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Clinical Aspect of Dengue
in Pediatric Case
International Symposium: Integrated Research and Action on Dengue
Yogyakarta, 29-30 November 2013
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 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)
Re
du
ce d
en
gu
e m
orta
lity b
y a
t lea
st 50
% b
y 2
02
0
CF
R d
en
gu
e ca
ses, In
do
ne
sia 1
96
8-2
01
2
20
25
30
35
40
45
CRF(%)
Ba
selin
e o
f CF
R in
ye
ar 2
01
0 =
0.9
3%
0 5
10
15
20
196819691970197119721973197419751976197719781979198019811982198319841985198619871988198919901991199219931994199519961997199819992000200120022003200420052006200720082009201020112012
CRF(%)
Ye
ar
CF
R
So
urce
: DG
of C
DC
& E
H, In
do
ne
sian
MO
H, 2
01
2
DHF Cases in Outbreak 2004in six hospitals in Jakarta, Indonesia
Re assessment byWHO dengue criteria diagnosis 1997
DF DHF non shock
DHF w/ shock
Total
DF 232 9 0 241
Dia
gnos
is
in s
ourc
e do
cum
ent
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%.
Dia
gnos
is
in s
ourc
e do
cum
ent
Citraresmi E, Hadinegoro SR. Sari Ped 2007;8:8-14.
• DF and DHF are different disease entity• DF
• no plasma leakage,• no hypovolemic shock
Important to differentiate between DF and DHF
• 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)
After time of fever
defervescence(fever ceased)
Dengue Fever
Time of fever
defervescence
(fever ceased)
DF vs DHF
Dengue Fever
• good clinical conditions,
• good appetite
Dengue Hemorrhagic Fever• worst clinical conditions,
• followed by hypovolemic
shock
Red
uces d
engu
e mo
rbid
ity b
y at least 2
5%
by
20
20
50
60
70
80
90
IR(cases/100000personyears)
Ba
selin
e o
f IR in
ye
ar 2
01
0 =
27
.09
%S
ou
rce: D
G o
f CD
C &
EH
, Ind
on
esia
n M
OH
, 20
12
0
10
20
30
40
196819691970197119721973197419751976197719781979198019811982198319841985198619871988198919901991199219931994199519961997199819992000200120022003200420052006200720082009201020112012
IR(cases/100000personyears)
Ye
ar
IR
De
ng
ue
case
incid
en
ce is still h
igh
Incidence Dengue Cases Moved to
Older Age Group
40
50
60
70
DH
F in
cid
ence
(%
)
• Since year of
2000, incidence in
young adult increased
• Since 2008, 50-60%
incidence dengue
0
10
20
30
DH
F in
cid
ence
(%
)
Year
<1 year 1-4 years 5-14 years >15 years
incidence dengue
cases was adult
• Children have higher
mortality compared to
adult cases
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 • 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 • 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
Close monitor at the time of
fever defervescence
Fever shows the days of
illness
Every course of illness has
potential clinical issues
Course of dengue illness
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 guidelinesGuideline 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. • Classification on severe dengue.
• Case management depend on disease severity
WHO-SEARO
2011• Use warning signs for early shock detection.
• 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 1966
WHO
WHO criteria diagnosis guidelineDengue mortality in Indonesia 1968-2009
1975WHO1986 WHO
1997 WHO-TDR 2009
The dengue case mortality reduced significantly within 40 years
WHO-SEARO2011
20
13
Classification of dengue severity
WHO 1997 vs 2009
Dept of Child Health
Cipto Mangunkusumo hospital,
Jakarta 2010-2011
Suspected dengue cases
(N=194)N (%)
Laboratory-confirmed 152 (78.4)
Age (year) 1 to 4 20 (13.2)
5 to 9 52 (34.2)
> 10 76 (50)
34
(22.4 %)
59
(38.8 %)
59
(38.8 %)
6
(3.9 %)
90
(59.2 %)
56
(36.8 %)
0
10
20
30
40
50
60
70
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)
> 10 76 (50)
Sex Male 84 (55.3)
Secondary infection 130 (85.5)
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 systemo Admission/ observe
o Send home with good follow up
• Monitoring
Proper IV fluid management
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
Patient with fever 2-7
days, to differentiate
whose patient has
warning signs
TRIAGE
HospitalizedOutpatient
care
1. Need direct hospitalization
2. Need closed monitor
3. Treat as outpatient
Triage System
Actions:
treat, monitor &
observed
Emergency + warning signs
Treat properly
One Day Care (24 hours) for
closed monitor
Discharge:
observation
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
at a-febrile phase
• Refused oral intake
• Recurrent vomiting
• Severe abdominal pain
• Bleeding tendency:
epistaxis, blackstool,
hematemesis, menorrh
agia haemoglobinuria• Severe abdominal pain
• Lethargy, change of
behavior
