Curriculum Vitae

Name
Place/Birth
Education :

: KURNIA FITRI JAMIL

: Medan, 8 February 1965

- Medical Doctor Graduate

: FK-UI (Jakarta, 1992)
- Internist Graduate
: FK-UNPAD (Bandung, 2003)
- Health Magister Graduate
: FK-UNPAD (Bandung, 2004)
- Consultant of Tropical Infection: Colegium of Internal
Medicine Indonesia (Kolegium Ilmu Penyakit Dalam di Jakarta, 2008)
- Pasca Sarjana Ph.D Program : FK-UGM, Yogyakarta (start 2008-...)
- Fellow of Indonesian Society of Internal Medicine (PB.PAPDI, 2009)
- Course of Internal Medicine (Germany, 2004, Netherland, 2006)
- International Workshop of Internal Medicine (France, 2007)
- Course Tropical Diseases & Genetics (Australia, 2008)
- Course of Biology Molecular of Tropical Medicine (Germany, 2009)
- International of Tropical Medicine & Infectious Diseases (UGM, 2010)

Occupation:
- Staff of Internal Medicine, Medical Faculty of Syiah Kuala University/RSUZA
- Head of Infectious Diseases and Tropical Medicine Division,
Internal Medicine Dept- Zainoel Abidin General Hospital
- Coordinator of Skills Medical Laboratory of Faculty of Medicine Unsyiah
- Consultant of HIV/AIDS Group Zainoel Abidin General Hospital
- Head of PETRI Aceh Branch

MANIFESTASI KLINIK
MALARIA BERAT
KURNIA FITRI JAMIL
Divisi Penyakit Tropik & Infeksi
Bagian/SMF. Ilmu Penyakit Dalam
FK-UNSYIAH/RSUZA
BANDA ACEH - 2011

MALARIA
RINGAN

MALARIA DAPAT
MENYEBABKAN
KEMATIAN

400 Gigitan
Nyamuk

200
Meng-infeksi
Manusia

100 Malaria
Klinis

26%
Malaria Berat

2-- 6%

Plasmodium Falciparum, Vivax, Knowlesi

dapat menyebabkan Malaria Berat

10 50 %

Kematian

MALARIA BERAT
Ditemukan Aseksual Plasmodium F/V/K, dengan salah satu :
MALARIA SEREBRAL
ANEMIA BERAT HB < 5 gr% / Ht < 15% + parasit >

10000
GAGAL GINJAL AKUT < 400 ml/24 jam & Kreat > 3 mg%
EDEMA PARU / ARDS
HIPOGLIKEMI < 40 mg%
SYOK SISTOLIK < 70 mmHg / Anak < 50 mmHg
PERDARAHAN SPONTAN / DIC
KEJANG BERULANG > 2 x/ 24 jam
ASIDOSIS Ph <7.25 , Plasma Bicarb < 15 mmol/L
HAEMOGLOBINURIA
HIPERPARASITEMIA > 5 %
MALARIA DGN BILIRUBIN > 3 MG% + gagal Organ lain
HIPERTERMIA > 40 C (Oral)

SEVERE MALARIA
DEFINITION : Patient, Plasmosium Asexual parasitemia,with one
or more CLINICAL or LABORATORY FEATURES :
PROSTRATION
IMPAIRED CONSCIOUSNESS
RESPIRATORY DISTRESS
MULTIPLE CONVULSIONS
CIRCULATORY COLLAPSE
PULMONARY EDEMA
ABNORMAL BLEEDING
JAUNDICE
HAEMOGLOBINURIA

SEVERE ANAEMIA
HYPOGLYCAEMIA
ACIDOSIS
RENAL IMPAIRMENT
HYPERLACTATAEMIA
HYPERPARASITEMIA

WHO: Guidelines for the Treatment of Malaria 2010

BEDA MALARIA BERAT PADA DEWASA &

ANAK
Batuk
Kejang
Ikterik
Lama sakit
Lama koma
Hiperparasitemia
Hipoglikemia
Gagal ginjal
Tek.I.K naik
Edema paru
Perdarahan
Ggn brain stem
Sequelae Neuro.

ANAK

DEWASA

Sering
Sangat sering
Jarang
Pendek (1-2 hr)
Pendek (1-2 hr)
Sering
Sering sebelum Rx
Jarang
Sering/naik
Jarang
Jarang
Lebih sering
> 10 %

Jarang
Sering
Sering
Panjang (5-7 hr)
Panjang (2-4 hr)
Jarang
Sering sesudah Rx/Hml
Sering
Jarang/ normal
Sering
---10 %
Jarang
<5%

Syndromes of severe malaria:

1. Children
1. Severe anemia
2. Metabolic acidosis
3. Cerebral malaria
Exacerbated by:
hypovolemia
hypoglycemia
salicylate toxicity
Renal failure rare
Lung injury/ARDS rare

Syndromes of severe malaria:

2. non-immune adults
Multiorgan failure:
Hyperparasitemia
Acute renal failure
Jaundice
Metabolic acidosis
Hypoglycemia
Acute respiratory
distress syndrome
Anemia/thrombocytop
enia
Cerebral malaria

Prognostic value & frequency of SM in

adults / children
Children

Adults

+
+++
+++
+
+++
+++
+++
++
+
+

?
++
+++
++
+++
+++
++
+
+
+

Clinical manifestations or
Laboratory finding
Prostration
Impaired counciousness
Respiratory distress ( acidotic breathing )
Multiple convulsions
Circulatory collapse
Pulmonary Edema (radiological)
Abnormal bleeding
Jaundice
Haemoglobinuria
Severe Anemia

Children

Adults

+++

+++

+++
+++
+++
+
+/+/+
+/+++

++
+
+
+
+
+
+++
+
+

Classifications Severe Malaria

in Children

Group 1: (require parenteral Rx & Support.Tx )

1. Prostration ( inability to sit upright), 3 subsgroup :
Prostrate but fully concious
Prostrate with impaired conciousness not coma
Coma
2. Respiratory distress ( acidotic breathing
Mild nasal flaring &/ or mild intercostal indrawing
Severe mark intercoctal indrawing or deep
acidotic

Group 2 (able to take oral Rx, require supervised) :

1. Haemoglobin < 5 gr% or haematocrit < 15%
2. > = 2 convulsions in 24 hours

Group 3 : require parenteral Tx because of persistent

vomiting, not in group 1 or 2.

