PENGOBATAN DAN PENCEGAHAN

MALARIA
(Treatment and Prevention Malaria)

Paul Harijanto , SpPD-KPTI, FINASIM

2015
 CURRENT APPROACH MALARIA TREATMENT

Based on microscopic diagnosis

Combination therapy
Must radical treatment
Outcome focus on clinical cure, parasitological
clearance, and blocking transmission
Monitoring therapeutic efficacy antimalarial drugs based
on clinical and parasitological responses (in-vivo 28-42
days with or without ancillary measurements: drug
blood level, genotyping, and strain analysis using
molecular markers)
 Recommendation WHO 2010-2015
in using ACTs :

Artemether-lumefantrine ( AL )
Artesunate + amodiaquine ( AS + AQ )
Artesunate + mefloquine ( AS + MQ )
Artesunate + sulfadoxine-pyrimethamine ( AS + S-P )
Dihydroartemisinin Piperaquine ( DHA-PPQ )
 Pengobatan Malaria
Tanpa Komplikasi FALSIPARUM/VIVAX

Malaria RINGAN/ Tanpa Komplikasi :

Dihidroartemisinin Piperakuin (DHP)
Artesunate + Amodiaquine (AS + Amo)
Artemether-Lumefantrine (AL)

Lini Pertama =
A.C.T + Primakuin
PILIHAN ACT TERGANTUNG ACT & Pola Resistensi
Kegagalan pada AS +Amo di Lampung, Papua dan Sulawesi Utara
FDC ( Fixed dose combination ) pilihan
Efek samping seminimal mungkin
A
.
 Pengobatan Malaria Falsiparum/ Vivax
dengan Dihydroartemisinin-Piperakuin (DH-P)

Jumlah tablet per hari menurut berat badan

5-<8 8-<11 11-<17 17-<25 25-<36 36-<60 60- >80
Hari Jenis kg kg kg kg kg kg <80 kg kg
obat
1-3 DHP 1 1 2 3 4 5

F Prima
- - 1 1 1
1 kuin

V Prima
- - 1 1 1
1-14 kuin

Dihydroartemisinin(DH) : 2-4 mg ( 2,2mg)/kgBB (1tablet = 40 mg)

Piperakuin phosphate(P): 16-32mg (18mg/kgBB (1tablet = 320 mg)
Primakuin : 0.25 mg/kg BB
Peditrik tab : 20 mg DH 160 piperakuin, No high fat meal
DOSIS PRIMAKUIN SESUAI WHO 2015
 Pengobatan AS + Amo, P. Falsiparum / VIVAX
Menurut Berat Badan

Jumlah tablet perhari menurut

Hari Jenis obat berat badan
4.5 - 9 kg 9 - <18 kg 18- <36 kg >36kg

1-3 Artesunat 1 2 4

Amodiakuin 1 2 4

F-1 Primakuin - - 1
V
Primakuin - 1
1-14

Dosis obat : Amodiakuin basa = 10mg/kgBB (7.5-15) dan Artesunat =

4mg/kgBB (2-10); Non-FDC 1 tab AS=20 mg, 1 tbl Amo 200mg (~153 mg basa).
FDC : 25 mgAS- 67.5mg Amo ; 50 mgAS 135 mg Amo ; 100 mg AS 270 mg
Amo . PQ : 0.25 mg/kg BB/ hari (Falc)
Lini II ACT. Dosis penggunaan artemeter-lumefantrine (A-L)

Jenis obat Umur <3 >3-8 > 9 14 > 14 th

tahun tahun th
Hari Berat Badan Jam 5 <15 15 <25 kg 25 <35 > 35 kg
(Kg) kg kg
1 A-L 0 jam 1 2 3 4

A-L 8 jam 1 2 3 4

Primakuin 12 jam 1 2 2-3

2 A-L 24 jam 1 2 3 4

A-L 36 jam 1 2 3 4

3 A-L 48 jam 1 2 3 4

A-L 60 jam 1 2 3 4
 WHO package of interventions for the
prevention and control of malaria during
pregnancy

