The origins and relatedness 1 structure of mixed infections vary 2 with local prevalence of P . falciparum 3 malaria 4

Abstract Individual malaria infections can carry multiple strains of Plasmodium falciparum with 14 varying levels of relatedness. Yet, how local epidemiology affects the properties of such mixed 15 infections remains unclear. Here, we develop an enhanced method for strain deconvolution from 16 genome sequencing data, which estimates the number of strains, their proportions, 17 identity-by-descent (IBD) profiles and individual haplotypes. Applying it to the Pf3k data set, we find 18 that the rate of mixed infection varies from 29% to 63% across countries and that 51% of mixed 19 infections involve more than two strains. Furthermore, we estimate that 47% of symptomatic dual 20 infections contain sibling strains likely to have been co-transmitted from a single mosquito, and 21 find evidence of mixed infections propagated over successive infection cycles. Finally, leveraging 22 data from the Malaria Atlas Project, we find that prevalence correlates within Africa, but not Asia, 23 with both the rate of mixed infection and the level of IBD. 24