title: Return of chloroquine-susceptible falciparum malaria in Malawi was a reexpansion of diverse susceptible parasites.
abstract: The spread of drug-resistant Plasmodium falciparum malaria has been a major impediment to malaria control and threatens prospects for elimination. We recently demonstrated the return of chloroquine-susceptible malaria in Malawi after chloroquine use was abandoned. In this study, we trace the origins of chloroquine-resistant and chloroquine-susceptible parasites in Malawi by sequencing the P. falciparum chloroquine resistance transporter gene (pfcrt) and by genotyping microsatellites flanking this gene in isolates from infections that occurred in Malawi from 1992 through 2005. Malaria parasites from 2005 harbored the expected wild-type pfcrt haplotype associated with chloroquine susceptibility and have maintained high levels of diversity without linkage disequilibrium, which suggests that the return of chloroquine susceptibility is not the result of a back mutation in a formerly resistant parasite or a new selective sweep. Chloroquine-susceptible parasites that predominate in Malawi likely represent a reexpansion of the susceptible parasites that survived in the population despite widespread drug pressure in the region.
authors.affiliation: Center for Vaccine Development, University of Maryland School of Medicine, 685 W. Baltimore Street, Baltimore, MD 21201, USA. mlaufer@medicine.umaryland.edu
authors.forename: Miriam K
authors.initials: MK
authors.lastname: Laufer
authors.forename: Shannon
authors.initials: S
authors.lastname: Takala-Harrison
authors.forename: Fraction K
authors.initials: FK
authors.lastname: Dzinjalamala
authors.forename: O Colin
authors.initials: OC
authors.lastname: Stine
authors.forename: Terrie E
authors.initials: TE
authors.lastname: Taylor
authors.forename: Christopher V
authors.initials: CV
authors.lastname: Plowe
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000494:pharmacology* / Q000627:therapeutic use; D002648:Child; D002738:Chloroquine / Q000494:pharmacology* / Q000627:therapeutic use; D004351:Drug Resistance / Q000235:genetics; D005828:Genetics, Population; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000453:epidemiology / Q000469:parasitology*; D008295:Malawi / Q000453:epidemiology; D026901:Membrane Transport Proteins / Q000235:genetics*; D018895:Microsatellite Repeats; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics; D015800:Protozoan Proteins / Q000235:genetics*; D017422:Sequence Analysis, DNA; D013997:Time Factors
chemical_list: D000962:Antimalarials; D026901:Membrane Transport Proteins; C416369:PfCRT protein, Plasmodium falciparum; D015800:Protozoan Proteins; D002738:Chloroquine