TY - JOUR
T1 - Association of molecular markers in Plasmodium falciparum crt and mdr1 with in vitro chloroquine resistance
T2 - A Philippine study
AU - Hatabu, Toshimitsu
AU - Iwagami, Moritoshi
AU - Kawazu, Shin ichiro
AU - Taguchi, Nao
AU - Escueta, Aleyla D.
AU - Villacorte, Elena A.
AU - Rivera, Pilarita T.
AU - Kano, Shigeyuki
N1 - Funding Information:
The study was conducted in the context of a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan, from August 1999 to March 2005 in 3 provinces of the Philippines. A total of 18 P. falciparum positive blood samples were collected in Kalinga during the years 2003–2005 (2004 Annual Parasite Incidence (API) was 3.6/1000), 29 isolates from 2001–2005 in Palawan (2004 API was 16.3/1000), and 31 isolates from 1999–2002 in Davao del Norte (API was 14.26/1000 in 2001 and 7.81/1000 in 2002, respectively) ( Fig. 1 ). APIs were collected from Annual Reports of the Provincial Health offices of Kalinga, Palawan and Davao del Norte. Informed consent was obtained from all patients prior to blood collection. Favourable technical and ethical reviews of this project were made by the University of the Philippines Manila. This study was performed according to the ethical guidelines for epidemiological studies provided by the Ministry of Education, Culture, Sports, Science and Technology and the Ministry of Health, Labour and Welfare of Japan.
Funding Information:
This study was supported in part by a Grant-in-Aid for Scientific Research (B) (16406012 and 19406013) from the Ministry of Education, Culture, Sports, Science and Technology of Japan. The authors thank the microscopists at the Center for Health Development and Provincial Hospital, Kalinga, Kilusan Ligtas Malaria Palawan, and Tagum Provincial Hospital, Davao del Norte for their kind assistance and support. The authors also thank the anonymous reviewers for important comments to revise the manuscript significantly.
PY - 2009/6
Y1 - 2009/6
N2 - Specific mutations in the pfcrt 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 pfcrt 72-76 allelic types, CVMDT and SVMDT, were detected. The frequency of the pfcrt K76T mutation in the isolates that were successfully 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 polymorphisms in these genes and in vitro CQ susceptibility. The results of this study indicate that mutations in pfcrt and pfmdr1 are not predictive of in vitro CQ resistance in Philippine isolates and may therefore not be suitable as molecular markers for surveillance.
AB - Specific mutations in the pfcrt 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 pfcrt 72-76 allelic types, CVMDT and SVMDT, were detected. The frequency of the pfcrt K76T mutation in the isolates that were successfully 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 polymorphisms in these genes and in vitro CQ susceptibility. The results of this study indicate that mutations in pfcrt and pfmdr1 are not predictive of in vitro CQ resistance in Philippine isolates and may therefore not be suitable as molecular markers for surveillance.
KW - Chloroquine resistance
KW - Philippines
KW - pfcrt
KW - pfmdr1
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UR - http://www.scopus.com/inward/citedby.url?scp=64849116595&partnerID=8YFLogxK
U2 - 10.1016/j.parint.2009.01.010
DO - 10.1016/j.parint.2009.01.010
M3 - Article
C2 - 19567229
AN - SCOPUS:64849116595
SN - 1383-5769
VL - 58
SP - 166
EP - 170
JO - Parasitology International
JF - Parasitology International
IS - 2
ER -
