Ida Safitri Laksono

Dept of Child Health, Faculty of Medicine UGM

RSUP Dr. Sardjito, Yogyakarta

Outline of presentation
Introduction
Overview of the three guidelines
Dengue Guideline 1997
Background and evidence related to Dengue Guideline
2009
Dengue Guideline 2011
National Dengue Guideline?
Summary
Introduction
GLOBAL burden of dengue
Global incidence of dengue has grown dramatically in
recent decades
About two fifths of the world's population are now at risk
Dengue is found in tropical and sub-tropical climates
worldwide, mostly in urban and semi-urban areas
Dengue is the most prevalent arboviral disease with high
morbidity, mortality & socio-economical costs.

Cont
Case management
Despite its complexity in pathogenesis and manifestation
the management is relatively simple and inexpensive
No specific treatment rely on fluid management.
Appropriately and timely implemented, it could save the
lives of patients
Current situation : the most effective way to prevent
dengue transmission is to combat disease-carrying
mosquitoes
The development of vaccines and drugs is challenging but
potential to change this.
1997 2009 2011
Dengue guidelines
1997 2009 2011
T
i
t
l
e

Guideline for treatment
of DF and DHF in small
hospitals WHO Searo
1999
Dengue Guidelines for
diagnosis, treatment,
prevention and control
WHO TDR 2009
Comprehensive guideline
for prevention and
control of Dengue and
DHF WHO Searo 2011
P
a
g
e
s

33 160 212
C
o
n
t
e
n
t

Clinical manifestation,
diagnosis, case management
Chapters : (6)
Epidemiology and burden of
disease, clinical
management, vector
management, lab diagnostic
tests, surveillance and
emergency response, new
avenues
Chapters : (15)
Epidemiology, disease
burden,clinical
manifestation and diagnosis,
lab diagnosis, management,
surveillance, vector, vector
management, IVM, Combi,
PHC approach, case
investigation, monitoring,
strategic plan (bi-regional
plan)
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 II
DHF grade III Severe dengue
( severe plasma leakage,
severe hemorrhage,
severe organ
involvement)
DHF grade III
DHF grade IV DHF grade IV
* Expanded dengue
syndrome
Adult management Adult management
Probable an acute febrile illness with two or more of the
following manifestations:
Headache
Retro-orbital pain
Myalgia
Arthralgia
Rash
Haemorrhagic manifestations
Leukopenia;
and
Supportive serology (a reciprocal HI antibody titre 1280, a
comparable IgG ELISA titre or a positive IgM antibody test on a
late acute or convalescent-phase serum specimen );
or
Occurence at the same location and time as other confirmed
ases of dengue fever.

Confirmed a case confirmed by laboratory criteria
Reportable any probable or confirmed case should be reported






Grade Sign and Symptomps Laboratory
DF DHF without plasma leakage
DHF I Fever with non-specific constitutional
symptoms; the only hemorrhagic
manifestation is a positive tourniquet test
&/or easy bruising
evidence of plasma leakage
Thrombocytopenia
(platelet count
100,000/L)
II DHF grade I plus spontaneous bleeding
III Circulatory failure manifested by a rapid, weak
pulse, narrowing of pulse pressure, or
hypotension, cold & clammy skin, restlessness
IV Profound shock with undetectable blood
pressure
WHO Dengue Classification 1997

DF DHF
1. Fever 2-7 days
+ +
2. Bleeding tendency
Positive tourniquet test or
Spontaneous bleeding
+/- +
3. Thrombocytopaenia
100,000/mm
+/- +
4. Plasma leakage
Pleural effusion /ascites
/hypoproteinaemia
20% increase in HCT from baseline
- +
Lancet Inf Dis 2006; 6: 297-302
Lancet 2006; 368: 170-173
The stages of the dengue case classification development
Numerous publications describing the
difficulties using DF/DHF/DSS
A systematic review of the issue
Bandyopadhyay S et al., TMIH 2006, Volume 11 no 8 pp 12381255
The DenCo study
(dengue and control)
Two expert consensus meetings
La Habana 2007 and Kuala Lumpur 2007
A global expert consensus meeting
Geneva 2008
Dengue guidelines validation studies
(forthcoming publication)
TDR report (summary recommendations)
(planned for 03/2010)
- numerous reports of the difficulties using
DF/DHF/DSS: epidemiology has changed

