The malaria parasites Plasmodium falciparum and Plasmodium vivax differ in key biological processes and associated clinical effects, but consequences on population-level transmission dynamics are difficult to predict. This co-endemic malaria study from Guyana details important epidemiological contrasts between the species by coupling population genomics (1,396 spatiotemporally-matched parasite genomes) with sociodemographic analysis (nationwide patient census). We describe how P. falciparum forms large, interrelated subpopulations that sporadically expand but generally exhibit restrained dispersal, whereby spatial distance and patient travel statistics predict parasite identity-by-descent (IBD). Case bias towards working-age adults is also strongly pronounced. P. vivax exhibits 46% higher average diversity (π) and 6.5x lower average IBD. It occupies a wider geographic range, without evidence for outbreak-like expansions, only microgeographic patterns of isolation-by-distance, and weaker case bias towards adults. Possible latency-relapse effects also manifest in various analyses. For example, 11.0% of patients diagnosed with P. vivax in Greater Georgetown report no recent travel to endemic zones, and P. vivax clones recur in 11/46 patients incidentally sampled twice during the study. Polyclonality rate is also 2.1x higher than in P. falciparum, does not trend positively with estimated incidence, and correlates uniquely to selected demographics. We discuss possible underlying mechanisms and implications for malaria control.

The authors have declared no competing interest.

This study was supported by the Bill & Melinda Gates Foundation (INV-009416). This study was also supported with federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under Grant Number U19AI110818 to the Broad Institute. Sampling in Venezuela was additionally supported by the Scottish Funding Council Global Challenges Research Fund (GCRF) Small Grants Fund SFC/AN/12/2017 and the GCRF Vector-borne Disease Control Network (EP/T003782/1).

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The Institutional Review Board of the Harvard University Area Human Research Protection Program (protocol IRB18-1638) gave approval for this work.

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