@article{fdi:010087447,
  title = {{E}levated plasma interleukin-8 as a risk factor for mortality in children presenting with cerebral malaria},
  author = {{R}oyo, {J}ade and {V}ianou, {B}. and {A}ccrombessi, {M}. and {K}inkpe, {E}. and {A}yedadjou, {L}. and {D}ossou-{D}agba, {I}. and {L}adipo, {Y}. and {A}lao, {M}. {J}. and {B}ertin, {G}wladys and {C}ot, {M}ichel and {B}oumediene, {F}. and {H}ouze, {S}. and {F}aucher, {J}. {F}. and {A}ubouy, {A}gn{\`e}s and {N}euro, {C}. {M}. {G}rp},
  editor = {},
  language = {{ENG}},
  abstract = {{B}ackground {C}erebral malaria ({CM}) is a neuropathology which remains one of the deadliest forms of malaria among {A}frican children. {T}he kinetics of the pathophysiological mechanisms leading to neuroinflammation and the death or survival of patients during {CM} are still poorly understood. {T}he 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. {I}n 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.{M}ethods {C}hildren presenting with {CM} (n = 70) due to {P}. falciparum infection were included in southern {B}enin and divided according to the clinical outcome into 50 children who survived and 20 who died. {C}linical 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. {L}uminex technology and enzyme immunoassay kits were used to measure 17 plasma and 7 urinary biomarker levels, respectively. {D}ata were analysed by univariate analysis using the nonparametric {M}ann-{W}hitney {U} test and {P}earson's {C}hi2 test. {A}djusted and multivariate analyses were conducted separately for plasma and urinary biomarkers to identify {CM} mortality risk factors.{R}esults {U}nivariate analysis revealed higher plasma levels of tumour necrosis factor ({TNF}), interleukin-1beta ({IL}-1 beta), {IL}-10, {IL}-8, {C}-{X}-{C} motif chemokine ligand 9 ({CXCL}9), granzyme {B}, and angiopoietin-2 and lower urinary levels of prostanglandine {E}2 metabolite ({PGEM}) in children who died compared to those who survived {CM} ({M}ann-{W}hitney {U}-test, {P}-values between 0.03 and < 0.0001). {T}he multivariate logistic analysis highlighted elevated plasma levels of {IL}-8 as the main risk factor for death during {CM} (adjusted odd ratio = 14.2, {P}-value = 0.002). {V}alues obtained during follow-up at {D}3 and {D}30 revealed immune factors associated with disease resolution, including plasma {CXCL}5, {C}-{C} motif chemokine ligand 17 ({CCL}17), {CCL}22, and urinary 15-{F}2t-isoprostane.{C}onclusions {T}he main risk factor of death during {CM} was thus elevated plasma levels of {IL}-8 at inclusion. {F}ollow-up of patients until {D}30 revealed marker profiles of disease aggravation and resolution for markers implicated in neutrophil activation, endothelium activation and damage, inflammatory and oxidative response. {T}hese results provide important insight into our understanding of {CM} pathogenesis and clinical outcome and may have important therapeutic implications.},
  keywords = {{C}erebral malaria ; {C}hildren ; {B}enin ; {C}ytokine ; {P}lasma ; {U}rine ; {I}mmunologic marker ; {N}euro{CM}},
  booktitle = {},
  journal = {{I}nfectious {D}iseases of {P}overty},
  volume = {12},
  numero = {1},
  pages = {8 [15 p.]},
  ISSN = {2095-5162},
  year = {2023},
  DOI = {10.1186/s40249-023-01059-2},
  URL = {https://www.documentation.ird.fr/hor/fdi:010087447},
}