Marked heterogeneity in malaria infection rate in a Malian longitudinal cohort
Abstract Variation in malaria infection risk, a product of disease exposure and immunity, is poorly understood. We genotypically profiled over 13,000 blood samples from a six-year longitudinal cohort in Mali to characterize malaria infection dynamics with detail. We generated Plasmodium falciparum a...
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Nature Portfolio
2025-07-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-61462-1 |
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| author | Emily LaVerriere Zachary M. Johnson Meg Shieh Nadege Nziza Galit Alter Caroline O. Buckee Peter D. Crompton Boubacar Traore Tuan M. Tran Daniel E. Neafsey |
| author_facet | Emily LaVerriere Zachary M. Johnson Meg Shieh Nadege Nziza Galit Alter Caroline O. Buckee Peter D. Crompton Boubacar Traore Tuan M. Tran Daniel E. Neafsey |
| author_sort | Emily LaVerriere |
| collection | DOAJ |
| description | Abstract Variation in malaria infection risk, a product of disease exposure and immunity, is poorly understood. We genotypically profiled over 13,000 blood samples from a six-year longitudinal cohort in Mali to characterize malaria infection dynamics with detail. We generated Plasmodium falciparum amplicon sequencing data from 464 participants (aged 3 months – 25 years) across the six-month 2011 transmission season and profiled a subset of 120 participants across the subsequent five annual transmission seasons. We measured infection rate as the molecular force of infection (molFOI, number of genetically distinct parasites acquired over time). We found that molFOI varied extensively among individuals (0–55 in 2011) but was independent of age and consistent within individuals over multiple seasons. Reported bednet usage was nearly universal. The HbS allele was associated with lower molFOI, and functional antibody signatures for the CSP C-term and RH5 antigens were correlated with low molFOI participants, identifying candidate immune correlates of protection. The large inter-individual variability in molFOI and consistency of intra-individual infection rate over time exhibits much greater dynamic range than malaria case incidence, and is most likely due to heterogeneous exposure to infectious mosquito bites. This and other factors contributing to variable infection risk should be considered in future clinical trials and implementation of malaria interventions. |
| format | Article |
| id | doaj-art-b1c65a2fc2bb426e9174177e43978120 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-b1c65a2fc2bb426e9174177e439781202025-08-20T03:43:27ZengNature PortfolioNature Communications2041-17232025-07-0116111310.1038/s41467-025-61462-1Marked heterogeneity in malaria infection rate in a Malian longitudinal cohortEmily LaVerriere0Zachary M. Johnson1Meg Shieh2Nadege Nziza3Galit Alter4Caroline O. Buckee5Peter D. Crompton6Boubacar Traore7Tuan M. Tran8Daniel E. Neafsey9Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public HealthDepartment of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public HealthDepartment of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public HealthRagon Institute of MGH, MIT, and HarvardRagon Institute of MGH, MIT, and HarvardDepartment of Epidemiology, Harvard T.H. Chan School of Public HealthMalaria Infection Biology and Immunity Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of HealthMali International Center of Excellence in Research, University of Sciences, Technique and Technology of BamakoDivision of Infectious Diseases, Department of Medicine, Indiana University School of MedicineDepartment of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public HealthAbstract Variation in malaria infection risk, a product of disease exposure and immunity, is poorly understood. We genotypically profiled over 13,000 blood samples from a six-year longitudinal cohort in Mali to characterize malaria infection dynamics with detail. We generated Plasmodium falciparum amplicon sequencing data from 464 participants (aged 3 months – 25 years) across the six-month 2011 transmission season and profiled a subset of 120 participants across the subsequent five annual transmission seasons. We measured infection rate as the molecular force of infection (molFOI, number of genetically distinct parasites acquired over time). We found that molFOI varied extensively among individuals (0–55 in 2011) but was independent of age and consistent within individuals over multiple seasons. Reported bednet usage was nearly universal. The HbS allele was associated with lower molFOI, and functional antibody signatures for the CSP C-term and RH5 antigens were correlated with low molFOI participants, identifying candidate immune correlates of protection. The large inter-individual variability in molFOI and consistency of intra-individual infection rate over time exhibits much greater dynamic range than malaria case incidence, and is most likely due to heterogeneous exposure to infectious mosquito bites. This and other factors contributing to variable infection risk should be considered in future clinical trials and implementation of malaria interventions.https://doi.org/10.1038/s41467-025-61462-1 |
| spellingShingle | Emily LaVerriere Zachary M. Johnson Meg Shieh Nadege Nziza Galit Alter Caroline O. Buckee Peter D. Crompton Boubacar Traore Tuan M. Tran Daniel E. Neafsey Marked heterogeneity in malaria infection rate in a Malian longitudinal cohort Nature Communications |
| title | Marked heterogeneity in malaria infection rate in a Malian longitudinal cohort |
| title_full | Marked heterogeneity in malaria infection rate in a Malian longitudinal cohort |
| title_fullStr | Marked heterogeneity in malaria infection rate in a Malian longitudinal cohort |
| title_full_unstemmed | Marked heterogeneity in malaria infection rate in a Malian longitudinal cohort |
| title_short | Marked heterogeneity in malaria infection rate in a Malian longitudinal cohort |
| title_sort | marked heterogeneity in malaria infection rate in a malian longitudinal cohort |
| url | https://doi.org/10.1038/s41467-025-61462-1 |
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