1. Use of insecticide treated nets (ITNs) to

prevent infection
2. Intermittent Preventive Treatment (IPT)
To prevent asymptomatic infections among
pregnant women living in areas of moderate or high
transmission of P. falciparum
3. Effective management and prevention of
malaria illness and anaemia.
 TREATMENT OF MALARIA IN PREGNANCY

I. UNCOMPLICATED MALARIA
First trimester:
Quinine (orally) + Clindamycin for 7 days.
ACT should be used if it is the only effective
treatment available.
Second and third trimesters:
Dihydroartemisinin-piperaquin (DHP)
Artemether plus Lumefantrine (AL)
Artesunate-amodiaquine (AS+Amo)
 Terapi malaria dengan HIV

Pilihan :
Artemether-Lumefantrine ( perlu monitoring )
Pasien dgn Lopinavir / Ritonavir/ azatanavir :
- lower exposure DHA
- conflicting results with quinine
- decreased AUC avotaquone ( 2-4 x)
 Malaria co-infected Tuberculosis

Rifampicine decreased exposure to quinine ,

5 x recrudescence
Rifampicine decreased exposure
mefloquine 3 x
Rifampicine : lower exposure to
artemether-lumefantrine
 Malaria with uncomplicated
hyperparasitemia
Low transmissin area mortality begin > 2 %
In Thailand, 4% parasitemia, 3% mortality (
30 x uncomplicated non hyperparasitemia )
Longer course ACT with parenteral/ oral
Monitoring delayed clearence or
recrudescence
 KLASIFIKASI RESPON PENGOBATAN ( WHO 2003 )

Kegagalan Pengobatan Dini - Berkembangnya menjadi malaria berat pada hari H1,
( ETF = Early Treatment Failure) H2, H3 disertai parasitemia
- Parasitemia pada H3 dengan temperatur aksiler>37.5C
- Parasitemia H2 > H0
- Parasitemia H3 >= 25% H0
Kegagalan Pengobatan Kasep - Berkembangnya tanda bahaya malaria berat setelah
( LCF = Late Clinical [& H3 dan parasitemia ( jenis parasit = H0)
Parasitological] Failure ) - Parasitemia dan temp. aksiler >37.5C pada H4 - H28

( LPF = Late Parasitological - Parasitemia H7, H14, H21, dan H28 ( Parasit = H0)
Failure )

Respon Klinis & Parasitologis - Tidak ada parasitemia sampai D28 dengan abaikan
Adekuat ( ACPR = Adequate temp. aksiler, tidak sesuai dengan kriteria ETF/
Clinical and Parasitological LCF/LPF.
Response)
WHO Guideline 2006-2015 on treatment failure
 Drug regimens for prophylaxis against malaria
Drugs Tab size Adult Child Preg Initiate Discontinued
mg dose

