Update on

Management of
Pedatrc
Dengue
Yulia Iriani
Dsease Burden
2.5 bon peope 2/5 of the word's

popua@on are at rsk.
50 mon dengue n fec@ons occur
wordwde
annuay.
500 000 requre hospta za@ on each
year.
90% are chdren < 5 years 2.5% de.

Endemc n >100 countres
Dsease burden
Indonesia:
Ma|or pubc heath
probem.
Leadng cause of
hospta za@ on and
death among
chdren.
Hyperendemcty wth a
4 serotypes crcua@ng n
urban areas.
Spreadng to rura areas.
Causes of DHF Death
Deayed dagnoss:
OPD proonged shock
IPD ud overoad by hypotonc
sou @ ons (5% D/ N/2 at M rate)
Not proper IV ud management
Proonged shock grade
IV
Wthout proper treatment
> 4 hours
o Hepa@c faure prognoss 50%
survva o + Rena faure
prognoss 10% survva o + 3
organ faure prognoss Mrace
> 10 hours Death !!!
Goas of dengue
management
Recognze dengue nfec@on at an
eary stage;
Detect the eary onset of pasma
eakage n
these pa@ents; and
Appropratey manage dehydr a@ on
and
hypovoema.
Reduce mortaty and morbdty
Vrus, Vector and
Transmsson
Ethoogca agent
Aedes aegyp*
Dengue transmsson

Dsease
Pathogeness
Current Hypothess
DENV tropsm
Ces of the mmune system
Organ pathoogy
Endothea ces
Vrus vruence
An@body--Dependent Enhancement

Compement system ac@va@on
Autommunty
Host gene@c factors
Cross--Reac@ve T--Ce response
Vrus vruence
Certan DENV stran responsbe for
more
severe dsease
Prmary nfec @ on wth DENV--1
foowed by
nfec@on wth DENV--2 or DENV--3
Dherent serotype may vary n ther
abty to
nfect dherent ce type
Proposed mode of heteroogous mmunty n secondary dengue vrus nfec @ ons and ts mpc a@ ons for the
pathogeness of dengue hemorrhagc fever. Prmary DENV--2 nfec @ on and sequen @ a DENV--1 and DENV--2 nfec @ ons
are compared for ustr a@ on purposes. The nave T ce repertore (pae coors) key contans some ces wth
hgher avdty for DENV--1 than DENV--2 (red; DENV--1 > DENV--2) and other ces wth hgher avdty for DENV--2 than
DENV--1 (bue; DENV--2 > DENV--1). Durng prmary nfec @ on, T ce popu a@ ons wth hgher avdty for the nfec @ ng
serotype are preferen @ ay expanded and enter the memory poo (shown as darker coors). When DENV--2 nfec @ on
foows DENV--1 nfec @ on, the memory T ce popu a@ ons wth hgher avdty for the earer nfec @ on expand more
rapdy than do nave T ce popu a@ ons. Because these DENV--1specc memory T ces have ower avdty for
DENV--2, vra cearance mechansms are subop @ ma, whereas pronammatory responses contrbute to dsease.
Secondary Infec@on or
Immune
Model of an.body-dependent enhancement of dengue infec.on
An@body (Ab)--dependent enhancement of nfec@on occurs when preexs@ng an@bodes present
n the body from
a prmary (rst) dengue vrus (DENV) nfec@on bnd to an nfec@ng DENV par@ce durng a
subsequent nfec@on
wth a dherent dengue serotype. The an@bodes from the prmary nfec@on cannot neutraze
the vrus. Instead,
the Abvrus compex akaches to receptors caed Fcy receptors (FcyR) on crcua@ng
monocytes. The an@bodes
Enhancement Hypothess
hep the vrus nfect monocytes more emcenty. The outcome s an ncrease n the overa
repca@on of the vrus
and a hgher rsk of severe dengue.
2007 Nature Publishing Group Whtehead, S. S. et al. Prospects for a dengue vrus
vaccne. Nature Reviews
Microbiology5, 518528 (2007). do:10.1038/nrmcro1690 A rghts reserved

Transent
autommunty
Cross--react wth some sef--an@gens
An @ --NS1 Ab cross--reac @ ve wth
endothea ces coud trgger
these ces to express NO and
undergo apoptoss (141), enhance
expresson IL--6, IL--8, ICAM--1, human
thrombocyte cause
thrombocytopena
Cnca Manfesta@on

