Plasmodium falciparum gene expression signatures and antibody profiling implicate the fikk, phist, and surf multigene families in severe malaria syndromes

Plasmodium falciparum is the most virulent Plasmodium species, responsible for the life-threatening severe malaria syndromes of cerebral malaria and severe malarial anemia. In a Mali case-control study, we determined parasite gene expression in cerebral malaria, severe malarial anemia, and concurrent disease featuring both syndromes by comparing RNA-seq data from severe malaria cases to matched uncomplicated malaria controls with or without a history of cerebral malaria. While severe malarial anemia comparisons produced comparatively low levels of differential expression, the comparisons of cerebral malaria and concurrent disease yielded significant differential expression of multigene families (fikk, phist, and surf) implicated in processes that escalate disease severity, such as cytoadherence and erythrocytic remodeling. We probed custom microarrays featuring these antigens with acute and convalescent sera. Children with severe malaria developed antibody responses to subsets of these proteins following severe malaria infection, suggesting exposure to these antigens during illness and their potential as targets in the development of natural protective immunity against severe malaria. Our findings address knowledge gaps surrounding parasite gene expression in severe malarial anemia. Further, these results broaden the scope of multigene families implicated in severe malaria pathogenesis and underscore the utility of transcriptome-wide approaches for a comprehensive understanding of severe disease, particularly when developing therapeutics or vaccines.

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Publication Details

Journal
Journal of Infection
Published
2025-11-14
DOI
https://doi.org/10.1016/j.jinf.2025.106655
Citations
1
Primary Topic
Malaria Research and Control
Type
article
Field-Weighted Citation Impact
1.88

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article

Plasmodium falciparum gene expression signatures and antibody profiling implicate the fikk, phist, and surf multigene families in severe malaria syndromes

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1 citations
Journal of Infection
Malaria Research and Control
1.88
article

Plasmodium falciparum gene expression signatures and antibody profiling implicate the fikk, phist, and surf multigene families in severe malaria syndromes

Joana C. Silva, Mahamadou S. Sissoko, Ali Thera, Rafal S. Sobota, Philip L. Felgner, Shannon Takala‐Harrison, Bourèma Kouriba, Matthew B. Laurens, Beryl B. Cummings, Emily M. Stucke, Mark A. Travassos, Emily Silzel, Christopher V. Plowe, Drissa Coulibaly, James B. Munro, Bourama Tangara, Antoine Dara, Haikel N. Bogale, Jonathan G. Lawton, Bourama Kané, Kirsten E. Lyke, Youssouf Tolo, Amadou Niangaly, Mahamadou A. Théra, Abdoulaye K. Koné, Karim Traoré, Kieran Tebben, Fayçal Maïga, Sunit Sebastian, Algis Jasinskas, Mody Sissoko, Aarti Jain, Amed Ouattara, Modibo Daou, Rie Nakajima, Bouréima Guindo, Biraj Shrestha, A. Diawara, Ogobara K. Doumbo, I Diarra, Amidou Traore
article en
1 citations

Abstract

Plasmodium falciparum is the most virulent Plasmodium species, responsible for the life-threatening severe malaria syndromes of cerebral malaria and severe malarial anemia. In a Mali case-control study, we determined parasite gene expression in cerebral malaria, severe malarial anemia, and concurrent disease featuring both syndromes by comparing RNA-seq data from severe malaria cases to matched uncomplicated malaria controls with or without a history of cerebral malaria. While severe malarial anemia comparisons produced comparatively low levels of differential expression, the comparisons of cerebral malaria and concurrent disease yielded significant differential expression of multigene families (fikk, phist, and surf) implicated in processes that escalate disease severity, such as cytoadherence and erythrocytic remodeling. We probed custom microarrays featuring these antigens with acute and convalescent sera. Children with severe malaria developed antibody responses to subsets of these proteins following severe malaria infection, suggesting exposure to these antigens during illness and their potential as targets in the development of natural protective immunity against severe malaria. Our findings address knowledge gaps surrounding parasite gene expression in severe malarial anemia. Further, these results broaden the scope of multigene families implicated in severe malaria pathogenesis and underscore the utility of transcriptome-wide approaches for a comprehensive understanding of severe disease, particularly when developing therapeutics or vaccines.

Journal of InfectionVol. 91(6)
University of Maryland, Baltimore (US), University of California, Irvine (US), University of Bamako (ML), Université des Sciences, des Techniques et des Technologies de Bamako (ML), Irvine University (US)
National Institutes of Health, School of Medicine, University of Maryland, National Heart, Lung, and Blood Institute, National Institute of Allergy and Infectious Diseases
Openalex Percentile: Top 11%
Malaria Research and Control
1.88
DOIOpen Access PDFOpenAlex
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