- confirmation of the above

- clear evidence for classifying in dengue
and severe dengue

- large differences of DHF case definitions
between countries; application difficult
- dengue is just one disease entity with
different clinical presentations and often with
unpredictable clinical evolution and outcome
-further design: 1) dengue with or without
warning signs and 2) severe dengue
- analysis showing user-friendliness
and acceptance of dengue/severe dengue

- final analysis and recommendations

- overall summary report/recommendations



DF/DHF/DSS application study
Santamaria R et al. , accepted at TMIH 2009, September


1
9
9
0
s
-
2
0
0
9
A global expert meeting reviewing
"chain of evidence (planned for 03/2010)
Dengue case classification by severity
Without
with
warning signs
1.Severe plasma leakage
2.Severe haemorrhage
3.Severe organ impairment
Severe dengue Dengue warning signs
Probable dengue
Live in/travel to dengue
endemic area. Fever and 2
of the following criteria:
Nausea, vomiting
Rash
Aches and pains
Tourniquet test positive
Leucopenia
Any warning sign
Laboratory confirmed
dengue
(important when no sign of plasma
leakage)
Warning signs*
Abdominal pain or
tenderness
Persistent vomiting
Clinical fluid accumulation
Mucosal bleed
Lethargy; restlessness
Liver enlargement >2cm
Laboratory: Increase in HCT
concurrent with rapid
decrease in platelet count
* Requiring strict observation
and medical intervention
1. Severe plasma leakage
leading to:
Shock (DSS)
Fluid accumulation with
respiratory distress
2. Severe bleeding
as evaluated by clinician
3. Severe organ involvement
Liver: AST or ALT>=1000
CNS: Impaired
consciousness
Heart and other organs
Criteria for dengue warning signs
Criteria for severe dengue
W
H
O
/
T
D
R

2
0
0
9
The full model of the revised WHO dengue case classification

Dengue without warning signs
Probable dengue
live in /travel to dengue endemic area.
Fever and 2 of the following criteria:
Nausea, vomiting
Rash
Aches and pains
Tourniquet test positive
Leucopenia
Any warning sign
Dengue with warning signs
Warning signs
Abdominal pain or tenderness
Persistent vomiting
Clinical fluid accumulation
Mucosal bleed
Lethargy, restlessness
Liver enlargement >2 cm
Increase in HCT concurrent with rapid decrease in
platelet count
back
Severe Dengue
Severe plasma leakage leading to:
Shock (DSS)
Fluid accumulation with respiratory distress
Severe bleeding as evaluated by clinician
Severe organ involvement
Liver: AST or ALT 1000
CNS: Impaired consciousness
Heart and other organs
Evidence from 2009 Dengue Guideline
Multicentre prospective study on dengue
classification in four South-east Asian and
three Latin American countries
(Neal Alexander et.al, 2011)


