from dr. Ida Savitri, SpA(K)

1. Case 1
 Anak perempuan 7 th dirujuk oleh SpA ke RSS
dengan:
 Demam naik turun 4 hari
 Mual (+), muntah (-), hepatomegali , RL (+)
 Pada hari dirujuk diperiksa lab dengan hasil :
 Hct : 39%, Hb:12,4, JL: 4000/uL, diftel DBN, JT:
150.000/uL. NS1 Dengue (-)
Q: Apa diagnosis kerja/ DD pasien ini?

2. Case 2
 Anak laki2, 4 th datang ke poli/ IRD RSS dengan :
 Demam tinggi naik turun , 2 hari
 Batuk sedikit, tidak pilek
 Mual/muntah (-)
 Pusing
 Menurut ibu ada anak tetangga yang dirawat di RSS 1
minggu yll dengan DB
Q: Apa diagnosis kerja/DD anak ini?

3. Ida Safitri Laksono
Dept of Child Health, Faculty of Medicine UGM
RSUP Dr. Sardjito, Yogyakarta

4. 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

5. 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.

6. 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.

7. 1997 2009 2011

8. Dengue guidelines
1997 2009 2011
Guideline for treatment Dengue – Guidelines for Comprehensive guideline
Title
of DF and DHF in small diagnosis, treatment, for prevention and
hospitals – WHO Searo prevention and control – control of Dengue and
1999 WHO TDR 2009 DHF – WHO Searo 2011
Pages
33 160 212
Clinical manifestation, Chapters : (6) Chapters : (15)
diagnosis, case management Epidemiology and burden of Epidemiology, disease
disease, clinical burden,clinical
management, vector manifestation and diagnosis,
Content
management, lab diagnostic lab diagnosis, management,
tests, surveillance and surveillance, vector, vector
emergency response, new management, IVM, Combi,
avenues PHC approach, case
investigation, monitoring,
strategic plan (bi-regional
plan)

9. Diagnosis Classification
1997 2009 2011
Dengue fever Dengue without Dengue fever
warning signs
DHF grade I Dengue with warning DHF grade I
signs
DHF grade II DHF grade II
DHF grade III Severe dengue DHF grade III
( severe plasma leakage,
severe hemorrhage,
severe organ
involvement)
DHF grade IV DHF grade IV
* Expanded dengue
syndrome
Adult management Adult management

11.  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
cases of dengue fever.
 Confirmed – a case confirmed by laboratory criteria
 Reportable – any probable or confirmed case should be reported

12. Grade Sign and Symptomps Laboratory
DF DHF without plasma leakage
DHF I Fever with non-specific constitutional Thrombocytopenia
symptoms; the only hemorrhagic (platelet count
manifestation is a positive tourniquet test 100,000/ L)
&/or easy bruising
evidence of plasma leakage
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

13. WHO Dengue Classification 1997
DF DHF
1. Fever 2-7 days + +
2. Bleeding tendency


Positive tourniquet test or
Spontaneous bleeding
+/- +
3. Thrombocytopaenia
 ≤ 100,000/mm³
+/- +
4. Plasma leakage
Pleural effusion /ascites
- +

/hypoproteinaemia
 ≥ 20% increase in HCT from baseline

15. Lancet Inf Dis 2006; 6: 297-302
Lancet 2006; 368: 170-173

16. The stages of the dengue case classification development
1
Numerous publications describing the - numerous reports of the difficulties using
9 difficulties using DF/DHF/DSS DF/DHF/DSS: epidemiology has changed
9
A systematic review of the issue - confirmation of the above
0 Bandyopadhyay S et al., TMIH 2006, Volume 11 no 8 pp 1238–1255
´s The DenCo study - clear evidence for classifying in dengue
- (dengue and control) and severe dengue
2 DF/DHF/DSS application study - large differences of DHF case definitions
0 Santamaria R et al. , accepted at TMIH 2009, September between countries; application difficult
- dengue is just one disease entity with
0 Two expert consensus meetings different clinical presentations and often with
La Habana 2007 and Kuala Lumpur 2007
9 unpredictable clinical evolution and outcome
A global expert consensus meeting -further design: 1) dengue with or without
Geneva 2008
warning signs and 2) severe dengue
Dengue guidelines validation studies - analysis showing user-friendliness
(forthcoming publication) and acceptance of dengue/severe dengue
A global expert meeting reviewing - final analysis and recommendations
"chain of evidence“ (planned for 03/2010)
TDR report (summary recommendations) - overall summary report/recommendations
(planned for 03/2010)

