title: Intermittent preventive treatment with sulfadoxine-pyrimethamine does not modify plasma cytokines and chemokines or intracellular cytokine responses to Plasmodium falciparum in Mozambican children.
abstract: BACKGROUND
  Cytokines and chemokines are key mediators of anti-malarial immunity. We evaluated whether Intermittent Preventive Treatment in infants with Sulfadoxine-Pyrimethamine (IPTi-SP) had an effect on the acquisition of these cellular immune responses in Mozambican children. Multiple cytokines and chemokines were quantified in plasma by luminex, and antigen-specific cytokine production in whole blood was determined by intracellular cytokine staining and flow cytometry, at ages 5, 9, 12 and 24 months.
  
  
  RESULTS
  IPTi-SP did not significantly affect the proportion of CD3+ cells producing IFN-γ, IL-4 or IL-10. Overall, plasma cytokine or chemokine concentrations did not differ between treatment groups. Th1 and pro-inflammatory responses were higher than Th2 and anti-inflammatory responses, respectively, and IFN-γ:IL-4 ratios were higher for placebo than for SP recipients. Levels of cytokines and chemokines varied according to age, declining from 5 to 9 months. Plasma concentrations of IL-10, IL-12 and IL-13 were associated with current infection or prior malaria episodes. Higher frequencies of IFN-γ and IL-10 producing CD3+ cells and elevated IL-10, IFN-γ, MCP-1 and IL-13 in plasma were individually associated with increased malaria incidence, at different time points. When all markers were analyzed together, only higher IL-17 at 12 months was associated with lower incidence of malaria up to 24 months.
  
  
  CONCLUSIONS
  Our work has confirmed that IPTi-SP does not negatively affect the development of cellular immune response during early childhood. This study has also provided new insights as to how these cytokine responses are acquired upon age and exposure to P. falciparum, as well as their associations with malaria susceptibility.
  
  
  BACKGROUND
  ClinicalTrials.gov: NCT00209795.
authors.affiliation: Centro de Investigação em Saúde da Manhiça, Manhiça, Mozambique.
authors.forename: Diana
authors.initials: D
authors.lastname: Quelhas
authors.forename: Laura
authors.initials: L
authors.lastname: Puyol
authors.forename: Llorenç
authors.initials: L
authors.lastname: Quintó
authors.forename: Tacilta
authors.initials: T
authors.lastname: Nhampossa
authors.forename: Elisa
authors.initials: E
authors.lastname: Serra-Casas
authors.forename: Eusébio
authors.initials: E
authors.lastname: Macete
authors.forename: Pedro
authors.initials: P
authors.lastname: Aide
authors.forename: Sergi
authors.initials: S
authors.lastname: Sanz
authors.forename: John J
authors.initials: JJ
authors.lastname: Aponte
authors.forename: Denise L
authors.initials: DL
authors.lastname: Doolan
authors.forename: Pedro L
authors.initials: PL
authors.lastname: Alonso
authors.forename: Clara
authors.initials: C
authors.lastname: Menéndez
authors.forename: Carlota
authors.initials: C
authors.lastname: Dobaño
mesh_terms: D000962:Antimalarials / Q000494:pharmacology / Q000627:therapeutic use*; D018925:Chemokines / Q000097:blood*; D002648:Child; D004338:Drug Combinations; D005434:Flow Cytometry; D006801:Humans; D015994:Incidence; D007223:Infant; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism* / Q000469:parasitology; D016778:Malaria, Falciparum / Q000097:blood / Q000188:drug therapy* / Q000453:epidemiology / Q000517:prevention & control*; D009073:Mozambique / Q000453:epidemiology; D010963:Plasmodium falciparum / Q000187:drug effects / Q000502:physiology*; D011739:Pyrimethamine / Q000494:pharmacology / Q000627:therapeutic use*; D013413:Sulfadoxine / Q000494:pharmacology / Q000627:therapeutic use*; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology
chemical_list: D000962:Antimalarials; D018925:Chemokines; D004338:Drug Combinations; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D011739:Pyrimethamine