Limited Geographical Origin and Global Spread of Sulfadoxine-Resistant dhps Alleles in Plasmodium falciparum Populations
Year: 2011
Type: article
Abstract: BACKGROUND: Plasmodium falciparum malaria resistant to chloroquine and pyrimethamine originated in limited foci and migrated to Africa. It remains unresolved whether P. falciparum resistance to sulfadoxine, which is conferred by mutations in dihydropteroate synthase (DHPS), evolved following a similar pattern. METHODS: The dhps locus of 893 P. falciparum isolates from 12 countries in Asia, the Pacific Islands, Africa, and South America was sequenced. Haplotypes of 6 microsatellite loci flanking the dhps locus were determined to define the genetic relationships among sulfadoxine-resistant lineages. RESULTS: Six distinct sulfadoxine-resistant lineages were identified. Highly resistant lineages appear to have originated only in Southeast Asia and South America. Two resistant lineages found throughout Southeast Asia have been introduced to East Africa, where they appear to have spread. CONCLUSIONS: The infrequent selection of parasites highly resistant to sulfadoxine and the subsequent migration of resistant lineages from Asia to Africa are similar to the patterns observed in chloroquine and pyrimethamine resistance. These findings strongly suggest that the global migration of resistant parasites has played a decisive role in the establishment of drug-resistant P. falciparum parasites, and that similar patterns may be anticipated for the spread of artemisinin resistance.
Institutions: Tokyo Women's Medical University, Howard Hughes Medical Institute, University of Tsukuba, Nagasaki University, Institute of Tropical Medicine, Nagasaki University, Cambodia National Malaria Center, Divine Word University, Universidade de São Paulo, Research Institute for Microbial Diseases, The University of Osaka, The University of Osaka
Language: English
Topic: Malaria Research and Control
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: Establishment of an experimental model system for a highly accelerated evolution using mutator malaria parasites generated by the disparity mutagenesis, Population genetic analysis of dynamism of malaria drug resistance in Papua New Guinea, Development of predictive model for future prevalence of antimalarial-resistant gene using microsatellite polymorphism
OpenAlex ID: W2159287794