International Symposium: Integrated Research and Action on Dengue

Yogyakarta, 29-30 November 2013

Clinical Aspect of Dengue

in Pediatric Case
Sri Rezeki S Hadinegoro

Dept of Child Health Faculty of Medicine, University of

Indonesia, Dr Cipto Mangunkusumo Hospital, Jakarta
Outline
• Global strategy for dengue prevention and
control
• Difficulty in reduced morbidity
• Issues in dengue diagnosis
• Steps for dengue management
• Indonesian experience
Global strategy for dengue prevention and
control, 2012-2020
Goal : To reduce the burden of dengue*

• To reduce dengue mortality by at least 50% by 2020

• To reduce dengue morbidity by at least 25% by
2020
• To estimate the true burden of the disease by 2015

* The year of 2010 used as the baseline

(WHO, Geneva 2012)

 Reduce dengue mortality by at least 50% by 2020
CFR dengue cases, Indonesia 1968-2012
Baseline of CFR in year 2010 = 0.93%
45
40
35
30
CRF(%)

25
20
CFR
15
10
5
0 1968
1969
1970
1971
1972
1973
1974
1975
1976
1977
1978
1979
1980
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
2008
2009
2010
2011
2012
Year
Source: DG of CDC & EH, Indonesian MOH, 2012
 DHF Cases in Outbreak 2004
in six hospitals in Jakarta, Indonesia
Re assessment by
WHO dengue criteria diagnosis 1997
in source document

DF DHF non DHF w/ Total

shock shock
Diagnosis

DF 232 9 0 241
DHF non shock 850 201 0 1051
DHF w/ shock 2 0 200 202

Total 1106 189 200 1494

• Number of DF and DHF w/o shock cases in source document were 241 and
1051, meanwhile in reassessment were 1106 and 189 respectively.
• Reassessment for CFR 1,5% 4,9%
• National data 2004: 1,1%.
Citraresmi E, Hadinegoro SR. Sari Ped 2007;8:8-14.
 Important
to differentiate between DF and DHF
• DF and DHF are different disease entity
• DF
• no plasma leakage,
• no hypovolemic shock
• mild bleeding
• good outcome
• Key is monitor at time of early shock phase or
when fever ceased (day 3-5 of illness)
 DF vs DHF
Time of fever After time of fever
defervescence
defervescence
(fever ceased)
(fever ceased)

Dengue Fever
• good clinical conditions,
• good appetite

Dengue Hemorrhagic Fever

• worst clinical conditions,
• followed by hypovolemic
shock
 IR(cases/100000personyears)

Reduces dengue morbidity by at least 25% by 2020

10
20
30
40
50
60
70
80
90
Source: DG of CDC & EH, Indonesian MOH, 2012
0
1968
1969
1970
1971
1972
1973
1974
1975
1976
1977
1978
1979
Dengue case incidence is still high

1980
1981
1982
1983
1984
1985
1986
1987
1988
1989
Year

1990

Baseline of IR in year 2010 = 27.09%

1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
2008
2009
2010
2011
2012
IR
 Incidence Dengue Cases Moved to
Older Age Group
70
• Since year of
60
2000, incidence in
50 young adult increased
• Since 2008, 50-60%
DHF incidence (%)

40

incidence dengue
30
cases was adult
20
• Children have higher
10 mortality compared to
adult cases
0

Year

<1 year 1-4 years 5-14 years >15 years

 Difficulties to reduce dengue
morbidity
• All serotype of dengue virus are circulated in
Indonesia
• Difficulty to sustain vector control activities
• Decrease the community participation in
support the vector control program
• Increased urbanization
• Crowded public housing in most cities
• Future time: dengue vaccine
 Issues in dengue diagnosis
• How to differentiate between DF with DHF
• When use the “warning signs”
• Monitor at the time of fever defervescence is essential for
early detection of dengue shock
• Unusual manifestation and organ involvement were
classified as expanded dengue syndrome
• Special attention to high risk group
• International Code of Diseases (ICD) X
• A90 for dengue fever,
• A91 for dengue hemorrhagic fever
Course of dengue illness
Fever shows the days of
illness

Close monitor at the time of

fever defervescence

Every course of illness has

potential clinical issues

Thrombocytopenia is a good
prognostic value, Hct for
guidance the volume
replacement

Diagnostic laboratory should

be performed in the right time

Case management depends on

phase of dengue illness
 WHO dengue guidelines
Guideline Issues
WHO 1997 Basic knowledge on epidemiology, pathogenesis,
diagnosis and case management, dengue
outbreak, and vector control

WHO-TDR 2009 • Warning signs to catch more dengue cases

• Classification on severe dengue.
• Case management depend on disease severity

WHO-SEARO • Use warning signs for early shock detection.

