TATALAKSANA MALARIA PADA ANAK

Yulia Iriani
Divisi Infeksi dan Penyakit Tropis KSM/Bagian Ilmu Kesehatan Anak FK UNSRI/RSMH

PENDAHULUAN

Definisi malaria: infeksi akut hingga kronik yang disebabkan oleh salah satu atau lebih spesies
Plasmodium, ditandai dengan panas tinggi bersifat intermiten, anemia, dan hepato-
splenomegali. Konfirmasi diagnosis: pemeriksaan darah tepi (apusan tebal & tipis) untuk
memastikan adanya parasit Plasmodium.

Spesies parasit: P. falciparum, P. vivax, P. ovale, P. malariae, P. knowlesi

Faktor genetik, status imun, usia pejamu memengaruhi

• Epidemiologi
• Patogenesis
• Gambaran klinis
• Tatalaksana

ETIOLOGI
• Plasmodium falciparum malaria tropikana
o Paling ganas, kadar parasitemia paling tinggi
o satu-satunya parasit malaria yang menimbulkan penyakit mikrovaskular.
o Malaria serebral, edema paru, anemia, problem renal
• Plasmodium vivax --> malaria tertiana
o Tanpa pengobatan: berakhir dalam 2 – 3 bulan. Relaps 50% dalam beberapa
minggu – 5 tahun setelah penyakit awal.
• Plasmodium ovale --> malaria ovale
o ≈ infeksi P. vivax, lebih ringan. Seringkali sembuh tanpa pengobatan
• Plasmodium malariae --> malaria kuartana
o Asimtomatis dalam waktu lama
• Plasmodium knowlesi --> malaria knowlesi
o gejala demam menyerupai malaria falciparum

EPIDEMIOLOGI
• Malaria merupakan masalah global. Transmisi terjadi di > 100 negara, dana mengenai >
1,6 triliun manusia
• Daerah transmisi utama: Afrika, Asia, Amerika Utara.
• P. falciparum & P. malariae: sebagian besar
• P. falciparum: predominan di Afrika, Haiti, New Guinea
• P. vivax: predominan di Banglades, Amerika, India, Pakistan, Sri Lanka
• P. vivax & P. falciparum predominan di Asia Tenggara, Amerika Utara, Oceania
• P. ovale: paling jarang, tu di Afrika
• P. knowlesi: Asia Tenggara, terutama Kalimantan, Malaysia, Philippines, Thailand,
the Thai-Burmese border, Singapore, dan Cambodia.
SIKLUS HIDUP DAN PATOGENESIS MALARIA
Siklus hidup Plasmodum meliputi fase seksual eksogen dan aseksual
• Fase seksual eksogen (sporogoni) dalam tubuh nyamuk
• Fase aseksual (skizogoni) dalam tubuh pejamu perantara / manusia
• Daur dalam darah (skizogoni eritrosit)
• Daur dalam sel parenkim hati / stadium jaringan (skizogoni ekso-eritrosit)
• Infeksi malaria melalui transfusi hanya menghasilkan siklus eritrositer karena tidak
melalui sporozoit yang memerlukan siklus hati sehingga dapat diobati dengan mudah.

• Siklus hidup stadium aseksual (manusia) diawali dengan fase exoeritrositer. Saat nyamuk
menggigit manusia, sporozoit di dalam saliva nyamuk masuk ke aliran darah (1).
• Dalam beberapa menit sporozoit sampai ke hati dan menyerang hepatosit (2); hepatosit
terinfeksi matang menjadi skizon dalam waktu 4 minggu.
• Pada infeksi P. vivax and P. ovale, beberapa skizon dapat tetap ada (dormant) sebagai
hipnozoit (3) untuk beberapa minggu – tahun sebelum menyebabkan kekambuhan klinis.
• Dengan rupturnya skizon (selama 6-9 hari), ribuan merozoit dilepaskan ke aliran darah (4).
• Pada fase eritrositer, merozoit menyerang eritrosit (membentuk tropozoit cincin à
tropozoit lanjut à skizon darah awal à skizon matur) dan juga menjalani siklus
reproduksi aseksual (5) atau berkembang menjadi bentuk seksual non multiplikasi
(gametosid) (6).
Siklus hidup dan patogenesis malaria (Gambar a) dan perkembangan malaria pada
R E V I E yang
populasi W rentan dan peluang untuk pengobatan (Gambar b).

(b) Perkembangan malaria pada

(a) Siklus hidup dan patogenesis malaria
a b
populasi rentan dan peluang
pengobatan
Blood stage Cerebral malaria
Hypoxic brain Edema and hemorrhage
Brain tissue BBB disruption

Trophozoite Schizont Merozoites Microvascular

obstruction ROS
RBC Adherence or Hb Cerebral
Gametophyte NO Heme Antidisease therapies
sequestration malaria
maturation NO needed to improve survival
Invasion (18% die)
iRBC
Inflammation Monocyte Apoptotic EC
iRBC
(ring) Circulating mature Cure
RBC gametocyte Parenchymal and axonal damage • Antiparasite
treatment Acidosis Severe
Severe anemia • Transfusion (15% die) anemia
Mosquito No drugs (1% die)
• Supportive care
Drugs to reduce transmission Hemolysis RBC
Rosetting
iRBC O2 Progression to
Merozoites delivery Blood
Symptom-prompted severe malaria
transfusion
Bystander Antiparasite treatment
hemolysis Cure Symptomatic malaria
RBC
Hb

No drugs Progression
Immediate Resolution
development Metabolic acidosis Intermittent presumptive
Delayed Antiparasite treatment
Impaired RBC Cure Asymptomatic
development
Impaired deformability parasitemia
erythropoiesis Impaired
vasoregulation O2 Hypoxia Infection Mosquito
Sporozoite Sporozoite delivery transmission
NO
Lactic Anaerobic glycolysis Susceptible
acid population
Hypnozoite Platelet Vascular
(P. vivax, P. ovale) leakage
Inflammation
Primaquine (surrounding
tissue)
Reduced blood flow EC apoptosis

Figure 1 Severe malaria in children. (a) Life cycle and pathogenesis of malaria. Malaria infections begin with the injection of parasite sporozoites
Infeksi malaria
by infected mosquitoesdimulai dengan
during a blood suntikaninvade
meal. Sporozoites parasit sporozoit
hepatocytes olehinto
and proliferate nyamuk
merozoites.yang
One P.terinfeksi selama
falciparum sporozoite
into 40,000 merozoites per liver cell over 6 d. During P. vivax and Plasmodium ovale infection, some sporozoites also differentiate into hypnozoites
develops

