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dc.contributor.authorBediako, Yaw
dc.contributor.authorAdams, Rhys
dc.contributor.authorReid, Adam J.
dc.contributor.authorValletta, John Joseph
dc.contributor.authorNdungu, Francis M.
dc.contributor.authorSodenkamp, Jan
dc.contributor.authorMwacharo, Jedidah
dc.contributor.authorNgoi, Joyce Mwongeli
dc.contributor.authorKimani, Domtila
dc.contributor.authorKai, Oscar
dc.contributor.authorWambua, Juliana
dc.contributor.authorNyangweso, George
dc.contributor.authorDe Villiers, Etienne P.
dc.contributor.authorSanders, Mandy
dc.contributor.authorLotkowska, Magda Ewa
dc.contributor.authorLin, Jing Wen
dc.contributor.authorManni, Sarah
dc.contributor.authorAddy, John W.G.
dc.contributor.authorRecker, Mario
dc.contributor.authorNewbold, Chris
dc.contributor.authorBerriman, Matthew
dc.contributor.authorBejon, Philip
dc.contributor.authorMarsh, Kevin
dc.contributor.authorLanghorne, Jean
dc.identifier.citationBediako , Y , Adams , R , Reid , A J , Valletta , J J , Ndungu , F M , Sodenkamp , J , Mwacharo , J , Ngoi , J M , Kimani , D , Kai , O , Wambua , J , Nyangweso , G , De Villiers , E P , Sanders , M , Lotkowska , M E , Lin , J W , Manni , S , Addy , J W G , Recker , M , Newbold , C , Berriman , M , Bejon , P , Marsh , K & Langhorne , J 2019 , ' Repeated clinical malaria episodes are associated with modification of the immune system in children ' , BMC Medicine , vol. 17 , 60 .
dc.descriptionThe study received funding from the UK Medical Research Council, (MRC Programme grant #: MR/M003906/1). MB and AR are supported by the Wellcome Trust (Grant #: WT 206194).en
dc.description.abstractBackground There are over 200 million reported cases of malaria each year, and most children living in endemic areas will experience multiple episodes of clinical disease before puberty. We set out to understand how frequent clinical malaria, which elicits a strong inflammatory response, affects the immune system and whether these modifications are observable in the absence of detectable parasitaemia. Methods We used a multi-dimensional approach comprising whole blood transcriptomic, cellular and plasma cytokine analyses on a cohort of children living with endemic malaria, but uninfected at sampling, who had been under active surveillance for malaria for 8 years. Children were categorised into two groups depending on the cumulative number of episodes experienced: high (≥ 8) or low (< 5). Results We observe that multiple episodes of malaria are associated with modification of the immune system. Children who had experienced a large number of episodes demonstrated upregulation of interferon-inducible genes, a clear increase in circulating levels of the immunoregulatory cytokine IL-10 and enhanced activation of neutrophils, B cells and CD8+ T cells. Conclusion Transcriptomic analysis together with cytokine and immune cell profiling of peripheral blood can robustly detect immune differences between children with different numbers of prior malaria episodes. Multiple episodes of malaria are associated with modification of the immune system in children. Such immune modifications may have implications for the initiation of subsequent immune responses and the induction of vaccine-mediated protection.
dc.relation.ispartofBMC Medicineen
dc.subjectImmune activationen
dc.subjectSystems immunologyen
dc.subjectQR180 Immunologyen
dc.subjectSDG 3 - Good Health and Well-beingen
dc.titleRepeated clinical malaria episodes are associated with modification of the immune system in childrenen
dc.typeJournal articleen
dc.contributor.institutionUniversity of St Andrews. Statisticsen
dc.description.statusPeer revieweden

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