Journal Article

Selective Sweeps and Genetic Lineages of Plasmodium falciparum Drug -Resistant Alleles in Ghana

de Souza, Dziedzom K., Ghansah, Anita, Poe, Amanda C., Griffing, Sean M., Asamoa, Kwame, Alam, Md Tauqeer, Slutsker, Laurence, Duah, Nancy O., Wilson, Michael D., Vinayak, Sumiti, Koram, Kwadwo A., Barnwell, John W., Udhayakumar, Venkatachalam

2011

Overview

Background. In 2005, Ghana adopted artemisinin-based combination therapy (ACT) for primary treatment of falciparum malaria. A comprehensive study of the drug-resistance—associated mutations and their genetic lineages will lead to a better understanding of the evolution of antimalarial drug resistance in this region. Methods. The pfcrt, pfmdr1, dhps, and dhfr mutations associated with chloroquine (CQ) and sulfadoxine-pyrimethamine (SP) resistance and the microsatellite loci flanking these genes were genotyped in Plasmodium falciparum isolates from Ghana. Results. The prevalence of mutations associated with both CQ and SP resistance was high in Ghana. However, we observed a decrease in prevalence of the pfcrt K76T mutation in northern Ghana after the change in drug policy from CQ to ACT. Analysis of genetic diversity and differentiation at microsatellite loci flanking all 4 genes indicated that they have been under strong selection, because of CQ and SP use. The triple-mutant pfcrt and dhfr alleles in Ghana were derived from Southeast Asia, whereas the double-mutant dhfr, dhps, and pfmdr1 alleles were of African lineage. Conclusion. Because of the possible role of pfmdr1 in amodiaquine and mefloquine resistance, demonstrating selection on pfmdr1 and defining lineages of resistant alleles in an African population holds great importance.

• Publisher: Oxford University Press
• Subject: Alleles / Amino Acid Substitution / Antimalarials / Antimalarials - pharmacology / Biological and medical sciences / Biological Evolution / Child, Preschool / Chloroquine - pharmacology / Dihydropteroate Synthase - genetics / DNA, Protozoan - genetics / Drug Combinations / Drug Resistance / Evolution / Evolution, Molecular / Evolutionary genetics / Fundamental and applied biological sciences. Psychology / Genetic loci / Genetic mutation / Genotype / Ghana / Haplotypes / Humans / Infant / Infant, Newborn / Infectious diseases / Life cycle. Host-agent relationship. Pathogenesis / Major and Brief Reports / Malaria / Malaria, Falciparum - parasitology / Medical sciences / Membrane Transport Proteins - genetics / Microbiology / Microsatellite Repeats / Microsatellites / Multidrug Resistance-Associated Proteins - genetics / Mutation, Missense / Parasites / Plasmodium falciparum - classification / Plasmodium falciparum - drug effects / Plasmodium falciparum - genetics / Plasmodium falciparum - isolation & purification / Protozoa / Protozoan Proteins - genetics / Pyrimethamine - pharmacology / Sulfadoxine - pharmacology / Tetrahydrofolate Dehydrogenase - genetics