Sickle cell haemoglobin status shapes malaria parasite genotype in asymptomatic infections.

IF 18.7 1区生物学 Q1 MICROBIOLOGY

Nature Microbiology Pub Date : 2026-10-08 DOI:10.1038/s41564-026-02502-4

Helena D Hopson, Alejandra Herbert-Mainero, Aline Gaelle Bouopda-Tuedom, Charlène Tina Nanssong-Vomo, Brigitte Tumamo Fotso, Belinda Claire Kiam, Ibrahima Ibrahima, Clément Onguene, Luc Abate, Radoslaw Igor Omelianczyk, Heather D Evans, Lyra E Horton, Gavin Band, Tracey J Lamb, Lawrence S Ayong, Sandrine E Nsango, Ellen M Leffler

{"title":"Sickle cell haemoglobin status shapes malaria parasite genotype in asymptomatic infections.","authors":"Helena D Hopson, Alejandra Herbert-Mainero, Aline Gaelle Bouopda-Tuedom, Charlène Tina Nanssong-Vomo, Brigitte Tumamo Fotso, Belinda Claire Kiam, Ibrahima Ibrahima, Clément Onguene, Luc Abate, Radoslaw Igor Omelianczyk, Heather D Evans, Lyra E Horton, Gavin Band, Tracey J Lamb, Lawrence S Ayong, Sandrine E Nsango, Ellen M Leffler","doi":"10.1038/s41564-026-02502-4","DOIUrl":null,"url":null,"abstract":"Sickle cell haemoglobin (HbS) confers protection against symptomatic malaria caused by Plasmodium falciparum. HbS carriers with symptomatic malaria harbour parasites enriched for P. falciparum sickle-associated alleles (Pfsa+), which appear to partially overcome HbS-mediated protection, but their role in asymptomatic infections is unclear. Here we conducted a cross-sectional survey of 2,246 healthy schoolchildren in a region of high malaria transmission in Cameroon. Analysing the parasite Pfsa and the human HbS genotypes for 1,701 asymptomatic P. falciparum infections confirmed that heterozygous HbS (HbAS) and homozygous non-HbS (HbAA) genotypes have similar rates of asymptomatic infection. However, the HbS genotype is strongly associated with parasites carrying the Pfsa+ alleles at the Pfsa1 and Pfsa3 loci, indicating a selective advantage for these alleles in HbS carriers. Our findings reveal that the protective effect of HbS is complex: HbS has a protective effect before symptoms appear against Pfsa- parasites and Pfsa+ alleles may contribute to the lower rates of symptomatic disease observed in HbS carriers. In HbS-mediated protection against malaria, both resistance and tolerance and ongoing co-evolution with parasites should be considered.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":" ","pages":""},"PeriodicalIF":18.7000,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature Microbiology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1038/s41564-026-02502-4","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MICROBIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Sickle cell haemoglobin (HbS) confers protection against symptomatic malaria caused by Plasmodium falciparum. HbS carriers with symptomatic malaria harbour parasites enriched for P. falciparum sickle-associated alleles (Pfsa⁺), which appear to partially overcome HbS-mediated protection, but their role in asymptomatic infections is unclear. Here we conducted a cross-sectional survey of 2,246 healthy schoolchildren in a region of high malaria transmission in Cameroon. Analysing the parasite Pfsa and the human HbS genotypes for 1,701 asymptomatic P. falciparum infections confirmed that heterozygous HbS (HbAS) and homozygous non-HbS (HbAA) genotypes have similar rates of asymptomatic infection. However, the HbS genotype is strongly associated with parasites carrying the Pfsa⁺ alleles at the Pfsa1 and Pfsa3 loci, indicating a selective advantage for these alleles in HbS carriers. Our findings reveal that the protective effect of HbS is complex: HbS has a protective effect before symptoms appear against Pfsa^- parasites and Pfsa⁺ alleles may contribute to the lower rates of symptomatic disease observed in HbS carriers. In HbS-mediated protection against malaria, both resistance and tolerance and ongoing co-evolution with parasites should be considered.

查看原文本刊更多论文

镰状细胞血红蛋白状态影响无症状感染中的疟原虫基因型。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Nature Microbiology Immunology and Microbiology-Microbiology

CiteScore

44.40

自引率

1.10%

发文量

226

期刊介绍： Nature Microbiology aims to cover a comprehensive range of topics related to microorganisms. This includes: Evolution: The journal is interested in exploring the evolutionary aspects of microorganisms. This may include research on their genetic diversity, adaptation, and speciation over time. Physiology and cell biology: Nature Microbiology seeks to understand the functions and characteristics of microorganisms at the cellular and physiological levels. This may involve studying their metabolism, growth patterns, and cellular processes. Interactions: The journal focuses on the interactions microorganisms have with each other, as well as their interactions with hosts or the environment. This encompasses investigations into microbial communities, symbiotic relationships, and microbial responses to different environments. Societal significance: Nature Microbiology recognizes the societal impact of microorganisms and welcomes studies that explore their practical applications. This may include research on microbial diseases, biotechnology, or environmental remediation. In summary, Nature Microbiology is interested in research related to the evolution, physiology and cell biology of microorganisms, their interactions, and their societal relevance.