GUIDELIN
ES
WHO 1997 WHO/TDR 2009 WHO SEARO
2011
Manfesta@on of Dengue Vrus
Infec@on
20
able.
Expanded dengue syndrome
(Unusua or atypca
manfesta@ons of dengue)
Course of Dengue
Iness
Course of Dengue
Iness
Pasma eakage
24 48 hours,
3rd 7th day of ness (usuay: 4
th

5
th
daya)
Tme of fever defervesence
Fever dmnshed
Febre shock/cr @ ca phase
Dengue Fever
Absence of fever, clinical
improvement, return of
appetite
emp
Time of fever defervescence
(Saat suhu reda)
Day of illness
Time of fever defervescence DHF
Clinical worsening, malaise,
agitated, cold and calmy
extremities, fast breathing,
reduced OUP, no appetite
emp
Time of fever defervescence
e!er phase Critical phase "eco!ery phase
#ari sa$it
Cnca Course of DHF
Cnca Case
Den@on
Cnca Case
Den@on
WHO/TDR 2009
WHO/TDR
2009
"Dengue s one dsease en @ ty wth
dherent cnca presen ta@ ons and
osen wth unpredctabe cnca
evou @ on and outcome"
CRITERIA FOR DENGUE
WARNING SIGNS
Probabe
Dengue
ve n /trave to dengue
endemc
area.
Fever and 2 of the foowng
crtera:
Nausea, vom @ ng
Rash
Aches and pans
Tournquet test pos @ ve
Leukopena
Any warnng sgn
Laboratory--conrmed
dengue (mportant when no
sgn of pasma eakage)
Warnng Sgns*
Abdomna pan or
tenderness
Persstent vom @ ng
Cnca ud accumu a@ on
Mucosa beed
Lethargy, restessness
Lver enargment >2 cm
Laboratory: ncrease n
HCT concurrent wth
rapd decrease n pateet
count
*(requrng strct observ a@ on
and
medca
nterven @ on)
Laboratory--conrmed dengue
(mportant when no sgn of pasma eakage)
CRITERIA FOR SEVERE
DENGUE
Severe
pasma
eakageeadng
to:
Shock (DSS)
Fud
accumu a@ on
wth
respratorydstr
ess
Severe
beedng
as evauated
by
cncan
Severe
organ
nvovement

Lver: AST or
ALT
>=1000
CNS:
Impared
conscousness

Heart and
other
organs
Cnca Case
Den@on
WHO 1997
WHO SEARO 2011
Cnca Case Den@on

Probabe Dengue
Fever
Conrmed Dengue
Fever
Fever of 2 to 7 days
dur a@ on, wth two or
more of the foowng:
Headache, retroorbta
pan, myaga,
arthraga, rash,
hemorrhagc
manfes ta@ ons,
eukopena, and
suppor @ ve seroogy or
occurrence at the same
oc a@ on and @me as
other conrmed cases
of
dengue.
Conrmed by aboratory
crtera (so a@ on of the
dengue vrus,
demonstr a@ on of the
dengue vrus
an @ gen, seroogy,
or genomc
sequence).
Cnca Case
Den@on
Probabe Dengue
Fever
Conrmed Dengue Fever
Acute febre ness wth >= 2 of the
foowng:
Headache.
Retro--orbta pan.
Myaga.
Arthraga/bone pan.
Rash.
Haemorrhagc manfesta@ons.
Leucopena (wbc 5000
ces/mm3).
! hrombocytopenia "platelet
count #$5% %%%
cells&mm'(.
! )ising haematocrit "5 * $%+(.
and at east one of foowng:
Suppor @ ve seroogy on snge serum
sampe:
@tre >1280 wth HI test, comparabe
IgG @tre
wth ELISA, or pos@ve IgM.
Occurrence at the same oc a@ on and
@me as
conrmed cases of dengue fever.
Probabe case and at east one of the
foowng:
Isoa@on of dengue vrus from serum,
CSF or
autopsy sampes.
Fourfod or greater ncrease n
serum IgG (by HI test) or ncrease n
IgM an @ body specc to dengue vrus.

