MALARIA

Prof Dr. dr. Djoni Djunaedi, SpPD, KPTI

DEFINISI:
Penyakit infeksi akut atau kronis
Disebabkan oleh Plasmodium malariae
Ditularkan melalui gigitan nyamuk Anopheles

Ditandai dengan:
Demam paroksismal
Anemia
Splenomegali

ETIOLOGI:
Plasmodium:
Falciparum

Vivax
Malariae
Ovale
Berghei

EPIDEMIOLOGI:
Tersebar di 103 negara
Menjangkiti sekitar 1 milyar penduduk
Angka kematian mencapai 1 -3 juta kasus/tahun
Menempati peringkat ke-5 penyebab kematian
Menempati 3 besar penyakit yang mengancam
nyawa (terutama di Negara Berkembang di samping HIV dan TBC)
Di Kabupaten Malang: 320 350 kasus/tahun (52 kasus
di antaranya di rawat di RSSA dalam kondisi sakit parah

Kendala pemberantasan:
Resistensi Plasmodium terhadap obat
Resistensi vektor terhadap insektisida

Malaria-endemic countries in the Americas (2007)

White NJ, Breman JG. Malaria and babesiosis: Diseases caused by red blood cell parasites. In Harrisons Principles of Internal Medicine. 16th
ed. NY: MacGraw-Hill Co. 2005: 1220

Malaria-endemic countries in Africa, the Middle

East, Asia, and South Pacific (2007)

White NJ, Breman JG. Malaria and babesiosis: Diseases caused by red blood cell parasites.
In Harrisons Principles of Internal Medicine. 16th ed. NY: MacGraw-Hill Co. 2005: 1220

Malaria transmission cycle from mosquito to human

White NJ, Breman JG. Malaria and babesiosis: Diseases caused by red blood cell parasites.
In Harrisons Principles of Internal Medicine. 16th ed. NY: MacGraw-Hill Co. 2005: 1220

PERUBAHAN ERITROSIT PADA MALARIA:

Eritrosit yang mengandung parasit malaria:
Bentuk ireguler
Bersifat lebih antigenik
Deformitas berkurang

Timbul knobs (suatu protein adesi yang berkemampuan melekat)

cytoadherence

rosettes

penyumbatan kapiler (aglutinasi)

iskemia

umur eritrosit <

Penghancuran parasit dalam limpa

splenic processing and infiltration

Thick blood films of Plasmodium falciparum

A. Trophozoites
B. Gametocytes

White NJ, Breman JG. Malaria and babesiosis: Diseases caused by red blood cell parasites.
In Harrisons Principles of Internal Medicine. 16th ed. NY: MacGraw-Hill Co. 2005: 1220

Thick blood films of Plasmodium vivax

A. Throphozoites
B. Schozonts
C. Gametocytes

White NJ, Breman JG. Malaria and babesiosis: Diseases caused by red blood cell parasites.
In Harrisons Principles of Internal Medicine. 16th ed. NY: MacGraw-Hill Co. 2005: 1220

Thick blood films of Plasmodium ovale

A. Throphozoites
B. Schozonts
C. Gametocytes

White NJ, Breman JG. Malaria and babesiosis: Diseases caused by red blood cell parasites.
In Harrisons Principles of Internal Medicine. 16th ed. NY: MacGraw-Hill Co. 2005: 1220

Thick blood films of Plasmodium malariae

A. Throphozoites
B. Schozonts
C. Gametocytes

White NJ, Breman JG. Malaria and babesiosis: Diseases caused by red blood cell parasites.
In Harrisons Principles of Internal Medicine. 16th ed. NY: MacGraw-Hill Co. 2005: 1220

Characterictics of Plasmodium species infecting humans

Finding for indicated species
Characteristic

P. falciparum

P. vivax

P. ovale

P. malariae

Duration of intrahepatic
phase (days)

5,5

15

Number of merozoites
released per infected
hepatocyte

30.000

10.000

15.000

15.000

Duration of erythrocytic
cycle (hours)

48

48

50

72

Red cell prference

Younger cells (but can

invade cells of all ages)

Red cells up to 14 days

old

Reticulocytes

Older cells

Morphology

Usually only ring forms;

banana-shaped
gametocytes

Irregularly shaped
large rings and
tropozoites; enlarged
erythrocytes;
Schuffners dots

