title: Asymptomatic Multiclonal Plasmodium falciparum Infections Carried Through the Dry Season Predict Protection Against Subsequent Clinical Malaria.
abstract: BACKGROUND
  Immunity to the antigenically diverse parasite Plasmodium falciparum is acquired gradually after repeated exposure. Studies in areas of high malaria transmission have shown that asymptomatic individuals infected with multiclonal infections are at reduced risk of febrile malaria during follow-up.
  
  
  METHODS
  We assessed the relationship between the genetic diversity of clones in P. falciparum infections that persist through the dry season and the subsequent risk of febrile malaria in 225 individuals aged 2-25 years in Mali, where the 6-month malaria and dry seasons are sharply demarcated. Polymerase chain reaction-based genotyping of the highly polymorphic merozoite surface protein 2 gene was performed on blood samples collected at 5 cross-sectional surveys.
  
  
  RESULTS
  In an age-adjusted analysis, individuals with multiclonal P. falciparum infections before the rainy season were at reduced risk of febrile malaria, compared with individuals who were uninfected (hazard ratio [HR], 0.28; 95% confidence interval [CI], .11-.69). In contrast, there was no significant association between risk of malaria and having 1 clone at baseline (HR, 0.71; 95% CI, .36-1.40).
  
  
  CONCLUSIONS
  The results suggest that persistent multiclonal infections carried through the dry season contribute to protection against subsequent febrile malaria, possibly by maintaining protective immune responses that depend on ongoing parasite infection.
authors.affiliation: Unit of Infectious Diseases, Department of Medicine Solna.
authors.forename: Klara
authors.initials: K
authors.lastname: Sondén
authors.affiliation: Mali International Center of Excellence in Research, University of Sciences, Technique, and Technology of Bamako.
authors.forename: Safiatou
authors.initials: S
authors.lastname: Doumbo
authors.affiliation: Unit of Biostatistics, Department of Epidemiology, Institute for Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Ulf
authors.initials: U
authors.lastname: Hammar
authors.affiliation: Unit of Infectious Diseases, Department of Medicine Solna.
authors.forename: Manijeh
authors.initials: M
authors.lastname: Vafa Homann
authors.affiliation: Unit of Biostatistics, Department of Epidemiology, Institute for Environmental Medicine, Karolinska Institutet, Stockholm, Sweden Mali International Center of Excellence in Research, University of Sciences, Technique, and Technology of Bamako.
authors.forename: Aissata
authors.initials: A
authors.lastname: Ongoiba
authors.affiliation: Mali International Center of Excellence in Research, University of Sciences, Technique, and Technology of Bamako.
authors.forename: Boubacar
authors.initials: B
authors.lastname: Traoré
authors.affiliation: Unit of Biostatistics, Department of Epidemiology, Institute for Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Matteo
authors.initials: M
authors.lastname: Bottai
authors.affiliation: Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland.
authors.forename: Peter D
authors.initials: PD
authors.lastname: Crompton
authors.affiliation: Unit of Infectious Diseases, Department of Medicine Solna.
authors.forename: Anna
authors.initials: A
authors.lastname: Färnert
mesh_terms: D000293:Adolescent; D000328:Adult; D000375:Aging; D000953:Antigens, Protozoan / Q000235:genetics / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D006801:Humans; D016778:Malaria, Falciparum / Q000175:diagnosis / Q000276:immunology* / Q000517:prevention & control; D008297:Male; D010963:Plasmodium falciparum / Q000235:genetics* / Q000276:immunology; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism; D011891:Rain; D012621:Seasons; D013997:Time Factors; D055815:Young Adult
chemical_list: D000953:Antigens, Protozoan; D015800:Protozoan Proteins; C065974:merozoite surface protein 2, Plasmodium
keywords: P. falciparum; children; genotyping; immunity; malaria; msp2