Malaria

Dr. Niniek Burhan Sp.PD-KPTI

Divisi Tropik Infeksi

Ilmu Penyakit Dalam
FKUB - RSSA
Malaria
40% of worlds
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
Malaria - Vectors

Anopheles freeborni
Malaria Vectors (cont.)

Anopheles balabacensis A. gambiae

A. freeborni A. stephensi
Malaria Vectors (cont.)
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) )
Patogenesis Malaria
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
 Immunitas
Sitokin
Inflamasi
Genetik
Umur
Kehamilan
Manifestation of Plasmodium
Infection

Benign Malaria (Uncomplicated Malaria)

Severe Malaria (Malaria with
Complications)
 Pathogenesis of Severe Malaria
Parasitemi
Parasitemi
a
a

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

Microvascular
Microvascular Cytokines
Cytokines
Obstruction
Obstruction Release
Release

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

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

The second model

suggests sequestration is
Ring stages the main culprit
In falciparum infections
only early stages (rings) are
found in the peripheral
blood
Trophozoites and schizonts
are sequestered to the
post-capilary venules by
attachment to the
endothelium
Trophopzoites & schizonts
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
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
 Tanda & Gejala Malaria :
Malaria ringan :
merasa dingin/ menggigil, panas, berkeringat,
sakit kepala
pucat
Malaria berat :
panas dengan kuning, tidak sadar/kejang
Sesak nafas, tak ada kencing/ kencing hitam
 GEJALA - PRODROMAL
Kelesuan ( malaise )
Sakit kepala
Sakit belakang
Nyeri tulang/ otot
Anorexsia
Perut tak enak
Diarea ringan
Merasa dingin di punggung
Gejala Malaria
Karakteristik : Demam periodik, Anemia, Splenomegali
Demam periodik ( Trias Malaria ):
Dingin/ menggigil ( 15 - 60 menit )
Panas ( 1 - 2 jam )
Berkeringat
Periode bebas demam 12jam(P.f), 36(P.v), 72(P.m),
24(P.k)
Sakit kepala
Gejala gastro-intestinal : mual & muntah, nyeri
epigastrium
Non-spesifik : diarea, batuk
Malaria the disease
Clinical Features
 MALARIA VIVAX
M. TERTIANA, Benigna, inkubasi 12 - 20 hari
Serangan demam sore hari
Manifestasi klinis bisa ringan - berat
Splenomegali H 4 - 5
Mortalitas rendah, morbiditas tinggi
Gejala prodromal ringan
Demam ireguler 2-4 hari, menjadi intermiten
Anemia sering pada anak-anak
Penderita semi-imun gejala tidak spesifik
 MALARIA MALARIAE
Malaria Quartana
Banyak di Afrika & Amerika Latin
Inkubasi 18 - 40 hari
Gejala ringan, insidious, nausea, muntah,
herpes labialis, anemia jarang.
Parasitemia sebelum gejala demam
Splenomegali sering hanya ringan
Komplikasi jarang, dapat terjadi sindroma
nefrotik
 MALARIA OVALE
Bentuk paling ringan
Inkubasi 11 - 16 hari, periode laten 4 tahun
Terjadi infeksi ganda, P. ovale tak tampak
Gejala klinis seperti vivax, lebih ringan,
puncak panas lebih rendah dan lama demam
lebih pendek
Dapat sembuh spontan tanpa obat
Menggigil jarang, splenomegali jarang
 MALARIA FALSIPARUM
Malaria Tropika, inkubasi 9 -14 hari
Bentuk paling berat: sering anemia, panas ireguler,
splenomegali dan parasitemia
Sering demam tinggi > 40 C
Gejala prodromal lebih sering
Sering menimbulkan komplikasi ( M. berat ):
kejang, serebral, ikterus, ggl ginjal.
Splenomegali lebih cepat, sering pada minggu I,
nyeri pada perabaan.
Parasitemia dapat tinggi
 PLASMODIUM KNOWLESI

Dulu hanya menginfeksi kera (Macaca Mullata)

Sejak th 2004 dilaporkan retrospeksif di Serawak
Vector Anopheles leucosphyrus group (An. Laten,
cracens)
Misdiagnosis sebagai malaria malariae,
mikroskopik menyerupai P. malariae
Klinis TIDAK seperti malariae, demam tiap 24 jam,
diarea, nyeri abdomen dan ditemukan
hiperparasitemia > 250.000/uL
Dapat memberikan komplikasi ikterik, hipotensi,
gagal ginjal, serebral dan gagal pernafasan
Diagnosa pasti identifikasi dengan PCR
Malaria the disease

Malaria tertiana:
48h between fevers
(P. vivax and ovale)

Malaria quartana:
72h between fevers
(P. malariae)