menghisap darah.
that remain dormant in the Sporozoit
liver for monthsmenyerang hepatosit
to years before undergoing divisiondan berkembang
and development biak menjadi
into merozoites. Only one drugmerozoit.
family, the
8-aminoquinolines such as primaquine, kills hypnozoites. However, the 8-aminoquinolines are toxic in glucose-6-phosphate dehydrogenase (G6PD)-
Satu sporozoit
deficient P. falciparum
humans, a common deficiency inberkembang menjadi
malaria-endemic regions 40.000
of the world. merozoit
Consequently, per sel
elimination of P. hati
vivax andselama 6 hari.
P. ovale may require new
Selama infeksi
antihypnozoite P. can
drugs that vivax
be safely dan Plasmodium
administered ovale,
to a population in whichbeberapa
G6PD deficiency sporozoit
is prevalent. Thejugablood berdiferensiasi
stage of malaria begins when
hepatic merozoites invade erythrocytes. Within 12 h of invasion, the parasite remodels the red blood cell (RBC), facilitating the growth of the parasite
menjadi hipnozoit
and transporting PfEMP1 to yang tetap tidak
the erythrocyte aktif
membrane. di hati
Infected RBCsselama
(iRBCs) bindberbulan-bulan
to endothelium through hingga
PfEMP1bertahun-tahun
primarily to avoid clearance by
the spleen. Sequestration of infected RBCs injures endothelial cells (ECs) and disrupts blood flow, causing tissue hypoxia and lactic acidosis. These
sebelum mengalami pembelahan dan perkembangan menjadi merozoit. Hanya satu
mechanisms contribute to organ-specific syndromes such as cerebral malaria and placental malaria when sequestration occurs in the brain or placenta.
kelompok obat, and
Hemolysis of infected 8-aminoquinolines
bystander (uninfected) RBCs seperti primakuin,
causes anemia that may beyang dapatbymembunuh
exacerbated hipnozoit.
impaired erythropoiesis. HemolysisAkan
also contributes
to endothelial injury and dysfunction as free hemoglobin (Hb) catalyzes oxidative damage and consumes nitric oxide (NO), a regulator of endothelial
tetapi, 8-aminoquinolines
cells. Merozoites develop in the sequestered bersifat
RBCs, andtoksik pada
the rupture individu
of infected dengan
erythrocytes causes defisiensi glukosa-6-fosfat
fever and rigors. Most merozoites invade uninfected
dehidrogenase (G6PD), defisiensi umum di daerah endemik malaria di dunia. Akibatnya,
RBCs and circulate as ring-stage parasites, but a small fraction of merozoites develop into male and female gametocytes that infect mosquitoes when
taken up during a blood meal. Gametocytes continue to circulate after treatment at the asexual blood stages; therefore, safe drugs to kill circulating
eliminasi
gametocytes P. vivax
would help indan P. ovale
P. falciparum mungkin
elimination. memerlukan
ROS, reactive oxygen species;obat antihypnozoite
BBB, blood-brain baru yang
barrier. (b) Progression dapat
of malaria in a susceptible
population and opportunities for treatment. Approximately 2 billion people live in areas where malaria is transmitted. In regions where malaria is
diberikan denganparasitemia
endemic, asymptomatic aman pada populasi
is common di mana
and contributes defisiensi
to transmission. G6PDpresumptive
Intermittent lazim terjadi.
treatment given to a population helps to
Stadium darah malaria dimulai ketika merozoit hati menyerang eritrosit. Dalam 12 jam
eliminate parasites from asymptomatic carriers. Of the ~500 million symptomatic cases of malaria globally each year, only about 1% progress to severe
malaria. The major severe malaria syndromes are cerebral malaria, acidosis (respiratory distress) and severe anemia. Effective antidisease therapies that
invasi, parasitwithmengubah
can be combined parasite-killing bentuk sel darah
drugs are needed to improvemerah (RBC),
survival from severememfasilitasi
malaria. pertumbuhan parasit
dan mengangkut PfEMP1 ke membran eritrosit. Sel darah merah yang terinfeksi (iRBC)
chloroquine-resistant as well as chloroquine-sensitive P. falciparum. at the 4-amino position. Examples of side chains in these ‘reversed
mengikat
Examples includeendotel melalui
such well-known PfEMP1
antimalarial drugs asterutama
pyronaridine untuk menghindari
chloroquine’ compounds include pembersihan limpa. and other
dibemethins, imipramine
Sekuestrasi
and piperaquine sel darah
(Fig. merahwith
1), compounds yang terinfeksi
4-amino side chainmencederai
varia- pharmacophoressel endotel predicteddan mengganggu
to confer reversal activity aliran
21,22. Ferroquine,

tions on the 7-chloro-4-aminoquinoline moiety of chloroquine and a potent new organometallic chloroquine analog that carries a ferro-
darah, menyebabkan
certain other 3- or 7-substituted hipoksia jaringan14–18
4-aminoquinolines dan asidosis
. The laktat.
risk of cenyl groupMekanisme
in the side chainini berkontribusi
23, also seems to fall withinpada this theoreti-
sindrom
arrhythmia, spesifik
as indicatedorganby hERG seperti
(humanmalaria
ether-a-go-goserebral
related gene dancal malaria
framework. plasenta
Successfulsaat
phase sekuestrasi
1 trials of ferroquineterjadi
24 and AQ-13, a

channel assays, remains a concern for the 4-aminoquinoline short-chain analog of chloroquine25, have raised hope that these and
diproduct)
otak atau plasenta. Hemolisis sel darah merah yang terinfeksi dan eritrosit di sekitarnya
compounds. These risks must be considered in light of the safety record other 4-aminoquinolines will be successful in clinical development
(tidak terinfeksi)
of chloroquine, evidence menyebabkan anemia yang
that the ratio of hERG half-maximum inhibi-dapat and joindiperburuk
pyronaridine and oleh eritropoiesis
piperaquine yang
as alternative drugs for use
terganggu. Hemolisis
tory concentration (IC 50 ) to juga berkontribusi terhadap cedera dan disfungsi endotel karena
free drug concentration may not be a reli- against chloroquine-resistant malaria.
able predictor of human risk and the suggestion that 4-aminoquinoline Various studies have identified a number of antimalarial com-
hemoglobin bebas
candidates with higher hERG (Hb)IC50 mengkatalisis
values have lower riskkerusakan
of arrhythmia oksidatif
pounds thatdan mengonsumsi
show greater activity againstoksida nitrat
chloroquine-resistant than
(NO), regulator
in comparison sel endotel.
to chloroquine 18,19 . Merozoit berkembang dalam sel darah P.merah
chloroquine-sensitive falciparum yang
and havetersekuester,
IC50 values that are linked
Although chemosensitizing agents are not sufficiently active at to PfCRT isotype26,27. Combinations of various antimalarial pairs may
dan pecahnya eritrosit yang terinfeksi menyebabkan demam dan rigor. Sebagian besar
concentrations that can be safely and effectively used in humans20, also act in synergy or in antagonism, depending on the exact muta-
merozoit menyerang
their resistance-reversing sel has
activity darah
inspiredmerah yang
the synthesis tidak terinfeksi
of chloro- tions encoded dan
by thebersirkulasi
PfCRT allele12,27 sebagai parasit raise the
. These observations
stadium cincin, tetapi sebagian kecil merozoit berkembang menjadi gametosit jantan combat
quine derivatives that incorporate various chemosensitizer moieties possibility of drug combinations that together may dan malaria
betina yang menginfeksi nyamuk saat diambil selama menghisap darah. Gametosit terus
158 VOLUME 19 | NUMBER 2 | FEBRUARY 2013 NATURE MEDICINE
 beredar setelah pengobatan pada tahap darah aseksual; oleh karena itu, obat yang aman
untuk membunuh gametosit yang bersirkulasi akan membantu eliminasi P. falciparum.
Kira-kira 2 miliar orang tinggal di daerah tempat penularan malaria. Di daerah di mana
malaria endemik, parasitemia asimtomatik sering terjadi dan berkontribusi pada penularan.
Terapi presumtif intermiten yang diberikan kepada suatu populasi membantu menghilangkan
parasit dari karier asimtomatik. Dari ~ 500 juta kasus gejala malaria di seluruh dunia setiap
tahun, hanya sekitar 1% yang berkembang menjadi malaria berat. Sindrom malaria berat yang
utama adalah malaria serebral, asidosis (gangguan pernapasan) dan anemia berat.
Pengobatan efektif untuk mengatasi penyakit ] yang dikombinasikan dengan obat pembunuh
parasit diperlukan untuk meningkatkan kelangsungan hidup dari malaria berat.
Secara umum, proses patologi penting pada malaria meliputi:
• Demam
• Akibat ruptur eritrosit à merozoit dilepas ke sirkulasi
• Anemia
• Akibat hemolisis, sekuestrasi eritrosit di limpa dan organ lain, dan depresi sumsum
tulang
• Kejadian immunopatologi
• Aktivasi poliklonal à hipergamaglobulinemia, pembentukan kompleks imun,
depresi immun, pelepasan sitokin seperti TNF
• Anoxia jaringan
• parasit P. falciparum matur: timbul knob pada permukaan sel darah merah
berparasit yang memfasilitasi cytoadherence P. falciparum-parasitized red cells ke
sel-sel endotel vaskular otak, ginjal, organ yang terkena lainnya à obstruksi aliran
darah & kerusakan kapiler à leakage protein dan cairan vaskular, edema, serta
anoxia jaringan otak, jantung, paru, usus, ginjal.

Karakteristik spesies plasmodium tertera pada tabel berikut ini.

