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Plasmodium vivax and immunopathogenesis: study of interactions between endothelium, platelets and microparticles in parasite cytoadherence

Grant number: 11/23664-6
Support Opportunities:Scholarships in Brazil - Post-Doctoral
Effective date (Start): March 01, 2012
Effective date (End): November 30, 2014
Field of knowledge:Biological Sciences - Parasitology - Protozoology of Parasites
Principal Investigator:Fabio Trindade Maranhão Costa
Grantee:Stefanie Costa Pinto Lopes
Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

The higher pathogenicity of falciparum malaria is ascribed to cytoadhesion of the P. falciparum-infected erythrocytes (Pf-iEs) in the microvasculature of vital organs (e.g. brain, lungs and placenta). Although this phenomenon is not yet noted for P. vivax, clinical complications similar to those observed for severe falciparum malaria are now described to P. vivax, suggesting that key pathogenic mechanisms are shared by the two parasites. However, P. vivax pathogenesis remains unknown and a better understanding of the pathological mechanisms triggered by this parasite may prove be useful in the development of new approaches to the control and treatment of Brazil's predominant Plasmodium species (83.6%). Recently, we have shown that P. vivax-infected erythrocytes (Pv-iEs) obtained after Percoll enrichment from several patients were able to cytoadhere under static or flow conditions to lung and brain endothelial cells and to placenta cryosections. Furthermore, in a case series of 17 autopsies of P. vivax infected patients, acute respiratory distress syndrome (ARDS) was the most common complication. Importantly, the finding of Pv-iEs inside pulmonary capillaries, in absence of any remarkable peripheral parasitemia, strongly suggests that cytoadhesion occurs in severe vivax malaria. Therefore, given the increasing number of reports showing severe disease in vivax malaria, the proven ex vivo adhesive capacity and the probably in vivo sequestration, this project aims to elucidate the cytoadhesion phenomenon in P. vivax, finding the role of each cell involved (e.g. endothelium, infected-erythrocytes and platelets) and the participation of other potential mediators (e.g. microparticles, cytokines, antibodies). (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
VERINAUD, LIANA; PINTO LOPES, STEFANIE COSTA; NARANJO PRADO, ISABEL CRISTINA; ZANUCOLI, FABIO; DA COSTA, THIAGO ALVES; DI GANGI, ROSARIA; ISSAYAMA, LUIDY KAZUO; CARVALHO, ANA CAROLINA; BONFANTI, AMANDA PIRES; NIEDERAUER, GUILHERME FRANCIO; et al. Violacein Treatment Modulates Acute and Chronic Inflammation through the Suppression of Cytokine Production and Induction of Regulatory T Cells. PLoS One, v. 10, n. 5, . (11/17965-3, 11/23664-6, 12/01892-0, 14/02631-0)

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