DIAGNOSIS OF 114 CASES SEVERE MALARIA

RSUD. Dr. Zainoel Abidin Banda Aceh

Severe Malaria 48 (42%)

Clinical Malaria 35 (31%)
Stroke 7 (6%)
Hepatitis 5 (4%)
Typhoid fever 4 (3.5%)
Gastritis 3 (2.6%)
Liver absces 2 (2%)
Pneumonia 2 (2%)
Dehydration 1%
Pharyngitis 1%
Chronic Renal Failure 1%
Urinary Tract Infection 1%

Malaria cerebral 25 (52%)

Malaria + jaundice 22 (46%)
Malaria + ARF 1 (2%)
Malaria + jaundice 16 (46^)
Malaria + ARF 9 (26%)
Malaria cerebral 6 (17%)
Hyperparasitemia 3 (11%)

Sepsis 1 %
Nephrolithiasis 1%
Syncope 1%
Epilepsy 1%

RELATIONSHIP BETWEEN ORGAN

INVOLVEMENT AND MORTALITY
in Severe Malaria

Severe Malaria in
Indonesia
Not ONLY in Endemic Malaria Area

(East Indonesia )
Spreading to Jawa & Bali ( Denpasar,
Malang, Surabaya, Yogya, Semarang,
Bandung & Jakarta )
Also reported in Sumatra (Padang,
Riau, Batam, Lampung, Palembang,
Aceh)

PATOGENESIS
MALARIA CEREBRAL
MEKANISME OBSTRUKSI KAPILER :
Rosetting ( penggerombolan eritrosit )
Sitoadherensi ( perlekatan eritrosit ke endothel )

MEKANISME IMUNOLOGIK : pembentukan

sitokin, nitrit oxide

MEKANISME PENINGKATAN TEKANAN INTRACRANIAL : hanya kasus anak
MEKANISME ENDOTOKSIN

MEKANISME PATOGENESIS:
ROSSETTING

PRBC

MEKANISME SITOADHEREN
EP

PRBC

Knob

ENDOTEL

MEKANISME PATOGENESIS
PRBC

Pf-EMP-1

ICAM-1

ELAM VCAM

CD-36

TSP
ENDOTEL

Pathophysiology 1. Red cell

destruction/impaired production

Pathophysiology 2:
cytoadherence

Cytoadherence: cerebral
malaria: brain histology

Pathophysiology 3: dysregulated
cytokine response

GPI
,

LT

Is NO protective in malaria?
NO: antiparasitic effects:
inhibits parasite growth in vitro

NO: antitoxic effects:

inhibits TNF production
downregulates expression of endothelial adhesion

molecules (ICAM-1 etc..)

inhibits host cell apoptosis in tissues

NO: rodent models:

either no effect or disease-protective

Indonesian subjects
Severe malaria (SM)
- cerebral malaria
- non-cerebral malaria

Uncomplicated malaria

(UM)
Healthy controls (HC)
Rural (RHC)
Urban (UHC)

Nitric oxide synthesis from

arginine

L-arginine

NO synthase

L-citrulline +

NO

INVASI ERITROSIT
MEROZOIT

ANEMIA

RING

TROPOZOIT

SIZON
PECAH
GPI

EFEK FISIK
PADA ERI
MANUSIA

EFEK
METABOLIK
PARASIT

KNOB, SITOADER
DEFORM HILANG

PEMAKAIAN GLU
HIPOGLIKEMI
LAKTIK ASIDOSIS

OBSTRUKSI
MIKROVAS.

HIPOXIA
HIPOGLIKEMI

TNF

DEMAM
HIPOGLIKEMI

SEREBRAL, RENAL, PARU

LAIN KOMPLIKASI

CEREBRAL MALARIA
10 % of falciparum malaria
80 % fatal cases
30.5 % mortality in

Indonesia (Adults)
30-50% children in Africa

DEFINITION
PRACTICAL :
IMPAIRMENT OF CONSCIOUSNESS OR
CONVULSION IN PATIENT EXPOSED TO
MALARIA
RESEARCH
AN UNROUSABLE COMA MORE THAN 30
MINUTES, POSITIVE MALARIA SMEAR, WITHOUT
OTHER CAUSES ENCEPHALOPATHY
GCS : < 11 /15 or 9 / 11

Clinical Manifestations

Glasgow Coma Scale

Respon mata

: spontan
dgn suara
dgn nyeri
tak ada reaksi

Respon Bicara : normal respon

bingung
berkata kacau
suara merintih
tak ada suara
: gerakan normal
dapat melokalisir nyeri
fleksi thdp nyeri
extensi
decerebrate rigidity
tak ada reaksi
TOTAL

