Diagnosis & Treatment of

Malaria
Malaria
 40% of world’s
population is at risk
 300 - 500 million
cases per year
 1.5 to 2.0 million
deaths per year (most
of these are children
under 6 years old in
Africa)
 400 Gigitan
Nyamuk

200 Menginfeksi
Manusia

100 Malaria Klinis

2 – 6% Malaria
Berat
Penyebab MALARIA Pada Manusia
5 Jenis Plasmodium

 P. vivax : Malaria vivax ( demam tiap 3 hari)

 P. falciparum : Malaria falsiparum ( demam tiap 24 -
48 jam )
 P. malariae : Malaria malariae/ quartana ( demam
tiap 4 hari )
 P. ovale : Malaria ovale ( seperti vivax )
 P. knowlesi ( dahulu menginfeksi binatang, demam
tiap hari) )
Malaria Life Cycle
Oocyst
Sporozoites

Mosquito Salivary
Zygote Gland

Exo-
erythrocytic Hypnozoites
(hepatic) cycle
Gametocytes

Erythrocytic
Cycle
Malaria life cycle

 Sex and sporogony in

the mosquito
 Extraerythrocytic
schizogony in the liver
 Merogony in the blood
phase
 Gamogony in the blood
and mosquito gut
 Pathogenesis of Severe Malaria

Parasitemia
Parasitemia

RBC
RBC Destruction
Destruction Parasite
Parasite Sequestration
Sequestration Immune
Immune Response
Response

Microvascular
Microvascular Cytokines
Cytokines
Obstruction
Obstruction Release
Release

Tissue
Tissue Ischaemia,
Ischaemia, Local
Local && Systemic
Systemic
Hypoxia
Hypoxia Inflammation
Inflammation

Complications
Complications // Dysfunction
Dysfunction of
of
Vital
Vital Organs
Organs
Sequestration & cytoadherence

 Cytoadherence correlates
with pathogenesis (but high
cytokine levels induce
expression of endothelial
adhesins enhancing
attachment)
 Infected RBCs will adhere to
the endothelium as well as
to each other
Sequestration & cytoadherence

 Rosetting (adhesion of
infected RBCs to other
RBCs) and clumping
(adhesion between
infected cells) was first
observed in in vitro culture
 Rosetting was also found
in 50% of field isolates and
correlated strongly with the
severity of the observed
disease
Malaria the disease

 Asimtomatik
 Acut Malaria,
uncomplicated
 Severe Malaria

WHO-TDR
Malaria the disease

 9-14 day incubation

period
 Fever, chills,
headache, back and
joint pain
 Gastrointestinal
symptoms (nausea,
vomiting, etc.)
Malaria the disease
Malaria the disease
Incubation Period

 Plasmodium falciparum 9 – 14 days

 Plasmodium vivax 12 – 17 days – 12 mo
 Plasmodium ovale 16 – 18 days
 Plasmodium malariae 18 – 40 days
 Plasmodium knowlesi 9 – 12 days
Types of Infections
 Recrudescence
 exacerbation of persistent undetectable
parasitemia, due to survival of erythrocytic
forms, no exo-erythrocytic cycle (P.f., P.m.)
 Relapse
 reactivation of hypnozoites forms of parasite in
liver, separate from previous infection with
same species (P.v. and P.o.)
 Recurrence or reinfection
 exo-erythrocytic forms infect erythrocytes,
separate from previous infection (all species)

 Can not always differentiate

recrudescence from reinfection
Severity of disease and host factors

 Varies in severity and course

 Parasite factors
 Species and strain of parasite
 Geographic origin of parasite
 Size of inoculum of parasite
 Host factors
 Age
 Immune status
 General health condition and nutritional status
 Chemoprophylaxis or chemotherapy use
 Mode of transmission
 Mosquito
 Bloodborne, no hepatic phase (transplacental,
needlestick, transfusion, organ donation/transplant)
SEVERE MALARIA
DEFINITION: Patients with Plasmodium asexual parasitemia,
with one or more CLINICAL or LABORATORY FEATURES :
-PROSTRATION
-FAILURE TO FEED -SEVERE ANEMIA (5 GR% /
-IMPAIRED 15%)
CONSCIUOUSNESS -HYPOGLYCEMIA (< 40
-RESPIRATORY DISTRESS MG/dL)
-MULTIPLE CONVULSIONS, -ACIDOSIS ( < 15 Mmol/L)
> 2X/24 Hours -RENAL IMPAIRMENT ( > 3
-CIRCULATORY COLLAPSE mg% )
(Systolic < 70 , children < 50) -HYPERLACTATEMIA ( > 5
-PULMONARY EDEMA mmol/L)
(Radiology) -HYPERPARASITEMIA ( >
-ABNORMAL BLEEDING 2% / 5% )
(Spontaneous)
-JAUNDICE + other vital organ
dysfunction WHO, 2010
-HEMOGLOBINURIA
 Faktor Predisposisi
Malaria Berat
 Anak usia Balita
 Wanita Hamil
 Immuno-compromized patients
 Penduduk daerah endemis yang lama
meninggalkan daerah tersebut dan
kembali mudik lagi
 Turis atau Wisatawan dari daerah
Hipoendemis
 Other methods of diagnosis of malaria

These are not routinely used in clinical practice. They include :

a) Antigen capture kits. Uses a dipstick and a finger prick blood

sample. Rapid test - results are available in 10-15 minutes.
Expensive and sensitivity drops with decreasing parasitaemia.
b) PCR based techniques. Detects DNA or mRNA sequences
specific to Plasmodium. Sensitivity and specificity high but test is
expensive, takes several hours and requires technical expertise.
c) Fluorescent techniques. Relatively low specificity and sensitivity.
Cannot identify the parasite species. Expensive and requires
skilled personnel.
d) Serologic tests. Based on immunofluorescence detection of
antibodies against Plasmodium species. Useful for epidemiologic
and not diagnostic purposes.
Diagnosis
 Clinical signs and symptoms
 Laboratory Examinations:
- Blood smear (thick and thin blood film)
- Rapid diagnostic test
(immunochromatography)
- PCR
MINISTRY OF HEALTH POLICIES

I. Diagnose must be confirm by

microscope or Rapid Diagnostic
Test
II. Treatment: Artemisinin-based
Combination Therapy (ACT).
Stop Monotherapy !
III.Prevention
Combination Therapy
 ACT : Artemisinin Combination Therapy
 Non ACT : (without artemisinin
derivatives)
 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
Treatment of Uncomplicated
Malaria
 First line : Artemisinin Combination
Therapy (ACT)
 Second line : non-ACT
 Adjunct treatment of
uncomplicated malaria
 Fever
 Acetominophen, paracetamol
 Avoid aspirin in kids due to risk of Reyes Syndrome
 Sponge baths
 Anemia
 Transfusion of RBCs may be needed
 Iron, folic acid
 Rehydration
 Solutions with extra glucose
 Pengobatan Lini I, P. falsiparum menurut umur
Jenis obat Jumlah tablet menurut kelompok umur
Har
i Dosis 0–1 2 – 11 1-4 5-9 10 - 14 > 15
tunggal bulan bulan tahun tahun tahun tahun

1 Artesunate ¼ ½ 1 2 3 4

Amodiakuin ¼ ½ 1 2 3 4

Primakuin -- -- ¾ 1½ 2 2-3

2 Artesunate ¼ ½ 1 2 3 4

Amodiakuin ¼ ½ 1 2 3 4

3 Artesunate ¼ ½ 1 2 3 4

Amodiakuin ¼ ½ 1 2 3 4
 Atau
Dihydroartemisinin + piperaquin +
Primakuin

• Efektif untuk Falciparum dan Vivaks

• FDC
•Disiapkan untuk seluruh Indonesia
Pengobatan dengan Dihydroartemisinin-Piperakuin (DH-P)

Jumlah tablet menurut kelompok umur

(dosis tunggal)
Hari Jenis obat
0-1 2 – 11 1–4 5–9 10 – 14 > 15
bulan bulan tahun tahun tahun tahun
1--3 DHP ¼ ½ 1 1,5 2 3-4
F, H1 Primakuin -- -- ¾ 1½ 2 2-3
V,H1 – 14 Primakuin - - ¼ ½ ¾ 1

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

Piperakuin phosphate(P): 16-32 mg/kgBB ( 1tablet = 320 mg)
Primakuin : 0.25 mg – 0.75 mg/kg BB
Treatment of Relapsing Malaria Vivax
 ACT 3 days
 Double-dose of primaquine for 14 days
 Pengobatan Malaria Vivaks RELAPS
Jenis obat Jumlah tablet menurut kelompok umur
Har Dosis 0–1 2 – 11 1-4 5-9 10 - 14 > 15
i tunggal bulan bulan tahun tahun tahun tahun

1 Artesunate ¼ ½ 1 2 3 4
Amodiakuin ¼ ½ 1 2 3 4
Primakuin -- -- 1/2 1 11/2 2
2 Artesunate ¼ ½ 1 2 3 4
Amodiakuin ¼ ½ 1 2 3 4

Primakuin -- -- 1/2 1 11/2 2

3 Artesunate ¼ ½ 1 2 3 4
Amodiakuin ¼ ½ 1 2 3 4

Primakuin -- -- 1/2 1 1 1/2 2

1/2
Primakuin 1 1 1/2 2
4-14
Causes of Treatment Failure
 Doctors
- Misdiagnosis
- Late diagnosis
- Late treatment
- Inadequate dose
 Patients
- Come late
- Non compliant
- Multiple complications
 Parasite
- Resistant to drug
Management of Treatment
Failure
 Treatment failure within 14 days is very
anusual
 Failure after 14 days : recrudenscence or
reinfection
 Rescue treatment :
- Alternative ACT known effective in this region
- Artesunat + tetracycline/doxycycline/clindamycine
- Quinine + tetracycline/doxycycline/clindamycine
 Pengobatan lini II alternatif kombinasi Kina + Doksisiklin/
Tetrasiklin/ Clindamycin (P. falciparum)

Hari Jenis obat Jumlah tablet menurut kelompok umur

Dosis tunggal 0-11 1-4 5- 9 10 - 14 > 15
bulan tahun tahun tahun tahun

1 Kina *) 3x½ 3x1 3x1½ 3 x (2-3)

Doksisiklin -- -- -- 2 x 50 mg 2 x 100 mg

Primakuin - ¾ 1½ 2 2–3
2-7 Kina *) 3x½ 3x1 3x1½ 3x2
Doksisiklin -- -- -- 2 x 50 mg 2 x 100 mg

Dosis TETRASIKLIN -- -- -- 4x4 mg/kg 4 x 250 mg

BB
Dosis -- -- -- 2x10 mg/kg 2x10 mg/kg
CLINDAMYCIN BB BB
 Pengobatan multiresisten vivax/ ovale dengan kombinasi Kina +
Doksisiklin/Tetrasiklin/Clindamycin (bila gagal pengobatan lini I)

Hari Jenis obat Jumlah tablet menurut kelompok umur

Dosis 0 - 11 1-4 5- 9 10 - 14 > 15

tunggal bulan tahun tahun tahun tahun

1-7 Kina *) 3x½ 3x1 3x1½ 3 x (2-3)

Doksisiklin -- -- -- 2 x 50 mg 2 x 100 mg

1 - 14 Primakuin - ¼ ½ ¾ 1

Dosis -- -- -- 4x4 mg/kg 4 x 250 mg

TETRASIKLIN BB

Dosis -- -- -- 2x10 2x10 mg/kg

CLINDAMYCIN mg/kg BB BB
 Treatment of
Severe Malaria
 PENYEBAB / ETIOLOGI
 Plasmodium falciparum
 Mixed plasmodium ( Falciparum+ vivax)
 Plasmodium vivax
 Plasmodium knowlesi
 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 mg)
Artemeter 3.2 mg/kg im pada hari I dibagi 2
dosis, dilanjutkan 1.6 mg/kg/ hari. Neurotoxicity in
TIDAK iv (1 amp = 80 mg) animal not human

