title: South American Plasmodium falciparum after the malaria eradication era: clonal population expansion and survival of the fittest hybrids.
abstract: Malaria has reemerged in many regions where once it was nearly eliminated. Yet the source of these parasites, the process of repopulation, their population structure, and dynamics are ill defined. Peru was one of malaria eradication's successes, where Plasmodium falciparum was nearly eliminated for two decades. It reemerged in the 1990s. In the new era of malaria elimination, Peruvian P. falciparum is a model of malaria reinvasion. We investigated its population structure and drug resistance profiles. We hypothesized that only populations adapted to local ecological niches could expand and repopulate and originated as vestigial populations or recent introductions. We investigated the genetic structure (using microsatellites) and drug resistant genotypes of 220 parasites collected from patients immediately after peak epidemic expansion (1999-2000) from seven sites across the country. The majority of parasites could be grouped into five clonal lineages by networks and AMOVA. The distribution of clonal lineages and their drug sensitivity profiles suggested geographic structure. In 2001, artesunate combination therapy was introduced in Peru. We tested 62 parasites collected in 2006-2007 for changes in genetic structure. Clonal lineages had recombined under selection for the fittest parasites. Our findings illustrate that local adaptations in the post-eradication era have contributed to clonal lineage expansion. Within the shifting confluence of drug policy and malaria incidence, populations continue to evolve through genetic outcrossing influenced by antimalarial selection pressure. Understanding the population substructure of P. falciparum has implications for vaccine, drug, and epidemiologic studies, including monitoring malaria during and after the elimination phase.
authors.affiliation: Malaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: Sean M
authors.initials: SM
authors.lastname: Griffing
authors.forename: Tonya
authors.initials: T
authors.lastname: Mixson-Hayden
authors.forename: Sankar
authors.initials: S
authors.lastname: Sridaran
authors.forename: Md Tauqeer
authors.initials: MT
authors.lastname: Alam
authors.forename: Andrea M
authors.initials: AM
authors.lastname: McCollum
authors.forename: César
authors.initials: C
authors.lastname: Cabezas
authors.forename: Wilmer
authors.initials: W
authors.lastname: Marquiño Quezada
authors.forename: John W
authors.initials: JW
authors.lastname: Barnwell
authors.forename: Alexandre Macedo
authors.initials: AM
authors.lastname: De Oliveira
authors.forename: Carmen
authors.initials: C
authors.lastname: Lucas
authors.forename: Nancy
authors.initials: N
authors.lastname: Arrospide
authors.forename: Ananias A
authors.initials: AA
authors.lastname: Escalante
authors.forename: David J
authors.initials: DJ
authors.lastname: Bacon
authors.forename: Venkatachalam
authors.initials: V
authors.lastname: Udhayakumar
mesh_terms: D000962:Antimalarials / Q000494:pharmacology / Q000627:therapeutic use; D004094:Dihydropteroate Synthase / Q000235:genetics; D004351:Drug Resistance / Q000235:genetics*; D058872:Epidemics / Q000517:prevention & control; D005787:Gene Frequency; D005838:Genotype; D005843:Geography; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D016778:Malaria, Falciparum / Q000453:epidemiology / Q000469:parasitology* / Q000517:prevention & control; D026901:Membrane Transport Proteins / Q000235:genetics; D018895:Microsatellite Repeats / Q000235:genetics; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics; D010568:Peru / Q000453:epidemiology; D010802:Phylogeny; D010963:Plasmodium falciparum / Q000145:classification* / Q000187:drug effects / Q000235:genetics*; D011158:Population Growth; D015800:Protozoan Proteins / Q000235:genetics; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics
chemical_list: D000962:Antimalarials; D004094:Dihydropteroate Synthase; D026901:Membrane Transport Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D015800:Protozoan Proteins; D013762:Tetrahydrofolate Dehydrogenase; C513498:Mdr1 protein, Plasmodium falciparum; C416369:PfCRT protein, Plasmodium falciparum