Curriculum vitae

Name : I Gusti Ngurah Made Suwarba

Place of birth/date : Jembrana, Juli 22 nd, 1964
Education :
• Medical doctor at Medical school of Udayana University (UNUD) in 1991
• Pediatrician at Child Health Department of UNUD/Sanglah Hospital in 2005
• Pediatric Neurology consultant at University of Indonesia/RSCM in 2011
• Doctoral degree at Udayana University in 2016
Occupation:
• Medical doctor at Puskesmas in Timor-timur 1992-1995
• Public Health Office at Covalima Timor-timur 1995-1999
• Child Health Department staff in UNUD/Sanglah Hospital 2007 - now
Organization :
• Member of Pediatric Neurology working Group
• Indonesia Pediatric society
• Member of International Child Neurology Association (ICNA) (ID P017)
• Member of Asia-Oceana Child Neurology Association (AOCNA) (ID P020)
DIAGNOSIS AND MANAGEMENT
JAPANESE ENCEPHALITIS

I Gusti Ngurah Made Suwarba

DEPARTEMEN/KSM ILMU KESEHATAN ANAK

FK UNUD/RSUP SANGLAH
Denpasar Bali
 JAPANESE ENCEPHALITIS (JE)

Infection of the central nervous system caused by the

Japanese encephalitis virus (JEV).
Life cycle JEV involves:
Pig as a amplifying hosts (Other animals: horses, goats,
cats, mice, chickens and bats)
water birds as a career
Culex mosquitoes as vectors

Bale, JF.Viral infection of the nervous system. Dalam: Swaiman KF, Ashwal S, Ferriero DM, Schor NF, penyunting. Pediatric neurology: Principles and practice. Edisi ke-5. China: Elsevier Saunders; 2012. h.1263-90.
Unni SK, Ruzek D, Chhatbar C, Mishra R, Johri MK, Singh SK. Japanese encephalitis virus: from genome to infectome. Microbes and Infection, 2011, 13: 312-21. Available from: www.elsevier.com/locate/micinf.
 JAPANESE
ENCEPHALITIS

• Leading form of viral encephalitis in children

in Asian countries, especially East Asia and
Asia southeast including Indonesia.
• Mortality rate 10-30%
• 30-50% of survivors: moderete and severe
neurological and psychiatric sequelae.

Kari K, Liu W, Gautama K Mammen MP, Clemens JD, Nisalak A, et al. A hospital-based surveillance for
Japanese encephalitis in Bali, Indonesia. BMC medicine; 2006, 4: 8. downloaded from:http
://www.biomedcentral.com/1741-7015/4/8,
 Etiology: JE virus

● Arbovirus group B, Spherical, 40-60 nm diameter,

core virion is composed of ribonucleic acid (RNA).
● Family : Flaviviridae
● Genus : Flavivirus
● Species : 1. JE
2. Dengue
3. Yellow fever
4. West Nile
5. Murry Vally encephalitis.

Solomon T et al. Neurological aspects of JE. JNNP 2000;68:405-415

Tiroumourougane SV. Japanese viral encephalitis. Postgrad Med J 2002;78:205-215
 The life cycle of the JEV

Tiwari S.2012.Japanese encephalitis: A Review Of The Indian Perspective. Department of Microbiology Sanjay Gandhi Post Graduate Institute of Medical Sciences Uttar Pradesh India.The Brazilian Journal of
Infectious Disease; 16 (6): 564-573.
JEV Life Cycle

Culex tritaeniorhynchus
 Distribusi geografis dan penyebaran genotipe JEV.
A, Indonesia (tidak termasuk Papua) dan Malaysia; B, Australia dan Papua;
C, Taiwan dan Filipina; D, Thailand, Kamboja, dan Vietnam; E, Jepang, Korea, dan Cina; F,
India, Sri Lanka, dan Nepal. Wilayah A berisi semua genotipe JEV, termasuk yang tertua.
Solomon T, Haolin N, David WCB, Ekkelenkamp M, Cardosa MJ, Barrett ADT. (2003) Origin and evolution of
Japanese encephalitis virus in Southeast Asia. Journal of virology. 77(5):p3091-3098
 Epidemiology

• Reported 68,000 cases of JE occur every year that mainly

affects children <15 years, especially in Asia.

• Most of JE virus infections are asymptomatic and only 1%

developed the diseases.

