Predictive criteria to study the pathogenesis of malaria-associated ALI/ARDS in mice.

Luana S Ortolan,Renato Barboza,Maria Regina D’ Império Lima,Daniela Debone,Oscar Murillo,Sabrina Epiphanio,Claudio R F Marinho,Michelle K Sercundes,Momtchilo Russo,Marcos Amaku,Stefano C F Hagen,José M Alvarez

doi:10.1155/2014/872464

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; we still 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 the suggested predictive criteria. We proposed a model to predict malaria-associated ALI/ARDS using breathing patterns (enhanced pause and frequency respiration) 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.

Highlights

Malaria is an infectious disease with a huge impact on public health and a high mortality rate
To characterize and discriminate the pathology associated with ALI/ARDS or HP, DBA/2 mice were infected with P. berghei ANKA-infected red blood cells and followed until their deaths
In agreement with previous results [14], we show that the majority of the DBA/2 mice infected with PbANKA who died of ALI/ARDS had PaO2/fraction of inspired O2 (FiO2) values between 200 and 300 mmHg, and we further demonstrate that mice that developed the more severe form of ARDS, presented PaO2/FiO2 values of ≤200 mmHg

Summary

Introduction

Malaria is an infectious disease with a huge impact on public health and a high mortality rate. Plasmodium infection may result in severe malaria that can lead to ALI/ARDS [4, 5]. P. falciparum, P. vivax, and P. knowlesi can develop ALI or ARDS with mortality rates of approximately 80% [6, 7]. Malaria-associated ALI/ARDS is thought to be due, in part, to increased alveolar permeability, parasite sequestration, and host immune response; the mechanisms behind it are largely unknown [4]. ALI/ARDS can occur at any time during an infection, even after treatment with antimalarial drugs when parasitemia has been reduced (reviewed in [4]). There is little information on malaria-associated ALI/ARDS progression, resulting in a lack of knowledge of the mechanisms of pathogenesis; the understanding of mouse models is essential

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