1576 TABLE 219-1 Characteristics of Plasmodium Species Infecting Humans
FINDING FOR INDICATED SPECIES
CHARACTERISTIC P. FALCIPARUM P. VIVAX P. OVALEa P. MALARIAE P. KNOWLESI
Duration of intrahepatic 5.5 8 9 15 5.5
phase (days)
Number of merozoites 30,000 10,000 15,000 15,000 20,000
released per infected
hepatocyte
Duration of erythrocytic 48 48 50 72 24
cycle (hours)
Red cell preference Younger cells (but can Reticulocytes and cells Reticulocytes Older cells Younger cells
invade cells of all ages) up to 2 weeks old
Morphology Usually only ring Irregularly shaped large Infected erythrocytes, Band or rectangular Resembles P. falciparum
forms; banana-shaped rings and trophozoites; enlarged and oval with forms of trophozoites (early trophozoites)
gametocytes enlarged erythrocytes; tufted ends; Schüffner’s common or P. malariae (later
Schüffner’s dots dots trophozoites, including
band forms)
Pigment color Black Yellow-brown Dark brown Brown-black Dark brown
Ability to cause relapses No Yes Yes No No
a
Genomic studies have revealed P. ovale to be two sympatric species: P. ovale curtisi and P. ovale wallikeri.

MANIFESTASI
in the insect’s midgut.KLINIS
This zygoteMALARIA
matures into an ookinete, which has been defined in terms of rates of microscopy-detected parasitemia
penetrates and encysts in the mosquito’s gut wall. The resulting oocyst or palpable spleens in children 2–9 years of age and has been classi-
Manifestasi
expands by asexual klinis tergantung
division until it bursts topada
liberatespesies plasmodium
myriad motile yang menginfeksi:
fied as hypoendemic (<10%), mesoendemic (11–50%), hyperendemic
•sporozoites,
Fase which then migrate in the hemolymph to the salivary (51–75%), and holoendemic (>75%). In holo- and hyperendemic areas
prodromal 2-3 hari sebelum parasit terdeteksi di
gland of the mosquito to await inoculation into another human at the (e.g., certain regions of tropical darah: sakit
Africa kepala,
or coastal fatigue,
New Guinea) where
anorexia, myalgia, demam ringan, dan nyeri dada, abdomen, atau sendi
next feed, thus completing the life cycle. there is intense P. falciparum transmission, people may sustain as much
as one infectious mosquito bite per day and are infected repeatedly
Presentasi klasik: paroksisme demam diselingi
•EPIDEMIOLOGY fatigue theiratau
lives. In“sehat”
PART 5

throughout such settings, malaria morbidity and mortal-

Malaria occurs throughout most of the tropical regions of the world ity are substantial during early childhood. Immunity against disease
• Berhubungan dengan ruptur skizon:
(Fig. 219-2). P. falciparum predominates in Africa, New Guinea, and is hard won in these areas following repeated symptomatic infections
Hispaniola (i.e., the Dominican Republic and Haiti); P. vivax is more in childhood, but, if the child survives, infections become increasingly
common in Central and South America. The prevalence of these two likely to be asymptomatic. These asymptomatic older children and
Infectious Disease

species is approximately equal on the Indian subcontinent and in
eastern Asia and Oceania. P. malariae is found in most endemic areas,
especially throughout sub-Saharan Africa, but is much less common.
P. ovale is relatively unusual outside of Africa and, where it is found,
comprises <1% of isolates. P. knowlesi causes human infections com-
monly on the island of Borneo and, to a lesser extent, elsewhere in
Southeast Asia, where the main hosts, long-tailed and pig-tailed
adults are a major source of malaria transmission. As control mea-
sures progress and urbanization expands, environmental conditions
become less conducive to malaria transmission, and all age groups
may lose protective immunity and become susceptible to illness.
Constant, frequent, year-round infection is termed stable transmission.
In areas where transmission is low, erratic, or focal, full protective
immunity is not acquired, and symptomatic disease may occur at all
 • P. vivax dan P. ovale tiap 48 jam
• P. malariae tiap 72 jam
• Kurang terlihat pada P. falciparum atau infeksi majemuk
• Gambaran klinis malaria pada anak tidak sama dengan dewasa
• Anak > 2 bulan + non immun: gejala bervariasi dari demam tidak tinggi & sakit
kepala sampai demam tinggi > 40oC dengan sakit kepala, mengantuk, anorexia,
nausea, muntah, diare, pucat, sianosis, splenomegali, hepatomegali, anemia,
trombositopenia, hitung lekosit normal atau rendah, atau kombinasi.
• Relaps jangka panjang:
• Akibat pelepasan merozoit dari sumber ekso-eritrosit di hati (P. vivax dan P. ovale)
atau persisten di dalam eritrosit (P. malariae).
• Gejala khas setelah beberapa minggu setelah kembali dari daerah endemis à infeksi P.
vivax, P. ovale, P. malariae
• P. falciparum à malaria berat
• Mortalitas:
• hampir 100% tanpa pengobatan,
• tatalaksana
LAMPIRAN adekuat: 20%

Algoritme 1.
DIAGNOSIS Alur
MALARIA
Penemuan Penderita Malaria

Algoritme penemuan penderita malaria

Langkah diagnostik malaria

Anamnesis
• Berasal dari/riwayatKU TATALA
KSpergi
ANA KASU ke daerah endemis malaria
S MALARI
A

BU KU SA 19
• Lemah, nausea, muntah, nafsu makan (-), nyeri punggung, nyeri daerah perut, pucat,
mialgia, dan atralgia
• Pejamu: immun atau non immun
• Pejamu immun: gejala klinis minimal
• Malaria infeksi tunggal, non immun: terdiri atas beberapa serangan demam dengan
interval tertentu (paroksisme), diselingi periode bebas demam. Sebelum demam pasien
merasa lemah, nyeri kepala, tidak ada nafsu makan, mual atau muntah
• Infeksi campuran (> 1 jenis Plasmodium): demam terus menerus (tanpa interval)
• Periode paroksisme terdiri atas
• stadium dingin (cold stage),
• stadium demam (hot stage), dan
• stadium berkeringat (sweating stage).
Berhubungan dengan ruptur skizon:
• P. vivax dan P. ovale tiap 48 jam
• P. malariae tiap 72 jam
• Kurang terlihat pada P. falciparum atau infeksi majemuk
• Paroksisme jarang pada anak, stadium dingin seringkali bermanifestasi sebagai kejang.

Tabel. Tanda dan gejala malaria

Gejala Frekuensi % (n) Tanda klinis Frekuensi % (n)

Demam 97 (605) Temperatur > 39°C 30 (320) *

Menggigil 88 (510) Splenomegali 26 (581)

Sakit kepala 86 (527) Hepatomegali 11 (475)

Fatigue/malaise 82 (394) Ikterus 7 (469)

Berkeringat 71 (311) Ruam 4 (516)

Myalgia 71 (72) Perubahan SSP 2 (460)

Nausea atau muntah 51 (76)

Nausea 36 (333)

Muntah 31 (348)

Faringitis 25 (72)

Classic tertian fever 23 (83)

Nyeri abdomen 21 (418)

Diarrhea 18 (426)

Batuk 18 (404)

Pemeriksaan Fisik
• Uncomplicated malaria: malaria simtomatik, tanpa gejala berat, atau tanpa bukti
disfungsi organ
• Malaria berat
• Mortalitas:
• hampir 100% meninggal tanpa pengobatan,
• tatalaksana adekuat: 20%
• Definisi malaria berat: ditemukannya Plasmodium falciparum atau Plasmodium
vivax atau Plasmodium knowlesi stadium aseksual dengan minimal satu dari
manifestasi klinis sebagai berikut:
• Perubahan kesadaran (GCS<11, Blantyre <3)
• Kelemahan otot (tak dapat duduk/berjalan)
• Kejang berulang-lebih dari dua episode dalam 24 jam
• Asidosis metabolik (bikarbonat plasma <15 mmol/L).
• Edema paru (didapat dari gambaran radiologi atau saturasi oksigen <92%
dan frekuensi pernafasan > 30 kali/menit)
• Gagal sirkulasi atau syok: pengisian kapiler > 3 detik, tekanan sistolik <80
mm Hg (pada anak: <70 mmHg)
• Jaundice (bilirubin>3mg/dL dan kepadatan parasit >100.000/uL pada
malaria falciparum, pada malaria knowlesi kepadatan parasit >20.000/uL)
• Perdarahan spontan abnormal
• Hipoglikemi (gula darah <40 mg%)
• Anemia berat pada anak < 12 tahun : Hb <5 g/dl , Hematokrit <15% pada
endemis tinggi dan ; Hb <7g/dl, Hematokrit <21% untuk endemis sedang-
rendah ; pada dewasa Hb<7g/dl atau hematokrit <21%
• Hiperparasitemia (parasit >2 % eritrosit atau 100.000 parasit /μL di daerah
endemis rendah atau > 5% eritrosit atau > 250.000 parasit /μl di daerah
endemis tinggi)
• Hiperlaktemia (asam laktat >5 mmol/L)
• Gangguan fungsi ginjal (kreatinin serum >3 mg/dL) atau ureum darah >20
mmol/L
• Catatan: pada penderita tersangka malaria berat, terapi dapat segera diberikan berdasarkan
pemeriksaan RDT

