Abstract
BackgroundThe pathogenesis of pulmonary oedema (PE) in patients with severe malaria is still unclear. It has been hypothesized that lung injury depends, in addition to microvascular obstruction, on an increased pulmonary capillary pressure and altered alveolar-capillary membrane permeability, causing pulmonary fluid accumulation.MethodsThis study compared the histopathological features of lung injury in Southeast Asian patients (n = 43) who died from severe Plasmodium falciparum malaria, and correlated these with clinical history in groups with or without PE. To investigate the expression of mediators that may influence fluid accumulation in PE, immunohistochemistry and image analysis were performed on controls and sub-sets of patient with or without PE.ResultsThe expression of leukocyte sub-set antigens, bronchial interleukin (IL)-33, γ-epithelium sodium channel (ENaC), aquaporin (AQP)-1 and -5, and control cytokeratin staining was quantified in the lung tissue of severe malaria patients. Bronchial IL-33 expression was significantly increased in severe malaria patients with PE. Malaria patients with shock showed significantly increased bronchial IL-33 compare to other clinical manifestations. Bronchial IL-33 levels were positively correlated with CD68+ monocyte and elastase + neutrophil, septal congestion and hyaline membrane formation. Moreover, the expression of both vascular smooth muscle cell (VSMC) and bronchial γ-ENaC significantly decreased in severe malaria patients with PE. Both VSMC and bronchial γ-ENaC were negatively correlated with the degree of parasitized erythrocyte sequestration, alveolar thickness, alveolar expansion score, septal congestion score, and malarial pigment score. In contrast AQP-1 and -5 and pan cytokeratin levels were similar between groups.ConclusionsThe results suggest that IL-33 may play a role in lung injury during severe malaria and lead to PE. Both VSMC and bronchial γ-ENaC downregulation may explain pulmonary fluid disturbances and participate in PE pathogenesis in severe malaria patients.
Highlights
The pathogenesis of pulmonary oedema (PE) in patients with severe malaria is still unclear
AQP-1 b μm c μm d μm AQP-5 e μm f μm g μm Cytokeratin h μm i μm j μm this study demonstrated a similar range of leukocyte sub-sets (CD3, CD8, CD68, and neutrophil) among PE, non-PE and healthy subjects, the total score of WBC accumulation was significantly higher in severe malaria patients compared to normal cases
The results demonstrate that the vascular smooth muscle cell (VSMC) expression of γ-epithelial Na+ channel (ENaC) was significantly decreased in patients with PE compared with non-PE and healthy subjects
Summary
The pathogenesis of pulmonary oedema (PE) in patients with severe malaria is still unclear. Ampawong et al Malar J (2015) 14:389 distress syndrome (ARDS), the cause of death in adults with severe malaria-associated lung injury [2,3,4]. Hospital-based case series of severe malaria have reported clinical development of pulmonary oedema (PE) in 9–23 % of patients [5,6,7]. Autopsy studies [8, 9] in patients dying from severe falciparum malaria have revealed heavy oedematous lungs, congested pulmonary capillaries, thickened alveolar septa, intra-alveolar haemorrhages, hyaline membrane formation, and serous pleural as well as pericardial effusions. In addition to alveolar oedema and haemorrhages, the alveolar capillaries are filled with sequestrated P. falciparum-infected red blood cells and host leukocytes, such as malarial pigment-laden macrophages. In some series pulmonary involvement is as common as coma [13, 14]
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