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 5,5 8 9 15
phase (days)
Number of merozoites 30.000 10.000 15.000 15.000
released per infected
hepatocyte
Duration of erythrocytic 48 48 50 72
cycle (hours)
Red cell prference Younger cells (but can Red cells up to 14 days Reticulocytes Older cells
invade cells of all ages) old
Morphology Usually only ring forms; Irregularly shaped Infected erythrocytes, Band or rectangular
banana-shaped large rings and enlarged and oval with forms of trophozoites
gametocytes tropozoites; enlarged tufted ends; common
erythrocytes; Schuffners dots
Schuffners dots
Pigment color Black Yellow-brown Dark brown Brown-black

Ability to cause No Yes Yes No

relapses

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 Failure to localize or respond appropriately to noxiuos stimuli; coma persisting for > 30
coma/cerebral malaria 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, Hematocrit of < 15% or hemoglobin level of < 50 g/L (<5g/dL) with parasitemia of >
normocytic anemia 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 Bleeding Anuria
Hyperventilation (respiratory distress) Deep coma Shock
Hypothermia (<36,50C) Repeated convulsions
Laboratory

Biochemistry
Hypoglycemia (<2,2 mmol.L) Elevated liver enzymes (AST/ALT 3 times upper limit of
Hyperlactatemia (>5 mmol/L) normal, 5-nucleotidase )
Acidosis (arterial pH <7,3; serum HCO3 <15 mmol/L) Elevated muscle enzymes (CPK , myoglobin )
Elevated serum creatinine (>265 mol/L) Elevated urate (> 600 mol/L)
Elevated total bilirubin (> 50 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+ 1 1
58 2+1 1 1 1 2 2

9 15 3+1 1 1 1 3 3 1
> 15 / 4+2 2 2 2 4 4 2
dewasa
 PEDOMAN PENGGUNAAN OBAT UNTUK MALARIA PARAH

Nama obat Dosis permulaan Dosis lanjutan

Kuinin 20 mg/kg BB kuinin dalam 100-200 cc D 5% / 10 mg/kg BB dilarutkan dalam 200 cc D 5% setiap
NaCl selama 4 jam, dianjutkan dengan 10 8 jam. Bila penderita sudah sadar, diberikan kinin
mg/kg BB dilarutkan dalam 200 cc D 5% oral, 600 mg 3x sehari, sampai hari ke 7
selama 4 jam

Kuinidin 15 mg basa/kg BB dilarutkan dalam 250 cc 7.5 mg basa/kg BB dalam 250 cc cairan isotonik
cairan isotonik selama 4 jam selama 4 jam, setiap 8 jam, dilanjutkan per oral
setelah penderita sadar

Klorokuin (untuk 10 mg/kg BB dalam 500 cc larutan isotonik 5 mg basa/kg BB dalam 500 cc larutan isotonis
yang masih sensitif) selama 8 jam 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
Mefloquine (Lariam) 250 mg garam (288 mg basa),
1x/mg
Doxycycline 100 mg 1x / hari
Chloroquine phosphate 500 mg garam (300 mg basa),
(Aralen) 1x/mmg
Primaquine 15 mg basa (26.3 mg garam),
1x/hari selama 14 hari
Hydroxychloroquine 400 mg garam (310 mg basa),
sulfate (Plaquine) 1x/mgg
Proguanil (Paludrine) 200 mg, 1x/hari, dikombinasikan
dengan Chloroquine per mmg
Dosis anak-anak
15 19 kg: tab/mgg
20 30 kg: tab/mgg
31 45 kg: tab/mmg
> 45 kg: 1 tab/mmg
Usia di atas 8 th: 2 mg/kg 1x/hari,
maksimum sama dengan dosis dewasa
5 mg/kg basa (8.3 mg/kg garam), 1x/mgg,
maksimum sama dengan dosis dewasa
0.3 mg/kg basa, (0.5 mg/kg garam), 1x/hari
selama 14 hari (maksimum 15 mg basa)
5 mg/kg basa (6.5 mg/kg garam),
1x/mgg.maksimum sama dengan dosis
dewasa (310 mg basa)
< 2 tahun: 50 mg/hari
2 6 tahun: 100 mg/hari
7 10 tahun: 150 mg/hari
> 10 tahun: 200 mg/hari