title: Multiclonal asymptomatic Plasmodium falciparum infections predict a reduced risk of malaria disease in a Tanzanian population.
abstract: Protective immunity to malaria is acquired after repeated exposure to the polymorphic Plasmodium falciparum parasite. Whether the number of concurrent antigenically diverse clones in asymptomatic infections predicts the risk of subsequent clinical malaria needs further understanding. We assessed the diversity of P. falciparum infections by merozoite surface protein 2 genotyping in a longitudinal population based study in Tanzania. The number of clones was highest in children 6-10 years and in individuals with long time to previous anti-malarial treatment. Individual exposure, analysed by circumsporozoite protein antibody levels, was associated with parasite prevalence but not with the number of clones. The risk of subsequent clinical malaria in children free of acute disease or recent treatment was, compared to one clone, reduced in individuals with multiclonal infections or without detectable parasites, with the lowest hazard ratio 0.28 (95% confidence interval 0.10-0.78 Cox regression) for 2-3 clones. The number of clones was not associated with haemoglobin levels. A reduced risk of malaria in asymptomatic individuals with multiclonal persistent P. falciparum infections suggests that controlled maintenance of diverse infections is important for clinical protection in continuously exposed individuals, and needs to be considered in the design and evaluation of new malaria control strategies.
authors.affiliation: Infectious Diseases Unit, Department of Medicine, Karolinska Institute, Karolinska University Hospital Solna, 17176 Stockholm, Sweden.
authors.forename: Sándor
authors.initials: S
authors.lastname: Bereczky
authors.forename: Anne
authors.initials: A
authors.lastname: Liljander
authors.forename: Ingegerd
authors.initials: I
authors.lastname: Rooth
authors.forename: Lea
authors.initials: L
authors.lastname: Faraja
authors.forename: Fredrik
authors.initials: F
authors.lastname: Granath
authors.forename: Scott M
authors.initials: SM
authors.lastname: Montgomery
authors.forename: Anna
authors.initials: A
authors.lastname: Färnert
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology; D000962:Antimalarials / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D005260:Female; D005838:Genotype; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D007223:Infant; D008137:Longitudinal Studies; D016778:Malaria, Falciparum / Q000097:blood / Q000453:epidemiology / Q000276:immunology* / Q000469:parasitology*; D008297:Male; D008875:Middle Aged; D009017:Morbidity / Q000639:trends; D010963:Plasmodium falciparum / Q000235:genetics* / Q000276:immunology*; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology; D013636:Tanzania / Q000453:epidemiology
chemical_list: D000953:Antigens, Protozoan; D000962:Antimalarials; D006454:Hemoglobins; D015800:Protozoan Proteins; C041595:circumsporozoite protein, Protozoan; C065974:merozoite surface protein 2, Plasmodium