Penatalaksanaan

Malaria Terkini

Asep Purnama
Fakultas Kedokteran Universitas Nusa Cendana
RSUD Dr. Tjark Corneille Hillers – Maumere

“Urgency on the Comprehention Of Tropical Disease”

Hotel NEO by Aston Kupang, 18 Nopember 2017
 MALARIA
• Penyakit yang disebabkan oleh Plasmodium
• Species penyebab malaria pada manusia
– P. falciparum, P. vivax, P. ovale, P. malariae, P. knowlesi

• P. knowlesi
– Parasit malaria ke-5 pada manusia
– Parasit malaria simian, zoonotik
– Siklus hidup aseksual, 24 jam [vs 72 jam]
– Morfologi secara mikroskopis mirip P. malariae
– Diagnosis dengan Polymerase Chain Reaction
Morfologi P. knowlesi
 Malaria Transmission Cycle
Exo-erythrocytic (hepatic) Cycle:
Sporozoites injected Sporozoites infect liver cells and
into human host during develop into schizonts, which release
blood meal merozoites into the blood

Parasites
mature in
mosquito
midgut and Dormant liver stages
MOSQUITO HUMAN
migrate to (hypnozoites) of P.
salivary vivax and P. ovale
glands

Parasite undergoes
sexual reproduction in
the mosquito
Some merozoites
differentiate into male or
female gametocyctes
Erythrocytic Cycle:
Merozoites infect red
blood cells to form
schizonts
 malaria life cycle.flv

10 November 2003 7 Prodigy© Pŗődũçțíŏñțę

 KEBIJAKAN TATALAKSANA
• Diagnosa malaria harus terkonfirmasi
mikroskop atau RDT [Stop Malaria Klinis]
• Artemisinin based Combination Therapy
[Stop Monotherapy]
• Terapi radikal
• Sembuh klinis, parasitologis dan mencegah
penularan selanjutnya
• Memantau efektifitas obat malaria
DIAGNOSIS
● Gejala dan tanda
● Pemeriksaan Laboratorium
- Blood smear [thick & thin blood film]
- Rapid Diagnostic Test
[immunochromatography]
- QBC [Semi quantitative buffy coat]
- PCR [Polymerase Chain Reaction]
Hasil Labor Berbeda
Hasil Labor Berbeda
SARAN PERBAIKAN
 KEBIJAKAN TATALAKSANA
• Diagnosa malaria harus terkonfirmasi
mikroskop atau RDT [Stop Malaria Klinis]
• Artemisinin based Combination Therapy
[Stop Monotherapy]
• Terapi radikal
• Sembuh klinis, parasitologis dan mencegah
penularan selanjutnya
• Memantau efektifitas obat malaria
 Standard Mono therapy
1995 - 2000 CQ3/SP1/Q7 + PQ1/PQ14

Combo-Therapy
2001-2003
Old-drug

New Drugs/ ACT

2004 AS + AQ

2008 New Drugs/ ACT

DHP (Papua)

2010 New Drugs/ ACT

DHP (Indonesia)
ARTEMISININ UPDATE

Artemisia annua vs Cosmos caudatus [Kenikir] WHO, 2004

 ARTEMISININ
• Spesifisitas yang luas terhadap berbagai stadium
parasit malaria
• Mampu menghambat produksi gametosit
 Lebih efektif daripada antimalaria lain
• Derivat :
– Dihidroartemisinin
– Artesunate
Relatif lebih poten
– Artemether daripada artemisinin
– Co-artemether
– Arteether

Yeung S, Pongtavornpinyo W, Hastings IM, Mills AJ, White NJ Am. J. Trop. Med. Hyg. 2004; 71(Suppl 2): 179–86.
McIntosh H,Olliaro P. Artemisinin derivatives for treating uncomplicated malaria. Cochrane Database of Systematic Reviews 1999.
Kumar S, Srivastava S. Current Science, 2005; 89(7): 1097-102.
 ARTEMISININ…(2)
• Segi farmakologis:
– Tidak perlu penyesuaian dosis pada gangguan fungsi hati
& ginjal
– Tidak ditemukan interaksi obat & efek samping yang
bermakna secara klinis
– T½ sangat pendek  Diberikan dalam jangka waktu lebih
panjang  mencegah kekambuhan