Pemeriksaan penunjang
• Konfirmasi diagnosis à Apus darah tepi
• Tebal: ada tidaknya Plasmodium
• Tipis: identifikasi spesies Plasmodium/tingkat parasitemia
• Abnormalitas hematologi:
• Trombositopenia: 70%
• Anemia: 25%
• Lekosit: Normal atau rendah, 5% lekositosis à faktor prognosis buruk.
• LFT: peningkatan transminase (25%), bilirubin (1/3), LDH (80%)
• Kadar bilirubin tinggi + LDH tinggi à hemolisis à kunci diagnosis
• Abnormalitas elektrolit: hiponatremia
• Peningkatan kreatinin serum
• Hipoglikemia: jarang, kecuali pada parasitemia yang tinggi
• Asidosis metabolik ~ penyakit berat
• Radiologi: tidak khas, edema paru non kardiogenik pada malaria berat.
Penyulit:
• Plasmodium falciparum
• Malaria cerebral, termasuk kejang & koma
• Black water fever (hemoglobinuria masif)
• Malaria algida (shock)
• Malaria biliosa (gangguan fungsi hati)
• Hipoglikemia
• Asidosis laktat
• Anemia berat
• Edema paru
• Splenomegali tropik (kronis)
• Plasmodium vivax
• Ruptur limfa lanjut (2-3 bulan setelah infeksi awal)
• Malaria cerebral
• Plasmodium malariae
• Glomerulonefritis kompleks immun dengan Ag parasit dan IgG pejamu

• Stadium darah parasit, apus darah tipis

• Gbr. 1: sel darah merah normal; Gbr. 2-18:
Tropozoit (Gbr. 2-10 merupakan tropozoit
stadium cincin); Gbr. 19-26: Skizon (Gbr. 26 skizon
ruptur); Gbr. 27,28: makrogametosid matur (♀);
Gbr. 29, 30: mikrogametosid matur (♂).
• Ilustrasi dari: Coatney GR, Collins WE, Warren M,
Contacos PG. The Primate Malarias. U.S.
Department of Health, Education and Welfare,
Bethesda, 1971.

GAMBAR. Apus Darah Tipis

• Gbr. 1: sel darah normal; Gbr. 2-6: Tropozoid muda
(stadium cincin); Gbr. 7-18: Tropozoid; Gbr. 28-29:
Makrogametosid (♀); Gbr. 30: mikrogametosid (♂).
• Ilustrasi dari: Coatney GR, Collins WE, Warren M,
Contacos PG. The Primate Malarias. U.S. Department of
Health, Education and Welfare, Bethesda, 1971.

• GAMBAR. Stadium-stadium dalam siklus hidup P. falciparum. A: Bentuk cincin (tropozoid awal).
B: Schizont matur, jarang terlihat di sediaan apus darah perifer karen sekuestrasi mikrovaskular.
C: Gametosid, bentuk pisang. Sumber: Division of Parasitic Diseases, US Centers for Disease
Control and Prevention, Atlanta.
 • Gambar. Apus darah tebal

DIAGNOSIS BANDING

Beberapa penyakit dapat memberikan tanda dan gejala klinis yang menyerupai malaria.
TABEL – DIAGNOSIS BANDING MALARIA (FEBRILE ILLNESS PADA TRAVELER)
Demam saja dengan sakit Dengan gejala gastrointestinal Dengan Rash dan Dengan Gejala
kepala Jaundice Respirasi
Meningitis Dysentry * Hepatitis Pneumonia
Bacteremia Appendicitis Leptospirosis Influenza
Dysentery * Enteric fever Bacteremia Endocarditis
Dengue Hepatitis Meningococcemia
Heat stroke Diverticulitis Endocarditis
Pyelonephritis Acute schistosomiasis Rickettsioses
Enteric fever Toxocariasis Viral encephalitis
Visceral leishmaniasis Leptospirosis Hemorrhagic
Brucellosis Ascending cholangitis
Trypanosomiasis Intestinal ischemia
Relapsing fever Babesiosis
Viral encephalitis Q fever
Babesiosis Organophosphate poisoning
Acute schistosomiasis Liver abscess
Q fever
* Including Shigella, Campylobacter, and toxin-producing or invasive E. coli.
- Including typhoid fever.
Including measles, Japanese B encephalitis, and rabies.

TATALAKSANA MALARIA
Tatalaksana malaria merujuk pada panduan yang dikeluarkan oleh Kementerian Kesehatan
Republik Indonesia dan badan kesehatan dunia (WHO). Pengobatan malaria yang dianjurkan
saat ini menggunakan DHP dan Primakuin. Pemberian kombinasi ini untuk meningkatkan
efektifitas dan mencegah resistensi. Malaria tanpa komplikasi diobati dengan pemberian DHP
secara oral. Disamping itu diberikan primakuin sebagai gametosidal dan hipnozoidal.
• Sifat/Cara Kerja Obat
• Klorokuin :
• Sizontosid darah
• anti gametosid, P.vivax dan
P.malariae
• Sulfadoksin-pirimetamin :
• Sizontosid darah
• Sporontosidal
• Kina :
• Sizontosid darah
• Anti gametosid,
• P.vivax dan P.malariae
• Primaquin :
• Anti gametosid à mencegah
penularan
• Anti hipnosoit à mencegah
relaps (P. vivax)
• Artesunat :
• Sizontosid darah,
• Amodiakuin :
• Struktur dan aktivitas sama dgn
klorokuin
• Tetracyclin :
• Sizontosid darah

Pengobatan malaria tergantung pada tahapan perkembangan parasit malaria sesuai spesies
plasmodium serta penyulit atau komplikasi yang terjadi.
 Tujuan pengobatan malaria meliputi:
• Uncomplicated malaria
• Mengobati infeksi, mencegah transmisi
• Mencegah timbulnya + penyebaran resistensi antimalaria
• Malaria berat
• Mencegah kematian
• Mencegah kecacatan
• Mencegah rekrudesens
• Malaria falciparum
• Mencegah terjadinya penyakit yang berat
• Malaria vivax:
• Pengobatan radikal à mengobati dan mencegah relaps

Standar pengobatan malaria di Indonesia Perubahan kebijakan obat anti malaria

(OAM) di Indonesia
Perubahan Kebijakan Obat Anti Malaria

2011 DHP
secara
2008 DHP nasional
di Papua
and Papua
2004
Barat
ACT
(artesunate +
1973 amodiaquine
Recommendations
Resistensi
Klorokuin
Diagnosis of malaria

All cases of suspected malaria should have a parasitological test (microscopy

Kebijakan obat anti malaria (OAM) di Tatalaksana uncomplicated malaria

Both microscopy and RDTs should be supported by a quality assurance programme.
Indonesia
Saat ini OAM yang digunakan program nasional adalah derivat
artemisinin dengan golongan aminokuinolin, yaitu: Treating uncomplicated malaria

Saat ini OAM yang digunakan program nasional adalah derivat

artemisinin dengan golongan aminokuinolin, yaitu: Treat children and adults with uncomplicated

Kombinasi tetap (Fixed Dose Combination = FDC) yang terdiri

atas Dihydroartemisinin dan Piperakuin (DHP). •
Kombinasi tetap (Fixed Dose Combination = FDC) yang terdiri •
1 (satu)
atastablet FDC mengandung
Dihydroartemisinin 40 mg dihidroartemisinin
dan Piperakuin (DHP). •
dan 320 mg piperakuin. Obat ini diberikan per – oral selama •
tiga hari dengan
1 (satu) tabletrange dosis tunggal
FDC mengandung harian
40 mg sebagai berikut:
dihidroartemisinin •
dan 320 mg piperakuin. Obat ini diberikan per – oral selama
tiga hari dengan dosis
Dihidroartemisinin range 2-4
dosismg/kgBB;
tunggal harian sebagai berikut:
Dihidroartemisinin
Piperakuin dosis 2-4 mg/kgBB;
dosis 16-32mg/kgBB Duration of ACT treatment
Piperakuin dosis 16-32mg/kgBB

