Klara Sondén1, Safiatou Doumbo2, Ulf Hammar3, Manijeh Vafa Homann1, Aissata Ongoiba4, Boubacar Traoré2, Matteo Bottai3, Peter D Crompton5, Anna Färnert1. 1. Unit of Infectious Diseases, Department of Medicine Solna. 2. Mali International Center of Excellence in Research, University of Sciences, Technique, and Technology of Bamako. 3. Unit of Biostatistics, Department of Epidemiology, Institute for Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. 4. 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. 5. Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland.
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.
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.
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