2011 • Classification of expanded dengue syndrome
for unusual manifestation, organ involvement,
co-morbidity.
• Lab investigation for A-B-C-S
WHO-SEARO
dengue case classification 2011

Source: Comprehensive guideline for prevention and control of dengue and dengue haemorrhagic fever.
Revised and expanded edition. Regional office for South-East Asia, New Delhi, India 2011.
 WHO criteria diagnosis guideline
Dengue mortality in Indonesia 1968-2009

WHO
1966

WHO
1975
WHO
1986 WHO
WHO-TDR WHO-SEARO
1997
2009 2011

2013
The dengue case mortality reduced significantly within 40 years
 Classification of dengue severity
WHO 1997 vs 2009

Suspected dengue cases

N (%)
Dept of Child Health (N=194)
Laboratory-confirmed 152 (78.4)
Cipto Mangunkusumo hospital, Age (year) 1 to 4 20 (13.2)
Jakarta 2010-2011 5 to 9 52 (34.2)
> 10 76 (50)
70 90 Sex Male 84 (55.3)
60
(59.2 %) Secondary infection 130 (85.5)

50 59 59 56
(38.8 %) (38.8 %) (36.8 %)
40
34
30
(22.4 %)
20
6
10 (3.9 %)
0
Dengue Fever ( DF )/Without Warning Signs DHF 1 and 2 ( DHF )/With Warning Signs DHF 3 and 4 ( DSS )/Severe Dengue

Traditional Revised Karyanti RM, 2012 (in progress publication)

Need harmonization between
guideline 2009 and 2011
• Warning signs (2009)
• is useful for early detection of dengue shock
• use after dengue infection is suggested (2011)
• Severe dengue (2009)
• is including unusual manifestations, organ
involvement, dengue with complication, co-
morbidity, co-infection called expanded dengue
syndrome (2011)
Steps for dengue management
• Early clinical diagnosis
• OPD with Triage system
o Admission/ observe
o Send home with good follow up
• Monitoring
• Proper IV fluid management
• Management of complications
• Early diagnosis of expanded dengue syndrome
• Discharge

Siripen Kalayanarooj: Informal Expert Consultation on Case Management of Dengue.

Colombo, Sri Lanka 12-14 August 2013
Triage System
Patient with fever 2-7
days, to differentiate
whose patient has TRIAGE
warning signs

1. Need direct hospitalization

Outpatient
2. Need closed monitor Hospitalized care
3. Treat as outpatient

Actions: Emergency + One Day Care Discharge:

treat, monitor & warning signs (24 hours) for observation
observed Treat properly closed monitor during fever

• By use the triage system (one day care=ODC),

reduced 76% hospitalization of suspected dengue cases
• ODC is very useful in outbreak situation
(Sri Rezeki Hadinegoro, 1998)
 “Warning Signs”
• No clinical improvement • Bleeding tendency:
at a-febrile phase epistaxis, blackstool,
• Refused oral intake
• Recurrent vomiting hematemesis, menorrh
agia haemoglobinuria
• Severe abdominal pain or hematuria
• Lethargy, change of • Giddines
behavior
• Decreased diuresis
• Pale, cold hand and foot within 4-6 hours

Early shock detection

 Suspected Dengue Infection
• Fever <7 days
• Skin rash
• Bleeding manifestations
(tourniquet test/spontaneous)
• Headache, retroorbital
pain, myalgia, arthralgia
• Leucopenia (≤4000/mL)
• Dengue case in the neighborhood

Warning signs
• No clinical improvement at afebrile phase • Bleeding tendency: epistaxis, black stool, hematemesis,
• Refused oral intake menorrhagia, black color urine (haemoglobinuria) or
• Recurrent vomiting hematuria
• Severe abdominal pain • Giddines
• Lethargy, change of behavior • Pale, cold extrimities
• Decreased diuresis within 4-6 hours
No Yes

No • Co-morbidity Yes Hospitalization Clinical & lab follow-up

• Social indication

Send home Warning DHF DHF with Expanded Dengue

managed at Closed signs shock Syndrome
out patient follow-up
• Organ involvement
clinic • Complication
• Co-morbidity
• Co-infection
Home care advice for patients
• Take adequate bed rest
• Adequate intake of fluids: milk, fruit juice, isotonic electrolyte
solution, ORS.
• Keep body temperature below 390C, give paracetamol
10mg/kg/dose every 6 hours, avoid aspirin, NSAID &
ibuprofen

• Take to hospital soon

Worst clinical manifestation at a-febrile phase
Severe abdominal pain
Recurrent vomiting,
Cold hand and foot and clamp
Lethargy
Bleeding
Dyspnea
Convulsion
Rate of infusion in non-shock case
 Dengue Shock Syndrome
Compensated Decompensated
• Tachycardia • Tachycardia
• Tachypnea • Hypotensive
• Pulse rate <20 mmHg • Narrow of pulse rate
• Capillary refill time > 2 • Hyperpnea or Kussmaul
seconds • Cyanosis
• Cold skin • Cold and clamp skin
• Decreased urine output
• Restless

Profound shock
un-palpable pulse, un-detectable blood pressure
Unusual manifestation, dengue with complication, and
several organ involvement
Six hospitals in Jakarta, dengue outbreak 2004

Dengue with complications 205 (46.7%) among 1494 cases

• Recurrent shock 34 (2.7%)
• Prolonged shock 16 (1.3%)
• Massive hemorrhage 12 (1.0%)
• Fluid overload 21 (1.7%)
• Encephalopathy 16 (1.3%)
• DIC 3 (0.2%)
• Others 6 (0.5%)

Ref. Citraresmi E, Hadinegoro SR. Sari Ped 2007;8:8-14.