Revised dose recommendation for dihydroartemisinin + piperaquine in young children

Kebijakan OAM (uncomplicated malaria) di Indonesia

• Malaria falciparum: DHP 3 hari + Primakuin 1 hari
• Malaria vivax dan ovale: DHP 3 hari + Primakuin 14 hari
• Malaria malariae: DHP 3 hari with ACT to patients with

is not required.
 untuk malaria vivaks selama 14 hari dengan dosis 0,25 mg/
kgBB. Primakuin tidak boleh diberikan pada bayi usia < 6
bulan dan ibu hamil juga ibu menyusui bayi usia < 6 bulan dan
penderita kekurangan G6PD. Pengobatan malaria falsiparum
dan malaria vivaks adalah seperti yang tertera di bawah ini:

Kebijakan OAM (uncomplicated falciparum+malaria)

Dihidroartemisinin-Piperakuin(DHP) di Indonesia
Primakuin

Tabel 1. Pengobatan Malaria falsiparum menurut berat badan

dengan DHP dan Primakuin

Jumlah tablet per hari menurut berat badan

Hari Jenis obat 5 kg >5-6 kg >6-10 kg >10-17 kg >17-30 kg >30-40 kg >40-60 kg >60-80 kg >80 kg

0-1 2-<6 6-12 <5 5-9 10-14 15 15 15

bulan bulan bulan tahun tahun tahun tahun tahun tahun

1-3 DHP ½ ½ 1 1½ 2 3 4 5

1 Primakuin - - ¼ ¼ ½ ¾ 1 1 1

Guidelines for the treatment of malaria 3RD E D I T I O N

BUKU SA
KU TATALA
Treating uncomplicated malaria
KSANA K in special risk groups
ASUS MALARIA
10
First trimester of pregnancy
Treat pregnant women with uncomplicated

Infants less than 5kg body weight

malaria with

Patients co-infected with HIV

In people who have HIV/AIDS and uncomplicated malaria, avoid

WHO treatment guidelines 3rd ed, 2015 31

Non-immune travellers
Treat travellers with uncomplicated malaria returning to non-endemic
settings with ACT.

Hyperparasitaemia
People with
failure, severe malaria and death and should be closely monitored, in addition
to receiving ACT.
WHO treatment guidelines 3rd ed, 2015

Treating uncomplicated , , P. malariae or malaria

Blood stage infection

32

malaria.

In areas with chloroquine-susceptible infections, treat adults and children with

uncomplicated , , or malaria with either ACT

In areas with chloroquine-resistant infections, treat adults and children with

uncomplicated , , or

malaria with quinine.

10
Kebijakan OAM (uncomplicated vivax malaria) di Indonesia

Tabel 2. Pengobatan Malaria vivaks dan ovale menurut berat

badan dengan DHP dan Primakuin

Jumlah tablet per hari menurut berat badan

Preventing relapse
Hari Jenis obat 5 kg in or kg >10-17
>5-6 kg >6-10 malaria
kg >17-30 kg >30-40 kg >40-60 kg >60-80 kg >80 kg

0-1 2-<6 6-12 <5 5-9 10-14 15 15 15

bulan bulan
for preventing relapse. bulan tahun tahun tahun tahun tahun tahun

1-3 DHP ½ ½ 1 1½ 2 3 4 5
To prevent relapse, treat or
1-14 Primakuin - - ¼ ¼ ½ ¾ 1 1 1

Catatan :
Pencegahan relaps pada malaria vivax dan ovale:
a. Sebaiknya dosis pemberian DHP berdasarkan berat badan,
• apabila
Menggunakanpenimbanganstatusberat
G6PDbadan pasien
tidak dalam memandu
dapat dilakukan pemberian primakuin untuk
maka
pengobatan
for potential relaps
primaquine-induced haemolysis.
pemberian obat dapat berdasarkan kelompok umur.
•b. Apabila
Pertimbangan risiko dan manfaat
ada ketidaksesuaian pemberian
antara umur danprimakuin bila status G6PD tidak diketahui
berat badan
dan pemeriksaan
(pada G6PD tidak
tabel pengobatan), makatersedia
dosis yang dipakai adalah
of adding primaquine. berat badan.
berdasarkan
• Pada defisiensi G6PD moderat, pertimbangkan pencegahan relaps dengan menggunakan
c. Untuk anak dengan obesitas gunakan dosis berdasarkan berat
primakuin
Pregnant basa women
and breastfeeding dosis 0,75 mg/kgBB 1 kali seminggu, selama 8 minggu, dengan supervisi
badan ideal.
medis ketat
d. Primakuin tidak boleh diberikan pada ibu hamil dan ibu
with chloroquine until delivery and breastfeeding are completed, then, on the
menyusui bayi < 6 bulan.
Tatalaksana malaria
e. Pemberian berat harus disertai edukasi pemantauan
Primakuin
Treating
warnasevere malaria
urin selama 3 hari pertama setelah minum obat. Jika
warna urin menjadi coklat
Treat adults and children with severe tua(including
malaria atau hitam, segera hentikan
infants, pregnant
pengobatan dan rujuk ke rumah sakit.
artesunate for at least 24 h and until they can tolerate oral medication. Once
a patient has received at least 24 h of parenteral therapy and can tolerate oral
therapy, complete
melalui treatment with
anamnesis ada3 days of ACT (add
keluhan atausingle dose primaquine
riwayat warna urin
coklat
kehitaman setelah minum obat (golongan sulfa, primakuin,
kina,
Revised doseklorokuin danforlain-lain),
recommendation segera inkirim
parenteral artesunate youngke fasilitas pelayanan
children
kesehatan rujukan atau rumah sakit. Dosis primakuin pada

minggu diberikan selama 8 minggu dengan pemantauan warna

urin dan
Parenteral kadar
alternatives hemoglobin.
where .
artesunate is not available
If artesunate is not available, use artemether in preference to quinine for
2) Pengobatan
treating children and adults malaria vivaks
with severe yang relaps
malaria.
Pengobatan kasus malaria vivaks relaps (kambuh) diberikan
dengan
WHO treatment regimen
guidelines 3rd ed, 2015 ACT yang sama tetapi dosis Primakuin 31

OAM untuk Malaria Berat

IA
S MALAR
• Artesunat 2,4 mg/kg/kali
K U TA TA ivANatau
LAKS A KASUim pada saat masuk (jam = 0), kemudian pada 12 jam
dan 24 jam,B kemudian satu kali sehari sampai hari11ke 7.11
UKU S A

atau
• Kina dihidroklorid intravena 1 mg garam/kgBB/dosis atau 10 mg basa/kgBB/dosis
dalam 10 cc/kgBB larutan dekstrosa 5% atau larutan NaCl 0,9% diberikan perinfus
dalam 4 jam, diulangi tiap 8 jam dengan dosis yang sama sampai terapi oral dapat
dimulai. Keseluruhan pemberian obat adalah 7 hari dengan dosis total 21 kali (Kina
drip bukan merupakan obat pilihan utama malaria berat di Indonesia)
 Dosing of artesunate
a shortened life span,injection in in
resulting severe malaria haemolysis. Thus, post-treatment
the observed
haemolysis is a predictable event related to the life-saving effect of artesunate.
Hyperparasitaemic patients must be followed
Revised dose recommendation up carefully
for parenteral to identifyin
artesunate late-onset
anaemia.
young children with severe malaria

7.4.2 | PARENTERAL ALTERNATIVES WHEN

ARTESUNATE IS NOT AVAILABLE
Parenteral alternatives when artesunate is not available
and the main biologically active metabolite dihydroartemisinin following
If parenteral artesunate is not available, use intramuscular artemether in
preference to quinine for treating children and adults with severe malaria.

WHO treatment guidelines 3rd ed, 2015 31

across all age groups.