4
3
2

5
4
3
2

Respon motorik

1
6

5
4
3
2
1
3 -- 15

Extensi pada malaria cerebral

CLINICAL MANIFESTATION
NEUROLOGICAL SYNDROME : DIFFUSE, POTENTIALLY RAPIDLY
REVERSIBLE ENCEPHALOPATHY ASSOCIATED WITH LOSS OF
CONSCIOUSNESS AND FITTING

mild meningism, no neck rigidity

dysconjugate gaze
vertical nystagmus
N.VI palsy
dolls eye, oculovestibular reflex normal response
symetri UMN, increased tone & jerk, clonus, extensor
plantar response + , brisk Jaw jerk
pout reflex + , abdominal reflex -, cremasteric reflex + .
cerebellar sign present

Malaria
Retinopathy

A. Gambaran retina pada

penderita malaria serebral GCS
14, dengan anemia Hb 8.2 gr
%. Tampak gambaran
perdarahan dan papiledema.
B. Gambaran retina pada
penderita malaria serebral GCS
8, edemaparu dan demam
kencing hitam. Tampak
gambaran pemutihan retina.
( Maude RJ, Beare NAR, et all, Trans. R.
Soc. Trop.Med & Hyg, 2009, 103:665-671)

DIFFERENTIAL DIAGNOSIS CM
INFECTION :
MENINGITIS,
ENCEPHALITIS,
TYPHOID FEVER,
SEPTIC SHOCK
STROKE & HEAD INJURY
METABOLIC COMA
ECCLAMPSIA
ALCOHOLISM , INTOXICATION

8 hours after
admission

24 hours
after admission

Ikterik &
Cerebral

Malaria cerebral , jaundice, in Dr.Zainoel Abidin Hospital

GANGGUAN FAAL HATI PADA

MALARIA BERAT
IKTERIK SERING DIJUMPAI ( RINGAN

BERAT )
IKTERIK TERGANTUNG JUMLAH PARASIT
IKTERIK ( HEMOLISIS / DISFUNGSI HATI )
BILIOUS REMITENT FEVER
( IKTERIK, HIPERPARASITEMIA, SEREBRAL
& GAGAL GINJAL Algid Malaria )
AKIBAT:
- Hipoalbuminemia
- Gangguan koagulasi
- Penurunan klirens

Malaria hepatitis ( Deller

1967 )
Gagal hati jarang
Hepatomegali sering, nyeri

ringan, splenomegali
Hiperbilirubinemia ( direk &
indirek )
Transaminase meningkat ringan
- sedang, jarang > 200 i.u
Waktu protrombin memanjang

HIPOGLIKEMIA
Bila gula darah < 40 mg%
Sering dijumpai pada ibu hamil

( primi- gravida)
Pada anak-anak sering sebelum
pengobatan
Pada orang dewasa sering terjadi
sesudah pengobatan kina ( 3 jam
post terapi kina )

Patogenesa Hipoglikemia
Parasit memerlukan karbo-hidrat untuk

metabolismenya
Pada malaria dengan hiperbilirubin
aemia, terjadi kegagalan
glukoneogenesis
Kina menstimuli produksi insulin
( hiperinsulinemia )
Peningkatan Tumor Necrosis factor
( TNF-alfa )

ACUTE KIDNEY INJURY (AKI)

Malaria related Acute Kidney Injury

(MAKI)
Penurunan fungsi ginjal dalam 48 jam :
Peningkatan serum kreatinin 0.3 mg/dL, atau
Peningkatan serum kreatinn 50% dan nilai

dasar, atau
Penurunan urin output 0.5 ml/kg/jam untuk 6
jam

WHO : serum kreatinin > 3 mg/dL

Sering pada malaria dewasa dan jarang

pada anak

 Faktor untuk mempermudah MAKI :

Kehamilan
Parasitemia tinggi
Ikterik yang tinggi
Dehydrasi
NSAID

Faktor yang penting prognosa MAKI

Hipovolemia/ hipervolemia
Hiperparasitemia
Hemoconcentrasi
Hiperbilirubinemia
Hiperpireksia

Pulmonary Oedema in
sev.malaria
2 Types of Pulm.Oedema :

* Overload pulm.oedema
* ARDS

ARDS
A syndrome of severe
respiratory failure due to any
causes resulting in very low Pa
O2 (<70 torr) during
intermittent positive pressure
breathing (IPPB) with FiO2
50%.

PULMONARY
MANIFESTATION IN MALARIA
Historically :
Bronchitic
Pneumonic
Bronchopneumonic

Acute Lung Injury (ALI)

Acute Respiratory Distress

Syndrome (ARDS)

A.R.D.S
Occurs in P. Falciparum, P. Vivax, P. Ovale & ? P.

Knowlesi
Common in adult than children, pregnancy and
non-immune
Mechanism : Increased alveolar cappilary
permeability intravascular fluid loss into the
lungs
Presentation : initial presentation or after
initiation treatment
Clinical : acute onset dyspnea respiratory
failure

CLINICAL FINDING
Manifest abrupt onset dyspnoea, cough, tightness in

the chest that progresses rapidly over a few hours

Disorientation and agitation is frequently present.

Physical examination : signs of respiratory distress

( air hunger, use of accessory muscles of

respiration, suprasternal and intercostal indrawing ),
central and peripheral cyanosis (arterial
hypoxaemia), basal crepitations and expiratory
wheezing.

In these patients, high parasitaemia,acute renal

failure, hypoglycemia, metabolic acidosis,

disseminated intravascular coagulation (DIC), and
bacterial sepsis usually co-exist.