Laboratory investigation A-B-C-S
For patients who present with profound shock
or have complications, and cases with no clinical
improvement in spite of adequate
volume replacement

• A cidosis : blood gas

• B leeding : haematocrit
• C alcium : electrolyte, Ca++
• S ugar : blood sugar
 Compensated Dengue Shock Syndrome
• Give oxygen 2-4L/minute
• Check hematocrit
•Crystalloid RL/RA 10-20ml/kg.BW within 10-20 minutes

Yes Shock recovered No

IVFD 10ml/kg.BW, 1-2 hours Check Ht, blood gas, blood glucose,
calcium, bleeding (ABCS)
Correction soon for acidosis,
Stabile, hypoglycemia, hypocalcaemia
Decreased IVFD gradually
7, 5, 3 , and 1,5 Ht increased Ht decreased
ml/kg.BW/hour
2nd bolus for crystalloid
Or colloid 10-20ml/kg.BW Bleeding
within 10-20 minutes Unclear
Stop IVFD
maximal 48 hours
after shock recover Colloid 10-20ml/kg.BB
within 10-20menit, if shock
Blood transfusion
persist suggested blood
transfusion
Rate infusion in DSS case
 Decompensated Dengue Shock Syndrome
• Give oxygen 2-4L/minute
• Examine hematocrite, blood gas, blood glucose, calcium, bleeding (ABCS)
• Crystalloid or colloid 10-20ml/kg.BW within 10-20 minutes

Yes Shock recovered No

IVFD 10ml/kg.BW, 1-2 hours Evaluated Ht, blood gas, blood glucose,
calcium, bleeding (ABCS)
Correction soon for acidosis,
Stabile, hypoglycemia, hypocalcaemia
Decreased IVFD gradually
7, 5, 3 , and 1,5 Ht increased Ht decreased
ml/kg.BW/hour
2nd bolus for crystalloid
Or colloid 10-20ml/kg.BW Bleeding
within 10-20 minutes Unclear
Stop IVFD
maximal 48 hours
after shock recover Colloid 10-20ml/kg.BB
within 10-20menit, if shock
Blood transfusion
persist suggested blood
transfusion
High Risk Group
• Infants, elderly
• Obese patients
• Prolonged shock
• Significant bleeding
• Encephalopathy
• Underlying diseases
• Pregnancy
Clinical syndrome associated with Flavivirus diseases

Shock Hemorrhage
Dengue Dengue
Yellow fever Yellow fever
CCHF Chikungunya
West Nile fever CCHF
Rift valley fever Rift valley fever

Fever
Hepatitis Encephalitis
Yellow
Yellowfever
fever JE
Congo-crimean
Congo-crimeanhemorrhagic
hemorrhagic
fever Tick borne encephalitis
fever(CCHF)
(CCHF)
West Venezuelan encephalitis
WestNile
Nilefever
fever
Dengue Western equine encephalitis
Dengue
Eastern equine encephalitis

Zinsser Microbiology,1992.p.1020
Expanded dengue syndrome
(unusual or atypical manifestations)

• Unusual manifestations
• uncommon
• neurological (encephalopathy): convulsions,
changes in consciousness, transient paresis
• hepatic, renal, heart, other isolated organ
involvement

• Complication of severe profound shock,

• co-morbidity
• underlying conditions: DM, asthma, etc.
Dengue outbreak in Indonesia, 2004
Six referral hospitals in Jakarta
• Outbreak:88.3 (71.2 – 116.5)
Time of shock minutes
recovered • Non-outbreak: 48 (max 74,6)
minutes
• Inotropic agents: 43 18 patients
Over of prolonged or recurrent shock
treatment • Antibiotic used 895 (59.9%); antiviral
78 (5.2%) useless

• Outbreak 1998 : 6.1%

Increased CFR • Outbreak 2004 : DHF non-shock
0.2%; shock syndrome 8.4%
Conclusion
• Established “true burden of disease” is
essential in dengue reported cases
• Calculated mortality rate and morbidity of
dengue infection
• Dengue surveillance: for calculate the
effectiveness of dengue vaccine
Conclusion
• National policy on dengue management in
Indonesia based on WHO 2011 (harmonization
WHO dengue guideline 2009 and 2011)

• Dengue pediatric case management in Indonesia

is sufficient
• Dengue mortality decreased significantly
• Although dengue incidence is still high: need other
preventive intervention (exp. dengue vaccine)