Plasmodium vivax: pathogenesis and infectivity

Abstract

Globally, Plasmodium vivax is responsible for more than 80 million cases per year, with strong social impact outside Africa, mainly in Asia and the Americas. Brazil accounts for 50-60% of all malaria cases reported in the Americas, 85% of these infections are caused by P. vivax and transmission is almost exclusively restricted to the Amazon region (99.8%). Severe cases caused by P. vivax are pathologically similar to P. falciparum; it has been recently shown that P. vivax infections may also lead to complications. This observation challenges the concept that P. vivax is a "benign" species of parasite. Nevertheless, performing functional assays for studying P. vivax pathogenesis and infectivity still remain restricted to regional hospitals in endemic areas. This fact is mainly due to the lack of a reliable and reproducible long-term in vitro culture system. As a result of collaboration with referral hospitals in malaria endemic areas, we were able to develop an ex vivo invasion assay, and we also demonstrated that P. vivax-infected erythrocytes (Pv-iE) collected from infected patients are able to adhere to brain and lung endothelium and to placental cryosections. These findings suggest the involvement of P. vivax adhesive capacity in the pathological processes in these organs. Based on the field capacity installed and on the acquired know-how, we propose (i) to understand the mechanisms related to Pv-iE cytoadhesion and rosette formation (functional assays), and to identify potential parasitic ligand(s) involved (by means of molecular analysis and generation of monoclonal antibodies). (ii) We also plan to determine the impact of P. vivax infections in pregnant women and the consequences to the placental tissue (via histopathological analysis); and (iii) verify the potential vaccine antigens of P. vivax as well as the mechanisms related to infection of this parasite in human erythrocytes/reticulocytes, performing invasion assays and by epitope(s) mapping. Finally, by means of experimental infection of pregnant mice, (iv) we will evaluate the innate immune response and the parasite ligand(s) involved in the adhesion to the placental tissue. (AU)