Neutrophil extracellular traps are associated with organ dysfunction in children with severe malaria

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Background Neutrophil extracellular traps (NETs) have been implicated in the pathogenesis of severe malaria, and the prevention of NET formation is protective in experimental cerebral malaria. However, the role of NETs in different presentations of severe malaria and on admission complications is unknown. Methods The association of NET components (NET-C) with development of severe malaria and its complications were assessed in children aged 18 months to 12 years with cerebral malaria (n = 156), severe malarial anemia (n = 149), and community control children (n = 84). Results NET-C were higher in children with cerebral malaria and severe malarial anemia compared to community children (both p < 0.001) and were also higher in cerebral malaria than severe malarial anemia (p < 0.001). There was no association between NET-C and in-hospital mortality in cerebral malaria, but admission NET-C levels were associated with acute kidney injury in children with cerebral malaria and severe malarial anemia (p = 0.003 and p = 0.007, respectively) and with severe acute kidney injury (p = 0.001) and acidosis (p = 0.002) in children with cerebral malaria. Path analysis suggested that associations between NET-C and acute kidney injury or acidosis were mediated in part by endothelial activation, and that the association between platelet levels and acidosis was mediated in part by NET-C. Conclusion NET-C are associated with acute kidney injury and acidosis in children with severe malaria.