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)