Evaluation of the Traditional and Revised WHO
Classifications of Dengue Disease Severity
Sensitivity and specificity to capture Category III
care for DHF/DSS were 39.0% and 75.5%,
respectively; sensitivity and specificity for SD
were 92.1% and 78.5%, respectively
(Federico Narvaez et.al, 2011)
Usefulness and applicability of the revised dengue case
classification by disease: multicentre study in 18 countries
(Judit Barniol et.al, 2010)
DengueHow Best to Classify It
(Anon Srikiatkhachorn et.al, 2011)
Evidence from 2009 Dengue Guideline
Application of revised dengue classification criteria as a
severity marker of dengue viral infection in Indonesia
Binary logistic regression showed the revised dengue
classification system (p = 0.000, Wald:22.446) was better
in detecting severe dengue infections than the WHO
classification system (p = 0.175, Wald:6.339)
(Basuki PS et.al, 2010)
Dengue virus infection
Asymptomatic Symptomatic
Undefferentiated
fever
(viral syndrome)
Dengue Fever
(DF)
Dengue Haemorrhagic
Fever (DHF)
(with plasma leakage)
Without
haemorrhage
With unusual
haemorrhage
DHF non
shock
DHF with shock
Dengue Shock
Syndrome (DSS)
Expanded Dengue
syndrome/isolated
organophaty (unusual
manifestation)
2011
DF/
DHF
Grade Signs and Symptoms Laboratory
DF
Fever with two of the following:
Headache
Retro-orbital pain
Myalgia
Athralgia/bone pain
Rash
Haemorrhagic manifestations
No evidence of plasma leakage
Leucopenia (WBC <5000 cells/mm3)
Thrombocytopenia <150.000
cells/mm3)
Rising Hct (5-10%)
No evidence of plasma loss
DHF I
Fever and haemorrhagic manifestation
(positive tourniquet test) and evidence
of plasma leakage
Thrombocytopenia <100.000 cells/mm3
Hct rise >20%
DHF II
As in Grade I plus spontaneous bleeding Thrombocytopenia <100.000 cells/mm3
Hct rise >20%
*DHF III
As in Grade I or II plus circulatory
failure
Thrombocytopenia <100.000 cells/mm3
Hct rise >20%
*DHF IV
As in Grade III plus profound shock with
undetectable bloodpressure and pulse
Thrombocytopenia <100.000 cells/mm3
Hct rise >20%
*DHF III and IV are DSS
WHO classification of Dengue infections and grading of severity of DHF (2011)
Admission Criteria
1997 2009 2011
Signs of significant
dehydration (>10%
normal body weight)
- Any warning sign
- Coexisting conditions:
infancy, pregnancy, old
age, obesity, diabetes
mellitus, renal failure,
hypertension, chronic
hemolytic disease etc.
- Social circumstances:
living alone, living far
from health facility,
without reliable means of
transport.
- Shock: Resuscitation
and admission.
-Hypoglycemic patients
without leucopenia
and/or thrombocytopenia
-Those with warning
signs.
- High-risk patients with
leucopenia and
thrombocytopenia
1997 2009 2011
No Yes Yes
Home care card
Admission criteria
Warning signs 2009 & 2011
2009 2011
Abdominal pain + severe + or tenderness
Persistent vomiting, + + , lack of water intake
Clinical fluid accumulaton + -
Bleeding Mucosal
bleed
Epistaxis, black stool, haematemesis, excessive
menstrual bleeding, dark-coloured
urine (haemoglobinuria) or haematuria.
Lethargy and/or restlessness + + , sudden behavioural changes
Liver enlargement > 2 cm + -
Increase in Hct concurrent with rapid
decrease in platelet count
+ -
No clinical improvement or
worsening of the situation
- +
Giddiness - +
Pale,cold, a clammy hands and feet - +
Less/no urine output for 46 hours - +

.

Fluid management
1997 2009 2011
DHF grade I-II Dengue with warning
signs
DHF grade I-II
6-7 ml/kg/hour 5
ml/kg/hour 3
ml/kg/hour stop after
24-48 hours
isotonic solutions such as
0.9% saline, Ringers
lactate, or Hartmanns
solution. Start with 57
ml/kg/hour for 12 hours,
then reduce to 35
ml/kg/hr for 24 hours,
and then reduce to 23
ml/kg/hr or less
according to the clinical
response
maintenance (for one
day) + 5% deficit (oral
and IV fluid together), to
be administered over 48
hours
Cont
1997 2009 2011
DSS Severe Dengue-
compensated shock
DHF grade III
10-20 ml/kgBB bolus,
repeat if necessary
algorithm
isotonic crystalloid
solutions at 510
ml/kg/hour over one
hour. reassess
10 ml/kg in children or
300500 ml in adults over
one hour or by bolus, if
necessary
Further, fluid
administration should
follow the graph
Cont
2009 2011
Severe Dengue hypotensive shock DHF grade IV
Start with crystalloid or colloid
solution (if available) at 20 ml/kg as
a bolus given over 15 minutes to
bring the patient out of shock as
quickly as possible.
10 ml/kg of bolus fluid (10-15 min)

When the blood pressure is restored,
further intravenous fluid may be given
as in Grade 3.

