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.
News published in Agência FAPESP Newsletter about the scholarship: