ASSOCIATION OF MOLECULAR MARKERS IN Plasmoduim falciparum crt AND mdr1 WITH IN VITRO CHLOROQUINE RESISTANCE: A PHILIPPINE STUDY
BY: TOSHIMITSU HATABU, MORITOSHI IWAGAMI, SHIN-ICHIRO KAWAZU, NAO TAGUCHI, ALEYLA D. ESCUETA, ELENA VILLACORTE, PILARITA RIVERA, SHIGEYUKI KANO
SPECIFIC MUTATIONS IN THE pcfrt AND pfmdr1 GENES HAVE BEEN REPORTED TO BE ASSOCIATED WITH CHLOROQUINE-RESISTANT FALCIPARUM MALARIA PARASITES WORLDWIDE. THESE GENETIC MARKERS ARE CONSIDERED TO BE USEFUL TOOLS FOR THE ELUCIDATION OF SEVERAL ASPECTS OF THE EPIDEMIOLOGY OF DRUG-RESISTANT MALARIA. IN THIS STUDY, Plasmodium falciparum ISOLATES FROM THREE DISTINCT AREAS OF THE PHILIPPINES WERE ANALYZED FOR DRUG-RESISTANCE ASSOCIATED GENETIC MUTATIONS, AND THEIR ASSOCIATION WITH THE IN VITRO CHLOROQUINE (CQ) RESPONSE. TWO NOVEL pcfrt 72-76 ALLELIC TYPES, CVMDT AND SVMDT, WERE DETECTED. THE FREQUENCY OF THE pcfrt K76T MUTATION IN THE ISOLATES THAT WERE SUCCESFULLY TESTED FOR IN VITRO CQ SUSCEPTIBILITY WAS FOUND TO BE 100% IN KALINGA, 80% IN PALAWAN, AND 87% IN MINDANAO. THE FREQUENCY OF THE pfmdr1 N86Y MUTATION WAS 39% IN KALINGA, 35% IN PALAWAN, AND 93% IN MINDANAO ISOLATES. NO MUTATIONS WERE FOUND AT POSITIONS 1042 AND 1246 OF pfmdr1. HOWEVER, THERE WERE NO SIGNIFICANT ASSOCIATIONS FOUND BETWEEN THE POLYMORPHISMS IN THESE GENES AND IN VITRO CQ SUSCEPTIBILITY. THE RESULTS OF THIS STUDY INDICATE THAT MUTATIONS IN pcfrt AND pfmdr1 ARE NOT PREDICATIVE ON IN VITRO CQ RESISTANCE IN PHILIPPINE ISOLATES AND MAY THEREFORE AND MAY THEREFORE NOT SUITABLE AS MOLOECULAR MARKERS FOR SURVEILLANCE.
SPECIFIC MUTATIONS IN THE pcfrt AND pfmdr1 GENES HAVE BEEN REPORTED TO BE ASSOCIATED WITH CHLOROQUINE-RESISTANT FALCIPARUM MALARIA PARASITES WORLDWIDE. THESE GENETIC MARKERS ARE CONSIDERED TO BE USEFUL TOOLS FOR THE ELUCIDATION OF SEVERAL ASPECTS OF THE EPIDEMIOLOGY OF DRUG-RESISTANT MALARIA. IN THIS STUDY, Plasmodium falciparum ISOLATES FROM THREE DISTINCT AREAS OF THE PHILIPPINES WERE ANALYZED FOR DRUG-RESISTANCE ASSOCIATED GENETIC MUTATIONS, AND THEIR ASSOCIATION WITH THE IN VITRO CHLOROQUINE (CQ) RESPONSE. TWO NOVEL pcfrt 72-76 ALLELIC TYPES, CVMDT AND SVMDT, WERE DETECTED. THE FREQUENCY OF THE pcfrt K76T MUTATION IN THE ISOLATES THAT WERE SUCCESFULLY TESTED FOR IN VITRO CQ SUSCEPTIBILITY WAS FOUND TO BE 100% IN KALINGA, 80% IN PALAWAN, AND 87% IN MINDANAO. THE FREQUENCY OF THE pfmdr1 N86Y MUTATION WAS 39% IN KALINGA, 35% IN PALAWAN, AND 93% IN MINDANAO ISOLATES. NO MUTATIONS WERE FOUND AT POSITIONS 1042 AND 1246 OF pfmdr1. HOWEVER, THERE WERE NO SIGNIFICANT ASSOCIATIONS FOUND BETWEEN THE POLYMORPHISMS IN THESE GENES AND IN VITRO CQ SUSCEPTIBILITY. THE RESULTS OF THIS STUDY INDICATE THAT MUTATIONS IN pcfrt AND pfmdr1 ARE NOT PREDICATIVE ON IN VITRO CQ RESISTANCE IN PHILIPPINE ISOLATES AND MAY THEREFORE AND MAY THEREFORE NOT SUITABLE AS MOLOECULAR MARKERS FOR SURVEILLANCE.