Lung Injury in Uncomplicated and Severe Falciparum Malaria: A Longitudinal Study in Papua, Indonesia

Maguire, Graeme; Handojo, Tjandra; Pain, M. C. F.; Kenangalem, Enny; Price, Ric N.; Tjitra, Emiliana; Anstey, Nicholas M.

doi:10.1086/497697

Cited by 72 publications

(94 citation statements)

References 25 publications

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“…Clinical studies on lung function in adult and pediatric patients support the presence of capillary dysfunction manifested as impaired gas exchange and reduced peripheral reactive hyperemic index. 34,35 However, despite evidence of acute lung injury, the presence of overt pulmonary edema in severe malaria varies from 5 to 25% in adults and less than 10% in children. 32 In the latter group, respiratory distress is believed to be mainly central nervous system (CNS)-driven as a response to systemic metabolic acidosis.…”

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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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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“…In the erythrocytic phase, endothelial activation accounts for many factors involved in the development of severe malaria [49], such as increased adhesion of infected RBCs [50], increased expression of chemokines [51], and increased adhesion of leukocytes to peripheral organ microvasculature [52]. Several soluble proteins have been described such as inflammatory markers of endothelial activation during severe malaria.…”

Section: Molecular and Cellular Features Of The Malaria-induced Inflamentioning

confidence: 99%

Multiple Organ Dysfunction During Severe Malaria: The Role of the Inflammatory Response

Souza¹,

Pádua²,

Henriques³

2016

Current Topics in Malaria

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Severe malaria is a systemic illness characterized by the dysfunction of one or more peripheral organs, such as the lungs [acute respiratory distress syndrome (ARDS)] and kidneys [acute kidney injury (AKI)]. Several clinical and experimental studies suggest that features of the inflammatory response are related to the multi-organ dysfunction observed in severe malaria. Our group has been dedicated to studying the roles of proand anti-inflammatory mediators in the multi-organ dysfunction observed in experimental severe malaria, especially in the lungs, kidneys, and brain. Herein, we explore severe malaria as a pathology derived from intense inflammatory responses in different organs and further distinguish and compare these organ-specific inflammatory responses. The pathophysiological mechanism of severe malaria is not fully elucidated; however, it is important to study it as a complex inflammatory response assembled by different actors, each one orchestrating a different mechanism.

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“…En el pulmón, el secuestro de glóbulos rojos parasitados en el espacio alvéolo-capilar y la presencia de macrófagos y trombos de fibrina, se consideran las causas de la obstrucción vascular, edema, daño al endotelio capilar y a las células alveolares, los cuales permiten explicar alteraciones en el intercambio de gases; este proceso se empeora por la respuesta inflamatoria desencadenada, incluso después de suministrar el tratamiento para la malaria (85). El incremento en la permeabilidad alveolar se considera la alteración más prominente en la lesión pulmonar aguda y el síndrome de dificultad respiratoria aguda en el paludismo; el daño pulmonar se refleja tanto en lesiones estructurales observables en el alvéolo pulmonar, como en la alteración funcional debida a los cambios en la permeabilidad de la membrana endotelial.…”

Section: Obstrucción Vascular E Inflamaciónunclassified

Pathogenic mechanisms in Plasmodium falciparum malaria

Vásquez

Tobón

2012

biomedica

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Se presentan los mecanismos patogénicos más conocidos en la infección por Plasmodium falciparum durante la fase eritrocitaria y extraeritrocitaria. La obstrucción vascular, explicada por los fenómenos de secuestro de glóbulos rojos parasitados y la formación de rosetas, mediados por diversos ligandos y receptores endoteliales, además de los procesos inflamatorios instaurados ante la presencia del parásito, son aspectos centrales en la patogenia de la malaria que permiten explicar los procesos de disfunción, daño y muerte celular en diferentes órganos. A partir de eventos como la lesión y la destrucción de eritrocitos, hepatocitos y células endoteliales, la pérdida de integridad del endotelio y la activación de promotores de daño celular y de apoptosis, se explican alteraciones como el aumento de la permeabilidad vascular, la hipoxia y el metabolismo anaerobio, que conducen tanto a lesiones localizadas en órganos como cerebro y pulmón, como a un estado de acidosis generalizada y falla multisistémica.Palabras clave: malaria/etiología, Plasmodium falciparum, inflamación. Pathogenic mechanisms in Plasmodium falciparum malariaThe most recognized pathogenic mechanisms of the infection with Plasmodium falciparum, during both the erythrocytic and exo-erithrocytic stages are presented. Vascular obstruction explained by the sequestration of parasitized red blood cells and erythrocyte rosetting, mediated by different endothelial ligands and receptors, in addition to the inflammatory processes induced by the presence of the parasite, are central aspects in the pathogenesis of malaria that explain the processes of damage, dysfunction and cell death in various organs. Alterations such as increased vascular permeability, hypoxia and anaerobic metabolism leading to localized lesions in organs such as brain and lung, as well as to a generalized acidotic state with multisystem failure can be explained by events such as the injury and destruction of erythrocytes, hepatocytes and endothelial cells, the loss of endothelial integrity, and the activation of cell damage and apoptosis promoters.Key words: Malaria/ethiology, Plasmodium falciparum, inflamation.Los signos y síntomas clínicos en la malaria, o paludismo, expresión del daño ocasionado en diversos órganos y sistemas, se exacerban durante el período de multiplicación del parásito en el eritrocito, mientras que el estadio hepático y la presencia de gametocitos tradicionalmente no se han asociado con la sintomatología. La malaria causa lesiones estructurales y alteraciones funcionales y metabólicas, cuya presentación clínica está en función de la edad, el estado inmunitario y las características genéticas del huésped, y por la especie, el genotipo y la virulencia del parásito. Puede conducir a un cuadro clínico grave el cual casi siempre se observa en las infecciones causadas por Plasmodium falciparum. Las complicaciones informadas con mayor frecuencia incluyen anemia grave, malaria cerebral, síndrome de dificultad respiratoria aguda y falla renal (1); en los últimos años se vien...

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Lung Injury in Uncomplicated and Severe Falciparum Malaria: A Longitudinal Study in Papua, Indonesia

Cited by 72 publications

References 25 publications

Dynamic interactions ofPlasmodiumspp. with vascular endothelium

Dynamic interactions ofPlasmodiumspp. with vascular endothelium

Multiple Organ Dysfunction During Severe Malaria: The Role of the Inflammatory Response

Pathogenic mechanisms in Plasmodium falciparum malaria

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