Tatalaksana Suportif Malaria Berat
Other considerations
• Pemberian cairan, nutrisi, transfusi darah
• Penuhi kebutuhan volume cairan intravaskular dan jaringan dengan
pemberian oral atau parenteral
• Pelihara keadaan nutrisi
• Transfusi darah PRC atau whole blood apabila anemia dengan HB < 5 g/dl
atau Hb < 7 g/dL pada daerah transmisi rendah
• Perdarahan à beri komponen darah yang sesuai
• Pengobatan gangguan asam basa dan elektrolit
• Pertahankan fungsi sirkulasi dengan baik, bila perlu pasang CVP.
• Gagal
Artesunate ginjal as
is dispensed àaDialisis peritoneal
powder of artesunic acid, which is dissolved in
• Pertahankan oksigenasi jaringan, bila perlu berikan oksigen. Gagal nafas à ventilator
mekanik
intramuscular (bila
injection into mungkin)
the anterior thigh.
• Pertahankan kadar gula darah normal
The solution should be prepared freshly for each administration and should not
o
• Suhu
be stored. ≥ 39is Crapidly
Artesunate à Antipiretik, padatoriwayat
hydrolysed in-vivo kejang demam
dihydroartemisinin, which dapat diberikan lebih awal.
78 7 | Tr e a t m e n t o f s ev e r e m a l a r i a

Pemantauan
older children and Pengobatan Malaria
adults to both artesunate and the biologically active metabolite
Terapi
• Efektivitas ~ respons klinis dan pemeriksaan parasitologis
that young children have a larger apparent volume of distribution for both compounds
Kegagalan
and should•therefore pengobatan
receive a slightly dini,
higher dose bila penyakit
of parenteral artesunate berkembang
to achieve menjadi
• Malaria berat pada hari ke-1,2,3 dan dijumpai parasitemia, atau
• Parasitemia hari ke-3 dengan suhu aksilla > 37,5oC.
• Kegagalan pengobatan lanjut, 7 | Tr ebila
a t m e nperkembangan
t o f s ev e r e m a l a r i a penyakit
77 pada hari ke-4 – 28
• Secara klinis dan parasitologis
• Adanya malaria berat setelah hari ke-3 dan parasitemia, atau
• Secara parasitologis
• Adanya parasitemia pada hari ke-7, 14, 21, dan 28
• Suhu aksilla <37,5oC tanpa ada kriteria kegagalan pengobatan dini
• Respons klinis dan parasitologis memadai, apabila pasien sebelumnya tidak berkembang
menjadi kegagalan butir pertama atau kedua dan tidak ada parasitemia
• Penderita di follow up untuk diperiksa ulang sediaan darahnya pada hari ke 3, 7, 14, 28
dan dilanjutkan sampai akhir bulan 3.
•
 Algoritme 2.
Tatalaksana Penderita Malaria

Penderita Positif Malaria

Tanpa Komplikasi Malaria Berat

(Algoritme 3)

Dapat minum obat Tidak dapat minum obat

Berikan obat secara oral sesuai Berikan obat secara iv atau im

dengan jenis plasmodium (tabel (algoritme 3)
1-7). Pastikan obat diminum
sampai habis.

Bila klinis membaik, kembali Bila tidak ada perbaikan atau

untuk pemeriksaan ulang klinis memburuk dalam 3 hari
mikroskopis darah malaria pada pengobatan, segera kembali ke
hari ke-3, 7, 14, 21 dan 28 puskesmas/RS

Observasi dalam 28 hari

Hasil Negatif Hasil positif kembali pada Hasil positif kembali pada
hingga hari salah satu hari pemeriksaan salah satu hari pemeriksaan
ke-28 (H3,H7,14,21,28) dan klinis (H3,H7,14,21,28) tetapi Crosscheck hasil mikroskopis
tidak memburuk klinis memburuk dan kepatuhan minum obat.
Pemantauan klinis dan mikrsokopis
SEMBUH ulang 7 hari kemudian.

Bila hasil cross check positif dan klinis memburuk, berikan Pengobatan Lini
ke-2 yaitu kina (sesuai KMK No.H.K. 01/07/556/2019)

Gambar. Algoritme tatalaksana malaria

PENCEGAHAN MALARIA
• Faktor yang mempengaruhi:
• Daerah tujuan
• Pejamu BUKU SAKU TATALA
KSANA K
20 • Aktivitas
ASUS MA
LARIA

• Lama paparan
• Cara:
• Mencegah gigitan nyamuk
• Kemoprofilaksis
• 4 prinsip proteksi malaria – ABCD – :
• Be Aware of the risk, the incubation period, the possibility of delayed onset, and
the main symptoms.
• Avoid being Bitten by mosquitoes, especially between dusk and dawn.
• Take antimalarial drugs (Chemoprophylaxis) when appropriate, to prevent
infection from developing into clinical disease.
• Immediately seek Diagnosis and treatment if a fever develops 1 week or more
after entering an area where there is a malaria risk and up to 3 months (or,
rarely, later) after departure from a risk area.
• Perlindungan terhadap gigitan nyamuk
• Insect repellents
 • Mosquito net
• Mosquito coils
• Aerosol sprays
• Protective clothing

TABLE 219-8 Drugs Used in the Prophylaxis of Malaria 1589

DRUG USAGE ADULT DOSE PEDIATRIC DOSE COMMENTS

Atovaquone- Prophylaxis in areas 1 adult tablet 5–8 kg: ½ pediatric tabletb daily Begin 1–2 days before travel to malarious areas.
proguanil with chloroquine- or POa ≥8–10 kg: ¾ pediatric tablet daily Take daily at the same time each day while in the
(Malarone) mefloquine-resistant malarious areas and for 7 days after leaving such areas.
≥10–20 kg: 1 pediatric tablet daily
Plasmodium falciparum Atovaquone-proguanil is contraindicated in persons with 1589
TABLE 219-8 Drugs Used in the Prophylaxis of Malaria ≥20–30 kg: 2 pediatric tablets severe renal impairment (creatinine clearance rate, <30
• DRUG Obat malaria untuk pencegahan
USAGE ADULT DOSE daily
PEDIATRIC DOSE COMMENTS
mL/min). In the absence of data, it is not recommended
Atovaquone- Prophylaxis in areas 1 adult tablet ≥30–40
5–8 kg: ½ kg:pediatric
3 pediatric tablets
tablet b
daily for children
Begin 1–2 days weighing before <5travel
kg, pregnant
to malarious women, or women
areas.
proguanil with chloroquine- or PO ≥8–10 kg: ¾ pediatric tablet daily breast-feeding
daily Take daily at the infants
sameweighing
time each <5daykg.while
Atovaquone-
in the
a