Chest radiography :
Bilateral frontal opacities (alveolar

pattern), increased interstitial markings

The cardiac size is usually normal
Rarely, thickening of lung fissures,
interlobular septal lines
Pleural effusion
In assisted ventilator :
complications pneumothorax,

pneumomediastinum , pneumonia may

occur

Malaria dengan edema paru:

Komplikasi berat, sering fatal.
Sering pada dewasa.
Timbul cepat ( 1-2 hari Tx)
Ada 2 tipe :

1.Kelebihan cairan: tekanan vena

sentral , PAWP ,balance cairan +.
2. ARDS : tekanan vena sentral N/ ,
balance cairan N/+.

Chest
X-ray
18 hours
After
admission

Cerebral Malaria with infiltrate both lung

MM1-3

Definisi ARDS :
Gagal respirasi berat
Pa O2(<70torr) IPPB F1O2 50%
Faktor Predisposisi :
Hiperparasitisme
Gagal ginjal
Kehamilan / post partum
Hipoglikemi
Asidosis metabolik
Malaria serebral
Kelebihan cairan

CM-ARDS, RSUP 2000

Pulmonary Oedema in
sev.malaria
Dehydration
Low jugular venous
pressure
Skin tenting
Postural dizziness
Postural blood pressure
drop
of 15 mmHg
Tachycardia
Muscle cramps

Overhydration
Jugular venous naik
distention
Pitting oedema
Hypertension
Rales
Cardiomegaly
Third heart sound
Progressive
dyspnea
Orthopnea
Nocturnal cough

Edema paru:
Fisik ronki basah ke2 lap paru
Radiologi infiltrat intrathorakal/ alveolus

difus bilateral.
Hipoksemia

Hiperkapnia

} kesadaran
kejang
renjatan

DD : Pnemonia aspirasi
Asidosis Metabolik

ANEMIA BERAT
Hb. < 5 gr% atau Ht < 15 %
Parasit > 10.000 par/ uL
Bukan thallasemia, iron

deffeciency atau keadaan

lain yang dapat
menyebabkan anemia.

Malaria dengan
perdarahan:

Gejala: perdaraha gusi,petikie,

hematom, epiktaksi, perdarahan

sub conjungtiva.
Tanda: anemia, trombositosis,
koagulopati, KID >10%.
Berhubungan dengan : edema
paru, ikterik, hiperparasitemia

MM4-1

A child, 5 months, malaria falciparum ++++, Hb. 1.6 gr%

In RSMM-Timika Hospital, Papua

Perdarahan pada malaria berat : Hematom di pipi

Purpura ( perdarahan dibawah kulit, pada malaria

dengan trombosit 2000/ mm3

Asidosis metabolik:
Nafas Kussmaull, Auskultasi paru

normal
Kadar asam laktat
pH serum < 7,2
Bikarbonat rendah (<15 ml/l)
Berkaitan dengan : edema paru,
hiperparasitemia, syok, gagal ginjal,
hipoglikemia.

HYPOTENSION
(algid malaria)
Causes: gram - ve bacteriaemia, MOF
Management :

1. CVP : 0 -- 5 cm H2O with

crystalloid/
colloid infusion
2. I.V. Dopamine +/ dobutamine
3. Blood culture
4.Antibiotic ( Cephalosporin III)

Malaria Algid :
Malaria +renjatan : TD sistole < 80 mmHg.
Tanda-Tanda sirkulasi perifer:

(kulit dingin, lembab, nadi cepat, nyeri

epigastrium, mual, muntah, diare mirip kolera,
ikterik, parasitemia berat schizon dalam
darah, dll).
Dapat disebabkan P. knowlesi ( simian Malaria)
Berkaitan dengan :edema paru, asidosis,
sepsis bakteri gram -, perdarahan saluran
cerna.
DD : -Dehidrasi berat renjatan septik.
Setiap pasien malaria algid perlu kultur darah.

Infeksi sekunder bakteri:

Pnemonia aspirasi ( sering)
I.S.K ok kateter
Ulkus dikubitus terinfeksi
Infeksi pada tempat infus

Sepsis :
Gram >>
Sering : pseudomonas, E.Coli,
salmonela, streptokokus dll.
Curiga : fibris bekepanjangan parasit-,
syok menetap, leukositosis/neutropenia.

Diagnosis Banding:
Malaria Cerebral: encepalitis/

meninggitis (bakteri, virus, jamur),

ggn metabolik, stroke, intoksikasi
alkohol/obat, trauma kepala.
Malaria dengan ikterus :leptospirosis,
hepatitis tifosa, kolelitiasis dll.
Malaria algid : Sepsis bakterial berat,
IMA, dehidrasi berat , perdarahan
tersembunyi dll.
Edema paru :pnemonia aspirasi,
kelebihan cairan, intoksikasi obat, dll.

Prognosis :
Jumlah & beratnya disfungsi organ
Kecepatan diagnosis & mulai pengobatan

yang adekuat.
Indikator klinis:
- Derajat kesadaran prog jelek
- GGA +edema prog jelek
- asidosis berat prog jelek
- gagal nafas prog jelek
- perdarahan mortalitas >>
- Imun (splenektomi, steroid, dll)prog
jelek

Indikasi laboratorium:

Hiperparasitemia +Shizont perifer

Lekositosis
Kadar asam laktat CSS>, serum >6 mmoll/l
Kadar gula CSS<<
Kadar anti trombin III <<
Kreatinin>3 mg/dl, BUN >60 mg/dl
Hb < 7,1 g/dl.
GDS < 40 gr%
Bikarbonat serum
Transaminase > 3X N.

