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Plasmodium vivax: pathogenesis and infectivity

Grant number: 12/16525-2
Support Opportunities:Research Projects - Thematic Grants
Duration: August 01, 2013 - May 31, 2018
Field of knowledge:Biological Sciences - Parasitology - Protozoology of Parasites
Principal Investigator:Fabio Trindade Maranhão Costa
Grantee:Fabio Trindade Maranhão Costa
Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Associated researchers:Carla Cristina Judice Maria ; Cláudio Romero Farias Marinho ; Gerhard Wunderlich ; Irene da Silva Soares ; Julio Cesar Soares Aliberti ; Letusa Albrecht ; Marcus Vinícius Guimarães de Lacerda ; Pedro Vitor Lemos Cravo ; Stefanie Costa Pinto Lopes
Associated grant(s):17/50400-6 - Advancing academic partnership in the discovery of anti malarial microbial metabolites of botanicals, AP.R SPRINT
17/02353-9 - Bioinformatics, Chemiogenomics and Chemioinformatics applied to the Discovery of New Drugs and Biotechnological Products, AV.BR
14/17325-2 - Identification of the mechanism of action of violacein and intermediates against Plasmodium spp, AV.EXT
14/02143-6 - Protective effect of lipoxins against the development of severe forms of malaria, AV.EXT
13/19667-5 - Plasmodium splenic cytoadherence in the malarial infection, AV.EXT
Associated scholarship(s):13/25807-4 - Dissecting the mechanisms of infectivity in Plasmodium - Plasmodium yoelii experimental model with implications for the study in Plasmodium vivax., BP.PD
13/20509-5 - Analyses of the immunopathological and molecular mechanisms involved in cytoadherence of Plasmodium vivax, BP.DR

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)

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Scientific publications (24)
(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)
LOPES, STEFANIE C. P.; ALBRECHT, LETUSA; CARVALHO, BRUNA O.; SIQUEIRA, ANDRE M.; THOMSON-LUQUE, RICHARD; NOGUEIRA, PAULO A.; FERNANDEZ-BECERRA, CARMEN; DEL PORTILLO, HERNANDO A.; RUSSELL, BRUCE M.; RENIA, LAURENT; et al. Paucity of Plasmodium vivax Mature Schizonts in Peripheral Blood Is Associated With Their Increased Cytoadhesive Potential. Journal of Infectious Diseases, v. 209, n. 9, p. 1403-1407, . (12/16525-2)
NEVES, BRUNO J.; BRAGA, RODOLPHO C.; ALVES, VINICIUS M.; LIMA, MARILIA N. N.; CASSIANO, GUSTAVO C.; MURATOV, EUGENE N.; COSTA, FABIO T. M.; ANDRADE, CAROLINA HORTA. Deep Learning-driven research for drug discovery: Tackling Malaria. PLOS COMPUTATIONAL BIOLOGY, v. 16, n. 2, . (17/02353-9, 17/18611-7, 15/20774-6, 12/16525-2)
TAVELLA, T. A.; CASSIANO, G. C.; MARANHAO COSTA, FABIO TRINDADE; SUNNERHAGEN, P.; BILSLAND, E.; DONEV, R. Yeast-based high-throughput screens for discovery of kinase inhibitors for neglected diseases. ADVANCES IN PROTEIN CHEMISTRY AND STRUCTURAL BIOLOGY, VOL 124: PROTEIN KINASES IN DRUG DISCOVERY, v. 124, p. 35-pg., . (19/27626-3, 15/20774-6, 12/16525-2, 15/03553-6)
