title: Gradual acquisition of immunity to severe malaria with increasing exposure.
abstract: Previous analyses have suggested that immunity to non-cerebral severe malaria due to Plasmodium falciparum is acquired after only a few infections, whereas longitudinal studies show that some children experience multiple episodes of severe disease, suggesting that immunity may not be acquired so quickly. We fitted a mathematical model for the acquisition and loss of immunity to severe disease to the age distribution of severe malaria cases stratified by symptoms from a range of transmission settings in Tanzania, combined with data from several African countries on the age distribution and overall incidence of severe malaria. We found that immunity to severe disease was acquired more gradually with exposure than previously thought. The model also suggests that physiological changes, rather than exposure, may alter the symptoms of disease with increasing age, suggesting that a later age at infection would be associated with a higher proportion of cases presenting with cerebral malaria regardless of exposure. This has consequences for the expected pattern of severe disease as transmission changes. Careful monitoring of the decline in immunity associated with reduced transmission will therefore be needed to ensure rebound epidemics of severe and fatal malaria are avoided.
authors.affiliation: MRC Centre for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology, Faculty of Medicine, Imperial College London, London W2 1PG, UK jamie.griffin@imperial.ac.uk.
authors.forename: Jamie T
authors.initials: JT
authors.lastname: Griffin
authors.affiliation: Mathematics Institute, University of Warwick, Coventry CV4 7AL, UK School of Life Sciences, University of Warwick, Coventry CV4 7AL, UK Department of Clinical Sciences, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK.
authors.forename: T Déirdre
authors.initials: TD
authors.lastname: Hollingsworth
authors.affiliation: Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK.
authors.forename: Hugh
authors.initials: H
authors.lastname: Reyburn
authors.affiliation: Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK.
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Drakeley
authors.affiliation: Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK.
authors.forename: Eleanor M
authors.initials: EM
authors.lastname: Riley
authors.affiliation: MRC Centre for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology, Faculty of Medicine, Imperial College London, London W2 1PG, UK.
authors.forename: Azra C
authors.initials: AC
authors.lastname: Ghani
mesh_terms: D000293:Adolescent; D000349:Africa / Q000453:epidemiology; D017677:Age Distribution; D002648:Child; D002675:Child, Preschool; D006801:Humans; D015994:Incidence; D007223:Infant; D007231:Infant, Newborn; D016778:Malaria, Falciparum / Q000453:epidemiology / Q000276:immunology* / Q000469:parasitology / Q000635:transmission; D008962:Models, Theoretical; D010963:Plasmodium falciparum / Q000502:physiology*; D011446:Prospective Studies; D012621:Seasons; D013636:Tanzania / Q000453:epidemiology; D055815:Young Adult
keywords: Plasmodium falciparum; immunity; malaria; mathematical model; severe