KEY SUCCEED FOR MANAGING

SEVERE MALARIA

Accuracy diagnosis ( microscopic

biochemical )
Malaria drug ( to combat resistency )
Ability to treat organ failure ( ICU &
Medical equipment )
Good man power( nurses --- doctor )
Good referral system

Curriculum Vitae
Name
Place/Birth
Education :

: KURNIA FITRI JAMIL

: Medan, 8 February 1968

- Medical Doctor Graduate

: FK-UI (Jakarta, 1992)
- Internist Graduate
: FK-UNPAD (Bandung, 2003)
- Health Magister Graduate
: FK-UNPAD (Bandung, 2004)
- Consultant of Tropical Infection: Colegium of Internal
Medicine Indonesia (Kolegium Ilmu Penyakit Dalam di Jakarta, 2008)
- Pasca Sarjana Ph.D Program : FK-UGM, Yogyakarta (start 2009-...)
- Fellow of Indonesian Society of Internal Medicine (PB.PAPDI, 2009)
- Course of Internal Medicine (Germany, 2004, Netherland, 2006)
- International Workshop of Internal Medicine (France, 2007)
- Course Tropical Diseases & Genetics (Australia, 2008)
- Course of Biology Molecular of Tropical Medicine (Germany, 2009)
- International of Tropical Medicine & Infectious Diseases (UGM, 2010)

Occupation:
- Staff of Internal Medicine, Medical Faculty of Syiah Kuala University/RSUZA
- Head of Infectious Diseases and Tropical Medicine Division,
Internal Medicine Dept- Zainoel Abidin General Hospital
- Coordinator of Skills Medical Laboratory of Faculty of Medicine Unsyiah
- Consultant of HIV/AIDS Group Zainoel Abidin General Hospital
- Head of PETRI Aceh Branch

MALARIA:
RECENT MANAGEMENT
KURNIA FITRI JAMIL
Divisi Penyakit Tropik & Infeksi
Bagian/SMF. Ilmu Penyakit Dalam
FK-UNSYIAH/RSUZA
BANDA ACEH - 2014

Outline
Case illustration

Facts sheet

Uncomplicated malaria

Severe malaria

Malaria in pregnancy

Prevention

Cases (per 1,000) by country, 2009

Estimated
Estimated300-500
300-500million
million
clinical
clinicalcases
caseseach
eachyear
year

WHO. World Malaria Report 2010

Mortality (per 1,000) by country, 2009

Approximately
Approximately2.5
2.5million
milliondie
die
each
eachyear
year

WHO. World Malaria Report 2010

P. falciparum Resistance, 2009

WHO.

Countries at risk of transmission, 2009

WHO. 2010

Insidence (per 1,000) Indonesia 2008

ACEH

2,03

SUM-UT
SUM-BAR
RIAU
JAMBI

8,15
2,58
3,06
18,08

SUM-SEL

5,46

BENGKULU
LAMPUNG

22,96
2,79

BANGKA BELITUNG

40,58

RIAU
DKI JAKARTA
JAWA BARAT
JAWA TENGAH
D I YOGYAKARTA
JAWA TIMUR
BANTEN
BALI
NTB

13,32
0
0,58
0,07
0,03
0,71
0,03
0,17
21,85

NTT
KAL-BAR
KAL-TENG

0
3,23
11,21

KAL-SEL

4,20

KAL-TIM

8,59

SUL-UTARA

16,48

SUL- TENGAH

17,81

SUL- SELATAN

1,51

SUL- TENGGARA

10,26

GORONTALO

13,94

SUL- BARAT

11,98

MALUKU

39,65

MALUKU UTARA

51,42

IRIAN JAYA BARAT

84,74

PAPUA

167,47

Indonesia, Malaria cases

API: Annual Parasite Insidence
AMI: Annual Malaria Insidence

In
In2008:
2008:
AMI
AMIdecreased
decreasedto
to17.77
17.77
API
APIremains
remainsin
in0.16
0.16

Incidence rate tends to decrease, since Gebrak

Malaria or Roll Back Malaria (RBM) initiative in 2000.
Ministry of Health RI, 2008

Indonesia, Malaria Case Fatality Rate

National target by 2010: number of malaria sufferer

would be 5 per 1000 population
Ministry of Health RI, 2008

New Species Case

Human Malaria is caused by one of 4 protozoan parasites:

Plasmodium falciparum
Plasmodium vivax
Plasmodium ovale
Plasmodium malariae
Plasmodium knowlesi

( sighh et al, 2008)

http://www.tulane.edu/-wiser/malaria/cmb.html

Todays challenges
Malaria is still a big concern in Indonesia

health problem
Challenge of resistance in antimalarial
drug
Treatment policy to overcome the
problem by using artemisinine
derivatives
Clinical malaria diagnosis no longer used
Malarial elimination program in Indonesia

MALARIA

N
E

What
Tcan

M
T
N
A
O
D
I
E
Many cases worldwide
N
T
A
R
High mortality
N
T of severe malaria
E
Resistance to drugs
V
E
Serious effects in pregnancy
we
R
P

do?