(Malarone) mefloquine-resistant ≥40 kg: 1kg:adult tablet daily proguanil should be taken with
malarious areas and for 7 days after leaving such food or a milky drink.areas. 1589
TABLE 219-8 DrugsPlasmodiumUsed in thefalciparum
Prophylaxis of Malaria ≥10–20 1 pediatric tablet daily
Atovaquone-proguanil is contraindicated in persons with
Chloroquine Prophylaxis only in 300 mg of base 5≥20–30 mg of base/kg
kg: DOSE (8.3 mg of
2 pediatric tablets Begin 1–2 weeks before travel to malarious areas.
DRUG USAGE ADULT DOSE PEDIATRIC COMMENTS
severe renal impairment (creatinine clearance rate, <30
phosphate (Aralen areas with chloroquine- (500 mg of salt) salt/kg) daily PO once weekly, up to Take weekly on the same day of the week while in the
Atovaquone- Prophylaxis in areas c 1 adult mL/min).
Begin 1–2In the before
absence of data, it is not recommended
oncetablet 5–8 kg: ½adult pediatric
dosetablet
of 300daily days and fortravel to malarious areas.
b
and generic) sensitive P. falciparum PO weekly maximum mg malarious areas 4 weeks after leaving such
proguanil with chloroquine- or PO ≥30–40 kg: 3 pediatric tablets for
Takechildren
daily atweighing
the same <5time kg, pregnant
each women,
while in or women
mayday the
a
or areas with P. vivax of basekg: ¾ pediatric tablet daily areas.
≥8–10 Chloroquine phosphate exacerbate psoriasis.
(Malarone) mefloquine-resistant daily breast-feeding
malarious areas infants
and weighing
for 7 days <5
afterkg.leaving
Atovaquone-
such areas.
only ≥10–20 kg: 1 pediatric tablet daily proguanil should be taken with food or a milky drink.
Plasmodium falciparum ≥40years
kg: 1ofadult tablet dailyup to Atovaquone-proguanil is contraindicated in persons with
Doxycycline (many Prophylaxis in areas 100 mg PO ≥8 age: 2 mg/kg,
≥20–30 kg: 2 pediatric tablets Begin 1–2 days before travel to malarious areas. Take
Chloroquine Prophylaxis only inor 300(except
mg of in base adult
5daily
mg dose
of base/kg (8.3 mg of severe1–2
Begin renal impairment (creatinine clearance rate, <30
brand names and with chloroquine- qd daily at theweeks
same before time each travel
daytowhilemalarious
in the areas.
malarious
phosphate (Aralen mefloquine-resistant
areas with chloroquine- pregnant (500 mg of salt) salt/kg) PO once weekly, up to mL/min).
Take weekly In the absence of
daydata, it isweek
not while
recommended
generic) women; areas and foron4 the same
weeks after of the
leaving such areas. in the
and generic) sensitive PO once weekly maximum≥30–40 kg: 3 pediatric
adult dose of tablets
300 mg for childrenareas
malarious weighing and <5for 4kg,weeks
pregnant afterwomen,
leaving or women
P. P. falciparum
falciparum c c
see Comments) Doxycycline is contraindicated in children aged such
or areas with P. vivax daily
of base breast-feeding
areas. Chloroquine infants weighingmay
phosphate <5 kg. Atovaquone-
exacerbate
<8 years and in pregnant women after 15 weekspsoriasis.
of
only ≥40 kg: 1 adult tablet daily proguanil should be taken with food or a milky drink.
gestation.
Chloroquine (many
Doxycycline
Hydroxychloroquine Prophylaxis
An alternativeonly
in in
areas
to 300 mg
100
310 mg ofof base
PO base 5≥8 5 mg
mg of base/kg
years
of base/kg (8.3
of age: 2(6.5 mg of
mg/kg,
mg ofup to Begin 1–2
Begin 1–2 weeks
weeksbefore
days beforetravel
before traveltoto
travel tomalarious
malariousareas.
malarious areas.Take
areas.
phosphate
brand
sulfatenames(Aralen
and
(Plaquenil) areaschloroquine-
with with chloroquine-
chloroquine or
for primary (500
qd
(400 mg of
(except
mg ofinsalt)
salt) salt/kg)
salt/kg)
adult dose PO once
PO once weekly,
weekly, upup toto Take weekly
daily
Take weekly
at the same on the
on thetime
same
same each dayday
day of the
of the
while week
weekin thewhile
while in the
malarious
in the
and generic)
generic) sensitive P. only
prophylaxis falciparum
mefloquine-resistant in
c
PO once
once weekly
pregnant
PO weekly maximum adult
women; maximum adult dose
dose of of 310
300 mg mg malarious
areas areas
and areas
malarious for 4 weeks and for
and forafter
44 weeks
weeks
leaving after
such
after leaving
areas.
leaving such
such
P.orfalciparum
areasareas
withwith c P. vivax
chloroquine- see Comments) of of base
base areas. Hydroxychloroquine
Chloroquine
Doxycycline
areas. phosphate
is contraindicated mayin may exacerbate
children
exacerbate aged psoriasis.
psoriasis.
only
sensitive P. falciparumc or <8 years and in pregnant women after 15 weeks of
Doxycycline (many areas with P.invivax
Prophylaxis areas only 100 mg PO ≥8 years of age: 2 mg/kg, up to gestation.
Begin 1–2 days before travel to malarious areas. Take
brand names
Mefloquine and
Hydroxychloroquine
(Lariam withalternative
An chloroquine-
Prophylaxis in toareasor with 228qd (except
310 in
mg of base 5adult
≤9 mg dose
kg:of
4.6base/kg (6.5 mg of
mg of base/kg (5 mg of Begindaily at1–2theweeks
samebefore
weeks time each
before travel
travel daytotowhile in theareas.
malarious
malarious malarious
areas.
generic)
sulfate
and (Plaquenil)
generic) mefloquine-resistant
chloroquine for primary
chloroquine-resistant pregnant
(400
(250 mg ofwomen;
salt) salt/kg) PO once weekly weekly, up to areasweekly
Take and foron
weekly on4the weeks
the same
same after dayleaving
day of the
of such
theweek
weekwhileareas.
whileininthe the
P. falciparum
falciparumonly c
seeonce
Comments) Doxycyclineareas is contraindicated in after
children agedsuch
CHAPTER 219 CHAPTER

prophylaxis
P. c in PO weekly 10–19 maximum kg: adult dose
¼ tablet d of 310 mg
once weekly malarious areas and for
and for 44 weeks
weeks afterleaving
leaving suchareas.
areas with chloroquine- of base <8 years
areas. and in pregnant women
Hydroxychloroquine
Mefloquine is contraindicated after 15allergic
mayin exacerbate
persons weeks toofthis
psoriasis.
sensitive P. falciparumc or 20–30 kg: ½ tablet once weekly gestation.
drug or related compounds (e.g., quinine and quinidine)
areas with
Hydroxychloroquine An alternative to P. vivax only 31–45 kg: ¾
310 mg of base 5 mg of base/kg (6.5 mg of tablet once weekly and
Beginin 1–2
personsweeks with activetravel
before or recent depression,
to malarious areas.
sulfate (Plaquenil)
Mefloquine chloroquine in
(Lariam Prophylaxis forareas
primary
with 228(400mg mgofofbase
salt) ≥46salt/kg)
≤9 1POtablet
kg:4.6
kg: once
mg weekly,
ofonce
base/kg up(5tomg of generalized
weekly Take weekly
Begin 1–2 weeksanxiety disorder,
on thebefore
sametravel daypsychosis,
oftothe week
malarious schizophrenia,
while
areas.in the
and generic) prophylaxis only in
chloroquine-resistant PO once
(250 mg weekly maximumPOadult
of salt) salt/kg) oncedose
weeklyof 310 mg other
Take major
malarious
weeklyareaspsychiatric
on the and disorders,
for 4day
same weeks
of the or seizures.
after
week whileUse
leaving such with
in the
areas with
P. falciparum chloroquine-
c of base
PO once weekly 10–19 kg: ¼ tabletd once weekly caution
areas. in persons
Hydroxychloroquine with psychiatric
may
malarious areas and for 4 weeks after leaving such disturbances
exacerbate or aareas.
psoriasis.
Malaria 219

sensitive P. falciparumc or history of depression.

Mefloquine is contraindicatedMefloquine is not recommended
in persons allergic to thisfor
20–30 kg: ½ tablet once weekly persons with cardiac conduction
areas with P. vivax only drug or related compounds (e.g.,abnormalities.
quinine and quinidine)
Primaquine
Mefloquine (Lariam For prevention
Prophylaxis of malaria
in areas with 30 228mg mgofofbase
base 0.5 31–45 kg:
mg 4.6
≤9 kg: ¾
mgtablet
of base/kg oncemg
(0.8
of base/kg weekly and in1–2
(5ofmg of Begin persons
days
weeks with active
before
before travel or to
travel recent depression,
tomalarious
malarious areas.
areas.
and generic) in areas with mainly
chloroquine-resistant (52.6
(250 mgmg ofof salt) ≥46 kg: PO
salt) salt/kg) 1 tablet
onceuponce
qd, weekly weekly
to adult dose; generalized
Take daily
weekly atanxiety
onthethe disorder,
same
same time psychosis,
dayeach
of the dayweek schizophrenia,
while in the
while in the
CHAPTER

P. vivax
falciparumc PO qdonce weekly should 10–19 be kg:taken withd once
¼ tablet food weekly other majorareas
malarious psychiatric
and fordisorders,
7 weeks
4 days after or seizures.
afterleaving
leavingsuchUse with
suchareas.
areas.
caution
Primaquine
Mefloquine in persons with psychiatric
is contraindicated disturbances
persons
in persons with G6PD
allergic or
to athis
Malaria219 Malaria

