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Background: Malaria remains endemic in several countries of South America with low to moderate transmission intensity. Regional human migration through underserved endemic areas may be responsible for significant parasite dispersion making the disease resilient to interventions. Thus, the genetic characterization of malarial parasites is an important tool to assess how endemic areas may connect via the movement of infected individuals. Here, four sites in geographically separated areas reporting 80% of the malaria morbidity in Colombia were studied. The sites are located on an imaginary transect line of 1,500 km from the northwest to the south Pacific Coast of Colombia with a minimal distance of 500 km between populations that display noticeable ethnic, economic, epidemiological, and ecological differences. Methodology/Principal findings: A total of 624 Plasmodium vivax samples from the four populations were genotyped by using eight microsatellite loci. Although a strong geographic structure was expected between these populations, only moderate evidence of genetic differentiation was observed using a suite of population genetic analyses. High genetic diversity, shared alleles, and low linkage disequilibrium were also found in these P. vivax populations providing no evidence for a bottleneck or clonal expansions as expected from recent reductions in the transmission that could have been the result of scaling up interventions or environmental changes. These patterns are consistent with a disease that is not only endemic in each site but also imply that there is gene flow among these populations across 1,500 km. Conclusion /Significance: The observed patterns in P. vivax are consistent with a “corridor” where connected endemic areas can sustain a high level of genetic diversity locally and can restore parasite-subdivided populations via migration of infected individuals even after local interventions achieved a substantial reduction of clinical cases. The consequences of these findings in terms of control and elimination are discussed. [ABSTRACT FROM AUTHOR]