PFMDR1 (ASN)1042(ASP) AND (ASP)1246(TYR) POLYMORPHISMS, THOUGHT TO BEASSOCIATED WITH CHLOROQUINE RESISTANCE, ARE PRESENT IN CHLOROQUINE-RESISTANT AND CHLOROQUINE-SENSITIVE BRAZILIAN FIELD ISOLATES OF PLASMODIUM-FALCIPARUM

Parasite resistance to antimalarial drugs, particularly chloroquine, i s the most disturbing problem of malaria chemotherapy There is evidenc e that the codon 86(Tyr) polymorphism of the Pfindr1 gene is associate d with chloroquine resistance in West African Plasmodium falciparum. T he association of this and four other coding alterations of the Pfmdr1 gene with chloroquine resistance has not been extensively investigate d in South American isolates. In this study, we examined 51 Brazilian P. falciparum isolates for the presence or absence of (Asn)86(Tyr), (A sn)1042(Asp), and (Asp)1246(Tyr) polymorphisms. While these isolates w ere all sensitive in vitro to mefloquine, amodiaquine, and quinine, on ly 2 (4%) were chloroquine-sensitive. The findings reported here provi de the first observations of this kind on a large number of field para site samples from South America. We show that in vitro chloroquine-res istant and -sensitive strains carry the (Asn)1042(Asp) and (Asp)1246(T yr) polymorphisms and provide support for earlier suggestions that (As n)86(Tyr) may be rare or absent in South American P. falciparum. (C) 1 998 Academic Press.