title: Plasmodium falciparum: differential selection of drug resistance alleles in contiguous urban and peri-urban areas of Brazzaville, Republic of Congo.
abstract: The African continent is currently experiencing rapid population growth, with rising urbanization increasing the percentage of the population living in large towns and cities. We studied the impact of the degree of urbanization on the population genetics of Plasmodium falciparum in urban and peri-urban areas in and around the city of Brazzaville, Republic of Congo. This field setting, which incorporates local health centers situated in areas of varying urbanization, is of interest as it allows the characterization of malaria parasites from areas where the human, parasite, and mosquito populations are shared, but where differences in the degree of urbanization (leading to dramatic differences in transmission intensity) cause the pattern of malaria transmission to differ greatly. We have investigated how these differences in transmission intensity affect parasite genetic diversity, including the amount of genetic polymorphism in each area, the degree of linkage disequilibrium within the populations, and the prevalence and frequency of drug resistance markers. To determine parasite population structure, heterozygosity and linkage disequilibrium, we typed eight microsatellite markers and performed haplotype analysis of the msp1 gene by PCR. Mutations known to be associated with resistance to the antimalarial drugs chloroquine and pyrimethamine were determined by sequencing the relevant portions of the crt and dhfr genes, respectively. We found that parasite genetic diversity was comparable between the two sites, with high levels of polymorphism being maintained in both areas despite dramatic differences in transmission intensity. Crucially, we found that the frequencies of genetic markers of drug resistance against pyrimethamine and chloroquine differed significantly between the sites, indicative of differing selection pressures in the two areas.
authors.affiliation: Department of Protozoology, Institute of Tropical Medicine (NEKKEN), and the Global COE Program, Nagasaki University, Nagasaki, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Tsumori
authors.forename: Mathieu
authors.initials: M
authors.lastname: Ndounga
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Sunahara
authors.forename: Nozomi
authors.initials: N
authors.lastname: Hayashida
authors.forename: Megumi
authors.initials: M
authors.lastname: Inoue
authors.forename: Shusuke
authors.initials: S
authors.lastname: Nakazawa
authors.forename: Prisca
authors.initials: P
authors.lastname: Casimiro
authors.forename: Rie
authors.initials: R
authors.lastname: Isozumi
authors.forename: Haruki
authors.initials: H
authors.lastname: Uemura
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Tanabe
authors.forename: Osamu
authors.initials: O
authors.lastname: Kaneko
authors.forename: Richard
authors.initials: R
authors.lastname: Culleton
mesh_terms: D000293:Adolescent; D000483:Alleles; D000818:Animals; D000852:Anopheles / Q000254:growth & development / Q000469:parasitology; D000962:Antimalarials / Q000494:pharmacology*; D002738:Chloroquine / Q000494:pharmacology; D003223:Congo; D004351:Drug Resistance / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007303:Insect Vectors / Q000254:growth & development / Q000469:parasitology; D016778:Malaria, Falciparum / Q000469:parasitology* / Q000517:prevention & control / Q000635:transmission; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics; D020066:Merozoite Surface Protein 1 / Q000235:genetics; D009154:Mutation; D010963:Plasmodium falciparum / Q000187:drug effects / Q000235:genetics* / Q000254:growth & development; D015800:Protozoan Proteins / Q000235:genetics; D011739:Pyrimethamine / Q000494:pharmacology; D012641:Selection, Genetic; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics; D014507:Urbanization; D055815:Young Adult
chemical_list: D000962:Antimalarials; D026901:Membrane Transport Proteins; D020066:Merozoite Surface Protein 1; C416369:PfCRT protein, Plasmodium falciparum; D015800:Protozoan Proteins; D002738:Chloroquine; D013762:Tetrahydrofolate Dehydrogenase; D011739:Pyrimethamine