Antimalarial drug resistance in Plasmodium falciparum isolates from the Pacific Coast of Colombia.

Abstract

Antimalarial drug resistance has evolved repeatedly and independently in both Southeast Asia and South America, but functional studies of parasite resistance have almost all concentrated on Asian isolates. Colombia contributes nearly one-third of all Plasmodium falciparum cases in South America, primarily focused on the Pacific Coast. We assessed the presence of resistance associated genotypes and phenotypes in this region using a panel of P. falciparum isolates collected across 23 years, with a specific focus on sensitivity to historically used antimalarials chloroquine, mefloquine, pyrimethamine and sulfadoxine. The sensitivity profiles were predicted genetically using a combination of quantitative PCR assays and sequencing of known resistance-associated loci, including the artemisinin resistance-associated gene PfKelch13. The isolates were then assessed phenotypically by introduction to in vitro culture allowing both antimalarial sensitivity testing and the establishment of a biobank of Colombian isolates for further work. We established that multiple antimalarial resistance associated genotypes and phenotypes, particularly for chloroquine and mefloquine, persist across the Colombian Pacific Coast but found no evidence for the presence of artemisinin resistance-associated polymorphisms. The continued presence of resistance against historically used antimalarials argues against the use of these drugs as partner therapy for artemisinin and highlights the unique epidemiological environment of the Pacific Coast which allows for long-term maintenance of resistance.