Treatment of malaria
Ideally all patients should be treated in

hospital
Indications for hospital admission:
All children 1 year (and consider admitting

children up to 5 years where possible)

All pregnant patients
All patients 65 years
Immuno-compromised patients where
possible
Severe malaria or danger signs
GUIDELINES FOR THE TREATMENT OF MALARIA IN SOUTH AFRICA, 2009

Uncomplicated malaria
Symptomatic malaria without signs of

severity or evidence of vital organ

dysfunction.
Treatment objectives:
eradicate the infection
prevent the emergence and spread of drug

resistance
combination of two or more antimalarials with
different mechanisms of action
Always give a full course of effective treatment
Guidelines for the treatment of malaria, WHO 2010

Uncomplicated malaria
Treatment coverage:
Treatment of P.vivax or P.ovale infection
Treatment of mild/moderate P.falciparum

infection, P. falciparum and P.vivax

mixed infection

Antimalarial drugs:
ACT (1st line) / non-ACT (2nd line) + Primaquine

elines for the treatment of malaria in Indonesia, Ministry of Health RI, 2

Artemisinin derivatives
Very short T should be given in a longer

period to avoid relaps

Combination Artemisinin
T >
& other antimalarial
Drug with different
mechanism

Duration
therapy <
Prevent
resistance of
antimalarial drug

Davis TME, Karunajeewa HA, Ilett KF. Artemisinin-based combination therapies for uncomplicated malaria. MJA 2005; 182 (4):181-5.
Yeung S, Pongtavornpinyo W, Hastings IM, Mills AJ, White NJ Am. J. Trop. Med. Hyg. 2004; 71(Suppl 2): 17986.
McIntosh H,Olliaro P. Artemisinin derivatives for treating uncomplicated malaria. Cochrane Database of Systematic Reviews 1999.

Artemisinin derivatives
SHOULD NOT be used as
monotherapies for the
treatment of uncomplicated
malaria as this will promote
resistance to this critically
important class of
antimalarials

Available ACT in 2010, WHO

(Arthemisinin-based Combination Therapy)
Drugs

Composition

Form

Artemether +
lumefantrine

20 mg + 120 mg

Fixed dose tablets

Artesunate +
amodiakuin

25 mg + 67,5 mg
50 mg + 135 mg

Fixed dose tablets

100 mg + 270 mg
50 mg + 150 mg (base)

Co-blistered tablets

Artesunate +
meflokuin

200 mg + 250 mg

Co-blistered tablets

Dihidroartemisinin
+ piperakuin

40 mg + 320 mg

Fixed dose tablets

50 mg + 500/25 mg

Co-blistered tablets

Artesunate +
sulfadoksin /
pyrimethamine

World Health Organization. Antimalarial medicines procured by WHO.

2010

WHO recommended
ACTs

Artemether (20 mg) - lumefantrine (120mg)

(Coarthem) 2 x 4 tablet, in 3 days
Artesunate (4mg/BW/day) + amodiaquine

(10mg/BW/day)

(Artesdiaquine, Artesuamoon) once daily in

3days
Artesunate (4mg/BW/day once daily in 3 days) +
Mefloquine (25 mg/BW split over 2 or 3 days)
Artesunate (4mg/BW/day once daily in 3 days) +
Sulfadoxine-pyrimethamine (25mg/1.25mg base/BW on
1st day)

Guidelines for the treatment of malaria, WHO 2010

Uncomplicated malaria

Treatment of P.vivax or P.ovale infection (1)

FIRST LINE :

ACT

PRIMAQUINE

Artesunate (200mg/day, in 3 days)

+ amodiaquine (600mg/day, in 3
days)
Artemether 20 mg +
lumefantrine 120 mg;
2x4 tablets for 3 days
Dihydroartemisinin 40 mg +
piperaquine 320 mg
2 tablets initial dose,
2 tablets in the next 8, 24, and 32
hours

0.25
mg/BW/day
in 14 days

Guidelines for the treatment of malaria Ministry of Health RI, 2009, WHO 20

Uncomplicated malaria
Treatment of P.vivax or P.ovale infection (2)

SECOND LINE
QUININE SULFA

3 X 400-600
mg/day
in 7 days

PRIMAQUINE

0.25
mg/BW/day
in 14 days

delines for the treatment of malaria, Ministry of Health RI, 2009, WHO 2

Uncomplicated malaria
Treatment of P.vivax or P.ovale infection (3)

CHLOROQUINE SENSITIVE
CHLOROQUINE BASE 150 MG
PRIMAQUINE

1st day
tablets
2nd & 3rd day

:4+2
: 2 tablets

OR
1st & 2nd day
3rd day

1 X 15 mg
in 14 days

: 4 tablets
: 2 tablets

delines for the treatment of malaria, Ministry of Health RI, 2009, WHO 2

Uncomplicated malaria
Treatment of mild/moderate P.falciparum infection,
P. falciparum and P.vivax mixed infection (1)

FIRST LINE
ACT
+
PRIMAQUINE

P falciparum inf.
0.75 mg/BW
single dose
Mixed infection
Day 1-14: 0.25
mg/BW

delines for the treatment of malaria, Ministry of Health RI, 2009, WHO 2

Uncomplicated malaria
Treatment of mild/moderate P.falciparum infection,
P. falciparum and P.vivax mixed infection (2)

SECOND LINE
QUININE + DOXY/TETRA + PRIMAQUINE
Quinine: 3x400-600 mg in 7 days
Doxycycline: 2 x 2 mg/BW in 7 days
Tetracycline:4 x 4-5 mg/BW in 7 days
Primaquine:
0.25mg/BW in 14 days vivax /mixed
0.75mg/BW single dose P.F inf.

Key tools of prevention

Be Aware: risk factor, incubation period,

symptom

Avoid being Bitten by mosquitoes

Chemoprophylaxis
Immediately seek Diagnosis & treatment: if

fever occur 1 week 3 months after arrival in

endemic areas

Malaria Risk

Prevention

Transmission risk very

low

Bite avoidance

TIPE II

Risk of malaria vivax or

falciparum which
sensitive to chloroquine

Bite avoidance +
Chemoprophylaxi
s (chloroquine)

TIPE III

Risk of malaria vivax

/falciparum, +
probability of
chloroquine resistance

TIPE I

High risk of malaria

TIPE IV

falciparum + drug
resistance
Moderate risk of
malaria falciparum +
high resistance

Bite avoidance +
Chemoprophylaxi
s (according drug
sensitivity in the
area)

WHO. International Travel & Health 2008

Avoid being Bitten by mosquitos

Insecticide treated net (ITN): (conventional

ITN or Long-lasting insecticidal nets (LLINs)

prevent infectious mosquito bites.

