High Plasma Levels of Soluble Endothelial Protein C Receptor Are Associated With Increased Mortality Among Children With Cerebral Malaria in Benin

Abstract

Loss of endothelial protein C receptor (EPCR) occurs at the sites of Plasmodium falciparum-infected erythrocyte sequestration in patients with or who died from cerebral malaria. In children presenting with different clinical syndromes of malaria, we assessed the relationships between endogenous plasma soluble EPCR (sEPCR) levels and clinical presentation or mortality. After adjustment for age, for treatment before admission, and for a known genetic factor, sEPCR level at admission was positively associated with cerebral malaria (P = .011) and with malaria-related mortality (P = .0003). Measuring sEPCR levels at admission could provide an early biological marker of the outcome of cerebral malaria.

Triggering receptor expressed on myeloid cells 1 (TREM‐1) and cytokine gene variants in complicated and uncomplicated malaria

“…One reason may be that the patients in our study were slightly older than those described in Ref. . Our report is, however, consistent with the study by Moxon et al ., who clearly demonstrated that unlike malaria, infection with several other pathogens can lead to plasma levels of EPCR above baseline values .…”

“…This vicious cycle, involving reducing the interaction between mEPCR and PC to promote pro‐inflammatory cytokine production, may aggravate the severity of malaria. At the genetic level, no association between any of the genotypes and disease phenotype was observed (Table ), confirming earlier studies .…”

“…This is in contrast to the findings of Moussiliou et al . , and difficult to comprehend. One reason may be that the patients in our study were slightly older than those described in Ref.…”

Laboratory evidence of disseminated intravascular coagulation is associated with a fatal outcome in children with cerebral malaria despite an absence of clinically evident thrombosis or bleeding

“…We suggest that, in Malawian children with CM, these observations are in keeping with intravascular coagulation that is restricted to the microvasculature, at sites of IE sequestration, and particularly in the vulnerable vascular bed of the brain. The markedly raised sTM levels, which are specific to retinopathy-positive CM, and the association between thrombomodulin levels and fatal outcomemore strongly than, and independently of, other coagulation factorsfurther support the role of the protein C pathway in the etiology of this intravascular coagulation in CM [4,16,40]. Thrombomodulin, which is a key receptor in the protein C pathway, is predominantly expressed in the microvasculature, and we have previously shown its lossputatively by receptor sheddingin association with fibrin deposition at sites of sequestration [16].…”

From the blood to the brain: avenues of eukaryotic pathogen dissemination to the central nervous system

“…found that EPCR is lost from endothelial cells at sites of iRBC sequestration [29], and in a study of children in Benin, high levels of soluble EPCR in the blood positively correlated with pediatric CM and mortality [30].…”