Predictive criteria to study the pathogenesis of malaria-associated ali/ards in mice

• Grant number: 14/14915-3
• Support Opportunities: Regular Research Grants - Publications - Scientific article
• Duration: August 01, 2014 - January 31, 2015
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal Investigator: Sabrina Epiphanio
• Grantee: Sabrina Epiphanio
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Malaria-associated acute lung injury/acute respiratory distress syndrome (ALI/ARDS) often results in morbidity and mortality. Murine models to study malaria-associated ALI/ARDS have been described, yet we lack a method of distinguishing which mice will develop ALI/ARDS before death. This work aimed to characterize malaria-associated ALI/ARDS in a murine model and to demonstrate the first method to predict whether mice are suffering from ALI/ARDS before death. DBA/2 mice infected with Plasmodium berghei ANKA developing ALI/ARDS or hyperparasitemia (HP), were compared using histopathology, PaO2 measurement, pulmonary X-ray, breathing capacity, lung permeability and serum vascular endothelial growth factor (VEGF) levels according to either the day of death or suggested predictive criteria. We proposed a model to predict malaria-associated ALI/ARDS using respiratory (enhanced pause and frequency respiratory) and parasitemia as predictive criteria from mice whose cause of death was known to retrospectively diagnose the sacrificed mice as likely to die of ALI/ARDS as early as 7 days after infection. Using this method, we showed increased VEGF levels and increased lung permeability in mice predicted to die of ALI/ARDS. This proposed method for accurately identifying mice suffering from ALI/ARDS before death will enable the use of this model to study the pathogenesis of this disease (AU)