Suppositories, 10 mg/kg at 0 & 4 hr

Artemisinin 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

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

2.4 2.4 2.4 2.4

Mg/ Mg/ 2.4
Mg/ Mg/
KgBB KgBB Mg/
KgBB KgBB KgBB

ARTESUNATE I.V/ I.M

* ARTEMETER , hanya I.M , dosis 1,6 mg/kg BB

 ARTESUNATE
I.V / I.M

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

 Setelah pasien sadar/KU membaik, tx. Awal

parenteral dapat diubah dgn. Tx. Oral
 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
Terima Kasih
Malaria
 40% of world’s
population is at risk
 300 - 500 million
cases per year
 1.5 to 2.0 million
deaths per year (most
of these are children
under 6 years old in
Africa)
 ARTESUNATE
I.V / I.M

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

 Setelah pasien sadar/KU membaik, tx. Awal

parenteral dapat diubah dgn. Tx. Oral
 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
 Pengobatan Pre-referral

 Dianjurkan sebelum merujuk setidaknya dosis

pertama obat antimalaria parenteral sudah
diberikan.
 Obat yang dipilih :
 Artemether i.m. atau Artesunate i.m.
 Artesunate atau artemisinin supositoria
 Kina i.m.
 Kina i.v. (didampingi petugas medis ) ??
 TREATMENT OF ORGAN FAILURE

 ENCEPHALOPATHY/CONVULSION
 RENAL FAILURE
 ACIDOSIS
 HYPOGLYCAEMIA
 HYPERBILIRUBINAEMIA
 RESPIRATORY FAILURE
 HYPOTENSION
 SEPSIS
 SEVERE ANEMIA
CONVULSIONs
 Uncommon in adults
 High flow oxygen and appropriate airway
management
 Lorazepam i.v. (0.1 mg/kg) or
 Rectal/i.v. diazepam (0.5 mg/kg)
 If repeated doses are not effective  loading
Phenytoin (18 mg/kg over 20 minutes), or
Phenobarbital (15-20 mg/kg over 10 minutes)
ACUTE KIDNEY INJURY (AKI)
 Malaria related Acute Kidney Injury (MAKI)
 Penurunan fungsi ginjal dalam 48 jam :
- Peningkatan serum kreatinin 0.3mg/dL atau
- Peningkatan serum kreatinin 50% dari nilai
dasar,atau
- Penurunan urin output 0.5ml/kg/jam untuk 6
jam
 WHO : serum kreatinin > 3mg/dL
 Sering pada malaria dewasa dan jarang pada
anak
Management of AKI
 Appropriate Anti-Malaria
 Maintenance Fluid & Electrolytes
 Renal Replacement Therapy
 Treatment Complications
 Management of infections
 Avoid Nephrotoxic agent
Fluid & Diuretics
 Oliguria/dehydrated : infusion of NS 20
ml/kgBW/60 minutes
- auscultation, JVP observation/200ml
- CVP monitoring (0 - +5)
- No urine  diuretic challenge
 Furosemide 40mg initially, no urine  100
mg. 200 mg, 400 mg every 30 minutes, no
urine, dopamine 2.5 – 5 ug/kg/min (if no
improved outcome)
Dialysis
 Early dialysis improved survival
 Intermittent HD (daily/alternating)
 Continuous venovenous hemofiltration
 Continuous atriovenous hemofiltration
 Peritoneal Dialysis Less effective
 Indications : uremic symptoms, volume overload
(pulmonary edema, congestive heart failure),
pericardial rub, HCO3 < 15 mEq/L. K > 6.5
mEq/L
Adequacy of Dialysis
 Dialysis is considered adequate when the
post dialysis creatinine and urea levels
decrease to 50% or less of predialysis
values
PULMONARY MANIFESTATION IN
MALARIA