17. The full model of the revised WHO dengue case classification
Dengue case classification by severity
Dengue ± warning signs Severe dengue
with 1.Severe plasma leakage
Without warning signs 2.Severe haemorrhage
3.Severe organ impairment
Criteria for dengue ± warning signs Criteria for severe dengue
Probable dengue Warning signs* 1. Severe plasma leakage
Live in/travel to dengue • Abdominal pain or leading to:
endemic area. Fever and 2 tenderness • Shock (DSS)
of the following criteria: • Persistent vomiting • Fluid accumulation with
• Nausea, vomiting • Clinical fluid accumulation respiratory distress
• Rash • Mucosal bleed
• Aches and pains • Lethargy; restlessness 2. Severe bleeding
• Tourniquet test positive • Liver enlargement >2cm as evaluated by clinician
• Leucopenia • Laboratory: Increase in HCT
3. Severe organ involvement
• Any warning sign concurrent with rapid
• Liver: AST or ALT>=1000
Laboratory confirmed decrease in platelet count
WHO/TDR 2009
• CNS: Impaired
dengue
(important when no sign of plasma * Requiring strict observation consciousness
leakage) and medical intervention • Heart and other organs

18. 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)

19. Dengue with warning signs
Warning signs ( appear in the critical period)*
 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

20. 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

21. 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)

22. Evidence from 2009 Dengue Guideline
 Usefulness and applicability of the revised dengue case
classification by disease: multicentre study in 18 countries
(Judit Barniol et.al, 2010)
 Dengue—How Best to Classify It
(Anon Srikiatkhachorn et.al, 2011)
• 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)

24. Dengue virus infection
2011
Asymptomatic Symptomatic
Expanded Dengue
syndrome/isolated
Undefferentiated
organophaty (unusual
fever
manifestation)
(viral syndrome)
Dengue Haemorrhagic
Dengue Fever
Fever (DHF)
(DF)
(with plasma leakage)
Without With unusual DHF non DHF with shock
haemorrhage haemorrhage shock Dengue Shock
Syndrome (DSS)

25. WHO classification of Dengue infections and grading of severity of DHF (2011)
DF/
DHF
Grade Signs and Symptoms Laboratory
DF Fever with two of the following: • Leucopenia (WBC <5000 cells/mm3)
• Headache • Thrombocytopenia <150.000
• Retro-orbital pain cells/mm3)
• Myalgia • Rising Hct (5-10%)
• Athralgia/bone pain • No evidence of plasma loss
• Rash
• Haemorrhagic manifestations
• No evidence of plasma leakage
DHF I Fever and haemorrhagic manifestation Thrombocytopenia <100.000 cells/mm3
(positive tourniquet test) and evidence Hct rise >20%
of plasma leakage
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 Thrombocytopenia <100.000 cells/mm3
failure Hct rise >20%
*DHF IV As in Grade III plus profound shock with Thrombocytopenia <100.000 cells/mm3
undetectable bloodpressure and pulse Hct rise >20%
*DHF III and IV are DSS

26. clinical and laboratory finding from patients
Hospitalized in pediatric ward RS Dr. Sardjito – 2006
DF (%) DHF (%) OR (95%CI)
24 48
Cough-coryza 5 (20) 8 (16) 0.76 (0.22-2.63),p=0.91
Headache 12 (50) 29 (60) 1.52 (0.57-4.00), p=0.55
Abdominal pain 7 (29) 25 (52) 2.64 (0.92-7.5), p=0.11
Nausea-vomiting 10 (41) 18 (37) 0.84 (0.30-2.30), p=0.93
Arthralgia 18 (75) 37 (77) 1.12 (0.35-3.5), p=0.92
Hepatomegaly 12 (50) 40 (83) 5 (1.66-15.00),p<0.01
Bleeding 5 (20) 17 (35) 1.28 (0.48-3.5), p=0.80
-epistaxis 6 (25) 15 (31)
-petekie 0 (0) 14 (29)
-gastrointestinal 0 2 (1)
-hematuria
Leucopenia 15 (62) 40 (83) 3 (0.97-9.21), p=0.09
(AL<4000)
Platelet <100.000 12 (50) 41 (85) 5.85 (1.88-18.17), p=<0.01
Confirmed by serology26

27. Admission criteria
1997 2009 2011
Admission Criteria
Signs of significant - Any warning sign - Shock: Resuscitation
dehydration (>10% - Coexisting conditions: and admission.
normal body weight) infancy, pregnancy, old -Hypoglycemic patients
age, obesity, diabetes without leucopenia
mellitus, renal failure, and/or thrombocytopenia
hypertension, chronic -Those with warning
hemolytic disease etc. signs.
- Social circumstances: - High-risk patients with
living alone, living far leucopenia and
from health facility, thrombocytopenia
without reliable means of
transport.
Home care card
1997 2009 2011
No Yes Yes

28. Warning signs 2009 & 2011
2009 2011
Abdominal pain + severe + or tenderness
Persistent vomiting, + + , lack of water intake
Clinical fluid accumulaton + -
Bleeding Mucosal Epistaxis, black stool, haematemesis, excessive
bleed 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 4–6 hours - +

29. WHO Searo 2011,

31.  The first two clinical criteria, plus thrombocytopenia
and hemoconcentration or a rising Hct are sufficient
to establish a “clinical diagnosis of DHF”. The presence
of liver enlargement in adition to the first two clinical
criteria is suggesting of DHF before the onzet of
plasma leakage. ( WHO Searo 2011, p.24)

34. Fluid management
1997 2009 2011
DHF grade I-II Dengue with warning DHF grade I-II
signs
6-7 ml/kg/hour 5 isotonic solutions such as maintenance (for one
ml/kg/hour 3 0.9% saline, Ringer’s day) + 5% deficit (oral
ml/kg/hour – stop after lactate, or Hartmann’s and IV fluid together), to
24-48 hours solution. Start with 5–7 be administered over 48
ml/kg/hour for 1–2 hours, hours
then reduce to 3–5
ml/kg/hr for 2–4 hours,
and then reduce to 2–3
ml/kg/hr or less
according to the clinical
response

35. Cont…
1997 2009 2011
DSS Severe Dengue- DHF grade III
compensated shock
10-20 ml/kgBB bolus, isotonic crystalloid 10 ml/kg in children or
repeat if necessary solutionsat 5–10 300–500 ml in adults over
algorithm ml/kg/hour over one one hour or by bolus, if
hour. →reassess necessary
Further, fluid
administration should
follow the graph

36. Cont…
2009 2011
Severe Dengue – hypotensive shock DHF grade IV
Start with crystalloid or colloid 10 ml/kg of bolus fluid (10-15 min)
solution (if available) at 20 ml/kg as
a bolus given over 15 minutes to When the blood pressure is restored,
bring the patient out of shock as further intravenous fluid may be given
quickly as possible. 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.

37. Transfusion in Severe Bleeding
2009 2011
Give 5–10ml/kg of fresh-PRC or 10– 10 ml/kg of FWB or 5 ml/kg of freshly
20ml/kg of FWB at an appropriate rate PRC
and observe the clinical response.
Reassess, repeat if necessary

38. Discharge criteria
Criteria 1997 2009 2011
Absence of fever 24 hours 48 hours 24 hours
without the without the
use of anti- use of anti-
fever therapy fever therapy
Clinical + + (general well-being, appetite, +
improvement hemodynamic status, urine
output, no respiratory distress)
Return of appetite + - +
Good urine output + - +
Stable hematocrit + + (without intravenous fluids) +
Elapse from shock At least 2 days - At least 2-3
recovery days
No respiratory + - +
distress
Platelet count > 50,000/ L Increasing trend > 50,000/ L

39. National guideline
Ditjen PPM –PLP 2004 Ditjen Yanmed
, IDAI, PAPDI, IDSAI, PERDIC
I, PDS PATKLIN, PPNI - 2005

40. 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

42. 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

43. 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 4–6 hours.
back

44. Admission criteria 2009 – p 47 back
Warning signs Any of the warning signs (Textbox C)
Signs & symptoms Dehydrated patient, unable to tolerate oral fluids
related to hypotension Giddiness or postural hypotension
(possible plasma Profuse perspiration, fainting, prostration during deferescence
leakage) 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 Rising hematocrit
further investigation 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

45. 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

46. Rate of Infusion in DSS (2011)
back

47. 1997
back