Areas with Chloroquine resistant Falciparum

Atovaquone- 250-100 1 tb/d Yes No 1-2 d 7 days

Proguanil 62.5-25

Mefloquine HCl 250 1 tb/w Yes Yes 3 wks 4 wks

Doxycycline 100 1 tb/d No No 1-2 d 4 wks

Areas with Chloroquine- sensitive Falciparum

Chloroquine 500 1tb/w Yes Yes 1 wk 4 wks

Areas with P. vivax, P ovale with/ without P. Faciparum

Primaquine 15 2 Yes No 1 wk 4 wks

primary tb/d

Primaquine 15 2 Yes No 1 day 7 days

Anti-relaps tb/d
 SEVERE MALARIA

DEFINITION : Patient, Plasmosium Asexual parasitemia,with one

or more CLINICAL or LABORATORY FEATURES :
PROSTRATION
SEVERE ANAEMIA ( Hb <5
IMPAIRED CONSCIOUSNESS ( GCS HYPOGLYCAEMIA( < 40 )
<11, Blantyre < 3 ) ACIDOSIS (base def <8,
RESPIRATORY DISTRESS HCO3 <15/ Pl. Lactate >5)
MULTIPLE CONVULSIONS ( > 2/ 24 hrs) RENAL IMPAIRMENT ( >3,
CIRCULATORY COLLAPSE / SHOCK ( blood urea > 20 mmol/L)
cap refil>3 or temp gradient on leg (mid HYPERPARASITEMIA, >10%
to prox limb), no hypotension; sys <80
adults, 70 in children + impaired perfuss)
PULMONARY EDEMA (CX-Ray/ O2 WHO: Guidelines for the
sat<92% room air + resp >30/min) ) Treatment
ABNORMAL BLEEDING of Malaria 2015
JAUNDICE ( > 3 mg/dL + par >100.000)
 PENYEBAB / ETIOLOGI

Plasmodium falciparum

Mixed plasmodium ( Falciparum+ vivax)

Plasmodium vivax

Plasmodium knowlesi
 PLASMODIUM KNOWLESI
Simian malaria ( Maccaca mullata)
Unusual presentation P. Malariae
Diagnosis by PCR
Acute diare, abdominal pain, jaundice
Algid malaria, hypotension
Renal failure, respiratory failure
 MANAGEMENT SEVERE MALARIA

SPECIFIC TREATMENT
ANTI MALARIAL DRUGS

ORGAN FAILURE TREATMENT

SUPPORTIVE TREATMENT
ANCILLARY TREATMENT
 SEQUAMAT
( 2005, Lancet, Agst )

AQUAMAT
2010, Lancet, Nov )
Pre-Treatment 12 hours after Artesunate

24 hours after Artesunate

MANAGEMENT SEVERE MALARIA IN PREGNANCY
 Penyesuaian dosis pada gangguan Fungsi Organ

ARTESUNATE : Tidak perlu penyesuaian dosis obat

derivat artemisinin pada gangguan fungsi hati dan atau
ginjal
Kina :Dosis kina parenteral diturunkan 1/3 setelah 48
jam pemberian pada :
Gagal ginjal akut
Gangguan fungsi hati
Tidak ada perbaikan klinis setelah 48 jam
Bila pasien sudah hemodialisis tidak perlu
pengurangan dosis kina
 Pengobatan lanjutan
Setelah pasien sadar/KU membaik, tx. Awal parenteral dapat
diubah dgn. Tx. Oral, paling kurang parenteral diberikan 3 x
pemberian ( 24 jam )
Diteruskan dengan :
ACT dosis lengkap (selama 3 hari): AL , AS + AQ
Artesunate/artemether tab. (total 7 hari ) + doksisiklin 3-5 Kg
BB 1 kali sehari selama 7 hari
Kina tab.(total 7 hari) + doksisiklin 7 hari
Bagi bumil, anak-anak : doksisiklin diganti dengan klindamisin 10
mg/Kg BB 2 kali sehari
 ACT baru
1. Artesunate Pyronaride (AP=Pyramax).
2. Artemisinin-Nafthoquine (AN = Arco)
3. Artemisinin-Pyronaridine
4. Dihydroartemisinin-pyronaridine
5. Artemisinin piperaquine
6. Artesunate - Lapdap
 OBAT baru non-ACT
Atovaquone proguanil (Malarone )

Fosmidomycin clindamycin

Arterolene piperaquine

Tafenoquine

CKD (cyclic-dependent kinases) inhibitors, KAF 156,

co-enzymA inhibitors, KAE609, dan Tigecycline
PAKATUAN WO PAKALAWIREN
Sampai Baku Dapa !
Dr. Paul Harijanto, Sp.PD-KPTI
Div. Penyakit Tropik & Infeksi
SMF/ Bag. Penyakit Dalam
FK UNSRAT/ RSUP Manado
RSU Bethesda -Tomohon

Telp.:
0431-351024/046 ( RSU Bethesda)
0812-430-2869 ( HP)
0431-351187 (Res)
E-mail : paulharijanto@gmail.com
 Figure 1 Q[i]ng h[a]o su or artemisinin 1 and derivatives dihydroartemisinin 2, artemether 3,
arteether 4, artesunic acid (artesunate) 5, and artelinate 6. The numbering scheme is that used by
Chemical Abstracts.

