title: Plasmodium falciparum malaria in children aged 0-2 years: the role of foetal haemoglobin and maternal antibodies to two asexual malaria vaccine candidates (MSP3 and GLURP).
abstract: BACKGROUND
  Children below six months are reported to be less susceptible to clinical malaria. Maternally derived antibodies and foetal haemoglobin are important putative protective factors. We examined antibodies to Plasmodium falciparum merozoite surface protein 3 (MSP3) and glutamate-rich protein (GLURP), in children in their first two years of life in Burkina Faso and their risk of malaria.
  
  
  METHODS
  A cohort of 140 infants aged between four and six weeks was recruited in a stable transmission area of south-western Burkina Faso and monitored for 24 months by active and passive surveillance. Malaria infections were detected by examining blood smears using light microscopy. Enzyme-linked immunosorbent assay was used to quantify total Immunoglobulin G to Plasmodium falciparum antigens MSP3 and two regions of GLURP (R0 and R2) on blood samples collected at baseline, three, six, nine, 12, 18 and 24 months. Foetal haemoglobin and variant haemoglobin fractions were measured at the baseline visit using high pressure liquid chromatography.
  
  
  RESULTS
  A total of 79.6% of children experienced one or more episodes of febrile malaria during monitoring. Antibody titres to MSP3 were prospectively associated with an increased risk of malaria while antibody responses to GLURP (R0 and R2) did not alter the risk. Antibody titres to MSP3 were higher among children in areas of high malaria risk. Foetal haemoglobin was associated with delayed first episode of febrile malaria and haemoglobin CC type was associated with reduced incidence of febrile malaria.
  
  
  CONCLUSIONS
  We did not find any evidence of association between titres of antibodies to MSP3, GLURP-R0 or GLURP-R2 as measured by enzyme-linked immunosorbent assay and early protection against malaria, although anti-MSP3 antibody titres may reflect increased exposure to malaria and therefore greater risk. Foetal haemoglobin was associated with protection against febrile malaria despite the study limitations and its role is therefore worthy further investigation.
authors.affiliation: Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou, Burkina Faso.
authors.forename: David Tiga
authors.initials: DT
authors.lastname: Kangoye
authors.affiliation: Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou, Burkina Faso.
authors.forename: Issa
authors.initials: I
authors.lastname: Nebie
authors.affiliation: Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou, Burkina Faso.
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Yaro
authors.affiliation: Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou, Burkina Faso.
authors.forename: Siaka
authors.initials: S
authors.lastname: Debe
authors.affiliation: Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou, Burkina Faso.
authors.forename: Safiatou
authors.initials: S
authors.lastname: Traore
authors.affiliation: Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou, Burkina Faso.
authors.forename: Oumarou
authors.initials: O
authors.lastname: Ouedraogo
authors.affiliation: Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou, Burkina Faso.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Sanou
authors.affiliation: Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou, Burkina Faso.
authors.forename: Issiaka
authors.initials: I
authors.lastname: Soulama
authors.affiliation: Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou, Burkina Faso.
authors.forename: Amidou
authors.initials: A
authors.lastname: Diarra
authors.affiliation: Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou, Burkina Faso.
authors.forename: Alfred
authors.initials: A
authors.lastname: Tiono
authors.affiliation: Kenyan Medical Research Institute, Centre for Geographic Medicine Research (Coast), Kilifi, 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: Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou, Burkina Faso.
authors.forename: Sodiomon Bienvenu
authors.initials: SB
authors.lastname: Sirima
authors.affiliation: Kenyan Medical Research Institute, Centre for Geographic Medicine Research (Coast), Kilifi, 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
mesh_terms: D000953:Antigens, Protozoan / Q000276:immunology*; D002050:Burkina Faso; D002675:Child, Preschool; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005319:Fetal Hemoglobin / Q000276:immunology*; D006801:Humans; D015994:Incidence; D007223:Infant; D007231:Infant, Newborn; D008137:Longitudinal Studies; D017780:Malaria Vaccines / Q000276:immunology*; D016778:Malaria, Falciparum / Q000453:epidemiology / Q000276:immunology*; D008297:Male; D008431:Maternal-Fetal Exchange / Q000276:immunology; D010963:Plasmodium falciparum / Q000276:immunology / Q000472:pathogenicity; D011247:Pregnancy; D015800:Protozoan Proteins / Q000276:immunology*; D018570:Risk Assessment
chemical_list: D000953:Antigens, Protozoan; D017780:Malaria Vaccines; D015800:Protozoan Proteins; C089133:merozoite surface protein 3, Plasmodium; C072492:glutamate-rich protein, Plasmodium; D005319:Fetal Hemoglobin