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Updated: Oct 10, 2026

Methods to Investigate the Regulatory Role of Small RNAs and Ribosomal Occupancy of Plasmodium falciparum
Published on: December 4, 2015
Sickle cell haemoglobin status shapes malaria parasite genotype in asymptomatic infections
Helena D Hopson1, Alejandra Herbert-Mainero1, Aline Gaelle Bouopda-Tuedom2
1Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT, USA.
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.
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