Acute Pulmonary Edema in falciparum Malaria

Brooks, Marion H.; Kiel, Frank W.Lieutenant Colonel; Sheehy, Thomas W.; Barry, Kevin G.

doi:10.1056/nejm196810032791402

Cited by 85 publications

(33 citation statements)

References 16 publications

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“…PEs and leukocytes sequester in the pulmonary microvasculature in human malaria infections, as demonstrated by both ultrastructural studies [13],[14],[15] and a reduced pulmonary capillary vascular component volume [2],[12]. Additionally, hemorrhage is a classic feature of non-malarial human ALI/ARDS [29],[33] and histopathological reports on malaria-induced ALI indicate that focal alveolar hemorrhages occur in humans [34],[35], similar to those observed in the PbA model. Progressive alveolar-capillary dysfunction has been reported in individuals with malaria immediately following appropriate antimicrobial therapy [2],[12].…”

Section: Discussionmentioning

confidence: 68%

Parasite Burden and CD36-Mediated Sequestration Are Determinants of Acute Lung Injury in an Experimental Malaria Model

et al. 2008

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Although acute lung injury (ALI) is a common complication of severe malaria, little is known about the underlying molecular basis of lung dysfunction. Animal models have provided powerful insights into the pathogenesis of severe malaria syndromes such as cerebral malaria (CM); however, no model of malaria-induced lung injury has been definitively established. This study used bronchoalveolar lavage (BAL), histopathology and gene expression analysis to examine the development of ALI in mice infected with Plasmodium berghei ANKA (PbA). BAL fluid of PbA-infected C57BL/6 mice revealed a significant increase in IgM and total protein prior to the development of CM, indicating disruption of the alveolar–capillary membrane barrier—the physiological hallmark of ALI. In contrast to sepsis-induced ALI, BAL fluid cell counts remained constant with no infiltration of neutrophils. Histopathology showed septal inflammation without cellular transmigration into the alveolar spaces. Microarray analysis of lung tissue from PbA-infected mice identified a significant up-regulation of expressed genes associated with the gene ontology categories of defense and immune response. Severity of malaria-induced ALI varied in a panel of inbred mouse strains, and development of ALI correlated with peripheral parasite burden but not CM susceptibility. Cd36 −/− mice, which have decreased parasite lung sequestration, were relatively protected from ALI. In summary, parasite burden and CD36-mediated sequestration in the lung are primary determinants of ALI in experimental murine malaria. Furthermore, differential susceptibility of mouse strains to malaria-induced ALI and CM suggests that distinct genetic determinants may regulate susceptibility to these two important causes of malaria-associated morbidity and mortality.

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Section: Discussionmentioning

confidence: 68%

Parasite Burden and CD36-Mediated Sequestration Are Determinants of Acute Lung Injury in an Experimental Malaria Model

et al. 2008

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“…30 In contrast to the findings in the brain, features consistent with acute lung injury are frequently found in the pulmonary microvasculature at autopsy of both adult and pediatric patients with severe falciparum malaria. [31][32][33] The findings include edema, microthrombi and leukocyte infiltration. The microvessels are densely packed with IRBC.…”

Section: Clinical Evidence Of Barrier Dysfunction In Severe Malariamentioning

confidence: 99%

Dynamic interactions ofPlasmodiumspp. with vascular endothelium

Gillrie

2016

Tissue Barriers

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Plasmodial species are protozoan parasites that infect erythrocytes. As such, they are in close contact with microvascular endothelium for most of the life cycle in the mammalian host. The hostparasite interactions of this stage of the infection are responsible for the clinical manifestations of the disease that range from a mild febrile illness to severe and frequently fatal syndromes such as cerebral malaria and multi-organ failure. Plasmodium falciparum, the causative agent of the most severe form of malaria, is particularly predisposed to modulating endothelial function through either direct adhesion to endothelial receptor molecules, or by releasing potent host and parasite products that can stimulate endothelial activation and/or disrupt barrier function. In this review, we provide a critical analysis of the current clinical and laboratory evidence for endothelial dysfunction during severe P. falciparum malaria. Future investigations using state-of-the-art technologies such as mass cytometry and organs-on-chips to further delineate parasite-endothelial cell interactions are also discussed.

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“…15,25 In this study, we show that P falciparum merozoite-associated proteins can contribute to the pathologic process by inducing alterations in junctional protein expression in primary microvascular endothelial cells in vitro, including those from the lung. These changes may serve to destabilize endothelial junctional complexes and allow the escape of macromolecules into the interstitium.…”

Section: Discussionmentioning

confidence: 70%

Src-family kinase–dependent disruption of endothelial barrier function by Plasmodium falciparum merozoite proteins

Gillrie

Gowda

Lee

et al. 2007

Blood

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Pulmonary complication in severe Plasmodium falciparum malaria is manifested as a prolonged impairment of gas transfer or the more severe acute respiratory distress syndrome (ARDS). In either clinical presentation, vascular permeability is a major component of the pathologic process. In this report, we examined the effect of clinical P falciparum isolates on barrier function of primary dermal and lung microvascular endothelium in vitro. We showed that parasite sonicates but not intact infected erythrocytes disrupted endothelial barrier function in a Srcfamily kinase-dependent manner. The abnormalities were manifested both as discontinuous immunofluorescence staining of the junctional proteins ZO-1, claudin 5, and VE-cadherin and the formation of interendothelial gaps in monolayers. These changes were associated with a loss in total protein content of claudin 5 and redistribution of ZO-1 from the cytoskeleton to the membrane and the cytosolic and nuclear fractions. There was minimal evidence of a proinflammatory response or direct cellular cytotoxicity or cell death. The active component in sonicates appeared to be a merozoite-associated protein. Increased permeability was also induced by P falciparum glycophosphatidylinositols (GPIs) and food vacuoles. These results demonstrate that parasite components can alter endothelial barrier function and thus contribute to the pathogenesis of severe falciparum malaria.

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Acute Pulmonary Edema in falciparum Malaria

Cited by 85 publications

References 16 publications

Parasite Burden and CD36-Mediated Sequestration Are Determinants of Acute Lung Injury in an Experimental Malaria Model

Parasite Burden and CD36-Mediated Sequestration Are Determinants of Acute Lung Injury in an Experimental Malaria Model

Dynamic interactions ofPlasmodiumspp. with vascular endothelium

Src-family kinase–dependent disruption of endothelial barrier function by Plasmodium falciparum merozoite proteins

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