Clinical malaria cases reflect the parasite population diversity of the asymptomatic reservoir in West Africa

Abstract Background Malaria transmission persists in Sahelian West Africa, with asymptomatic Plasmodium falciparum infections acting as a reservoir. Yet malaria epidemiology and research focus heavily on clinical cases. It remains unclear whether parasites causing clinical infections are genetically representative of the asymptomatic reservoir. Methods A one-year cohort study (2021–2022) was conducted in four villages in the Kedougou district of Senegal and two villages in the Kati district of Mali, collecting 1,133 P. falciparum -positive samples from asymptomatic and clinical infections. Using parasite molecular barcodes and whole-genome sequencing, we estimated multiplicity of infection (MOI), runs of homozygosity (RoH), and identity-by-descent (IBD) to compare parasite populations between infection types and across age groups. Results A total of 226 whole genomes and 728 barcodes were analysed, representing 78.2% (570/729) of clinical cases and 21.7% (158/728) of asymptomatic infections. MOI was high, with over 50% of infections being polyclonal, and did not differ by age or infection status. IBD analysis revealed a highly diverse parasite population, with transmission clusters including both asymptomatic carriers and clinical cases. Drug resistance allele frequencies were similar between groups. Conclusion Overall, we found no evidence of genetic differentiation between parasites from clinical and asymptomatic infections, suggesting that clinical cases reflect the broader parasite population sustaining transmission. These findings provide a basis for linking genomic metrics with epidemiological factors and for monitoring the impact of future interventions on the parasite population.