Identity-by-descent relatedness estimates with uncertainty characterise departure from isolation-by-distance betweenPlasmodium falciparumpopulations on the Colombian-Pacific coast

Characterising connectivity between geographically separated biological populations is a common goal in many fields. Recent approaches to understanding connectivity between malaria parasite populations, with implications for disease control efforts, have used estimates of relatedness based on identity-by-descent (IBD). However, uncertainty around estimated relatedness has not been accounted for to date. IBD-based relatedness estimates with uncertainty were computed for pairs of monoclonalPlasmodium falciparumsamples collected from five cities on the Colombian-Pacific coast where long-term clonal propagation ofP. falciparumis frequent. The cities include two official ports, Buenaventura and Tumaco, that are separated geographically but connected by frequent marine traffic. The fraction of highly-related sample pairs (whose classification accounts for uncertainty) was greater within cities versus between. However, based on both the fraction of highly-related sample pairs and on a threshold-free approach (Wasserstein distances between parasite populations) connectivity between Buenaventura and Tumaco was disproportionally high. Buenaventura-Tumaco connectivity was consistent with three separate transmission events involving parasites from five different clonal components (groups of statistically indistinguishable parasites identified under a graph theoretic framework). To conclude,P. falciparumpopulation connectivity on the Colombian-Pacific coast abides by accessibility not isolation-by-distance, potentially implicating marine traffic in malaria transmission with opportunities for targeted intervention. Further investigations are required to test this and alternative hypotheses. For the first time in malaria epidemiology, we account for uncertainty around estimated relatedness (an important consideration for future studies that plan to use genotype versus whole genome sequence data to estimate IBD-based relatedness); we also use a threshold-free approach to compare parasite populations, and identify clonal components in a statistically principled manner. The approaches we employ could be adapted to other recombining organisms with mixed mating systems, thus have broad relevance.