Kombinasi Artemisinin
Durasi pemberian
& antimalaria lain T½ >
obat <
Mekanisme kerja yang berbeda Mencegah timbulnya
resistensi
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): 179–86.
McIntosh H,Olliaro P. Artemisinin derivatives for treating uncomplicated malaria. Cochrane Database of Systematic Reviews 1999.
Kombinasi Artemisinin dengan Obat Lain
 AS Monoterapi vs ACT
100 Angka kesembuhan(%)
90
80
70
60
50
artesunte +
40 mefloquine
30 artesunate
20
10
0
Hari pengobatan
1 2 3 4 5 6 7
 Cost Effectiveness ACT
US $
25

20.73 20.77
20

15 13.88 13.88
11.31
10.15 9.79
10

4.37
5 2.83 2.07
0.04 0.08 0.13 0.51 0.91
0
SP AQ AQ+SP AQ+AS AM+LF

Drug Cost Indirect Cost Total Cost

Wiseman V, Kim M, Mutabingwa TK, Whitty CJM. PLoS Med 2006; 3(10): e373. DOI:10.1371/journal.pmed.0030373
Arthemisinin-based Combination Therapy
Drug Name Composition
Artemether + 20 mg + 120 mg Fixed dose tablets
lumefantrine
Artesunate + 25 mg + 67,5 mg
amodiakuin
50 mg + 135 mg Fixed dose tablets
100 mg + 270 mg
50 mg + 150 mg (base) Co-blistered tablets
Artesunate + 200 mg + 250 mg Co-blistered tablets
meflokuin
Dihidroartemisinin 40 mg + 320 mg Fixed dose tablets
+ piperakuin
Artesunate + 50 mg + 500/25 mg Co-blistered tablets
sulfadoksin /
pirimetamin

World Health Organization. Antimalarial medicines procured by WHO. 2009

 ACT DI INDONESIA
• Artesunate Amodiaquine (AS-AQ)
• Dihydroartemisinin Piperaquine (DHP)
• Artemether Lumefantrine (AL)
• Artesunate Naphthoquine
 TERAPI LINI PERTAMA
P. Falciparum
Artemisinin based Combination Therapy
Primakuin 0,25 mg/kgBB; Day 1
P. Vivax or P. Ovale
Artemisinin based Combination Therapy
Primakuin 0,25 mg/kgBB; Day 1-14
P. Falciparum + P. Vivax/P. Ovale
Artemisinin based Combination Therapy
Primakuin 0,25 mg/kgBB; Day 1-14
Terapi Lini I: Plasmodium falciparum
Hari Obat Jumlah tablet per hari menurut berat badan

<4 4-5 6–10 11-17 18-30 31-40 41-59 ≥60

kg kg kg kg kg kg kg kg

0-1 2-5 6-11 1-4 5-9 10-14 ≥15 ≥15

bln bln bln thn thn thn thn thn
1-3 DHP 1/3 1/2 1/2 1 1,5 2 3 4
1 P -- -- 1/4 1/4 1/2 3/4 1 1

DHP Dihidroartemisinin Piperakuin; P Primakuin

Dihydroartemisinin 2-4 mg (2.2mg)/kgBW (1 tablet = 40 mg)
Piperaquine 16-32mg (18mg/kgBW (1 tablet = 320 mg)
Primaquine 0.25 mg/kgBW
 Terapi Lini I: Plasmodium vivaks
Hari Obat Jumlah tablet per hari menurut berat badan

<4 4-5 6–10 11-17 18-30 31-40 41-59 ≥60

kg kg kg kg kg kg kg kg

0-1 2-5 6-11 1-4 5-9 10-14 ≥15 ≥15

bln bln bln thn thn thn thn thn
1-3 DHP 1/3 1/2 1/2 1 1,5 2 3 4
1-14 P -- -- 1/4 1/4 1/2 3/4 1 1