Woodrow, C J et al. Postgrad Med J 2005;81:71-78

Copyright 2005 BMJ Publishing Group Ltd.

 Golongan ARTEMISININ
Artemisinin, Artesunate, Artemether, Arteether, DHA

Qinghaosu Sesquiterpene Lactone

Larut dalam air dan diabsorbsi baik
Efek bunuh parasit yang cepat
Cepat dikonversi ke bahan aktif ( DHA)
t1/2 in malaria: 2 hours
Spektrum yang luas untuk semua jenis parasit dan staging
Bila dipakai monotherapy, perlu 7 hari
Direkomendasikan penggunaan ACT
 Artemisinin-base Combination Therapy
(A.C.T)
Rapid clerance parasites
Rapid resolution of symptoms
Reduce parasites by 10.000/cycle (past antimalarial only
100-1000 parasites/ cycle)
Eliminated rapidly:
when given to rapid drug elimination, should give on 7 days
When given comb with slow eliminated, shorter course
treatment ( 3 days are effective )
 The ideal ACT combination

Resisten obat pasangan belum terjadi

Pasangan obat mempunyai half-life panjang (> 4 hr)
Artemisinin membunuh bentuk asexual dgn cepat;
pasangan obat membersihkan parasit lainnya
Ditolerensi baik, toksisitas rendah
Artemisinin memiliki efek spectrum luas ( termasuk
membunuh gametosit)
Bila mungkin dosis tetap (Fixed dose )
Diproduksi secara standar Good Manufacturing
Practice (GMP)
Murah
Supply obat cukup
 Management Treatment Failures
Treatment failure within 14 days very
unusual :
32 trials (4917 patients), no failure on D14
7 trials failure at D14 ( 1 7 %)
Failure after 14 days : recrudescense or re-
infection
Rescue treatment :
Alternative ACT known effective in this region
Artesunate + tetracyclin/ doxycycline/ clindamycin
Quinine + tetracyclin/ doxycycline/ clindamycin
 RECOMMENDED DOSES OF ANTI MALARIAL DRUGS FOR
TREATMENT OF SEVERE MALARIA

DRUGS Dosis SIDE EFFECTS

ARTESUNATE
i.v. 2,4 mg/kg BB pada jam 0, dan jam
12, kemudian dilanjutkan jam 24,
48 dst sampai 7 hari. Dosis total 17
18 mg/ 7 hari ( 1 Amp= 60
Artemeter mg) Neurotoxicity in
3.2 mg/kg im pada hari I, dilanjutkan animal not human
1.6 mg/kg/ hari. TIDAK iv (1 amp
= 80 mg)
Artemisinin
Suppositories, 10 mg/kg at 0 & 4 hr
followed by 7 mg/kg at 24,36,48 &
60 hrs.

WHO 2006 : AS is the recommended FIRST CHOICE in area

low transmission
 Dosis ARTEMISININ PADA MALARIA
BERAT

0 JAM 12.J 24.J 48.J 72.J Max 7 hari

2.4 2.4 2.4 2.4 2.4

Mg/ Mg/ Mg/ Mg/ Mg/
KgBB KgBB KgBB KgBB KgBB

ARTESUNATE I.V/ I.M

ARTEMETER , hanya I.M , 3,2 mg/kg BB hari 1,

lanjut dosis 1,6 mg/kg BB hari berikutnya
 ARTESUNATE
I.V / I.M

ARTEMETHER I.M
1 Amp = 80mg
1 Fl = 60 mg