2 Current Treatment of Dengue Virus Infection

Current Treatment of Dengue
Virus Infection
Nur Farhanah
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SEMARANG, 26-27 MEI 2012
Epidemiology
Of the 2.5 billion people in the world living in dengue
endemic area
At risk of DF/DHF 1.3 billion live in 10 dengue endemic
countries of WHO SEA Region
In ASEAN countries 51 million people are infected /year

and 20,000 people (especially children) die
WHO SEARO (South-East Asia Region) Dengue
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Average Annual Number of Cases of DF/DHF reported to WHO
Source: WHO SEARO Dengue Guideline 2011
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Indonesia
The Ministry of Indonesian Health (ASEAN
Dengue Conference 1st :15 June 2011) reported
in 2010 Indonesia has the largest number of
dengue patients among the ASEAN
150,000 people were infected
1,400 people, mostly children, died
(Thailand 57,000 people were infected and 70
died)
ASEAN Dengue day June 15th
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http://www.pppl.depkes.go.id/_asset/_download/DBD_2011.gif
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http://www.pppl.depkes.go.id/_asset/_download/DBD_2011.gif
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IR DBD IND, JATENG & SEMARANG
Souce:P2B2 Dinkes Kota Semarang
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Source; P2B2 Dinkes Kota Semarang
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Dengue Virus Pathogenesis
BEE Martina, P. Koraka, Osterhaus

Clin.Microbiol. Rev 2009, 22 (4):564
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Platelet
aggregation
clusterin
Thrombocytopenia
C3a,C5a
Haemorrhagic
manifestations
Hypotension
/shock
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WHO Dengue Guidelines
1997
2009
2011
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WHO Dengue guidelines

2009
2009
2011
2011
Dengue Guidelines for

diagnosis, treatment,
prevention and control
WHO TDR 2009
Comprehensive guideline
for prevention and
control of Dengue and
DHF WHO Searo 2011
33
160
212
Clinical manifestation,
diagnosis, case
management
Chapters : (6)
Epidemiology and burden of
disease, clinical
management, vector
management, lab
diagnostic tests,
surveillance and emergency
response, new avenues
Chapters : (15)
Epidemiology, disease
burden,clinical
manifestation and
diagnosis, lab diagnosis,
management, surveillance,
vector, vector management,
IVM, Combi, PHC
approach, case
investigation, monitoring,
strategic plan (bi-regional
plan)
Guideline for treatment of

DF and DHF in small
hospitals WHO Searo
1999
Content
Page
s
Title
1997
1997
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WHO Dengue Guidelines

Diagnosis Classification
1997
2009
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2011
Dengue fever
Dengue without
warning signs
Dengue fever
DHF grade I
Dengue with warning

signs
DHF grade I
DHF grade II
DHF grade III
DHF grade II
Severe dengue
( severe plasma
leakage, severe
hemorrhage, severe
organ involvement)
DHF grade IV
DHF grade III
DHF grade IV
Expanded dengue
syndrome
Adult management
Adult management
WHO Dengue Guideline 1997

Manifestation of Dengue Virus Infection
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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
WHO Dengue Classification 1997
DF
DHF
2. Bleeding tendency
Positive tourniquet test or
Spontaneous bleeding
+/-
3. Thrombocytopaenia
100,000/mm
+/-
WHO Dengue Classification 1997
1. Fever 2-7 days
4. Plasma leakage
Pleural effusion /ascites
/hypoproteinaemia
20% increase in HCT from baseline
20% decrease in HCT from baseline
after volume-replacement treatment
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WHO 1997
Grade
DF
DHF
Sign and Symptomps
Laboratory
DHF without plasma leakage

I
Fever with non-specific constitutional

symptoms; the only hemorrhagic
manifestation is a positive tourniquet test
&/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
Thrombocytopenia
(platelet count
100,000/L)
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Suggested dengue case classification and
level of severity
Source: WHO Dengue Guideline 2009
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Manifestation of Dengue Virus Infection
Expanded
Syndrome/isolated
organopathy
(unusual manifestation)
Source: WHO SEARO Dengue Guideline 2011
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Expanded
Dengue
Syndrome or unusual manfestation
Ecpanded
dengue
syndrome
Neurological
Gastrointestinal/
hepatic
Renal
Cardiac
WHO SEARO Dengue Guideline 2011
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Expanded Dengue Syndrome or unusual manfestation

