Clinical and molecular aspects of severe malaria

Abstract

The erythrocytic cycle of Plasmodium falciparum presents a particularity in relation to other Plasmodium species that infect man. Mature trophozoites and schizonts are sequestered from the peripheral circulation due to adhesion of infected erythrocytes to host endothelial cells. Modifications in the surface of infected erythrocytes, termed knobs, seem to facilitate adhesion to endothelium and other erythrocytes. Adhesion provides better maturation in the microaerophilic venous atmosphere and allows the parasite to escape clearance by the spleen which recognizes the erythrocytes loss of deformability. Adhesion to the endothelium, or cytoadherence, has an important role in the pathogenicity of the disease, causing occlusion of small vessels and contributing to failure of many organs. Cytoadherence can also describe adhesion of infected erythrocytes to uninfected erythrocytes, a phenomenon widely known as rosetting. Clinical aspects of severe malaria, as well as the host receptors and parasite ligands involved in cytoadherence and rosetting, are reviewed here. The erythrocyte membrane protein 1 of P. falciparum (PfEMP1) appears to be the principal adhesive ligand of infected erythrocytes and will be discussed in more detail. Understanding the role of host receptors and parasite ligands in the development of different clinical syndromes is urgently needed to identify vaccination targets in order to decrease the mortality rates of this disease.

Malaria Pada Kehamilan Dan Konsekuensinya Pada Ibu Dan Janin

“…Anoksia jaringan terjadi karena adanya penyumbatan pembuluh darah di mikrovaskuler, akibat adanya proses cytoadherence, rosetting dan sekuestrasi [23].…”

Intervensi Cytoadherence Sebagai Peluang Untuk Pencegahan Dan Terapi Malaria Berat

“…Adhesi eritrosit menghasilkan maturasi yang lebih baik dalam lingkungan mikroaerofilik venous serta akan membuat parasit ini terhindar dari proses pembersihan dari limpa. Dalam tekanan gas yang rendah parasit akan lebih cepat berdiferensiasi dan eritrosit bentuk aseksual (trophozoite dan schizont) juga akan lebih cepat menjadi matur (1).…”

“…Knob ini akan memudahkan terjadinya adhesi pada sel endotel dan eritrosit lainnya.. Adhesi pada endotel atau cytoadherence, berperan penting dalam patogenesis penyakit, karena dapat menyebabkan oklusi pada pembuluh darah kecil serta dapat menyebabkan gagal fungsi pada beberapa organ. Protein membran eritrosit 1 dari P. falciparum (PfEMP-1) merupakan ligand adhesif utama dari eritrosit yang terinfeksi (1).…”

“…Selanjutnya antigen dari parasit akan muncul pada permukaan eritrosit terinfeksi. Eritrosit yang terinfeksi P. falciparum ini akan memicu terjadinya pengikatan pada sel endotel kapiler dan venular (Cytoadherence), sehingga menghasilkan sequestration pada postkapilar venule organ dalam (1).…”

Enlistment of omics technologies in the fight against malaria: Panacea or Pandora's Box?

“…47) Studies from other isolates corroborate this observation, 48) and this var group is implicated in severe malaria. [49][50][51] Classification of the var genes has also enabled researchers to single out unique var genes that fall outside the main groups. For example, during pregnancy-associated malaria var2CSA is believed to be the principal ligand that binds to chondroitin sulfate A in the placental endothelial lining.…”