20–30 kg: ½ tablet once weekly history

drug or of
deficiency. depression.
It is compounds
related Mefloquine
also contraindicated is not
(e.g., quinine during recommended
and quinidine)for
pregnancy.
31–45 kg: ¾ tablet once weekly persons
and in withiscardiac
persons conduction
with active abnormalities.
Primaquine Used for presumptive 30 mg of base 0.5 mg of base/kg (0.8 mg of This therapy indicated fororpersons
recent depression,
who have had
Primaquine For prevention
anti-relapse of malaria (52.6
therapy 30 mgmg of of
base ≥46mg
0.5
salt) salt/kg),kg:of1upbase/kg
tablet once
to adult (0.8weekly
dose,mgPO of qd generalized
Begin anxiety
1–2 exposure
prolonged days disorder,
before vivaxpsychosis,
to P.travel toand/or
malariousP. schizophrenia,
areas.
ovale. It is
in areas with
(terminal mainly
prophylaxis) (52.6
PO qd mg of salt)
for 14 salt/kg)
days for 14 days PO after
qd, updeparture
to adult dose;
from otherdaily
Take majoratpsychiatric
contraindicated theinsamepersonsdisorders,
time eachG6PD
with or
dayseizures.
while in Use
deficiency theaswith well
P. vivax
to decrease risk of PO qddeparture
after should
the be taken
malarious with food
area caution
malarious
as in persons
areas and for 7 days after leaving suchorareas.
during pregnancy. with psychiatric disturbances a
relapses of P. vivax and from the history
Primaquineof depression.
is Mefloquine
contraindicated in is not
persons recommended
with G6PD for
P. ovale malarious area persons with
deficiency. It is cardiac conduction abnormalities.
also contraindicated during pregnancy.
Primaquine
a Primaquine
For prevention of malaria 30 30 mgmg of
of base
base 0.5 mg
mg ofof base/kg
base/kgb (0.8
(0.8 mg
mg of of Begintherapy
1–2 days before travel to malarious areas.
An adult tablet containsUsed 250 for
mgpresumptive
of atovaquone and 100 mg 0.5
of proguanil hydrochloride. A pediatric This
tablet contains 62.5 is mgindicated
of atovaquone for persons
and 25who mghave had
of proguanil
inareas
areas
hydrochloride. cVery few anti-relapse
withtherapy
now have
mainly (52.6 mg
(52.6 mg of
chloroquine-sensitive
ofmalaria.
salt) salt/kg),
salt) salt/kg)
d
One tablet
PO qd, up todose,
up contains
to adult adult PO
228 mg
dose; Take daily atsalt).
ofqdbase prolonged
(250 mg ofexposure
the same to P.time
vivaxeachand/orday while
P. ovale.in the
It is
P. vivax prophylaxis)
(terminal PO qd
PO qd for 14 days for should be taken
14 days after with food from
departure malarious areasinand
contraindicated for 7 days
persons with after
G6PDleaving
deficiencysuchasareas.well
Abbreviation: G6PD, glucose-6-phosphate dehydrogenase. Primaquine is contraindicated in persons with G6PD
to decrease risk of after departure the malarious area as during pregnancy.
Source: CDC: www.cdc.gov/malaria/travelers/drugs.html.
relapses of P. vivax and from the deficiency. It is also contraindicated during pregnancy.
Primaquine P.Used
ovalefor presumptive malarious
30 mg of basearea 0.5 mg of base/kg (0.8 mg of This therapy is indicated for persons who have had
anti-relapse therapy (52.6 mg of salt) salt/kg), up to adult dose, PO qd prolonged exposure to P. vivax and/or P. ovale. It is
a
An adult tablet contains 250 mg of atovaquone and 100 mg of proguanil hydrochloride. bA pediatric tablet contains 62.5 mg of atovaquone and 25 mg of proguanil
Mefloquine
hydrochloride. c
Very few (terminal
(250 mgareasofnow prophylaxis)
salthave weekly, PO qd for 14
adult days for
dose) malaria.
chloroquine-sensitive has beend 14tablet
days contains
widely
One after departure
228 mgfrom
alternative to contraindicated
(250 mg of salt).in persons
atovaquone-proguanil
of base with G6PD deficiency as well
or mefloquine. Doxycycline is
to decrease risk of after departure the malarious area as during pregnancy.
used for malarial
Abbreviation: prophylaxis
G6PD, glucose-6-phosphate because it is usually
dehydrogenase.
relapses of P. vivax and from the effective against generally well tolerated but may cause vulvovaginal thrush, diarrhea,
multidrug-resistant falciparum malaria andmalarious
Source: CDC: www.cdc.gov/malaria/travelers/drugs.html.
P. ovale is reasonably
area well toler- and photosensitivity and is not recommended for prophylaxis in chil-
ated. Mefloquine has been associated with rare episodes of psychosis dren <8 years old or pregnant women after 15 weeks of gestation.
a
An adult tablet contains 250 mg of atovaquone and 100 mg of proguanil hydrochloride. bA pediatric tablet contains 62.5 mg of atovaquone and 25 mg of proguanil
and seizurescVery
hydrochloride. at prophylactic
few areas nowdoses; these reactions are
have chloroquine-sensitive moredOne
malaria. frequent Chloroquine
tablet contains can (250
228 mg of base no longer be relied upon to prevent P. falciparum
mg of salt).
at the higher
Mefloquine
Abbreviation: doses
(250
G6PD, used
mg of for
salt treatment.
weekly,
glucose-6-phosphate Moredose)
adult
dehydrogenase. common side widely
has been effects infections
alternativeinto
most areas but is still used to
atovaquone-proguanil or prevent and treat
mefloquine. malaria due
Doxycycline is
with
used prophylactic
Source:for
CDC:malarial doses of mefloquine
prophylaxis becauseinclude mild nausea,
it is usually
www.cdc.gov/malaria/travelers/drugs.html. effectivedizziness,
against to the other
generally human
well but mayspecies
Plasmodium
tolerated cause and for P. falciparum
vulvovaginal thrush,malaria in
diarrhea,
• Hal yang harus diperhatikan:
• Semua obat profilaksis harus diminum secara teratur selama tinggal di daerah
tujuan, dan harus tetap diminum sampai 4 minggu setelah pulang
• Tergantung jenis malaria di daerah tujuan, harus diberitahu kemungkinan P.ovale
atau P.vivax late onset
• Pola resistensi obat anti malaria à Indonesia: resisten klorokuin, pilihan obat
untuk pencegahan adalah Atovaquone-proguanil, doxycycline, or mefloquine
• Anak > = 8 tahun: doxycycline

MALARIA KONGENITAL

• Didapat dari ibu (prenatal atau perinatal)

à abortus, stillbirth, prematur (~ malaria parasitemia, anemia, TNFa↑), IUGR (~
placental insufficiency), kematian neonatal
• Umumnya pada ibu non immun dengan P. vivax dan P. malariae
• Gejala pertama timbul usia 10-30 hari (14 jam – beberapa bulan):
• Demam, gelisah, mengantuk, pucat, kuning, poor feeding, muntah, diare,
sianosis, dan hepatosplenomegali.
• Malaria pada kehamilan: berat à ES pada fetus atau neonatus, walaupun transmisi (-)
• Outcome malaria dalam kehamilan

• Definisi malaria kongenital:

• ditemukannya parasit malaria bentuk aseksual pada darah tepi dalam waktu 7
hari pertama kehidupan, atau lebih lama jika tidak ada kemungkinan infeksi post
partum melalui gigitan nyamuk (di daerah non endemis malaria)
• Diagnosis
• Sering terlambat
• 81%: 2 minggu setelah onset
• 19%: antara 3 – 24 minggu
• Apus darah tipis dan tebal (bayi dan ibu)
• Antimalaria
• Pada kasus malaria falciparum sensitif klorokuin
• Klorokuin 10 mg/kg dilanjutkan dengan 5 mg/kg pada 6, 24, 48
jam kemudian
• Pada kasus malaria falciparum resisten klorokuin:
• WHO merekomendasikan Artemisinin-based combination
therapy (ACT) dengan dosis mg/kg BB yang sama dengan dosis
anak dengan BB 5 kg.
Alternatif:
• Quinine sulfat (25 mg/kg dibagi 3 dosis 5 hari) + trimetropim
sulfametoksasol (8 mg/kb dibagi 2 dosis 5 hari)
• Quinine sulfat + sulfadoksin pirimetamin
• Quinine hidroklorid injeksi dilanjutkan dengan quinine oral
• Non falciparum malaria
• Malaria sensitif klorokuin
• Klorokuin 10 mg/kg dilanjutkan dengan 5 mg/kg pada
6, 24, 48 jam kemudian
• Primakuin tidak diperlukan (transmisi parasit
exoeritrositer (-))
• Malaria resisten klorokuin
• ACT