BITTENCOURT, NAJARA CARNEIRO; IUNG ENEMBRECK DA SILVA, ANA BEATRIZ; VIRGILI, NATALIA SILVEIRA; SCHAPPO, ANA PAULA; GERVASIO, JOAO HENRIQUE D. B.; PIMENTA, TAMIRYS S.; KUJBIDA JUNIOR, MARIO A.; VENTURA, ANA MARIA R. S.; LIBONATI, ROSANA M. F.; SILVA-FILHO, JOAO LUIZ; et al. Plasmodium vivaxAMA1: Implications of distinct haplotypes for immune response. PLoS Neglected Tropical Diseases, v. 14, n. 7, . (16/12855-9, 15/02808-0, 12/16525-2)
LIMA, MARILIA N. N.; NEVES, BRUNO J.; CASSIANO, GUSTAVO C.; GOMES, MARCELO N.; TOMAZ, KAIRA C. P.; FERREIRA, LETICIA T.; TAVELLA, TATYANA A.; CALIT, JULIANA; BARGIERI, DANIEL Y.; MURATOV, EUGENE N.; et al. Chalcones as a basis for computer-aided drug design: innovative approaches to tackle. Future Medicinal Chemistry, v. 11, n. 20, p. 2635-2646, . (17/02031-1, 13/13119-6, 17/02353-9, 17/18611-7, 12/16525-2, 18/24878-9)
ALBRECHT, LETUSA; LOPES, STEFANIE C. P.; IUNG ENEMBRECK DA SILVA, ANA BEATRIZ; BARBOSA, VANESSA; ALMEIDA, RODRIGO P.; SIQUEIRA, ANDRE M.; LEITE, JULIANA ALMEIDA; BITTENCOURT, NAJARA C.; DOS SANTOS, HELLEN GEREMIAS; BOURGARD, CATARINA; et al. Rosettes integrity protects Plasmodium vivax of being phagocytized. SCIENTIFIC REPORTS, v. 10, n. 1, . (13/20509-5, 12/16525-2, 13/25807-4, 17/18611-7)
BILSLAND, ELIZABETH; TAVELLA, TATYANA A.; KROGH, RENATA; STOKES, JAMIE E.; ROBERTS, ANNABELLE; AJIOKA, JAMES; SPRING, DAVID R.; ANDRICOPULO, ADRIANO D.; COSTA, FABIO T. M.; OLIVER, STEPHEN G.. Antiplasmodial and trypanocidal activity of violacein and deoxyviolacein produced from synthetic operons. BMC Biotechnology, v. 18, . (15/03553-6, 12/16525-2)
KAYANO, ANA CAROLINA A. V.; DOS-SANTOS, JOAO CONRADO K.; BASTOS, MARCELE F.; CARVALHO, LEONARDO J.; ALIBERTI, JULIO; COSTA, FABIO T. M.. Pathophysiological Mechanisms in Gaseous Therapies for Severe Malaria. Infection and Immunity, v. 84, n. 4, p. 874-882, . (12/16525-2)
CRAVO, PEDRO; MACHADO, RENATO B.; LEITE, JULIANA A.; LEDA, TAIZY; SUWANARUSK, ROSSARIN; BITTENCOURT, NAJARA; ALBRECHT, LETUSA; JUDICE, CARLA; LOPES, STEFANIE C. P.; LACERDA, MARCUS V. G.; et al. In silico epitope mapping and experimental evaluation of the Merozoite Adhesive Erythrocytic Binding Protein (MAEBL) as a malaria vaccine candidate. Malaria Journal, v. 17, . (12/16525-2)
BARBOZA, RENATO; LIMA, FLAVIA AFONSO; REIS, ARAMYS SILVA; MURILLO, OSCAR JAVIER; MACHADO PEIXOTO, ERIKA PAULA; BANDEIRA, CARLA LETICIA; FOTORAN, WESLEY LUZETTI; SARDINHA, LUIS ROBERTO; WUNDERLICH, GERHARD; BEVILACQUA, ESTELA; et al. TLR4-Mediated Placental Pathology and Pregnancy Outcome in Experimental Malaria. SCIENTIFIC REPORTS, v. 7, . (12/16525-2, 11/17880-8, 14/20451-0, 14/09964-5, 15/06106-0, 13/00981-1, 11/19048-8, 13/16417-8, 09/53889-0)