• Surveilence JE in children <12 from (2001-2003) in Bali JE

incidence rate of 8.2 per 100,000 children/year.

Kari K, Liu W, Gautama K Mammen MP, Clemens JD, Nisalak A, et al. A hospital-based surveillance for Japanese encephalitis in Bali, Indonesia. BMC medicine; 2006,
MOH RI. Japanese encephalitis is correlated with the amount of rice field Pig Farming Area and Bird Swamp. 2017.
Suwarba IGN, Andayani AR, Sukrata IW, Sunetra W. Japanese encephalitis incidence and its association with the length of stay and long-term outcome in 2015, Bali-Indonesia. Bali Med J. 2016:5;135-7.
 Epidemiology Japanese Encefalitis

Tiwari S.2012.Japanese encephalitis: A Review Of The Indian Perspective. Department of Microbiology Sanjay Gandhi Post Graduate Institute of Medical Sciences Uttar Pradesh India.The Brazilian Journal of
Infectious Disease; 16 (6): 564-573.
 Distribution of JE cases in Indonesia
2018

There are Bali, NTT, Yogjakarta, Jakarta, north Sulawesi, West Kalimantan, Batam
MOH RI. Japanese encephalitis is correlated with the amount of rice field Pig Farming Area and Bird Swamp. 2017.
 Cases of JE in Indonesia in 2014- 2018
Province 2014 2015 2016 2017 2018

AES JE + AES JE + AES JE + AES JE + AES JE +

Bali 55 6 (10,9%) 208 22 (10,5%) 226 17 (7,5%) 117 12 95 7

Kalbar 5 1 (20%) 13 3 (23,0%) 15 8 (53,3%) 8 - 14 5

Sulut 7 1 (14,5%) 35 4 (11,4%) 25 2 (8,0%) 15 - 18 -

Sumut 2 - - - - - - NA -

Jateng 5 1 (20%) - - 2 - 19 1 27 -

NTT - - 8 3 (37,5%) 13 8 (61,5%) 7 1 4 -

NTB - - - - 5 - 8 - 9 -

DI Y - - 31 6 (19,3%) 35 6 21 1 31 -
(17,14%)

Jabar - - 15 - - - 6 - 8 -

DKI - - 17 2 (11,7%) 4 1 (25%) 19 - 21 -

Kepri - - - - 1 1 (100%) 3 - 4 -

Total 74 9 (12,2%) 327 40 (12,2%) 326 43 223 15 231 12

(13,1%) (6.7% (5.2 %)
 Japanese Encephalitis Cases
every Regency in Bali 2014-2019

REGENCY/CIT 2014 2015 2016 2017 2018 2019(Juli)

Y
AES JE AES JE AES JE AES JE AES JE AES JE

Buleleng 11 0 48 8 44 6 15 2 17 0 1 0

Jembrana 13 3 8 3 5 1 1 0 11 2 1 0

Tabanan 4 2 26 1 38 2 25 1 11 0 2 0

Badung 4 0 50 4 40 0 58 0 0 0 0 0

Denpasar 8 0 36 2 36 3 23 0 51 3 48 3

Gianyar 4 0 8 0 19 0 8 0 8 1 3 0

Bangli 3 0 14 1 14 0 4 0 1 0 0 0

Klungkung 3 0 8 1 8 3 11 1 0 0 1 0

Karangasem 5 1 10 2 32 2 27 0 1 1 0 0

Total 55 6 208 22 246 17 172 4 100 7 56 3

Bali provincial health office, 2019

 Distribution of JE cases in Bali 2015

Bali is a area with highest JE inciden in Indonesia. We have found JE cases in all of
regency. The first human JE case in bali, we have found in 1989.

Center for Disease Control (Bali-CDC), Bali, 2017

 Pathogenesis

Lymph system
(replication)

First Blood stream

viremia

Cytotoxic edema
Brain tissue: replication
CNS and organ  destroy RES &
ekstraneural (replication) apparatus golgi Areas of the brain affected
can be in the thalamus,
basal ganglia, brain stem,
cerebellum, hippocampus
Second
Blood stream Systemic symptom and cortex serebral.
viremia
Click icon to add
picture
 Pearce JC, et all. Japanese encephalitis: the vectors, ecology and potential for expansion. JTM. 2018:25;16-26.
Campbell GL, Hills SL, Fischer M, Jacobson JA,dkk. Estimated global incidence of Japanese encephalitis: a systematic review. Bulletin WHO, 2012.
89:10.
 Clinical manifestations
1 Prodromal Stage

