@article{Post2021-oo,

title = {Altered ex-vivo cytokine responses in children with asymptomatic  Plasmodium falciparum infection in Burkina Faso: An additional  argument to treat asymptomatic malaria?},

author = {Annelies Post and Berenger Kabor\'{e} and Mike Berendsen and Salou Diallo and Ousmane Traore and Rob J W Arts and Mihai G Netea and Leo A B Joosten and Halidou Tinto and Jan Jacobs and Quirijn Mast and Andr\'{e} Ven},

doi = {10.3389/fimmu.2021.614817},

issn = {1664-3224},

year  = {2021},

date = {2021-06-09},

urldate = {2021-06-09},

journal = {Front. Immunol.},

volume = {12},

pages = {614817},

publisher = {Frontiers Media SA},

abstract = {Introduction: Patients with clinical malaria have an increased 

 risk for bacterial bloodstream infections. We hypothesized that 

 asymptomatic malaria parasitemia increases susceptibility for 

 bacterial infections through an effect on the innate immune 

 system. We measured circulating cytokine levels and ex-vivo 

 cytokine production capacity in asymptomatic malaria and 

 compared with controls. Methods: Data were collected from 

 asymptomatic participants \<5 years old with and without positive 

 malaria microscopy, as well as from hospitalized patients \<5 

 years old with clinical malaria, bacteremia, or 

 malaria/bacteremia co-infections in a malaria endemic region of 

 Burkina Faso. Circulating cytokines (TNF-$alpha$, IFN-$gamma$, 

 IL-6, IL-10) were measured using multiplex assays. Whole blood 

 from asymptomatic participants with and without positive malaria 

 microscopy were ex-vivo stimulated with S. aureus, E. coli LPS 

 and Salmonella Typhimurium; cytokine concentrations 

 (TNF-$alpha$, IFN-$gamma$, IL-1$beta$, IL-6, IL-10) were 

 measured on supernatants using ELISA. Results: Included were children with clinical malaria (n=118), bacteremia (n=22), malaria and bacteremia co-infection (n=9), asymptomatic malaria (n=125), and asymptomatic controls (n=237). Children with either 

 clinical or asymptomatic malaria had higher plasma cytokine 

 concentrations than controls. Cytokine concentrations correlated 

 positively with malaria parasite density with the strongest correlation for IL-10 in both asymptomatic (r=0.63) and clinical malaria (r=0.53). Patients with bacteremia had lower circulating 

 IL-10, TNF-$alpha$ and IFN-$gamma$ and higher IL-6 

 concentrations, compared to clinical malaria. Ex-vivo whole 

 blood cytokine production to LPS and S. aureus was significantly 

 lower in asymptomatic malaria compared to controls. Whole blood 

 IFN-$gamma$ and IL-10 production in response to Salmonella was 

 also lower in asymptomatic malaria. Interpretation: In children 

 with asymptomatic malaria, cytokine responses upon ex-vivo 

 bacterial stimulation are downregulated. Further studies are 

 needed to explore if the suggested impaired innate immune 

 response to bacterial pathogens also translates into impaired 

 control of pathogens such as Salmonella spp.},

note = {Copyright © 2021 Post, Kabor\'{e}, Berendsen, Diallo, Traore, Arts, Netea, Joosten, Tinto, Jacobs, de Mast and van der Ven.

PMID: 34177883 

PMCID: PMC8220162},

keywords = {Asymptomatic Diseases, asymptomatic malaria, bacteraemia, Bacteremia, bloodstream infection, Burkina Faso/epidemiology, Cells, Child, Cultured, Cytokines/metabolism, Endemic Diseases, Female, Humans, Infant, iNTS, Lipopolysaccharides/immunology, Malaria/epidemiology/immunology, Male, Parasite Load, Plasmodium falciparum/physiology, Preschool, Salmonella},

pubstate = {published},

tppubtype = {article}

}