Malaria tropica:
irregular high fever
(P. falciparum)
Clinical presentation

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)
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
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
Plasmodium Malaria
falciparum
vivax Berat
knowlesi
26%

KEMATIAN
10 - 50 %
 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
 Plasmodium Infection
in Pregnancy

Mother
Mother Fetus
Fetus

Immune Parasite
System Sequestrati
on in
Placenta
IUGR,
IUGR, IUFD,
IUFD,
Fetal
Fetal Distress,
Distress,
Low
Low Birth
Birth
Tends
Tends to
to Weight,
Weight,
present
present as
as Premature
Premature
Severe
Severe Labour
Labour
Malaria
Malaria (Congenital
(Congenital
Malaria)
Malaria)
 Diagnosis
Malaria is a multisystem disease. It presents with a wide variety of non-specific clinical
features: there are no pathognomonic symptoms or signs. Many patients have fever,
general aches and pains and malaise and are initially misdiagnosed as having flu.

P. falciparum malaria can be rapidly progressive and fatal. Prompt diagnosis saves lives
and relies on astute clinical assessment:

A good history
Residence or a recent visit (in the preceding 3 months) to a malaria endemic area
History of fever (may be paroxysmal in nature)
Recognise significance of non-specific clinical features such as vomiting, diarrhoea,
headache, malaise
Physical examination
Identify signs consistent with malaria: fever, pallor, jaundice, splenomegaly
Exclude other possible causes of fever (e.g. signs of viral and bacterial infections)

The diagnosis of malaria should be considered in any

unwell person who has been in a malarious area
recently
 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.
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: use LLIN, IRS, personal
protections, etc.
 Alur
AlurDiagnosis
Diagnosis

Diagnosis malaria biasanya dilakukan secara klinik dan

epidemiologik yaitu berdasarkan ada tidaknya gejala klinis dan
riwayat pernah mengunjungi daerah endemik malaria

Diagnosis pasti malaria baru dapat ditegakkan bila pada

Pemeriksaan sediaan darah penderita ditemukan parasit

Gold standar

Diagnosis imunologik/serologik digunakan untuk

mendeteksi adanya antibodi spesifik terhadap parasit
malaria atau antigen spesifik terhadap plasmodium
maupun eritrosit yang terinfeksi plasmodiun
Reaksi pembentukan kompleks antigen-antibodi
 Pemeriksaan hapusan
darah
Serology - IFA
PCR
1. Paling sensitif:
Deteksi antibodi
2. PCR
3. Pemeriksaan blood smear
4. RDT: deteksi antigen
 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)
Uncomplicated Malaria
Symptoms: fever, chills, headache,
body pains, diarrhea, vomiting, cough
Signs: anemia, thrombocytopenia

Symptoms may be very nonspecific

Synchronous infections with
predictable cycles of symptoms are
rare
 Principles of management
of uncomplicated malaria
Prompt and accurate diagnosis
Assess for signs of complicated/severe malaria
Can occur with low parasitemias
Can develop after parasites clear peripherally
Prompt use of appropriate antimalarial drugs
Monitor clinical and parasitological improvement
Cure parasitic and/or clinical
Ancillary treatment
Instructions for future prevention of malaria
Malaria Falsiparum
Lini Pertama
Artesunat + Amodiakuin + Primakuin
DHP + Primakuin

Lini Kedua
Kina + Doksisiklin/Tetrasiklin +
Primakuin
 Pengobatan Lini I, P. Falsiparum menurut umur
Jenis obat Jumlah tablet menurut kelompok umur
Har
i Dosis 01 2 11 1-4 5-9 10 - 14 > 15
tunggal bulan bulan tahun tahun tahun tahun

1 Artesunate 1 2 3 4

Amodiakuin 1 2 3 4

Primakuin -- -- 1 2 2-3

2 Artesunate 1 2 3 4

Amodiakuin 1 2 3 4

3 Artesunate 1 2 3 4

Amodiakuin 1 2 3 4
 Pengobatan lini II alternatif kombinasi Kina + Doksisiklin/
Tetrasiklin/ Clindamycin ( bila gagal pengobatan lini I )

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 *) 3x 3x1 3x1 3 x (2-3)

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

Primakuin - 1 2 23
2-7 Kina *) 3x 3x1 3x1 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
 Atau
Dihydroartemisinin + piperaquin +
Primakuin

Efektif untuk Falciparum dan Vivaks

FDC
Baru tersedia di bbrp propinsi : Indonesia
Timur, Sumatra
Disiapkan untuk seluruh Indonesia
Pengobatan dengan Dihydroartemisinin-Piperakuin (DH-P)