2 Acute Stage

3 Sub-acute Stage

4 Convalescent Stage
SK Saxena, Tiwari S, Saxena R, Mathur A, Nair MPN. Japanese encephalitis: an emerging and spreading Arbovirosis. 2012. Available fromwww.interchopen.com,
Campbell GL, Hills SL, Fischer M, Jacobson JA, Hoke CH, Hombach JM, et al. Estimated global incidence of Japanese encephalitis: a systematic review. WHO Bulletin, 2012. 89:10.
CASES OF JE IN SOME COUNTRIES
JE case

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DIAGNOSIS

- Clinically JE is undistinguishable from acute

encephalitis of other etiologies.

- Lab test is needed for JE diagnosis.

- Detection of virus specific IgM in CSF and serum

(MAC ELISA). Not a routine procedure

SK Saxena, Tiwari S, Saxena R, Mathur A, Nair MPN. Japanese encephalitis: an emerging and spreading Arbovirosis. 2012. Available
fromwww.interchopen.com,
DIAGNOSIS DIAGNOSIS
Japanese Ensefalitis Ensefalitis
(Ig M anti JE (Ig M anti JE
positive)
negative)
 Gambaran lesi CT scan kepala

Udem serebri fase akut dan lesi thalamus Gambaran lesi setelah 3 bulan, edema
bilateral serebri berkurang dan berkurangnya
resolusi lesi di thalamus
Handique dkk. Temporal lobe involvement in japanese encephalitis: problems in differential diagnosis. AJNR Am J Neuroradiol. 2006;27:1027-
31
 Gambaran lesi MRI kepala

Keterlibatan kepala dan badan hipokampus Lesi di thalamus bolateral dan basal ganglia
kiri
Lesi melebar ke amigdala dan lesi Keterlibatan insular kiri
substansia nigra bilateral
Handique dkk. Temporal lobe involvement in japanese encephalitis: problems in differential diagnosis. AJNR Am J Neuroradiol. 2006;27:1027-
31
 MANAGEMENT

No specific treatment
(simptomatic and suportive only)

The main problem:

BRAIN EDEMA

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 EDEMA SEREBRAL

VASOGENIC INTERSTITIAL
CYTOTOXIC
• tumor, intracranial • Increases hidrostatik
• Brain injury traumatis, presure CSF,: hidrosefalus
diffuse axonal injury ,/ hematome, infark,
HIE. abses, and CNS
• Decreas CSF Volume
infection.
• hypertonis/hyperosmol
• steroid
er

Textbook of Pediatric Intensive Care, 3rd ed, Rogers,1996. p. 646; figure 18.1.
Allen CH, Ward JD. Crit Care Clin 1998; 14:485
 Brain Edema, the sulci
Brain Edema, the sulci
disappears,the ventricle
disappears,the ventricle narrows
narrows, infark
and infarcts in one hemisphere
midline shift

Citotoxic Edema :
Hiperosmoler Fluid
 MANNITOL
Mannitol is prepared as a 20 % solution.
The recommended dose is 0.25 to 1 g/kg IV bolus in 10-20
minutes

osmotic diuretic establishing an osmotic gradient

between plasma and parenchymal tissue  reduction
in brain water content
Mechanism of action
R heology effect decrease blood viscosity
and hematocrit  increase CBF and oxygen
delivery
Chesnut RM.. New Horiz 1995; 3:581.
 HYPERTONIC SALINE (NaCl 3%)

Alone or in Establishing NaCl 3% with

combination with an osmotic initial bolus
dextran or gradient that dose 5- 10
hydroxyethyl reduces brain mL/kg body
starch, has been water content. weight
shown to Decrease the administered 5
decrease ICP and risk of – 10 minutes,
increase CPP in hypovolemia OR infusion
pediatric patients dose 0.1-1
ml/kg/hour

Munar F, Ferrer AM, de Nadal M, et al. J Neurotrauma 2000; 17:41.