• Pale, cold hand and foot
agia haemoglobinuria
or hematuria
• Giddines
• Decreased diuresis
within 4-6 hours
Early shock detection
Suspected Dengue Infection
Warning signs
• No clinical improvement at afebrile phase
• Refused oral intake
• Recurrent vomiting
• Severe abdominal pain
• Lethargy, change of behavior
• Bleeding tendency: epistaxis, black stool, hematemesis,
menorrhagia, black color urine (haemoglobinuria) or
hematuria
• Giddines
• Pale, cold extrimities
• Decreased diuresis within 4-6 hours
• Headache, retroorbital
pain, myalgia, arthralgia
• Leucopenia (≤4000/mL)
• Dengue case in the neighborhood
• Fever <7 days
• Skin rash
• Bleeding manifestations
(tourniquet test/spontaneous)
DHF DHF with
shock
Expanded Dengue
Syndrome
Warning
signsClosed
follow-up• Organ involvement
• Complication
• Co-morbidity
• Co-infection
• Decreased diuresis within 4-6 hours
YesNo
• Co-morbidity
• Social indicationNo Yes Hospitalization
Send home
managed at
out patient
clinic
Clinical & lab follow-up
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 paracetamol10mg/kg/dose every 6 hours, avoid aspirin, NSAID & ibuprofenibuprofen
• 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
Compensated
• Tachycardia
• Tachypnea
• Pulse rate <20 mmHg
• Capillary refill time > 2
• Tachycardia
• Hypotensive
• Narrow of pulse rate
Hyperpnea or Kussmaul
Decompensated
Dengue Shock Syndrome
• Capillary refill time > 2
seconds
• Cold skin
• Decreased urine output
• Restless
• Hyperpnea or Kussmaul
• Cyanosis
• Cold and clamp skin
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%)
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
Shock recoveredYes
IVFD 10ml/kg.BW, 1-2 hours
No
Check Ht, blood gas, blood glucose,
calcium, bleeding (ABCS)
Correction soon for acidosis,
Stabile,
Decreased IVFD gradually
7, 5, 3 , and 1,5
ml/kg.BW/hour
Stop IVFD
maximal 48 hours
after shock recover
Correction soon for acidosis,
hypoglycemia, hypocalcaemia
Ht decreasedHt increased
2nd bolus for crystalloid
Or colloid 10-20ml/kg.BW
within 10-20 minutes
Bleeding
Colloid 10-20ml/kg.BB
within 10-20menit, if shock
persist suggested blood
transfusion
Blood transfusion
Unclear
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
Shock recoveredYes
IVFD 10ml/kg.BW, 1-2 hours
No
Evaluated Ht, blood gas, blood glucose,
calcium, bleeding (ABCS)
Correction soon for acidosis,
Stabile,
Decreased IVFD gradually
7, 5, 3 , and 1,5
ml/kg.BW/hour
Stop IVFD
maximal 48 hours
after shock recover
Correction soon for acidosis,
hypoglycemia, hypocalcaemia
Ht decreasedHt increased
2nd bolus for crystalloid
Or colloid 10-20ml/kg.BW
within 10-20 minutes
Bleeding
Colloid 10-20ml/kg.BB
within 10-20menit, if shock
persist suggested blood
transfusion
Blood transfusion
Unclear
High Risk Group
• Infants, elderly
• Obese patients
• Prolonged shock
• Significant bleeding• Significant bleeding
• Encephalopathy
• Underlying diseases
• Pregnancy
Shock
DengueYellow fever
CCHFWest Nile feverRift valley fever
Hemorrhage
DengueYellow feverChikungunya
CCHFRift valley fever
Clinical syndrome associated with Flavivirus diseases
Yellow feverCongo-crimean hemorrhagic
fever (CCHF)West Nile fever
Dengue
JETick borne encephalitis
Venezuelan encephalitisWestern equine encephalitisEastern equine encephalitis
Fever
Zinsser Microbiology,1992.p.1020
Hepatitis Encephalitis
Yellow fever
Congo-crimean hemorrhagicfever (CCHF)
West Nile fever
Dengue
Expanded dengue syndrome(unusual or atypical manifestations)
• Unusual manifestations• uncommon
• neurological (encephalopathy): convulsions, changes in consciousness, transient paresis changes in consciousness, transient paresis
• hepatic, renal, heart, other isolated organ involvement
• Complication of severe profound shock, • co-morbidity
• underlying conditions: DM, asthma, etc.
• Outbreak:88.3 (71.2 – 116.5) minutes
• Non-outbreak: 48 (max 74,6) minutes
Time of shock recovered
• Inotropic agents: 43 � 18 patients of prolonged or recurrent shockOver
Dengue outbreak in Indonesia, 2004Six referral hospitals in Jakarta
of prolonged or recurrent shock
• Antibiotic used 895 (59.9%); antiviral 78 (5.2%) �useless
Over treatment
• Outbreak 1998 : 6.1%
• Outbreak 2004 : DHF non-shock 0.2%; shock syndrome 8.4%
Increased CFR
Conclusion
• Established “true burden of disease” is
essential in dengue reported cases
• Calculated mortality rate and morbidity of
dengue infectiondengue 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 • 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)