Respiratory
Musculoskeletal
Lymphoreticular/bone
marrow
Eye
others
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WHO classification of Dengue infections and grading of severity of DHF (2011)

DF/
DHF
Grade
DF
Signs and Symptoms

Fever with two of the following:
Headache
Retro-orbital pain
Myalgia
Athralgia/bone pain
Rash
Haemorrhagic manifestations
No evidance of plasma leakage
Laboratory
Leucopenia (WBC <5000
cells/mm3)
Thrombocytopenia <150.000
cells/mm3)
Rising Hct (5-10%)
No evidance of plasma loss
DHF
Fever and haemorrhagic manifestation

(positive tourniquet test) and evidance
of plasma leakage
cells/mm3
Hct rise >20%
DHF
II
As in Grade I plus spontaneous

bleeding
cells/mm3
Hct rise >20%
*DHF
III
As in Grade I or II plus circulatory

failure
cells/mm3
Hct rise >20%
*DHF
IV
As in Grade III plus profound shock

with undetectable bloodpressure and
pulse
*DHF III and IV are DSS
cells/mm3
Hct rise >20%
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The Course of Dengue Illness
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Dengue Infection : immune response
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Diagnostic Tests
EASY to USE
Confidence
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CASE MANAGEMENT
WHO Guideline
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Admission criteria
1997
Signs of significant
dehydration (>10%
normal body weight)
2009
2011
-Any warning sign

-Coexisting condition :
infancy, pregnancy,old
age, obesity, DM,
renal failure,
hpertension, chronic
hemolytic disease etc
-Social circumstance :
living alone, far from
health facility, without
reliable means of
transport
-Any warning signs

-sign and symptom
related to hypotension
-Bleeding
-Organ impairment
-Finding through
further investigations
-Coexisting conditions
-Social economic
Fluid Management
1997
2009
2011
DHF grade I-II
Dengue with warning DHF grade I-II

signs
6-7ml/kg/hour
5ml/kg/hour3ml/
kg/hourstop after
24-48hours
start 5-7ml/kg/hour
for 1-2hours, reduce
to 3-5ml/kg/hour for
2-4hours, reduce to
2-3ml/kg/hour or less
according to clinical
respons
Maintenance (for 1
day)+5% deficit (oral
and i.v together) to
be administered over
48 hours
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Fluid Management
1997
2009
2011
DSS
Severe DengueCompensated Shock
DHF grade III
10-20ml/kgBB bolus
repeat if necessary
Isotonic crystalloid sol

5-10ml/kg/hour over
one hourreassess
10ml/kg in children or
300-500ml in adult
over one hour or by
bolus, if necessary .
Further fluid
administration should
follow the graph
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Fluid Management
2009
2011
Severe Dengue-hypotensive
shock
DHF grade IV
Initiate i.v fluid with crystalloid or

colloid (if available) at 20ml/kg as
bolus over 15 mnt
10ml/kg bolus fluid as fast as

possible, ideally within 10-1mnt.
When BP is restored, futher iv fluid
may be given as in grade 3. If
shock isnt reversible after the first
10ml/kg, repeat bolus 10 ml/kg
and lab results should be pursued
and corrected as soon as possible
Transfusion in Severe Bleeding

2009
5-10ml/kg of fresh PRC
or 10-20ml/kg of fresh
whole blood of an
appropriate rate and
observe clinical
response
2011
5ml/kg of PRC or
10ml/kg of fresh whole
blood
Reassess, repeat if
necessary
High Risk Patients (2011)

-
Infants and the elderly

Obesity
Pregnant women
Peptic ulcer disease
Woman who have menstruation or abnormal vaginal
bleeding
G-6PD deficiency
Thalassemia and other haemoglobinopathies
Congenital heart disease
Chronic diseases (DM, hypertension, asthma, IHD)
CRF, liver cirrhosis
Patients on steroid or NSAID treatment
Discharge criteria
Criteria
1997
2009
2011
Absence of fever
24hours without
antipyretic
48 hours
24hours without
antipyretic
Clinical
improvement
+general well
being,
apetite,hemodyna
mic status, urine
output,no resp
distress
Return of Apetite
Good urine output
Stable Ht
+(without iv fluid)
Elapse from
shock recovery
Al least 2 days
2-3 days
No resp distress
Platelet count
>50.000/ul
Increasing trend
>50.000/ul
National Guideline
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Tatalaksana
Protokol 1 : Penanganan tersangka
(probable)DBD dewasa tanpa syok
Protokol 2 : Pemberian cairan pada tersangka
DBD dewasa di ruang rawat
Protokol 3 : Penatalaksanaan DBD dengan
peningkatan Ht >20%
Protokol 4 : Penatalaksanaan Perdarahan
Spontan pada DBD dewasa
Protokol 5 : Tatalaksana SSD pada dewasa
Protokol 1. Penanganan Tersangka

