2 3 4 5 6 7 8 9 10 11 12
Y
Ag/Ab level
ACUTE PHASE
WD Santoso,2009
CONVALESENCE PHASE
IgM
IgG
NS1 Ag
Day
Fluid Management in Dengue
Hemorrhagic Fever
CME Faculty of Medicine University of Trisakti 2012
DHF Case Management With Ht Increase > 20%
5 % fluid deficiency
Initial fluid administration
Cristaloid 6-7 ml/kg/hr
3-4 hr evaluation
Improvement
Decrease in Ht & HR
Normal BP,
Increase in Urin Output
Cristaloid 5 ml/kg/hr
Improvement
Worsening in Vital Sign and Ht
Cristaloid 10 ml/kg/hr
Improvement
Worsening
Cristaloid 15 ml/kg/hr
Cristaloid 3 ml/kg/hr
Worsening
(shock signs)
Improvement
Stop Fluid therapy
24-48 hr
No Improvement
Increase in Ht & HR
BP decrease < 20 mmHg
Decrease Urin
Improvement
Shock & Hemorrhage
Management Protocol
WHO,2009
CME Faculty of Medicine University of Trisakti 2012
WHO,2009
Arterial Catheter
As soon as
practical
2005 Guideline
Central Venous
Catheter
Conclusion
1.
2.
3.
4.
5.
Dengue Hemorrhagic Fever is epidemiologically
spread in tropic area, included Indonesia
Working diagnostic of DHF supposed to be based on
WHO diagnostic criteria
Serologic examination can be done as a diagnostic
supportive test
Based on WHO guidelines 2009, Group A of DHF can
be managed in primary care, but group B and C should
be revered to hospital
Fluid therapy is a role of DHF treatment, and it should
be properly to decrease dengue morbidity and
mortality