 Historically :
- Bronchitic
- Pneumonic
- Bronchopnemonic
 Acute Lung Injury (ALI)
 Acute Respiratory Distress Syndrome
(ARDS)
ARDS
 Occurs in P falciparum, P vivax, 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
initation treatment
 Clinical: acute onset dyspnea  respiratory
failure
Management of ARDS

PRINCIPLES :
 Early Diagnosis
 Rapid Rx Anti Malarial
 Assisted ventilation
 Consider aggravating factors :
- Bacterial sepsis
- Secreting obstructive airways
- Pneumothorax
Management ALI/ARDS
 ICU
 Supported : prevent nosocomial infection, GI
bleed, thrombo-embolism; adequate nutritional
enteral intake
 Monitoring Oxygen saturation
 Fluid: ‘conservative’ (136 ± 491 ml), CVP 8 – 12
cmH2O
 Adrenalin is best avoided, other vasopressor
such as dopamine should be preferred
Management ALI/ARDS
 Spontaneous ventilation : a face mask with a
high O2 to deliver FIO2 of up to 0.5 to 0.6
 FIO2 > 0.6, CPAP > 10 cmH2O  mechanical
ventilator
Acidosis in Malaria
 The etiology is not well understood
 Increase production and impaired metabolism of
lactate and ketoacidosis
 Contributive factors : fever, severe anaemia,
hypovolemic, alteration rheological, end
products of parasites, decrease elimination
through hepatic blood flow, Reyes like syndrome
 Sodium bicarbonate  failed to improve lactat
acidosis
METABOLIC ACIDOSIS
 Occur in Acute Renal Failure :
- hypovolemic
- shock
- pulmonary edema
- hyperparasitemia
 Management :
- Dialysis
- NaBic if pH < 7.15, beware of Na overload 
pulmonary edema
 MALARIA DALAM KEHAMILAN
DAERAH ENDEMIS MALARIA
 Semua ibu hamil didaerah beresiko penularan malaria
pada kunjungan pertama (K1) di Ante Natal Care
dilakukan pemeriksaan laboratory (RDT atau
mikroskopis).
 Pengobatan Pf Pv atau mix tanpa komplikasi:
 pada ibu hamil usia < 3 bulan dengan Kina tablet.
 pada ibu hamil usia > 3 bulan dgn Artesunat+Amodiakuin tab
atau DHP.

 Ibu hamil tidak boleh diberikan Primakuin.

 MALARIA DALAM KEHAMILAN
DAERAH ENDEMIS MALARIA
 Pengobatan malaria berat:
 pada ibu hamil usia < 3 bulan dengan Kina per infus.
 pada ibu hamil usia > 3 bulan dengan Artesunate injeksi
intra vena bila di RS atau Artemeter injeksi intra
muscular bila di lapangan.
 Bila sudah dapat minum dilanjutkan tab Kina atau
Artesunat+Amodiakuin tablet atau Dihydroartemisinin
Piperaquin.
 Pencegahan terhadap gigitan nyamuk
diberikan kelambu berinsektisida.
Faktor Prognosis
 Kecepatan Diagnosis dan Pengobatan
- semakin cepat pengobatan semakin rendah
mortalitas
 Kegagalan Fungsi Organ
- semakin sedikit organ vital yang terlibat semakin
baik prognosis
 Kepadatan Parasit
- Prognosis buruk bila parasite count tinggi dan
terdapat skizon pada darah tepi
Prognosis
INDIKATOR KLINIS
o Derajad Kesadaran   prognosis jelek
o AKI + Edema  prognosis jelek
o Asidosis Berat  prognosis jelek
o Gagal Nafas  prognosis jelek
o Perdarahan  mortalitas 
o Imun  (Splenectomi, Steroid,dll.) 
prognosis jelek
New AntiMalarial Agent
 Artemisone (semi synthetic derivative of
arthemisinin)
 Febrifugine & analogues (extracts of
dichroa febrifuge Lourl Chang San)
 Fosmidomycine (Streptomyces
levendulae)
 Naphthyridine