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Current Treatment of Dengue

Virus Infection

Nur Farhanah

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

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

Source: WHO SEARO Dengue Guideline 2011

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

http://www.pppl.depkes.go.id/_asset/_download/DBD_2011.gif

http://www.pppl.depkes.go.id/_asset/_download/DBD_2011.gif

IR DBD IND, JATENG & SEMARANG

Souce:P2B2 Dinkes Kota Semarang

Source; P2B2 Dinkes Kota Semarang

Dengue Virus Pathogenesis

BEE Martina, P. Koraka, Osterhaus


Clin.Microbiol. Rev 2009, 22 (4):564

Platelet
aggregation

clusterin

Thrombocytopenia
C3a,C5a

Haemorrhagic
manifestations

Hypotension
/shock

WHO Dengue Guidelines

1997

2009

201
1

WHO Dengue guidelines


1997

2009

2011

WHO Dengue Guidelines


Diagnosis Classification

1997

2009

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

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 reporte d

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

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)

WHO Dengue Guideline 2009


Suggested dengue case classification and
level of severity

Source: WHO Dengue Guideline 2009

Manifestation of Dengue Virus Infection

Expanded
Syndrome/isolated
organopathy
(unusual manifestation)

Source: WHO SEARO Dengue Guideline 2011

Expanded
Dengue
Syndrome or unusual manfestation
Ecpanded
dengue
syndrome
Neurological

Gastrointestinal/
hepatic

Renal
Cardiac

WHO SEARO Dengue Guideline 2011

Expanded Dengue Syndrome or unusual manfestation


Respiratory
Musculoskeletal
Lymphoreticular/bone

marrow

Eye

others

WHO classification of Dengue infections and grading of severity of


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

Thrombocytopenia <100.000
cells/mm3
Hct rise >20%

DHF

II

As in Grade I plus spontaneous


bleeding

Thrombocytopenia <100.000
cells/mm3
Hct rise >20%

*DHF

III

As in Grade I or II plus circulatory


failure

Thrombocytopenia <100.000
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

Thrombocytopenia <100.000
cells/mm3
Hct rise >20%

The Course of Dengue Illness

Dengue Infection : immune response

WHO Dengue Guideline 2009

Diagnostic Tests
EASY to USE

Confidence

CASE MANAGEMENT
WHO Guideline

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 signs

DHF grade I-II

6-7ml/kg/hour
5ml/kg/hour 3ml/
kg/hour stop 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

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

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 Al least 2 days


recovery

2-3 days

No resp distress

Platelet count

>50.000/ul

Increasing trend

>50.000/ul

National Guideline

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)

Protokol 2. Pemberian Cairan pada Tersangka DBD


dewasa di Ruang Rawat

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,


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