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Depleted circulatory complement-lysis inhibitor (CLI) in childhood cerebral malaria returns to normal with convalescence

Lookup NU author(s): Dr Florence Burte



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Background: Cerebral malaria (CM), is a life-threatening childhood malaria syndrome with high mortality. CM is associated with impaired consciousness and neurological damage. It is not fully understood, as yet, why some children develop CM. Presented here is an observation from longitudinal studies on CM in a paediatric cohort of children from a large, densely-populated and malaria holoendemic, sub-Saharan, West African metropolis. Methods: Plasma samples were collected from a cohort of children with CM, severe malarial anaemia (SMA), uncomplicated malaria (UM), non-malaria positive healthy community controls (CC), and coma and anemic patients without malaria, as disease controls (DC). Proteomic two-dimensional difference gel electrophoresis (2D-DIGE) and mass spectrometry were used in a discovery cohort to identify plasma proteins that might be discriminatory among these clinical groups. The circulatory levels of identified proteins of interest were quantified by ELISA in a prospective validation cohort. Results: The proteome analysis revealed differential abundance of circulatory complement-lysis inhibitor (CLI), also known as Clusterin (CLU). CLI circulatory level was low at hospital admission in all children presenting with CM and recovered to normal level during convalescence (p < 0.0001). At acute onset, circulatory level of CLI in the CM group significantly discriminates CM from the UM, SMA, DC and CC groups. Conclusions: The CLI circulatory level is low in all patients in the CM group at admission, but recovers through convalescence. The level of CLI at acute onset may be a specific discriminatory marker of CM. This work suggests that CLI may play a role in the pathophysiology of CM and may be useful in the diagnosis and follow-up of children presenting with CM.

Publication metadata

Author(s): Abah SE, Burté F, Howell SA, Lagunju I, Shokunbi WA, Wahlgren M, Sodeinde O, Brown BJ, Holder AA, Fernandez-Reyes D

Publication type: Article

Publication status: Published

Journal: Malaria Journal

Year: 2021

Volume: 19

Online publication date: 26/04/2020

Acceptance date: 17/04/2020

Date deposited: 09/03/2022

ISSN (electronic): 1475-2875

Publisher: BioMed Central Ltd


DOI: 10.1186/s12936-020-03241-5


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