BOURGARD, CATARINA; ALBRECHT, LETUSA; KAYANO, ANA C. A. V.; SUNNERHAGEN, PER; COSTA, FABIO T. M.. Plasmodium vivax Biology: Insights Provided by Genomics, Transcriptomics and Proteomics. FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, v. 8, . (12/16525-2, 13/20509-5)
VERA, OMAIRA; DE BRITO, PAULA BRELAS; ALBRECHT, LETUSA; MONICK MARTINS-CAMPOS, KEILLEN; PIMENTA, PAULO F. P.; MONTEIRO, WUELTON M.; LACERDA, MARCUS V. G.; LOPES, STEFANIE C. P.; COSTA, FABIO T. M.. Purification Methodology for Viable and Infective Plasmodium vivax Gametocytes That Is Compatible with Transmission-Blocking Assays. Antimicrobial Agents and Chemotherapy, v. 59, n. 10, p. 6638-6641, . (12/16525-2)
JUDICE, CARLA C.; BOURGARD, CATARINA; KAYANO, ANA C. A. V.; ALBRECHT, LETUSA; COSTA, FABIO T. M.. MicroRNAs in the Host-Apicomplexan Parasites Interactions: A Review of Immunopathological Aspects. FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, v. 6, . (12/16525-2)
BITTENCOURT, NAJARA C.; LEITE, JULIANA A.; SILVA, ANA BEATRIZ I. E.; PIMENTA, TAMIRYS S.; SILVA-FILHO, JOAO LUIZ; CASSIANO, GUSTAVO C.; LOPES, STEFANIE C. P.; DOS-SANTOS, JOAO C. K.; BOURGARD, CATARINA; NAKAYA, HELDER I.; et al. Genetic sequence characterization and naturally acquired immune response to Plasmodium vivax Rhoptry Neck Protein 2 (PvRON2). Malaria Journal, v. 17, . (13/20509-5, 15/02808-0, 15/20774-6, 12/16525-2, 13/25807-4, 16/12855-9)
MOTTIN, MELINA; BORBA, JOYCE V. V. B.; BRAGA, RODOLPHO C.; TORRES, PEDRO H. M.; MARTINI, MATHEUS C.; PROENCA-MODENA, JOSE LUIZ; JUDICE, CARLA C.; COSTA, FABIO T. M.; EKINS, SEAN; PERRYMAN, ALEXANDER L.; et al. The A-Z of Zika drug discovery. DRUG DISCOVERY TODAY, v. 23, n. 11, p. 1833-1847, . (12/16525-2, 16/00194-8, 17/02353-9, 16/13805-5)
BASTOS, MARCELE F.; KAYANO, ANA CAROLINA A. V.; SILVA-FILHO, JOAO LUIZ; DOS-SANTOS, JOAO CONRADO K.; JUDICE, CARLA; BLANCO, YARA C.; SHRYOCK, NATHANIEL; SERCUNDES, MICHELLE K.; ORTOLAN, LUANA S.; FRANCELIN, CAROLINA; et al. Inhibition of hypoxia-associated response and kynurenine production in response to hyperbaric oxygen as mechanisms involved in protection against experimental cerebral malaria. FASEB JOURNAL, v. 32, n. 8, p. 4470-4481, . (12/16525-2, 16/12855-9, 14/20451-0, 16/07030-0)
BOURGARD, CATARINA; LOPES, STEFANIE C. P.; LACERDA, MARCUS V. G.; ALBRECHT, LETUSA; COSTA, FABIO T. M.. A suitable RNA preparation methodology for whole transcriptome shotgun sequencing harvested from Plasmodium vivax-infected patients. SCIENTIFIC REPORTS, v. 11, n. 1, . (12/16525-2, 13/20509-5, 17/18611-7)
DOS-SANTOS, JOAO CONRADO KHOURI; SILVA-FILHO, JOAO LUIZ; JUDICE, CARLA C.; KAYANO, ANA CAROLINA ANDRADE VITOR; ALIBERTI, JULIO; KHOURI, RICARDO; DE LIMA, DIOGENES S.; NAKAYA, HELDER; LACERDA, MARCUS VINICIUS GUIMARAES; DE PAULA, ERICH VINICIUS; et al. Platelet disturbances correlate with endothelial cell activation in uncomplicatedPlasmodium vivaxmalaria. PLoS Neglected Tropical Diseases, v. 14, n. 7, . (16/12855-9, 17/18611-7, 12/16525-2)
