Polymorphisms in the Plasmodium falciparum pfcrt and pfmdr-1 genes and clinical response to chloroquine in Kampala, Uganda

The molecular mechanism of chloroquine resistance in Plasmodium falciparum remains uncertain. Polymorphisms in the pfcrt and pfmdr-1 genes have been a ssociated with chloroquine resistance in vitro, although field studies are limited. In evaluations of known polymorphisms in parasites from patients w ith uncomplicated malaria in Kampala, Uganda, the presence of 8 pfcrt mutat ions and 2 pfmdr-1 mutations did not correlate with clinical response to th erapy with chloroquine. Most notably, the pfcrt lysine threonine mutation a t position 76, which recently correlated fully with chloroquine resistance in vitro, was present in 100% of 114 isolates, of which about half were fro m patients who recovered clinically after chloroquine therapy. These result s suggest that, although key pfcrt polymorphisms may be necessary for the e laboration of resistance to chloroquine in areas with high levels of chloro quine resistance, other factors, such as host immunity, may contribute to c linical outcomes.