The Relationship between Age and the Manifestations of and Mortality Associated with Severe Malaria

Dondorp, Arjen M.; Lee, Sue J.; Faiz, M. Abul; Mishra, Saroj K.; Price, Ric N.; Tjitra, Emiliana; Than, Marlar; Htut, Ye; Mohanty, Sanjib; Yunus, Emran Bin; Rahman, Ridwanur; Nosten, François; Anstey, Nicholas M.; Day, Nicholas P. J.; White, Nicholas J.

doi:10.1086/589287

Cited by 230 publications

(223 citation statements)

References 21 publications

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“…One could conclude that culture conditions were not ideal for maintaining the integrity of the EC barrier; however, these results could have an important relevance in severe malaria. Indeed, recent published articles have shown a clear association between acidosis and the prognostic of the disease (Dondorp et al, 2008), mortality being greatest in children where acidosis coexists with impaired consciousness (Maitland and Newton, 2005). These clinical results, compared with the results obtained in our study, suggest that acidosis could be a main factor in BBB breakdown.…”

Section: Discussionsupporting

confidence: 81%

“…As metabolic acidosis has been described as one of the strongest predictors of a fatal outcome in severe malaria (Dondorp et al, 2008), we decided to test whether the pH of the culture medium could be involved in the permeability enhancement observed. Results show that a decrease in the pH of the culture medium was correlated with an increase in the EC barrier permeability ( Figure 7A).…”

Section: Parasitized Red Blood Cells Metabolism Induces Endothelial Cmentioning

confidence: 99%

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Metabolic Acidosis Induced by Plasmodium Falciparum Intraerythrocytic Stages Alters Blood—Brain Barrier Integrity

Zougbédé

Miller

Ravassard

et al. 2010

J Cereb Blood Flow Metab

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The pathogenesis of cerebral malaria (CM) remains largely unknown. There is growing evidence that combination of both parasite and host factors could be involved in blood-brain barrier (BBB) breakdown. However, lack of adequate in vitro model of human BBB so far hampered molecular studies. In this article, we propose the use of hCMEC/D3 cells, a well-established human cerebral microvascular endothelial cell (EC) line, to study BBB breakdown induced by Plasmodium falciparum-parasitized red blood cells and environmental conditions. We show that coculture of parasitized erythrocytes with hCMEC/D3 cells induces cell adhesion and paracellular permeability increase, which correlates with disorganization of zonula occludens protein 1 expression pattern. Permeability increase and modification of tight junction proteins distribution are cytoadhesion independent. Finally, we show that permeability of hCMEC/D3 cell monolayers is mediated through parasite induced metabolic acidosis, which in turns correlates with apoptosis of parasitized erythrocytes. This new coculture model represents a very useful tool, which will improve the knowledge of BBB breakdown and the development of adjuvant therapies, together with antiparasitic drugs.

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Section: Discussionsupporting

confidence: 81%

Section: Parasitized Red Blood Cells Metabolism Induces Endothelial Cmentioning

confidence: 99%

Metabolic Acidosis Induced by Plasmodium Falciparum Intraerythrocytic Stages Alters Blood—Brain Barrier Integrity

Zougbédé

Miller

Ravassard

et al. 2010

J Cereb Blood Flow Metab

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“…The literature suggests that the most significant factors leading to death in severe falciparum malaria in adults and children are metabolic acidosis and coma, as well as severely decreased renal function. 27,82,122 P. coatneyi has been reported as causing natural and experimentally induced disease in a variety of NHP species. However, only cynomolgus macaques (M. fascicularis), 33,34,62,74 pig-tailed macaques (Macaca nemestrina), 62 stump-tailed macaques (Macaca arctoides), 98 and Bornean orangutans (Pongo pygmaeus) 84 have been reported to be susceptible to infection in nature, with or without clinical evidence of disease.…”

Section: Ecology Of Nhp Malariasmentioning

confidence: 99%

A Review of Plasmodium coatneyi–Macaque Models of Severe Malaria

et al. 2015

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Malaria remains one of the most significant public health concerns in the world today. Approximately half the human population is at risk for infection, with children and pregnant women being most vulnerable. More than 90% of the total human malaria burden, which numbers in excess of 200 million annually, is due to Plasmodium falciparum. Lack of an effective vaccine and a dwindling stockpile of antimalarial drugs due to increased plasmodial resistance underscore the critical need for valid animal models. Plasmodium coatneyi was described in Southeast Asia 50 years ago. This plasmodium of nonhuman primates has been used sporadically as a model for severe malaria, as it mimics many of the pathophysiologic features of human disease. This review covers the reported macroscopic, microscopic, ultrastructural, and molecular pathology of P. coatneyi infection in macaques, specifically focusing on the rhesus macaque, as well as describing the critical needs still outstanding in the validation of this crucial model of human disease.

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“…According to research by authors from Germany and Spain, hyperbilirubinemia and hyperparasitemia were most commonly associated severe malaria [21,26]. A multicentric study from Thailand showed that jaundice was present in 529 of 1050 patients (50.4%) with severe malaria and a hyperparasitemia was present in 33.3% [27].…”

Section: Discussionmentioning

confidence: 99%

Severe Imported Malaria in a Serbian Referral Center

Karić¹

2017

J Trop Dis

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The Relationship between Age and the Manifestations of and Mortality Associated with Severe Malaria

Abstract: Presenting syndromes in severe malaria depend on age, although the incidence and the strong prognostic significance of coma and acidosis are similar at all ages. Age is an independent risk factor for a fatal outcome of the disease.

Cited by 230 publications

References 21 publications

Metabolic Acidosis Induced by Plasmodium Falciparum Intraerythrocytic Stages Alters Blood—Brain Barrier Integrity

Metabolic Acidosis Induced by Plasmodium Falciparum Intraerythrocytic Stages Alters Blood—Brain Barrier Integrity

A Review of Plasmodium coatneyi–Macaque Models of Severe Malaria

Severe Imported Malaria in a Serbian Referral Center

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