Infected erythrocytes,
enlarged and oval with
tufted ends;
Schuffners dots

Band or rectangular
forms of trophozoites
common

Pigment color

Black

Yellow-brown

Dark brown

Brown-black

Ability to cause
relapses

No

Yes

Yes

No

White NJ, Breman JG. Malaria and babesiosis: Diseases caused by red blood cell parasites.
In Harrisons Principles of Internal Medicine. 16th ed. NY: MacGraw-Hill Co. 2005: 1220

Faktor manusia dikaitkan dengan

kerentanan terserang penyakit malaria:

Ras atau suku bangsa

Populasi dengan HBS

perkembangan P. falciparum terhambat

Kekurangan enzim tertentu

G6PD

memberikan perlindungan terhadap infeksi Plasmodium

Imunitas
Mencegah masuknya Plasmodium

Menekan perkembangan parasit

ANAMNESIS:

Riwayat demam intermiten atau terus-menerus

Riwayat dari atau pergi ke daerah endemik malaria
Trias malaria: menggigil, demam, banyak keringat
Di daerah endemik malaria, trias malaria mungkin tidak dijumpai
diare dapat merupakan gejala utama

MANIFESTASI KLINIS:
Konjungtiva pucat
Sklera ikterik
Splenomegali

Manifestation of severe Falciparum malaria

Signs

Manifestation

Major
Unarousable
coma/cerebral malaria

Failure to localize or respond appropriately to noxiuos stimuli; coma persisting for > 30
min after generalized convulsion

Acidemia/acidosis

Arterial pH < 7,25 or plasma bicarbonate level of < 15 mmol/L; venous lactate level
breathing, often termed respiratory distress

Severe normochromic,
normocytic anemia

Hematocrit of < 15% or hemoglobin level of < 50 g/L (<5g/dL) with parasitemia of >
100.000/L

Renal failure

Urine output (24 h) of < 400 mL in adults or < 12 mL/kg in children; no improvement with
rehydration; serum creatinine level of > 265 mol/L (> 3,0 mg/dL)

Pulmonary edema/ARDS

Noncardiogenic pulmonary edema, often aggravated by overhydration

Hypoglycemia

Plasma glucose level of < 2,2 mmol/L (< 40 mg/dL)

Hypotension/shock

Systolic blood pressure of < 50 mmHg in children 1-5 years or < 80 mmHg in adults;
core/skin temperature difference of > 100C

Bleeding/DIC

Significant bleeding and haemorrhage from the gums, nose, and gastrointestinal tract
and/or evidence of disseminated intravascular coagulation

Convulsions

More than 2 generalized seisures in 24 h

Hemoglobinuria

Macroscopic black, brown, or red urine; not associated with effects of oxidant drugs and
red blood cell enzyme defects (such as G6PD deficiency)

Sign

Manifestations

Other
Impaired conciousness

Obtunded but arousable

Extreme weakness

Prostration; inability to sit unaided

Hyperparasitemia

Parasitemia level of > 5% in nonimmune patients (> 20% in any patient)

Jaundice

Serum bilirubin level of > 50 mmol/L (> 3.0 mg/dL) if combined with other evidence of
vital-organ dysfunction

Features indicating a poor prognosis in severe falciparum malaria

Clinical
Marked agitation
Hyperventilation (respiratory distress)
Hypothermia (<36,50C)

Bleeding
Deep coma
Repeated convulsions

Anuria
Shock

Laboratory

Biochemistry
Hypoglycemia (<2,2 mmol.L)
Hyperlactatemia (>5 mmol/L)
Acidosis (arterial pH <7,3; serum HCO3 <15 mmol/L)
Elevated serum creatinine (>265 mol/L)
Elevated total bilirubin (> 50 mol/L)

Elevated liver enzymes (AST/ALT 3 times upper limit of

normal, 5-nucleotidase )
Elevated muscle enzymes (CPK , myoglobin )
Elevated urate (> 600 mol/L)

Hematology
Leukocytosis (>12.000/L)
Severe anemia (PCV < 15%)
Coagulopathy
Decreased platelet count (< 50.000/L)
Prolonged prothrombin time (> 3s)
Prolonged partial thromboplastin time
Decreases fibrinogen (< 200 mg/dL)

Parasitology
Hyperparasitemia
Increased mortality at > 100.000/L
High mortality at > 500.000/L
> 20% of parasites indentified as pigment-containing trophozoites and schizonts
> 5% of neutrophils with visible pigment

COMPLICATON OF SEVERE MALARIA

Cerebral malaria (death rate 20% in adults; 15% in children)
Hypoglycemia

(usual hypoglycemia signs e.g. sweating, tachycardia (-))

Lactic acidosis (correlates with hypoglycemia; failure in excretion lactic acid

via liver and kidney)

