Malaria associated acute lung injury and acute respiratory distress syndrome through in vitro and in vivo models

• Grant number: 11/19525-0
• Support type: Scholarships in Brazil - Post-Doctorate
• Effective date (Start): April 01, 2012
• Effective date (End): February 28, 2014
• Field of knowledge: Biological Sciences - Parasitology
• Principal Investigator: Sabrina Epiphanio
• Grantee: Elizabeth Helen Aitken
• Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 09/53256-7 - Distress syndrome in a murine model associated to the severe malaria: a study of parasite-host interaction, AP.JP

Abstract

It was estimated that in 2009 malaria was responsible for 781 000 deaths worldwide, and that 20% of Brazil's population was at risk of infection. Syndromes of severe malaria can include severe anaemia, cerebral malaria and acute lung injury/acute respiratory distress syndrome (ALI/ARDS). The later is little studied, and the mechanisms of pathology largely unknown, though it is a syndrome with high mortality. Mouse models can provide useful tools in elucidating the mechanisms of disease. The main objective of this project is to elucidate different aspects involved in the pathogenesis of ALI/ARDS by further characterising a mouse model for malaria associated ALI/ARDS and by using an in vitro model of Plasmodium/endothelium interaction in the lung. Using the mouse model we will characterise immunological markers of ALI/ARDS in serum, arterial blood gases and the interaction between Plasmodium and lung endothelial cells, over the course of infection. In addition, we will study ALI/ARDS pathology by ultrastrutural analysis. This work will be in conjunction with in vitro models assessing Plasmodium/endothelium adhesion, and resulting cell products and endothelium viability, using primary lung endothelium from mice with varying susceptibility to ALI/ARDS. We believe results obtained can increase understanding of the mechanisms of this syndrome. Importantly, results could also help identify biomarkers for malaria associated ALI/ARDS, which may aid early diagnosis.

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)

SERCUNDES, MICHELLE K.; ORTOLAN, LUANA S.; DEBONE, DANIELA; SOEIRO-PEREIRA, PAULO V.; GOMES, ELIANE; AITKEN, ELIZABETH H.; NETO, ANTONIO CONDINO; RUSSO, MOMTCHILO; D' IMPERIO LIMA, MARIA R.; ALVAREZ, JOSE M.; PORTUGAL, SILVIA; MARINHO, CLAUDIO R. F.; EPIPHANIO, SABRINA. Targeting Neutrophils to Prevent Malaria-Associated Acute Lung Injury/Acute Respiratory Distress Syndrome in Mice. PLOS PATHOGENS, v. 12, n. 12 DEC 2016. Web of Science Citations: 31.

AITKEN, ELIZABETH HELEN; BUENO, MARINA GALVAO; ORTOLAN, LUANA DOS SANTOS; ALVAREZ, JOSE M.; PISSINATTI, ALCIDES; MARTINS KIERULFF, MARIA CECLIA; CATAO-DIAS, JOSE LUIZ; EPIPHANIO, SABRINA. Survey of Plasmodium in the golden-headed lion tamarin (Leontopithecus chrysomelas) living in urban Atlantic forest in Rio de Janeiro, Brazil. Malaria Journal, v. 15, FEB 17 2016. Web of Science Citations: 6.

SOUZA, RODRIGO M.; ATAIDE, RICARDO; DOMBROWSKI, JAMILLE G.; IPPOLITO, VANESSA; AITKEN, ELIZABETH H.; VALLE, SUIANE N.; ALVAREZ, JOSE M.; EPIPHANIO, SABRINA; MARINHO, CLAUDIO R. F. Placental Histopathological Changes Associated with Plasmodium vivax Infection during Pregnancy. PLoS Neglected Tropical Diseases, v. 7, n. 2 FEB 2013. Web of Science Citations: 36.