DHP Dihidroartemisinin Piperakuin; P Primakuin

Dihydroartemisinin 2-4 mg (2.2mg)/kgBW (1 tablet = 40 mg)
Piperaquine 16-32mg (18mg/kgBW (1 tablet = 320 mg)
Primaquine 0.25 mg/kgBW
 Terapi Lini I: Infeksi Campur
P. falciparum + P. vivaks/P. ovale
Hari Obat Jumlah tablet per hari menurut berat badan

<4 4-5 6–10 11-17 18-30 31-40 41-59 ≥60

kg kg kg kg kg kg kg kg

0-1 2-5 6-11 1-4 5-9 10-14 ≥15 ≥15

bln bln bln thn thn thn thn thn
1-3 DHP 1/3 1/2 1/2 1 1,5 2 3 4
1-14 P -- -- 1/4 1/4 1/2 3/4 1 1

DHP Dihidroartemisinin Piperakuin; P Primakuin

Dihydroartemisinin 2-4 mg (2.2mg)/kgBW (1 tablet = 40 mg)
Piperaquine 16-32mg (18mg/kgBW (1 tablet = 320 mg)
Primaquine 0.25 mg/kgBW
 TERAPI LINI KEDUA
P. Falciparum
Quinine + Doxycyclin/Tetracyclin/Clindamycin
Primaquine 0,25 mg/kgBB; Day I
P. Vivax or P. Ovale
Quinine
Primaquine 0,25 mg/kgBB; Day I-XIV
P. Falciparum + P. Vivax/P. Ovale
Quinine + Doxycyclin/Tetracyclin/Clindamycin
Primaquine 0,25 mg/kgBB; Day I-XIV
 Terapi Lini Kedua
Plasmodium Falciparum
Days Drugs Number of tablets based on age-groups
Single dose 0-11 1-4 5- 9 10 - 14 > 15
mos mos years years years
1 Quinine *) 3x½ 3x1 3x1½ 3 x (2-3)
Doxycyclin -- -- -- 2 x 50 mg 2 x 100 mg

Primaquine - ¼ ½ ¾ 1
2-7 Quinine *) 3x½ 3x1 3x1½ 3x2
Doxycycline -- -- -- 2 x 50 mg 2 x 100 mg

-- -- -- 4x4 4 x 250 mg
TETRACYCLIN mg/kg BW
CLINDAMYCIN 2x10 2x10 2x10 2x10 2x10
mg/kg BW mg/kg BW mg/kg BW mg/kg BW mg/kg BW
 Terapi Lini Kedua
Plasmodium Vivax atau Plasmodium Ovale

Day Drugs Number of tablets based on age-groups

<1 1-4 5–9 10 - 14 > 15

years years years years years

1- 7 Quinine *) 3x½ 3x1 3x1½ 3x2

1-14 Primaquine - ¼ ½ ¾ 1

Quinine 10 mg/kg BW
Primaquine 0,25 mg/kgBB; Day I-XIV
 KEBIJAKAN TATALAKSANA
• Diagnosa malaria harus terkonfirmasi
mikroskop atau RDT [Stop Malaria Klinis]
• Artemisinin based Combination Therapy
[Stop Monotherapy]
• Terapi radikal
• Sembuh klinis, parasitologis dan mencegah
penularan selanjutnya
• Memantau efektifitas obat malaria
Artesunat-Amodiakuin dan Klorokuin pada Pengobatan
Malaria Vivaks di Puskesmas Kopeta, Maumere,
Nusa Tenggara Timur, 2007

Armedy Ronny Hasugian, Emiliana Tjitra

Pusat Teknologi Terapan Kesehatan dan Epidemiologi Klinik,
Badan Penelitian dan Pengembangan Kesehatan, Kementrian Kesehatan

HASIL:
Total 100 subjek monoinfeksi P. vivax yang memenuhi kriteria diobati
secara acak dengan AsAq atau Cq. Efikasi hari ke-28 AsAq
dibandingkan Cq secara Intention To Treat (ITT) adalah 93,7% versus
56,4%. Efikasi hari ke-28 AsAq per protocol (PP) adalah 93,6%
dibandingkan Cq 51,4%.

