title: IFNγ Responses to Pre-erythrocytic and Blood-stage Malaria Antigens Exhibit Differential Associations With Past Exposure and Subsequent Protection.
abstract: BACKGROUND
  The malaria-specific T-cell response is believed to be important for protective immunity. Antimalarial chemoprevention may affect this response by altering exposure to malaria antigens.
  
  
  METHODS
  We performed interferon γ (IFNγ) ELISpot assays to assess the cellular immune response to blood-stage and pre-erythrocytic antigens longitudinally from 1 to 3 years of age in 196 children enrolled in a randomized trial of antimalarial chemoprevention in Tororo, Uganda, an area of high transmission intensity.
  
  
  RESULTS
  IFNγ responses to blood-stage antigens, particularly MSP1, were frequently detected, strongly associated with recent malaria exposure, and lower in those adherent to chemoprevention compared to nonadherent children and those randomized to no chemoprevention. IFNγ responses to pre-erythrocytic antigens were infrequent and similar between children randomized to chemoprevention or no chemoprevention. Responses to blood-stage antigens were not associated with subsequent protection from malaria (aHR 0.96, P = .83), but responses to pre-erythrocytic antigens were associated with protection after adjusting for prior malaria exposure (aHR 0.52, P = .009).
  
  
  CONCLUSIONS
  In this high transmission setting, IFNγ responses to blood-stage antigens were common and associated with recent exposure to malaria but not protection from subsequent malaria. Responses to pre-erythrocytic antigens were uncommon, not associated with exposure but were associated with protection from subsequent malaria.
authors.affiliation: Department of Medicine, San Francisco General Hospital, University of California.
authors.forename: Prasanna
authors.initials: P
authors.lastname: Jagannathan
authors.affiliation: Infectious Diseases Research Collaboration.
authors.forename: Felistas
authors.initials: F
authors.lastname: Nankya
authors.affiliation: Department of Medicine, San Francisco General Hospital, University of California.
authors.forename: Cristina
authors.initials: C
authors.lastname: Stoyanov
authors.affiliation: Department of Medicine, San Francisco General Hospital, University of California.
authors.forename: Ijeoma
authors.initials: I
authors.lastname: Eccles-James
authors.affiliation: Infectious Diseases Research Collaboration.
authors.forename: Esther
authors.initials: E
authors.lastname: Sikyomu
authors.affiliation: Infectious Diseases Research Collaboration.
authors.forename: Kate
authors.initials: K
authors.lastname: Naluwu
authors.affiliation: Infectious Diseases Research Collaboration.
authors.forename: Samuel
authors.initials: S
authors.lastname: Wamala
authors.affiliation: Infectious Diseases Research Collaboration.
authors.forename: Mayimuna
authors.initials: M
authors.lastname: Nalubega
authors.affiliation: Department of Medicine, San Francisco General Hospital, University of California.
authors.forename: Jessica
authors.initials: J
authors.lastname: Briggs
authors.affiliation: Department of Medicine, San Francisco General Hospital, University of California.
authors.forename: Katherine
authors.initials: K
authors.lastname: Bowen
authors.affiliation: Infectious Diseases Research Collaboration.
authors.forename: Victor
authors.initials: V
authors.lastname: Bigira
authors.affiliation: Infectious Diseases Research Collaboration.
authors.forename: James
authors.initials: J
authors.lastname: Kapisi
authors.affiliation: Department of Medicine, Makerere University College of Health Sciences, Kampala, Uganda.
authors.forename: Moses R
authors.initials: MR
authors.lastname: Kamya
authors.affiliation: Department of Medicine, San Francisco General Hospital, University of California.
authors.forename: Grant
authors.initials: G
authors.lastname: Dorsey
authors.affiliation: Department of Medicine, San Francisco General Hospital, University of California Department of Pediatrics, University of California, San Francisco.
authors.forename: Margaret E
authors.initials: ME
authors.lastname: Feeney
mesh_terms: D000953:Antigens, Protozoan / Q000276:immunology*; D018890:Chemoprevention / Q000379:methods; D002675:Child, Preschool; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D006801:Humans; D007223:Infant; D007371:Interferon-gamma / Q000378:metabolism*; D008137:Longitudinal Studies; D008288:Malaria / Q000276:immunology / Q000517:prevention & control*; D008297:Male; D010961:Plasmodium / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014454:Uganda
chemical_list: D000953:Antigens, Protozoan; D007371:Interferon-gamma
keywords: IFNγ; T cell; antimalarial chemoprevention; falciparum; immunity; malaria