title: Dynamics and role of antibodies to Plasmodium falciparum merozoite antigens in children living in two settings with differing malaria transmission intensity.
abstract: BACKGROUND
  Young infants have reduced susceptibility to febrile malaria compared with older children, but the mechanism for this remains unclear. There are conflicting data on the role of passively acquired antibodies. Here, we examine antibody titres to merozoite surface antigens in the protection of children in their first two years of life in two settings with differing malaria transmission intensity and compare these titres to previously established protective thresholds.
  
  
  METHODS
  Two cohorts of children aged four to six weeks were recruited in Banfora, Burkina and Keur Soce, Senegal and followed up for two years. Malaria infections were detected by light microscopic examination of blood smears collected at active and passive case detection visits. The titres of antibodies to the Plasmodium falciparum recombinant merozoite proteins (AMA1-3D7, MSP1-19, MSP2-Dd2, and MSP3-3D7) were measured by enzyme-linked immunosorbent assay at 1-6, 9, 12, 15 and 18 months of age and compared with the protective thresholds established in Kenyan children.
  
  
  RESULTS
  Antibody titres were below the protective thresholds throughout the study period and we did not find any association with protection against febrile malaria. Antibodies to AMA1 and MSP1-19 appeared to be markers of exposure in the univariate analysis (and so associated with increasing risk) and adjusting for exposure reduced the strength and significance of this association.
  
  
  CONCLUSIONS
  The antibody levels we measured are unlikely to be responsible for the apparent protection against febrile malaria seen in young infants. Further work to identify protective antibody responses might include functional assays and a wider range of antigens.
authors.affiliation: Centre National de Recherche et de Formation sur le Paludisme (CNRFP), 01 BP 2208, Ouagadougou 01, Burkina Faso; Kenya Medical Research Institute, Centre for Geographic Medicine Research Coast (KEMRI-CGMRC), P.O. Box 230, Kilifi 80108, Kenya. Electronic address: DKangoye@kemri-wellcome.org.
authors.forename: David Tiga
authors.initials: DT
authors.lastname: Kangoye
authors.affiliation: Service de Parasitologie, Université Cheikh Anta Diop (UCAD), BP 5005 UCAD, Dakar, Senegal.
authors.forename: Victorine Atanase
authors.initials: VA
authors.lastname: Mensah
authors.affiliation: Kenya Medical Research Institute, Centre for Geographic Medicine Research Coast (KEMRI-CGMRC), P.O. Box 230, Kilifi 80108, Kenya.
authors.forename: Linda Muthoni
authors.initials: LM
authors.lastname: Murungi
authors.affiliation: Kenya Medical Research Institute, Centre for Geographic Medicine Research Coast (KEMRI-CGMRC), P.O. Box 230, Kilifi 80108, Kenya.
authors.forename: Irene
authors.initials: I
authors.lastname: Nkumama
authors.affiliation: Centre National de Recherche et de Formation sur le Paludisme (CNRFP), 01 BP 2208, Ouagadougou 01, Burkina Faso.
authors.forename: Issa
authors.initials: I
authors.lastname: Nebie
authors.affiliation: Kenya Medical Research Institute, Centre for Geographic Medicine Research Coast (KEMRI-CGMRC), P.O. Box 230, Kilifi 80108, Kenya; Nuffield Department of Medicine, Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Churchill Hospital, Oxford, United Kingdom.
authors.forename: Kevin
authors.initials: K
authors.lastname: Marsh
authors.affiliation: Service de Parasitologie, Université Cheikh Anta Diop (UCAD), BP 5005 UCAD, Dakar, Senegal.
authors.forename: Badara
authors.initials: B
authors.lastname: Cisse
authors.affiliation: Kenya Medical Research Institute, Centre for Geographic Medicine Research Coast (KEMRI-CGMRC), P.O. Box 230, Kilifi 80108, Kenya; Nuffield Department of Medicine, Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Churchill Hospital, Oxford, United Kingdom.
authors.forename: Philip
authors.initials: P
authors.lastname: Bejon
authors.affiliation: Kenya Medical Research Institute, Centre for Geographic Medicine Research Coast (KEMRI-CGMRC), P.O. Box 230, Kilifi 80108, Kenya.
authors.forename: Faith Hope Among'in
authors.initials: FH
authors.lastname: Osier
authors.affiliation: Centre National de Recherche et de Formation sur le Paludisme (CNRFP), 01 BP 2208, Ouagadougou 01, Burkina Faso.
authors.forename: Sodiomon Bienvenu
authors.initials: SB
authors.lastname: Sirima
mesh_terms: D000913:Antibodies, Protozoan / Q000097:blood*; D000953:Antigens, Protozoan / Q000276:immunology*; D002050:Burkina Faso / Q000453:epidemiology; D002648:Child; D002675:Child, Preschool; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007223:Infant; D008137:Longitudinal Studies; D008288:Malaria / Q000453:epidemiology / Q000276:immunology* / Q000635:transmission; D008297:Male; D052940:Merozoites / Q000276:immunology*; D010963:Plasmodium falciparum / Q000276:immunology*; D011446:Prospective Studies; D012675:Senegal / Q000453:epidemiology
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan
keywords: Antibody dynamics; Infants; Malaria; Merozoite antigens; Protective threshold