If shock is not reversible after the first
10 ml/kg, a repeat bolus of 10 ml/kg and
laboratory results should be pursued
and corrected as soon as possible.
Transfusion in Severe Bleeding
2009 2011
Give 510ml/kg of fresh-PRC or 10
20ml/kg of FWB at an appropriate rate
and observe the clinical response.
10 ml/kg of FWB or 5 ml/kg of freshly
PRC

Reassess, repeat if necessary
Discharge criteria
Criteria 1997 2009 2011
Absence of fever 24 hours
without the
use of anti-
fever therapy
48 hours 24 hours
without the
use of anti-
fever therapy
Clinical
improvement
+ + (general well-being, appetite,
hemodynamic status, urine
output, no respiratory distress)
+
Return of appetite + - +
Good urine output + - +
Stable hematocrit + + (without intravenous fluids) +
Elapse from shock
recovery
At least 2 days - At least 2-3
days
No respiratory
distress
+

- +
Platelet count > 50,000/L Increasing trend > 50,000/L
National guideline
Ditjen PPM PLP 2004 Ditjen Yanmed , IDAI, PAPDI,
IDSAI, PERDICI, PDS
PATKLIN, PPNI - 2005
Summary
Dengue disease burden is significantly increased
across continents
Case management is relatively simple and inexpensive
could saves the lives of patients
Revised guidelines ( 2009 and 2011) are available
Proposed National guideline ?


Changes might be slowly, difficult but inevitable
Signs of Significant Dehydration
- Tachychardia
- Increased capillary refill time (>2 second)
- Cool, mottled or pale skin
- Diminished peripheral pulses
- Changes in mental status
- Oliguria
- Sudden rise in haematocrit or continously elevated
haematocrit despite administration of fluids
- Narrowing of pulse pressure (< 20 mmHg)
- Hypotension (a late finding representing uncorrected
shock)

back
Warning signs (2011)
No clinical improvement or worsening of the situation just
before or during the
Transition to afebrile phase or as the disease progresses.
Persistent vomiting, not drinking.
Severe abdominal pain.
Lethargy and/or restlessness, sudden behavioural changes.
Bleeding: Epistaxis, black stool, haematemesis, excessive
menstrual bleeding, darkcoloured urine (haemoglobinuria)
or haematuria.
Giddiness.
Pale, cold and clammy hands and feet.
Less/no urine output for 46 hours.
back
Admission criteria 2009 p 47
back
Warning signs Any of the warning signs (Textbox C)
Signs & symptoms
related to hypotension
(possible plasma
leakage)
Dehydrated patient, unable to tolerate oral fluids
Giddiness or postural hypotension
Profuse perspiration, fainting, prostration during deferescence
Hypotension or cold extremities
Bleeding Spontaneous bleeding, independent of the platelet count
Organ impairment Renal, hepatic neurological or cardiac
- enlarged, tender lier, although not yet in shock
- Chest pain or respiratory distress, cyanosis
Findings through
further investigation
Rising hematocrit
Pleural effusion, ascites or asymptomatic gall bladder thickening
Co-existing conditions Pregnancy
Co-morbid conditions, such as diabetes mellitus, hypertension
peptic ulcer, hamolitic anemias and others
Overweight or obese (rapid venous access difficult in emergency)
Infancy or old age
Social circumstances Living alone, living far from healt facility, without reliable means
of transport
High-risk patients (2011)
infants and the elderly,
obesity,
pregnant women,
peptic ulcer disease,
women who have menstruation or abnormal vaginal bleeding,
haemolytic diseases such as glucose-6-phosphatase dehydrogenase (G-
6PD) deficiency,
thalassemia and other haemoglobinopathies,
congenital heart disease,
chronic diseases such as diabetes mellitus, hypertension, asthma,
ischaemic heart disease,
chronic renal failure, liver cirrhosis,
patients on steroid or NSAID treatment, and
others
back
Rate of Infusion in DSS (2011)

back
1997
back