KESIMPULAN:
Efikasi AsAq lebih baik secara signifikan dibandingkan CQ untuk
pengobatan P.vivax di Maumere.
 KEBIJAKAN PENGGANTIAN
OBAT MALARIA [WHO]

• Kegagalan pengobatan >10% dengan

monitoring pengobatan selama 28 hari

• Obat baru, uji klinis dengan angka

kesembuhan > 95%
 Surat Dirjen P2PL

 Nomor: PM 01.11/D/IV.1/1601/2012
 Tanggal: 28 Desember 2012
 Perihal: “Penghentian penggunaan
Klorokuin sebagai obat anti malaria”
Asep Purnama

www.rsudtchillers.net
Call center +62 85239132220
Surat Edaran Dinkes NTT
Dinkes Bid P2MK 09/443.33.02/I/2013

Asep Purnama

www.rsudtchillers.net
Call center +62 85239132220
 ARTI LINGKARAN WARNA

 WARNA HIJAU
Obat bebas: vitamin, mineral
 WARNA BIRU
Obat bebas terbatas: obat batuk
 WARNA MERAH
Asep Purnama
Obat keras: antibiotik
Harus dengan resep dokter
Obat Bebas Terbatas
atau Obat Keras ?
 KEBIJAKAN TATALAKSANA
• Diagnosa malaria harus terkonfirmasi
mikroskop atau RDT [Stop Malaria Klinis]
• Artemisinin based Combination Therapy
[Stop Monotherapy]
• Terapi radikal
• Sembuh klinis, parasitologis dan mencegah
penularan selanjutnya
• Memantau efektifitas obat malaria
 PRIMAQUINE
• Prevent relapse in vivax and ovale malaria
0.25 mg/kg BW daily, 14-day course

• The only potent gametocytocide in falciparum

malaria
0.25 mg/kg BW, single dose

• Except pregnant woman, infants aged < 6

months, women breastfeeding infants aged < 6
months, people with G6PD deficiency
 Prevalence of G6PD in Indonesia
Satyagraha et al
Eijkman Institute

Gunung Mas (19.9%)
Nias Pujon Kendari (1.3%)
(6%) Bangka Sampit (8.9%) Banjarmasin Maba Tantular 2010
Matsuoka 1986 (3.4%) (25.8%) (11.9%) (4.2%)
Kapuas‐ Waringin
Central Java Sumba(5.2%)
(40.9%)
(14%) Soemantri 1995 Sumba Timur (4.7%) Flores Palue Island
Tantular 2010 (5%) Matsuoka 2003
 KEBIJAKAN TATALAKSANA
• Diagnosa malaria harus terkonfirmasi
mikroskop atau RDT [Stop Malaria Klinis]
• Artemisinin based Combination Therapy
[Stop Monotherapy]
• Terapi radikal
• Sembuh klinis, parasitologis dan mencegah
penularan selanjutnya
• Memantau efektifitas obat malaria
 Efficacy and Safety of dihydroartemisinin‐
piperaquine for the treatment of 
uncomplicated Plasmodium falciparum and 
Plasmodium vivax Malaria in Several 
Sentinel Sites in Indonesia

Sikka, East Nusa Tenggara I Samarinda, East Kalimantan

Tomohon, North Sulawesi I South Halmahera, North Maluku
 Hasil studi monitoring efikasi
Site Code NT 1) SA2) MU 3) KI 4)
ACD Screening 5)  3100 601 807 871
PCD Screening 6)  480 385 111 150
Enrollment 7)  82 6 18 1
Pf 8)  46 9 8 1
APCR: 44 8 7 0
ETF: 0 0 0 0
LCF: 0 0 0 0
LPF: 0 0 0 0
LFU/WTH: 2 1 1 1
Pv 9)  36 35 10 0
APCR: 34 32 9 0
ETF: 0 0 0 0
LCF: 0 0 0 0
LPF: (1) 0 0 0
LFU/WTH: 1 3 1 0

