Population Genomics of Plasmodium malariae from Four African Countries

Plasmodium malariae is geographically widespread but neglected and may become more prevalent as P. falciparum declines. We completed the largest genomic study of African P. malariae to-date by performing hybrid capture and sequencing of 77 isolates from Cameroon (n=7), the Democratic Republic of the Congo (n=16), Nigeria (n=4), and Tanzania (n=50) collected between 2015 and 2021. There is no evidence of geographic population structure. Nucleotide diversity was significantly lower than in co-localized P. falciparum isolates, while linkage disequilibrium was significantly higher. Genome-wide selection scans identified no erythrocyte invasion ligands or antimalarial resistance orthologs as top hits; however, targeted analyses of these loci revealed evidence of selective sweeps around four erythrocyte invasion ligands and six antimalarial resistance orthologs. Demographic inference modeling suggests that African P. malariae is recovering from a bottleneck. Altogether, these results suggest that P. malariae is genomically atypical among human Plasmodium spp. and panmictic in Africa.