High-Level Chloroquine Resistance in Sudanese Isolates of Plasmodium falciparum Is Associated with Mutations in the Chloroquine Resistance Transporter Gene pfcrt and the Multidrug Resistance Gene pfmdr1

Polymorphisms were examined in 2 Plasmodium falciparum genes, as were chloroquine responses of clones and isolates from a village in eastern Sudan. There was a significant association between an allele of the P. falciparum chloroquine resistance transporter gene (pfcrt-T76) and both in vitro and in vivo resistance. There was a less significant association with the multidrug resistance gene pfmdr1-Y86 allele. A significant association between pfmdr1Y86 and pfcrt-T76 was apparent among resistant isolates, which suggests a joint action of the 2 genes in high-level chloroquine resistance. Drug resistance is a major obstacle to the control and management of malaria in countries where the disease is endemic. In particular, resistance to chloroquine, the most widely used, safe, and affordable antimalarial drug, has accelerated morbidity and mortality caused by the most pathogenic species of the malaria parasite, Plasmodium falciparum. There has been a prolonged