title: Cord blood IgG and the risk of severe Plasmodium falciparum malaria in the first year of life.
abstract: Young infants are less susceptible to severe episodes of malaria but the targets and mechanisms of protection are not clear. Cord blood antibodies may play an important role in mediating protection but many studies have examined their association with the outcome of infection or non-severe malaria. Here, we investigated whether cord blood IgG to Plasmodium falciparum merozoite antigens and antibody-mediated effector functions were associated with reduced odds of developing severe malaria at different time points during the first year of life. We conducted a case-control study of well-defined severe falciparum malaria nested within a longitudinal birth cohort of Kenyan children. We measured cord blood total IgG levels against five recombinant merozoite antigens and antibody function in the growth inhibition activity and neutrophil antibody-dependent respiratory burst assays. We also assessed the decay of maternal antibodies during the first 6months of life. The mean antibody half-life range was 2.51months (95% confidence interval (CI): 2.19-2.92) to 4.91months (95% CI: 4.47-6.07). The rate of decline of maternal antibodies was inversely proportional to the starting concentration. The functional assay of antibody-dependent respiratory burst activity predicted significantly reduced odds of developing severe malaria during the first 6months of life (Odds ratio (OR) 0.07, 95% CI: 0.007-0.74, P=0.007). Identification of the targets of antibodies mediating antibody-dependent respiratory burst activity could contribute to the development of malaria vaccines that protect against severe episodes of malaria in early infancy.
authors.affiliation: Kenya Medical Research Institute, Centre for Geographic Medicine Research, Coast, P.O. Box 230-80108, Kilifi, Kenya. Electronic address: lmurungi@kemri-wellcome.org.
authors.forename: Linda M
authors.initials: LM
authors.lastname: Murungi
authors.affiliation: Unit of Infectious Diseases, Department of Medicine, Solna, Karolinska Institutet, SE-171 76 Stockholm, Sweden.
authors.forename: Klara
authors.initials: K
authors.lastname: Sondén
authors.affiliation: Kenya Medical Research Institute, Centre for Geographic Medicine Research, Coast, P.O. Box 230-80108, Kilifi, Kenya.
authors.forename: Dennis
authors.initials: D
authors.lastname: Odera
authors.affiliation: Kenya Medical Research Institute, Centre for Geographic Medicine Research, Coast, P.O. Box 230-80108, Kilifi, Kenya.
authors.forename: Loureen B
authors.initials: LB
authors.lastname: Oduor
authors.affiliation: Kenya Medical Research Institute, Centre for Geographic Medicine Research, Coast, P.O. Box 230-80108, Kilifi, Kenya.
authors.forename: Fatuma
authors.initials: F
authors.lastname: Guleid
authors.affiliation: Kenya Medical Research Institute, Centre for Geographic Medicine Research, Coast, P.O. Box 230-80108, Kilifi, Kenya.
authors.forename: Irene N
authors.initials: IN
authors.lastname: Nkumama
authors.affiliation: Kenya Medical Research Institute, Centre for Geographic Medicine Research, Coast, P.O. Box 230-80108, Kilifi, Kenya.
authors.forename: Mark
authors.initials: M
authors.lastname: Otiende
authors.affiliation: Kenya Medical Research Institute, Centre for Geographic Medicine Research, Coast, P.O. Box 230-80108, Kilifi, Kenya; Centre National de Recherche et de Formation sur le Paludisme (CNRFP), 01 BP 2208, Ouagadougou 01, Burkina Faso.
authors.forename: David T
authors.initials: DT
authors.lastname: Kangoye
authors.affiliation: Kenya Medical Research Institute, Centre for Geographic Medicine Research, Coast, P.O. Box 230-80108, Kilifi, Kenya.
authors.forename: Greg
authors.initials: G
authors.lastname: Fegan
authors.affiliation: Unit of Infectious Diseases, Department of Medicine, Solna, Karolinska Institutet, SE-171 76 Stockholm, Sweden; Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Färnert
authors.affiliation: Kenya Medical Research Institute, Centre for Geographic Medicine Research, Coast, P.O. Box 230-80108, Kilifi, Kenya; African Academy of Sciences, P.O. Box 24916-00502, Nairobi, 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: Kenya Medical Research Institute, Centre for Geographic Medicine Research, Coast, P.O. Box 230-80108, Kilifi, Kenya.
authors.forename: Faith H A
authors.initials: FH
authors.lastname: Osier
mesh_terms: D000913:Antibodies, Protozoan / Q000276:immunology; D000953:Antigens, Protozoan / Q000276:immunology; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D005312:Fetal Blood / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D007223:Infant; D007630:Kenya; D016778:Malaria, Falciparum / Q000276:immunology*; D008297:Male; D010963:Plasmodium falciparum / Q000276:immunology*; D016897:Respiratory Burst; D012307:Risk Factors
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D007074:Immunoglobulin G
keywords: Antibody; Cord blood; Merozoite; Severe malaria