Indoor Residual Spraying (IRS): indoor

application of long-lasting chemical

insecticides (DDT)

Other vector (mosquito) controls: larviciding

and environmental management, repellent,

clothes, fogging, domestic insectiside

WHO, The Roll Back Malaria Partnership 2008: Global Malaria Action
Plan.

Chemoprophylaxis

Causal
Prophylaxis

Suppressive
Prophylaxis
Guidelines for Malaria Prevention in Travellers from the United Kingdom. 2007

Chemoprophylaxis
Recommended drugs:
Chloroquine
Proguanil
Chloroquine + proguanil
Mefloquine
Doxicycline
Atovaquone + proguanil

Guidelines for Malaria Prevention in Travellers from the United Kingdom. 2007

Chemoprophylaxis
Doxicycline
Recommended by Ministry of Health RI, 2009
Suppresive prophylaxis (effectivity ~

mefloquine)
Adult dose: 100mg/day, start on 1st -2nd day
before arrival, until 4 weeks after leaving out
the area
Not recommended for > 3 month of using,
children, and pregnant woman. (Ministry of
Health RI, 2009)
!! Predisposition of Candidosis vagina
Ohrt, C, Richie TL, Widjaja H et al. Annals of Internal Medicine. 1997;126:963-72
Guidelines for the treatment of malaria in Indonesia, Ministry of Health RI, 2009

Chemoprophylaxis
In pregnant traveller
Save: chloroquine and proguanil (+ folic

acid 5mg/day) less protection to resistant

strain
Mefloquine:
Few reported side effects
Carefully use for 2nd & 3rd trimester pregnancy in

area with chloroquine resistance

Doxicycline CONTRA INDICATED

Guidelines for Malaria Prevention in Travellers from the United Kingdom. 2007

Chemoprophylaxis
In pregnant traveller in endemic
area
Intermittent Preventive Treatment (IPT, WHO
2007): Recommended Sulfadoxinepyrimethamine
Single dose; minimum use is twice, since
trimester II until partus
Prevalence of HIV in pregnancy > 10% the 3rd
dose should be given on the last antenatal care

World Health Organization. Malaria in pregnancy: guidelines for measuring key monitoring and evaluation
indicators. 2007.
Gamble C, Ekwaru JP, ter Kuile FO. Insecticide-treated nets for preventing malaria in pregnancy. Cochrane
Database Syst Rev 2006;2: CD003755.

Chemoprophylaxis
For long term
Chemoprophylaxis is pointed for people

who traveling not in a long period

Not recommended for long term use (3
months)
Consider of using personal protection
(net, repellent, etc)

Guidelines for the treatment of malaria in Indonesia, Ministry of Health RI, 2009

Severe malaria
The presence of one or more of these features:
Clinical manifestation:

Laboratory test:

Prostration
Impaired consciousness

Severe anaemia
Hypoglycaemia

Respiratory distress
Multiple convulsions

Acidosis
Renal impairment

Circulatory collapse
Pulmonary oedema
Abnormal bleeding
Haemoglobinuria

Hyperlactataemia
Hyperparasitaemia

Jaundice
Guidelines for the treatment of malaria, WHO 2010

Severe malaria
Treatment objectives:
Prevent death
Prevention of recrudescence, transmission or

emergence of resistance
Prevention of disabilities

Principal treatment:
Supportive therapy
Antimalarial drug
Complication management
Guidelines for the treatment of malaria, WHO 2010

Severe malaria
Supportive therapy
Fluid, acid-base, and electrolyte balance
Antipyretic
Anti convulsants:
Diazepam 10 mg, IV

Guidelines for the treatment of malaria in Indonesia, Ministry of Health RI, 2

Guidelines for the treatment of malaria, WHO 2010

Severe malaria
Antimalarial drugs (1)
Artemisinin
Artemether
Day 1 : 3,2mg/BW/12hours (2 x 1,6mg/BW/12hours;im)
Day 2 - 4 : 1,6mg/BW/day, im

Artesunate
Day 1 : 2,4mg/BW, iv in 1st hour, 2,4mg/BW/iv in hour 12 & 24
Day 2 - 7 : 2,4mg/BW/hr, iv

After conscious continue with

Artesunate + amodiaquine OR
Quinine + Tetracycline / doxycycline / clindamycin
Guidelines for the treatment of malaria, WHO 2010

Severe malaria
Antimalarial drugs (2)

Quinine HCl 25%

Diluted in 500cc dextrose 5% or NaCl

0.9%, give during the first 4 hours, then

rest in the next 4 hours:
Loading dose: 20 mg/BW (single dose)
Maintenance dose: 10 mg/BW, repeat until
the patient able to receive oral medication
After conscious, continue by oral quinine

10mg/BW every 8 hours, + tetracycline /

doxicycline / clindamycin until day 7.
Guidelines for the treatment of malaria, WHO 2010

Severe malaria
Complication management
Hypoglycaemia
Dextrose 40%, IV bolus 25-50 cc, then dextrose

10%, drip 500 cc every 4-6 hours

Keep the nutrition intake (NGT)

Acute

kidney failure

Keep the fluid & electrolyte balance

Dyalisis (if there is an indication)

