Elevated plasma interleukin-8 as a risk factor for mortality in children presenting with cerebral malaria  

作　　者：Jade Royo Bertin Vianou Manfred Accrombessi Elisée Kinkpé Linda Ayédadjou Ida Dossou-Dagba YéléLadipo Maroufou Jules Alao Gwladys I.Bertin Michel Cot Farid Boumédiène Sandrine Houzé Jean François Faucher Agnès Aubouy 无 

机构地区：[1]UMR152 PHARMADEV,IRD,UPS,Toulouse University,35 Chemin Des Maraichers,31400 Toulouse,France [2]Clinical Research Institute of Benin(IRCB),Abomey Calavi,Benin [3]Faculty of Infectious and Tropical Diseases,Disease Control Department,London School of Hygiene and Tropical Medicine,London,UK [4]Paediatric Department,Calavi Hospital,Calavi,Benin [5]Paediatric Department,Mother and Child University and Hospital Center(CHU-MEL),Cotonou,Benin [6]UMR261 MERIT,IRD,Paris University,Paris,France [7]UMR 1094 EpiMaCT,Inserm,Limoges University Hospital,Limoges University,Limoges,France [8]French Malaria Reference Center,APHP,Bichat Hospital,Paris,France [9]Parasitology Laboratory,APHP,Bichat-Claude-Bernard Hospital,Paris,France [10]Infectious Diseases and Tropical Medicine Department,Limoges University Hospital,Limoges,France [11]NeuroCM Group

出　　处：《Infectious Diseases of Poverty》2023年第1期47-61,共15页贫困所致传染病（英文）

基　　金：This work was supported by a grant from the French National Research Agency(ANR-17-CE17-0001),including a PhD grant for Jade Royo.Bertin Vianou received a PHD grant called Research grant for a thesis in the South(ARTS)from the Institut de Recherche pour le Développement France(IRD).

摘　　要：Background Cerebral malaria(CM)is a neuropathology which remains one of the deadliest forms of malaria among African children.The kinetics of the pathophysiological mechanisms leading to neuroinflammation and the death or survival of patients during CM are still poorly understood.The increasing production of cytokines,chemokines and other actors of the inflammatory and oxidative response by various local actors in response to neuroinflammation plays a major role during CM,participating in both the amplification of the neuroinflammation phenomenon and its resolution.In this study,we aimed to identify risk factors for CM death among specific variables of inflammatory and oxidative responses to improve our understanding of CM pathogenesis.Methods Children presenting with CM(n=70)due to P.falciparum infection were included in southern Benin and divided according to the clinical outcome into 50 children who survived and 20 who died.Clinical examination was complemented by fundoscopic examination and extensive blood biochemical analysis associated with molecular diagnosis by multiplex PCR targeting 14 pathogens in the patients'cerebrospinal fluid to rule out coinfections.Luminex technology and enzyme immunoassay kits were used to measure 17 plasma and 7 urinary biomarker levels,respectively.Data were analysed by univariate analysis using the nonparametric Mann-Whitney U test and Pearson’s Chi2 test.Adjusted and multivariate analyses were conducted separately for plasma and urinary biomarkers to identify CM mortality risk factors.Results Univariate analysis revealed higher plasma levels of tumour necrosis factor(TNF),interleukin-1beta(IL-1β),IL-10,IL-8,C-X-C motif chemokine ligand 9(CXCL9),granzyme B,and angiopoietin-2 and lower urinary levels of prostanglandine E2 metabolite(PGEM)in children who died compared to those who survived CM(Mann-Whitney U-test,P-values between 0.03 and<0.0001).The multivariate logistic analysis highlighted elevated plasma levels of IL-8 as the main risk factor for death during CM(adjusted

关 键 词：Cerebral malaria CHILDREN BENIN Cytokine PLASMA Urine Immunologic marker NeuroCM 

分 类 号：R725.3[医药卫生—儿科]