Jumlah tablet menurut kelompok umur

(dosis tunggal)
Jenis 0-1 2 14 59 10 > 15
Hari bulan 11 14 tahu
obat
ta tah tahun n
bul hu un
an n
1--3 DHP 1 1,5 2 3-4
F, H1 Primakui -- -- 1 2 2-3
n
V,H1 Primakui - - 1
14 n
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
Malaria Vivaks dan Ovale
Lini Pertama
Artesunate+amodiakuin / DHP +
primakuin

Lini Kedua
Kina + Primakuin
 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 *) 3x 3x1 3x1 3 x (2-3)

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

1 - 14 Primakuin - 1

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

TETRASIKLIN BB

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

CLINDAMYCIN mg/kg BB BB
 Pengobatan Malaria Vivaks RELAPS
Jenis obat Jumlah tablet menurut kelompok umur
Har Dosis 01 2 11 1-4 5-9 10 - 14 > 15
i tunggal bulan bulan tahun tahun tahun tahun

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

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

3 Artesunate 1 2 3 4
Amodiakuin 1 2 3 4

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

1/2
Primakuin 1 1 1/2 2
4-14
 Malaria Malariae
Artesunate+amodiakuin / DHP selama 3
hari

Malaria Mix (P. Falciparum+P.vivax)

ACT selama 3 hari dan primakuin hr I dg
dosis 0.75 mg/kgBB dilanjutkan hari 2-14
dg dosis 0.25mg/kgBB
 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
 Treatment Failure (WHO, 2003)
Early Treatment Failure
Parasitemia with severe clinical complication of malaria on day
1,2,3
Parasitemia on day 2 is greater than day 0
Parasitemia in day 3 (>25% from day 0)
Parasitemia in day 3 shows positive result and axilla temperature
> 37.5C

Late Treatment Failure

Late clinical and parasitological failure (LCF) : Parasitemia (the
same species as day 0) with complication of severe malaria after
day 3, t axilla > 37.5 C with parasitemia between day 4-28.
Late parasitological failure (LPF) : Parasitemia is found (the same
species with the day 0) on day 7-28 without increased axilla
temperature (<37.5 oC).
Multidrug-resistant P.
falciparum
Focus in Southeast Asia
Border areas, forest transmission
Recommendations
Prophylaxis: Doxycycline
Treatment:
Quinine combinations, longer duration of therapy
High-dose MQ,artemisinin combinations
Identifying and documenting treatment
failure is critical
Malaria Dengan
Komplikasi
Regimen Pada Malaria Berat
Anti Malaria Pada Malaria Berat
 Terapi
Komplikasi
Pemberian Artesunate
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
 Prinsip Utama
Pencegahan Malaria
A-B-C-D
Be Aware sadari dan ketahui faktor resiko, masa
inkubasi, kemungkinan onset yang terlambat, dan gejala2
utama
Avoid being Bitten by mosquito Hindari gigitan nyamuk,
terutama saat sore dan malam hari
Chemoprophylaxis minum kemoprofilaksis yg sesuai
bila perlu
Immediately seek Diagnosis & treatment bila timbul
demam 1 mgg 3 bln setelah memasuki daerah endemis
Personal Protection
Protective clothing
Insect repellants
Household insecticide products
Window and door screens
Bed nets
Antimalarial
Chemoprophylaxis
Prevents disease, not infection
Appropriate for non-immune travelers
Practical only for some populations in
endemic areas
Consider:
immune status
intensity/duration of exposure
parasite drug resistance
resources for diagnosis and treatment
 Chemoprophylaxis
Sporozoites
Sporozoites Taken
Taken up
up by
by
Injected
Injected the
the Liver
Liver

Bite Causal
Causal
Bite
Prevention prophylaxis
prophylaxis
Parasites
Parasites Prevention
acts
acts here
here
develop
develop to
to
sporozoit
sporozoit stage
stage
in
in mosquito
mosquito
All
All 44 species
species develop
develop in
in
the
the liver
liver Vivax
Vivax and
and ovale
ovale
malaria
malaria also
also
Some
Some dont
dont multiply
multiply but
but have
have aa dormant
dormant
become
become gametocytes
gametocytes toto be
be Schizont
Schizont (hipnozoit)
(hipnozoit) stage
stage
taken
taken up
up by
by mosquitoes
mosquitoes in
in the
the liver
liver in
in the
the liver
liver

Parasites
Parasites multiplay
multiplay inin RBC
RBC
leading Hypnozoit
Hypnozoit
leading to
to clinical
clinical illness
illness
Parasites
Parasites released
released awake
awake and
and
to
to invade
invade and
and toto become
become
made
made develop
develop in
in schizonts
schizonts
Suppresses
Suppresses red
red blood
blood cells
cells (months
(months after
after
prophylaxis
prophylaxis exposure)
exposure)
acts
acts here
here
Terima Kasih