LIMA, MARILIA N. N.; CASSIANO, GUSTAVO C.; TOMAZ, KAIRA C. P.; SILVA, ARTHUR C.; SOUSA, BRUNA K. P.; FERREIRA, LETICIA T.; TAVELLA, TATYANA A.; CALIT, JULIANA; BARGIERI, DANIEL Y.; NEVES, BRUNO J.; et al. Integrative Multi-Kinase Approach for the Identification of Potent Antiplasmodial Hits. FRONTIERS IN CHEMISTRY, v. 7, . (18/05926-2, 13/13119-6, 18/07007-4, 17/02353-9, 17/18611-7, 12/16525-2, 18/24878-9, 15/20774-6)
LIMA, MARILIA N. N.; CASSIANO, GUSTAVO C.; TOMAZ, KAIRA C. P.; SILVA, ARTHUR C.; SOUSA, BRUNA K. P.; FERREIRA, LETICIA T.; TAVELLA, TATYANA A.; CALIT, JULIANA; BARGIERI, DANIEL Y.; NEVES, BRUNO J.; et al. Integrative Multi-Kinase Approach for the Identification of Potent Antiplasmodial Hits. RONTIERS IN CHEMISTR, v. 7, p. 14-pg., . (17/02353-9, 18/05926-2, 13/13119-6, 18/24878-9, 18/07007-4, 15/20774-6, 12/16525-2, 17/18611-7)
BASTOS, MARCELE F.; ALBRECHT, LETUSA; GOMES, ANGELICA M.; LOPES, STEFANIE C. P.; VICENTE, CRISTINA P.; DE ALMEIDA, RODRIGO P. M.; CASSIANO, GUSTAVO C.; FONSECA, ROBERTO J. C.; WERNECK, CLAUDIO C.; PAVAO, MAURO S. G.; et al. A new heparan sulfate from the mollusk Nodipecten nodosus inhibits merozoite invasion and disrupts rosetting and cytoadherence of Plasmodium falciparum. Memórias do Instituto Oswaldo Cruz, v. 114, . (17/18611-7, 12/16525-2, 10/18571-6, 15/20774-6)
LIMA, MARILIA N. N.; MELO-FILHO, CLEBER C.; CASSIANO, GUSTAVO C.; NEVES, BRUNO J.; ALVES, VINICIUS M.; BRAGA, RODOLPHO C.; CRAVO, PEDRO V. L.; MURATOV, EUGENE N.; CALIT, JULIANA; BARGIERI, DANIEL Y.; et al. QSAR-Driven Design and Discovery of Novel Compounds With Antiplasmodial and Transmission Blocking Activities. FRONTIERS IN PHARMACOLOGY, v. 9, . (12/16525-2, 13/13119-6, 17/02353-9, 15/20774-6, 16/16649-4)
BAIA-DA-SILVA, DJANE CLARYS; SALAZAR ALVAREZ, LUIS CARLOS; VERA LIZCANO, OMAIRA; MARANHAO COSTA, FABIO TRINDADE; PINTO LOPES, STEFANIE COSTA; ORFANO, ALESSANDRA SILVA; PASCOAL, DENNER OLIVEIRA; NACIF-PIMENTA, RAFAEL; RODRIGUEZ, IRIA CABRAL; VALE BARBOSA GUERRA, MARIA DAS GRACAS; et al. The role of the peritrophic matrix and red blood cell concentration in Plasmodium vivax infection of Anopheles aquasalis. PARASITES & VECTORS, v. 11, . (12/16525-2)
REIS, ARAMYS S.; BARBOZA, RENATO; MURILLO, OSCAR; BARATEIRO, ANDRE; PEIXOTO, ERIKA P. M.; LIMA, FLAVIA A.; GOMES, VINICIUS M.; DOMBROWSKI, JAMILLE G.; LEAL, VINICIUS N. C.; ARAUJO, FRANCIELE; et al. Inflammasome activation and IL-1 signaling during placental malaria induce poor pregnancy outcomes. SCIENCE ADVANCES, v. 6, n. 10, . (14/09964-5, 15/23395-6, 14/20451-0, 17/03939-7, 11/19048-8, 17/05782-8, 13/16417-8, 16/07030-0, 12/16525-2, 12/04755-3, 15/50650-7, 18/20468-0, 13/00981-1, 11/17880-8, 15/06106-0)

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