Non-cardiogenic pulmonary edema (mortality rate > 80%)

Renal impairment (related with erythrocytes sequestration
microcirculatory flow). Early HD good prognosis

Hematologic abnormalities (severe anemia, dyserythropoiesis, slight

coagulation abnormalities, mild thrombocytopenia)

Liver dysfunction mild hemolytic jaundice

Patients with falcifarum may develop deep jaundice with hemolytic,
hepatitic, and cholestatic components

Related incidence of severe complication of falcifarum malaria

Complications

Nonpregnant adults

Pregnant women

Children

Anemia

++

+++

Convulsion

+++

Hypoglycemia

+++

+++

Jaundice

+++

+++

Renal failure

+++

+++

Pulmonary edema

++

+++

DIFFERENTIAL DIAGNOSIS

Viral infection
Toxic typhoid fever
Fulminant hepatitis
Leptospirosis
Encephalitis

PENATALAKSANAAN MALARIA TANPA KOMPLIKASI

Jumlah tablet per hari, dosis tunggal
Tiap tablet klorokuin 250mg setara dengan 150 mg klorokuin basa
Menurut WHO

Menurut Depkes RI

Hari 1

Hari 2

Hari 3

Hari 4-5

Hari 1

Hari 2

Hari 3

<1

14

1+

58

2+1

9 15

3+1

> 15 /
dewasa

4+2

PEDOMAN PENGGUNAAN OBAT UNTUK MALARIA PARAH

Nama obat

Dosis permulaan

Dosis lanjutan

Kuinin

20 mg/kg BB kuinin dalam 100-200 cc D 5% /

NaCl selama 4 jam, dianjutkan dengan 10
mg/kg BB dilarutkan dalam 200 cc D 5%
selama 4 jam

10 mg/kg BB dilarutkan dalam 200 cc D 5% setiap

8 jam. Bila penderita sudah sadar, diberikan kinin
oral, 600 mg 3x sehari, sampai hari ke 7

Kuinidin

15 mg basa/kg BB dilarutkan dalam 250 cc

cairan isotonik selama 4 jam

7.5 mg basa/kg BB dalam 250 cc cairan isotonik

selama 4 jam, setiap 8 jam, dilanjutkan per oral
setelah penderita sadar

Klorokuin (untuk
yang masih sensitif)

10 mg/kg BB dalam 500 cc larutan isotonik

selama 8 jam

5 mg basa/kg BB dalam 500 cc larutan isotonis

selama 8 jam, diulang 3 kali (total 15 mg/kg BB)

Artesunate (IV)

250 mg drip dalam larutan isotonik

100 mg/hari selama 14 hari

Artemeter

160 mg suntikan (IM)

80 mg IM selama 14 hari

PROFILAKSIS

Obat antimalaria

Perorangan: baju panjang, insektisida, repelen, kasa/kelambu

Vaksin malaria:
Antisporozoit (pra-eri)
Stadium aseksual / eritrositik

Stadium seksual / transmisi (-)

PENATALAKSANAAN PROFILAKSIS MALARIA

Obat

Dosis dewasa

Dosis anak-anak

Mefloquine (Lariam)

250 mg garam (288 mg basa),

1x/mg

15 19 kg: tab/mgg
20 30 kg: tab/mgg
31 45 kg: tab/mmg
> 45 kg: 1 tab/mmg

Doxycycline

100 mg 1x / hari

Usia di atas 8 th: 2 mg/kg 1x/hari,

maksimum sama dengan dosis dewasa

Chloroquine phosphate
(Aralen)

500 mg garam (300 mg basa),

1x/mmg

5 mg/kg basa (8.3 mg/kg garam), 1x/mgg,

maksimum sama dengan dosis dewasa

Primaquine

15 mg basa (26.3 mg garam),

1x/hari selama 14 hari

0.3 mg/kg basa, (0.5 mg/kg garam), 1x/hari

selama 14 hari (maksimum 15 mg basa)

Hydroxychloroquine
sulfate (Plaquine)

400 mg garam (310 mg basa),

1x/mgg

5 mg/kg basa (6.5 mg/kg garam),

1x/mgg.maksimum sama dengan dosis
dewasa (310 mg basa)

Proguanil (Paludrine)

200 mg, 1x/hari, dikombinasikan

dengan Chloroquine per mmg

< 2 tahun: 50 mg/hari

2 6 tahun: 100 mg/hari
7 10 tahun: 150 mg/hari
> 10 tahun: 200 mg/hari