Notes:
1) NT: East Nusa Tenggara,  2) SA: North Sulawesi, 3) MU: North Molluccas, 4) KI: East Kalimantan, 5) ACD Screening: active

case detection screening, 6) PCD Screening: passive case detection screening, 7) Enrollment: total enrolled subjects, 8) 

Pf: total subjects with positive P. falciparum malaria, 9) Pv: total subjects with positive P. vivax malaria
Artemisinin Resistance?
Global Plan for Artemisinin
Resistance Containment
- GPARC -
 Drug development pipeline

All artemisinin 
based

New compounds 
(no artemisinins)

Source: MMV website
CLINICAL TRIALS ON ACTs

(ATS+PD)3

(ART+NTQ)1 VS
Parentral ATM vs QN
ATS3+AQ3 VS (DHA+PPQ)3
(ART+PPQ)2
(ATS+PD)3 vs
((ATM+LMF)3
CQ3 vs (CQ3+SP1) vs AQ3

IV ART vs QN
(ATS+PD)3 vs (ART+NTQ)1 VS
((CQ)3 (ATM+LMF)3 VS
(DHA+PPQ)3
(ATS+PD)3 vs (DHA+PP)Q3
((ATM+LMF)3 ATS3+AQ3 VS
(DHA+PPQ)3
Penelitian Malaria di Kab. Sikka

Lancet 2010; 375: 1457-67

Malaria Journal 2012, 11; 153
 SEVERE MALARIA
• DEFINITION: patient with plasmodium asexual
parasitemia, with one or more CLINICAL or
LABORATORY FEATURES
• CLINICAL FEATURES: Prostration, Failure to Feed,
Impaired Consciousness, Respiratory Distress,
Multiple Convulsions, Circulatory Collapse,
Pulmonary Edema, Abnormal Bleeding, Jaundice,
Hemoglobinuria
• LABORATORY FEATURES: Severe Anemia,
Hypoglycemia, Acidosis, Renal Impairment,
Hyperlactatemia,Hyperparasitemia
WHO: Guidelines for the Treatment of Malaria 2010
 MALARIA BERAT
Malaria Serebral
Malaria Biliosa, Bilirubin> 3 Mg% & Gagal Organ Lainnya
Gagal Ginjal Akut, Urine< 400 ml/24 jam & SC > 3 mg%
Hipoglikemi < 40 mg%
Syok, Sistolik < 70 mmHg / Anak < 50 mmHg
Anemia Hb < 5 Gr% / Ht < 15%
Edema Paru / ARDS
Perdarahan Spontan / DIC
Kejang Berulang
Asidosis PH <7.15 , Plasma Bicarb < 15 mmol/L
Haemoglobinuria
Hiperparasitemia > 5 %
Hipertermia > 40 C (Rectal)
 ETIOLOGI MALARIA BERAT

• Plasmodium falciparum
• Mixed plasmodium [Falciparum+ vivax]
• Plasmodium vivax
ETIOLOGY OF SEVERE MALARIA

• Plasmodium falciparum
• Mixed plasmodium [Falciparum+ vivax]
• Plasmodium vivax
• Plasmodium knowlesi
 MANAGEMENT OF SEVERE
MALARIA
Principle:
Early Diagnosis & Prompt Treatment

• Give parenteral Antimalarials

• Drug of choice: Artesunat IV
• 2,4mg/kgBW on admission [time = 0],
• then at 12 h and 24 h, then once a day

Oral treatment should be substituted as soon as

reliably possible:
• Artemisinin-based Combination Therapy or
• Quinine plus Doxycycline or Clindamycin
63
SUMMARY OF STUDIES: SHOW ARTESUNATE TO BE MORE
SAFE AND EFFICACIOUS THAN QUININE IN BOTH ADULTS
AND CHILDREN IN THE TREATMENT OF SEVERE MALARIA
Working Together
Fighting Malaria!!
THANK YOU
Epang Gawan

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