PATOFISIOLOGI

MALARIA
 Produksi Sitokin

Pelepasan GPI
(glycosylphosphatidylinositol)

Dikenali oleh TLR (toll-like

receptor) makrofag

Gejala sistemik:
- Demam
Produksi sitokin proinflamasi - Menggigil
(TNFα, IL-1)
- Nyeri kepala
- Berkeringat
White NJ. Malaria. In: Farrar J, White NJ, Hotez PJ, Junghanss T, Lalloo D, Kang G, eds. Manson’s Tropical Diseases. 23 rd ed. Philadelphia: Elsevier; 2014.
Miller LH, Ackerman HC, Su X, Wellems TE. Malaria biology and disease pathogenesis: insights for new treatments. Nat Med. 2013;9(2).
 Sitoadherensi

Ekspresi PfEMP-1
Invasi P. falciparum ke sel RBC terinfeksi adhesi ke
(P. falciparum erythrocyte
darah merah endotel pembuluh darah
membrane protein 1)

White NJ. Malaria. In: Farrar J, White NJ, Hotez PJ, Junghanss T, Lalloo D, Kang G, eds. Manson’s Tropical Diseases. 23 rd ed. Philadelphia: Elsevier; 2014.
Miller LH, Ackerman HC, Su X, Wellems TE. Malaria biology and disease pathogenesis: insights for new treatments. Nat Med. 2013;9(2).
 Sitoadherensi

Reseptor adhesi:

CD36 ICAM-1 CSA

Endotel, platelet, Endotel pembuluh

Plasenta
makrofag darah cerebral
White NJ. Malaria. In: Farrar J, White NJ, Hotez PJ, Junghanss T, Lalloo D, Kang G, eds. Manson’s Tropical Diseases. 23 rd ed. Philadelphia: Elsevier; 2014.
Miller LH, Ackerman HC, Su X, Wellems TE. Malaria biology and disease pathogenesis: insights for new treatments. Nat Med. 2013;9(2).
 Rosetting
Ekspresi PfEMP-1
(P. falciparum erythrocyte
membrane protein 1)

RBC terinfeksi adhesi ke

RBC sehat

Berikatan dengan molekul di

permukaan RBC sehat:
• Complement receptor CR1
• Heparan sulfat
• Antigen golongan darah A

White NJ. Malaria. In: Farrar J, White NJ, Hotez PJ, Junghanss T, Lalloo D, Kang G, eds. Manson’s Tropical Diseases. 23 rd ed. Philadelphia: Elsevier; 2014.
Miller LH, Ackerman HC, Su X, Wellems TE. Malaria biology and disease pathogenesis: insights for new treatments. Nat Med. 2013;9(2).
 Rosetting
Obstruksi
PfEMP-1 mikrovaskular

Sitoadheren

Sekuestrasi Variasi antigen

(menghilang dari sirkulasi)

Tropozoit matur & schizont Menghindari Menghindari

P. falciparum jarang (+) di destruksi RBC dikenali respon
apusan darah terinfeksi di limpa imun

White NJ. Malaria. In: Farrar J, White NJ, Hotez PJ, Junghanss T, Lalloo D, Kang G, eds. Manson’s Tropical Diseases. 23 rd ed. Philadelphia: Elsevier; 2014.
Miller LH, Ackerman HC, Su X, Wellems TE. Malaria biology and disease pathogenesis: insights for new treatments. Nat Med. 2013;9(2).
 Sitokin Otak Malaria serebral
Proinflamasi

Disfungsi liver:
Liver - ↓ klirens laktat
Sitoadheren - ↓ glukoneogenesis

Obstruksi
mikrovaskular - Malabsorbsi
GI tract - ↓ imunitas lokal
Rosetting
Acute tubular
Ginjal
necrosis  AKI

Rigiditas
membran RBC Insuffisiensi plasenta
Plasenta
 prematur, IUGR
White NJ. Malaria. In: Farrar J, White NJ, Hotez PJ, Junghanss T, Lalloo D, Kang G, eds. Manson’s Tropical Diseases. 23 rd ed. Philadelphia: Elsevier; 2014.
Miller LH, Ackerman HC, Su X, Wellems TE. Malaria biology and disease pathogenesis: insights for new treatments. Nat Med. 2013;9(2).
White NJ. Malaria. In: Farrar J, White NJ, Hotez PJ, Junghanss T, Lalloo D, Kang G, eds. Manson’s Tropical Diseases. 23 rd ed. Philadelphia: Elsevier; 2014.
Miller LH, Ackerman HC, Su X, Wellems TE. Malaria biology and disease pathogenesis: insights for new treatments. Nat Med. 2013;9(2).

Splenomegali
Rigiditas ↑↑ RBC terfiltrasi
membran RBC di limpa

Fagositosis ↑↑ Hemolisis
RBC terinfeksi Sel darah merah

Anemia
Ruptur
schizont Gangguan eritropoiesis
di sumsum tulang

Sitokin
proinflamasi ↑↑ Destruksi platelet
oleh makrofag

Adhesi dan aktivasi Trombositopenia &

platelet Koagulopati
Sitoadheren
Aktivasi kaskade
koagulasi
 ↓↓ ↑↑ Kebutuhan
Disfungsi liver
glukoneogenesis glukosa

Hipoglikemia
Metabolisme
glukosa oleh
parasit
Glikolisis Obstruksi
anaerob mikrovaskular
Produksi ↑↑
asam laktat RBC
Asidosis

Gangguan ↑↑ Produksi
ginjal akut ↓↓ klirens laktat
asam laktat
(AKI)

White NJ. Malaria. In: Farrar J, White NJ, Hotez PJ, Junghanss T, Lalloo D, Kang G, eds. Manson’s Tropical Diseases. 23 rd ed. Philadelphia: Elsevier; 2014.
Miller LH, Ackerman HC, Su X, Wellems TE. Malaria biology and disease pathogenesis: insights for new treatments. Nat Med. 2013;9(2).