Lung

oedema / ARDS

Fluid & electrolyte balance (max 1500 cc/24

hours)
Diuretic
Ventilator

Guidelines for the treatment of malaria, WHO 2010

Severe malaria
Exchange blood transfusion

Indication:
Parasitaemia> 30% without severe

complication
Parasitaemia> 10%:
With severe complication
With treatment failure after 12-24 hours

optimal antimalarial
With bad prognosis (old age, late stage
parasites/skizon in blood)

Malaria in pregnancy
More common
More atypical
More severe
More fatal
Selective treatment
Various complication

Malaria in pregnancy
2nd and 3rd trimesters of pregnancy are

more likely to develop severe malaria

Complication: anemia, pulmonary
oedema, hypoglycaemia
Maternal mortality is approximately 50%
Fetal death & premature labour are
common

Guidelines for the treatment of malaria, WHO 2010

Malaria in pregnancy
Principal treatment:
Supportive therapy
Antimalarial drug
Management of complication
Management of labour

Malaria in pregnancy
Supportive therapy
Supplementation of Fe & folic acid
Blood transfusion in severe anemia

(Hb<7g/dl)
Adequate nutrition

Nosten F, McGready R, Mutabingwa T. Case management of malaria in

pregnancy. Lancet Infect Dis 2007; 7:118-25.

Malaria in pregnancy
Antimalarial drugs (1)
Uncomplicated malaria falciparum (trimester I)
1
Episode
st

Quinine
+
Clindamycin

Repeat
Quinine +
Failure
Clindamycin
of
ACT
treatme
Artesunate
nt
+
Clindamycin

3 x 10 mg/BW/day
+
3 x 5 mg/BW/day

2 mg/BW/day
+
3 x 5 mg/BW/day

7
days

7
days

World Health organization. Guideline for the treatment of Malaria 2010. Geneva.
Case management of malaria in pregnancy. Lancet Infect Dis 2007;
7:118-25.

Malaria in pregnancy
Antimalarial drugs (2)
Uncomplicated malaria falciparum (trimester II

& III)
ACT
1st
Artesunate +
Episode
Clindamycin
Failure
of
treatme
nt

Other ACT
Artesunate +
Clindamycin
Quinine + Clindamycin

Dose
above

Dose
above

7 days

World Health organization. Guideline for the treatment of Malaria 2006. Geneva.
Case management of malaria in pregnancy. Lancet Infect Dis 2007;
7:118-25.

Malaria in pregnancy
Antimalarial drugs (3)
Choices of ACT
Artemether (20 mg) +
2 x 4 tablets/ day
lumefantrine (120 mg)
Artesunate (50 mg) +
1 x 4 tablets/ day
Amodiaquine (153 mg)
Artesunate (50 mg) +
1 x 4 tablets/ day
Sulfadoxine+
pyrimethamine
3 tablets only at day I
(500/25 mg)

3 days
3 days

3 days

1 x 4 tablets/ day
+
3 days
1 x 4 tablets/ day in
Artesunate (50 mg) +
+
day
I,
Mefloquine (250 mg)
2 days
1 x 2 tablets/ day in
Case management of malaria in pregnancy. Lancetday
InfectIIDis 2007; 7:118-25.,WHO 2010

Malaria in pregnancy
Antimalarial drugs (4)
Severe malaria
2 4 mg/BW at hour
Early fase Artesunate
0, 12 & 24; then
every 24 hours
Artesunate
+
Late fase
Clindamyci
n

2 mg/BW/day
3 x 5 mg/BW/day

Alternativ
20 mg/BW (loading
e for
Quinine
dose); then 10
early
mg/BW every 8 hours
fase
Alternativ Quinine +
3 x 10 mg/BW/day
e for late Clindamyci
3 x 5 mg/BW/day.
fase
n

Until
able of
oral
drug

Parenter
al

7 day

oral

7 day

Parenter
al

7 day

oral

Case management of malaria in pregnancy. Lancet Infect Dis 2007; 7:118-25, WHO 2010.

Malaria in pregnancy
Antimalarial drugs (5)
Malaria non-falciparum
Chloroquine (25 mg base /BW); except for P.

vivax in south Asia (around Indonesia) with

high resistance, choose quinine.
Alternative: Amodiaquine very limited data
about effectivity & safety in pregnancy

Case management of malaria in pregnancy. Lancet Infect Dis 2007; 7:118-25, WHO 2010.

Outcomes
WHO standard protocol classification:
Early treatment failure
Late treatment failure
Late clinical failure
Late parasitological failure

Adequate clinical and parasitological

response.

Outcomes
Early treatment failure

Day 1-3 occurrence of severe clinical sign

Day-2 parasite count > day o
Day-3 parasite count >25% day o
Day-3 (+) finding of asexual parasite & also
fever

Late treatment failure

Late clinical and parasitological failure:
Day 4-28: occurrence of severe clinical sign
Asexual parasite still existing & also fever

Late parasitological failure:

Occurrence of asexual parasite on day 7, 14, 21,

and 28 without fever.

Guidelines
for the
treatment of
malaria,
WHO 2010

Conclusions
Reported number of malaria cases & deaths remains high
Recommended use of ACT + Primaquine for

uncomplicated malaria
Recommended use of parenteral artemisinin derivative or

quinine for severe malaria

Recommended use of quinine + clindamycin (1 st trimester) OR

ACT (2nd & 3rd trimester or failure to quinine in 1 st trimester), for

malaria in pregnancy
Prevention by mosquito control, avoidance of mosquitos bite
and chemoprophylaxis

Thank You