Pfmdr1 Asn1042Asp and Asp1246Tyr polymorphisms, thought to be associated with chloroquine resistance, are present in chloroquine-resistant and -sensitive Brazilian field isolates of Plasmodium falciparum

Parasite resistance to antimalarial drugs, particularly chloroquine, is the most disturbing problem of malaria chemotherapy There is evidence that the codon 86(Tyr) polymorphism of the Pfindr1 gene is associated with chloroquine resistance in West African Plasmodium falciparum. The association of this and four other coding alterations of the Pfmdr1 gene with chloroquine resistance has not been extensively investigated in South American isolates. In this study, we examined 51 Brazilian P. falciparum isolates for the presence or absence of (Asn)86(Tyr), (Asn)1042(Asp), and (Asp)1246(Tyr) polymorphisms. While these isolates were all sensitive in vitro to mefloquine, amodiaquine, and quinine, only 2 (4%) were chloroquine-sensitive. The findings reported here provide the first observations of this kind on a large number of field parasite samples from South America. We show that in vitro chloroquine-resistant and -sensitive strains carry the (Asn)1042(Asp) and (Asp)1246(Tyr) polymorphisms and provide support for earlier suggestions that (Asn)86(Tyr) may be rare or absent in South American P. falciparum. (C) 1998 Academic Press.