(Probable) DD/DBD Dewasa tanpa Syok
Protokol 1. Penangan Tersangka (Probable)
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Protokol 2. Pemberian Cairan pada Tersangka DBD

dewasa di Ruang Rawat
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Protokol 3 PENATALAKSANAAN DBD dengan Ht >20%

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Protokol 4. Penatalaksanaan Perdarahan Spontan
pada DBD Dewasa
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Protokol 5. Tatalaksana Syok pada Dewasa

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Inotropik:vasoaktif Koreksi as bs,

elektr, glikemia,
anemiaInfx sekunder, KID
Transfusi PRC
10ml/KgBB
Koloid maksimal
30ml/Kg
Conclusion
The dengue pathogenesis is very multicomplex
Case management is simple and inexpensive
The cornerstone of treatment is early management of
fluid, and it could save the patients life
Revised guideline (2009 and 20011) are available and
could be applied according to clinical setting
The WHO guidelines 2009 has higher sensitivity in
diagnosing dengue cases (earlier hospitalization, fluid
administration and could be decrease of fatal cases)
WHO SEARO Guidelines 2011 has similar contents and
classifications as WHO Guidelines 1997
Be aware to dengue diagnosis and early managemenet
SPEED-1

2 Current Treatment of Dengue Virus Infection

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Current Treatment of Dengue

In ASEAN countries 51 million people are infected /year

WHO SEARO (South-East Asia Region) Dengue

Average Annual Number of Cases of DF/DHF reported to WHO

Source: WHO SEARO Dengue Guideline 2011

IR DBD IND, JATENG & SEMARANG

Souce:P2B2 Dinkes Kota Semarang

Source; P2B2 Dinkes Kota Semarang

Dengue Virus Pathogenesis

BEE Martina, P. Koraka, Osterhaus

WHO Dengue Guidelines

WHO Dengue guidelines

Dengue Guidelines for

Guideline for treatment of

WHO Dengue Guidelines

Dengue with warning

DHF grade III

WHO Dengue Guideline 1997

Probable an acute febrile illness with two or more of the following

WHO Dengue Classification 1997

WHO Dengue Classification 1997

1. Fever 2-7 days

Sign and Symptomps

DHF without plasma leakage

Fever with non-specific constitutional

DHF grade I plus spontaneous bleeding

Circulatory failure manifested by a rapid,

Profound shock with undetectable blood

WHO Dengue Guideline 2009

Source: WHO Dengue Guideline 2009

Manifestation of Dengue Virus Infection

Source: WHO SEARO Dengue Guideline 2011

WHO SEARO Dengue Guideline 2011

Expanded Dengue Syndrome or unusual manfestation

WHO classification of Dengue infections and grading of severity of DHF (2011)

Signs and Symptoms

Fever and haemorrhagic manifestation

As in Grade I plus spontaneous

As in Grade I or II plus circulatory

As in Grade III plus profound shock

The Course of Dengue Illness

Dengue Infection : immune response

WHO Dengue Guideline 2009

-Any warning sign

-Any warning signs

DHF grade I-II

Dengue with warning DHF grade I-II

Severe DengueCompensated Shock

DHF grade III

Isotonic crystalloid sol

Initiate i.v fluid with crystalloid or

10ml/kg bolus fluid as fast as

Transfusion in Severe Bleeding

High Risk Patients (2011)

Infants and the elderly

Good urine output

Protokol 1. Penanganan Tersangka

Protokol 2. Pemberian Cairan pada Tersangka DBD

Protokol 3 PENATALAKSANAAN DBD dengan Ht >20%

Protokol 4. Penatalaksanaan Perdarahan Spontan

pada DBD Dewasa

Protokol 5. Tatalaksana Syok pada Dewasa

Inotropik:vasoaktif Koreksi as bs,

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