Detec @ on of dengue vrus or Ag n
@ ssue,
serum or CSF by IHC, IFA or ELISA.
Detec @ on of dengue vrus genomc
sequences
by RT--PCR.
Cnca Case Den@on

WHO Gradng of DHF

Cnca Case Den@on

Cnca Management of
DHF
Prncpe of DHF
Management
Prmary abnorma@es n DHF
Vascuopathy
Thrombocytopena
Thrombopathy
Coaguopathy
Severe DIC
Strategy of DHF
Management
Suppor@ve therapy
Drug: as ndcated
Pasma eakage ,olume replacement
How to choose ud sou@on
25% need cood
Cnca course of DHF: unpredctabe
monitoring:
Eary detec @ on and prompt treatment of
crcuatory dsturbance cncay & PCV
beedng manfes ta@ on cncay and ab

Outpa@ent management of
pa@ents
wth
dengue
-arly
dengue
80% of p a@ ents make the rst vst to a
medca
doctor wthn the rst 2 days of fever
foow--up card
dagnoss of suspected dengue, sera fu--
bood--count resuts (to ncude, at east,
haematocrt |erythrocyte voume frac @ on|)
and ndcators for admsson, at the rst
medca contact.
Ora ud
Steps for OPD screenng durng dengue
outbreak
Outpa@ent management of
pa@ents
wth
dengue
)ecommenda.ons for ./.:
A febre p a@ ents at the rst vst to
get the
basene HCT, WBC and PLT.
wth warnng sgns.
fever >3 days.
crcuatory dsturbance/shock (+
gucose check). If eucopena and/or
thrombocytopena (+),
warnng sgns (+) mmedate medca
consuta@on.
Indca@on for admsson

Excessve famy concern or cant be
foowed up
Very weak, cant eat or drnk, not
drnkng/
feedng poory
Spontaneous beedng
Pateete counts 100.00/mm
3
and/or
rsng Hct
10 20%
Cnca deteror a@ on n defervescence
Severe abdomna pan/vom @ ng
Sgncant dehydr a@ on requrng v
uds
Admt mmedatey
Sgns of shock:
Rapd puse wth no fever
Proonged capary re @me
Cod cammy skn, mokng
Narrowng of puse pressure 20
mmHg
Hypotenson
Ogura, no urne for 4 6 hours
Change of conscousness
Management of Febre
Phase
Res@ng, ora uds
Reduc @ on of fever
Nutr @ ona support
Other suppor @ ve and symptom a@ c
treatment
AB not necessary; may ead to
compc a@ on
Sterod nehec @ ve; may cause harm
Management of Febre
Phase
IV uds: n case of doubt, provde
v uds
Guded by: sera Hct, vta sgns, urne
output
Voume: - md to moderate sotonc
dehydr a@ on (5 8% dect)
|ust correct dehydr a@ on, dscon @ nue
ASAP
Management of Cr@ca
Phase
Treatment of severe dengue (DHF and
DSS):
prompt assessment
repacement of ud needs
ve--savng, modfy the severty of
dsease and
prevent shock.
Warning Signs for Dengue Shock
Four Criteria for DHF
Fever
Hemorrhagic manifestations
Excessive capillar
permeabilit
!"","""#mm
$
platelets
Alarm Signals
Severe ab%ominal pain
&rolonge% vomiting
Abrupt change from fever
to hpothermia
'hange in level of
consciousness (irritabilit
or somnolence)
Initial Warning Signals
Disappearance of
fever
Drop in platelets
*ncrease in hematocrite
When Patients Develop DSS:
$ to + %as after onset of
smptoms
Management of Cri*cal
Phase
Management of Cr@ca
Phase
Indca@ons for IV ud:
P a@ en t cannot have adequate ora ud
ntake or
s vom@ng.
HCT con @ nues to rse 10%20%
despte ora
rehydra@on.
Impendng shock/shock.
Management of Cr @ ca Phase