Marcoux KK. AACN Clinical Issues. 2005;16(2):212-231.
SEIZURE Diazepam per rectal
5 mg suppositoria untuk BB <12 kg
MANAGEMENTPrehospital
0-10 menit
10 mg suppositoria utuk BB > 12 kg
Max 2x, jarak 5 menit

Hospital/IG Diazepam 0,2 – 0,5 mg/kg IV

D (kecepatan 2 mg/menit, max 10 mg 10 menit
ATAU
Midazolam 0,2 mg/kg IM/buccal max 10
mg

Kejang Bila kejang berhenti,

berlanjut
pertimbangkan
5-10’
rumatan
Fenitoin 5-10 mg/kg 20 menit
dibagi 2 dosis
ATAU
Fenitoin 20 mh/kg IV Fenobarbital 20 mg/kg IV Fenobarbital
diencerkan dalam 50 ml NaCl 0,9% selama 20 dengan kecepatan 10-20 mg/menit 3-5 mg/kg/hari
menit (2 mg/kg/menit) dosis max 1000 mg dibagi 2 dosis
dosis max 1000 mg

Catatan: Catatan:
Kejang Kejang
Dapat ditambahakan Dapat ditambahakan
berlanjut berlanjut
Fenitoin 5-10 mg/kg 5-10’ Fenobarbital 5-10 mg/kg
5-10’
30 menit

Fenobarbital 20 mg/kg IV Fenitoin 20 mg/kg IV

dengan kecepatan 10-20 mg/menit diencerkan dalam 50 ml NaCl 0,9% selama 20
dosis max 1000 mg menit (2 mg/kg/menit) dosis max 1000 mg

Kejang
berlanjut
5-10’

ICU > 60 menit

Refrakter SE

Midazolam Propofol Pentobarbital

Bolus 100-200 mcg/kg IV (max 10 mg) Bolus 1-3 mg/kg, dilanjutkan Bolus 5-15 mg/kg, dilanjutkan
dilanjutkan dengan infus kontinyu 100 dengan infus kontinyu 2-10 infus kontinyu 0,5-5
mcg/kg/jam, dapat dinaikkan 50 mcg/kg setiap 15 mg/kg/jam mg/kg/jam
menit
(max 2 mg/kg/jam)

Neuropediatric consensus, 2017

 PREVENTION
----------
THE MOST IMPORTANCE

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 Intervention Control • Mosquitoes (Vector)
of JE • Pigs (Reservoir)
• Human( Susceptible Host)

Human Vaccination is the best way to provide effective and

long-term prevention against JE

JE Vaccine ( WHO Vaccine are now used

Prequalification of CD-JEV
widely in many Asian
2013)
countries and reported of
JE cases has decreased
 26

JE Control Program
Development Plan

Development & Strengthening JE surveillance in 11 Provinces

Strengthening JE's laboratory network

(Litbangkes, BLK, B / BTKL-PP)

Improved The ability of laboratory diagnostics

Prevention:
JE vaccination has been implemented in Bali on March-April
2018

Indonesian MOH, 2016

Kemenkes RI. Petunjuk Teknis Indroduksi Vaksin Japanese Ensefalitis di Indonesia. 2017.
 L
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C
A
TI
O
N
S
E
N
TI
N
E
L
JE
 JE Vaccine introduction in Indonesia
Bali March-April 2018

Catch up in two phases

 Phase :1
• School-based vaccination
• Targeting all children from 6
Years to 14 Years
Phase:2
• Community-based vaccination
• Targeting all children 9 months to 5
years
• Plus who left out from phase 1

27

Indonesian MOH, 2016

 Result of JE Vaccine Introduction in Bali

March-April 2018
Regency/City Target Coverage (%)
JEMBRANA 63.176 103.08
TABANAN 84.272 104.13
BADUNG 148.644 98.22
GIANYAR 109.860 96.55
KLUNGKUNG 38.936 103.18
BANGLI 51.840 103.32
KARANGASEM 100.308 105.04
BULELENG 158.410 99.37
DENPASAR 207.364 97.68
BALI 962.810 100.12

We have immunizid almost 1 million children,with the coverage up to 100.12%. After that the
Indonesia MOH programed it as routine immunisasion in Bali starting from Mei 2018 and maybe
continue in other propince.
Bali provincial health office, 2018
 Adverse reaction JE Vaccine
(KIPI) in Bali
• Non serius : 474 (0.05%)
Fever, headache, rash, nausea-vomiting, diarrhea,urticaria,
abdominal pain, weak body

• Serius : (0.0008%)
Peumonia (2), ensefalitis(1), bacterial meningitis (3) kidney failure (1),
neuritis optica(1), ADEM (1)
Base on investigation: non related JE vacccine
MATUR SUKSMA