Polymorphism of proteins in malaria parasites following mefloquine treatment

Proteins in malaria parasites (Plasmodium falciparum) isolated from a patient in Thailand before treatment, and after recrudescence of infection subsequent to mefloquine treatment, were compared by two dimensional polyacrylamide gel electrophoresis (2D-PAGE) analysis. Nine 'pre-treatment' and six 'recrudescent' clones were studied. Variants of the enzyme glucose phosphate isomerase were also noted and mefloquine susceptibility of each clone was measured by in vitro tests. The 'pre-treatment' isolate was found to contain at least four genetically distinct clones, all sensitive to mefloquine, while the 'recrudescent' isolate contained at least two other types of clone, both showing increased tolerance to mefloquine. These two more tolerant types of clone differed from all the sensitive ones studied in regard to several different protein variants as shown by 2D-PAGE analysis. It is concluded that at least two (and probably more) genetically distinct clones of parasites with increased tolerance to mefloquine were present in the parasite population before mefloquine treatment was given, and were selected under mefloquine pressure.