Genera prncpes of ud therapy n
DHF
Cr @ ca perod: Isotonc crystaod
sou @ ons
Used hyper- - onco @ c cood sou @ ons
(osm. >300
mOsm/) such as dextran 40 or starch
sou @ ons n:
massve pasma eakage,
not respondng to the mnmum voume of
crystaod
Obese: dea body weght used as a
gude to
cacuate the ud voume
Management of Cr@ca
Phase
Genera prncpes of ud therapy
n DHF
Voume: mantenance +5%
dehydr a@ on, to mantan a "|ust
adequate" ntravascuar voume and
crcu a@ on.
Dur a@ on v ud
therapy
Wth shock: shoud not exceed 24 to 48
hours for
Wthout shock: may have to be onger but
not more
than 60 to 72
hours.
Requrement of ud based on dea body
weght
Rate of IV ud n aduts and
chdren
DHF Gr I and II
ud aowance (ora + IV): mantenance (for
one day)
+ 5% dect (ora and IV ud together),
admnstered
over 01 hours
Ad|usted accordng to the rate
of pasma oss, guded by :
cnca cond@on,
vta sgns,
urne output and
haematocrt eves.
Management of Cri*cal
Phase
Management of Cri*cal
Phase
DHF Gr I and II
Montorng durng Cr@ca
Phase
Montorn
g
Perpher
a
perfuson

Genera cond@on, appe@te, vom@ng, beedng
and other
sgns and symptoms
As frequenty as ndcated
Vta
sgns
every 24 hours n non--shock pa@ents
12 hours n shock p a@ ents
Sera

hematocr
t
every
4--6 hours
n stabe cases,
more frequent n unstabe p a@ ents or suspected
beedng
Urne

output

every 8 to 12 hours n uncompcated cases
houry n profound/proonged shock or ud
overoad
Management of Cri*cal
Phase
Dengue Shock
Syndrome
DSS: hypovoemc shock caused by
pasma
eakage
Fud resusc ta@ on s dherent from other
types of
shock.
DHF Grade III
>> respond to 10 m/kg over 1 hour or
bous
Fud ad|ustment - cnca cond @ on,
vta sgns,
urne output and haematocrt eves
Management of Cri*cal
Phase
Management of Cri*cal
Phase
Management of Cri*cal Phase
Rate of Infuson n DSS
Management of Cri*cal
Phase
Proonged/profound shock:

DHF Grade IV
Fud resuscta@on more vgorous
10 20 m/kg of bous ud as fast as
possbe,
deay wthn 10 to 15 mnutes faed:
2
nd
bous faed:
Co r rec@on ABCS
Inves @ g a@ on of ABCS
Management of Cri*cal
Phase
Laboratory
Inves@ga@ons
Profound shock
Compc a@ ons
No cnca
mprovement n
spte of
adequate
voume
repacement
ABCS
A--Acdoss
Bood gas
LFT, BUN,
Cr
C--Cacum
Eectroyt
e,
Ca++

B--Beedng
Haematoc
rt
S--Bood

suga
r
BS
(dextros @ c

k)
Management of Cri*cal
Phase
Treatment of
Compca@on
Eectroyte mbaance
Hyponatrema
Hypocacema 10% Ca guconate 1
mL/kg/dose, IV push sowy every 6 hours

Treatment of
Compca@on
Fud overoad:
avod the common causes of ud
overoad, whch
are
Eary IV ud therapy-- n the febre phase
Excessve use of hypotonc sou @ ons
Non--reduc @ on n the rate of IV ud aser n @ a
resusc ta@ on
Bood oss repaced wth uds n cases wth
occut beedng
|udcous ud remova usng coods wth
controed duress (furosemde 1 mg/kg
nfuson over 4 hours) or dayss
Treatment of
Compca@on
Large peura ehusons, asctes
Carefu @tra@ on of ntravenous uds
Large peura ehusons durng the
recovery phase
aser 48 hours -- sma doses of
furosemde (0.25--0.5 mg/kg at 6
hours nterva for 1 to 2 doses).
Avod nser @ on of ntercosta drans and
trachea
ntub a@ on
Treatment of
Compca@on
Dssemnated ntravascuar
coagua@on
Serousy sck p a@ ents + beedng and
DIC
heparn therapy and cryoprecptate (1
unt per 5 kg
body weght) foowed by pateets (4
unts/m2 or
10--20 mL/kg) wthn 1 hour and fresh
frozen pasma (FFP 10--20 mL/kg).
Frequent cnca assessment and
reguar coagu a@ on proe (PT, aPTT,
brnogen, pateet and FDP) are
mandatory, as ndcated
Crtera for dschargng

Fever (--), at east 24 hours wthout
an@pyre@c
Return of appe @ te.
Vsbe cnca mprovement.
S a@ sfactory urne output.
A mnmum of 23 days have eapsed
aser
recovery from shock.
No respratory dstress from peura
ehuson and
no asctes.
Pateet count >50 000/mm3.