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POLYMORPHISM OF THE PLASMODIUM FALCIPARUM MULTIDRUG RESISTANCE AND CHLOROQUINE RESISTANCE TRANSPORTER GENES AND IN VITRO SUSCEPTIBILITY TO AMINOQUINOLINES IN ISOLATES FROM THE PERUVIAN AMAZON

In vitro drug sensitivity to chloroquine (CQ), mefloquine (MQ) and quinine was investigated in 60 culture-adapted Plasmodium falciparum isolates from malaria patients in Padrecocha, a village in the Amazonian Department of Loreto, Peru. All isolates showed resistance to CQ, decreased susceptibility to quinine, and sensitivity to MQ. These isolates were examined for mutations in the P. falciparum multidrug resistance 1 (pfmdr1) and chloroquine resistance transporter (pfcrt) genes previously linked to CQ resistance. The mutations N86Y and D1246Y, two of the five mutations commonly observed in the pfmdr1 gene of CQ-resistant clones, were not found. The pfcrt mutation K76T, associated with CQ resistance, was identified in all the isolates tested. Sequence analysis of codons 72–76 in the pfcrt gene showed the haplotypes SVMNT and CVMNT.

Received February 3, 2003. Accepted for publication August 29, 2003.

Acknowledgments: We are grateful to Thomas E. Wellems for valuable comments on the manuscript, and to Dennis Kyle for providing the control strains D6 and W2. We also thank Maria del Carmen Parquet for her assistance with the molecular techniques, and Windell Rivera and Humberto Guerra for their kind help during this work.

Financial support: this study was partially supported by the Pan American Health Organization. Maria Cecilia Huaman and Ton That Ai Long are recipients of the "Monbusho Scholarship" awarded by the Ministry of Education, Science, Sports and Culture of the Government of Japan.

Disclaimer: The views expressed by the authors in this report do not necessarily reflect the views of the U. S. Army, U. S. Navy, or the Department of Defense.

Authors’ addresses: Maria Cecilia Huaman, Shusuke Nakazawa, and Ton That Ai Long, Institute of Tropical Medicine, Nagasaki University, Sakamoto 1-12-4, Nagasaki 852-8523, Japan. 1-12-4 Sakamoto, Nagasaki 852-8523, Japan, Telephone: 81-95-849-7838, Fax: 81-95-849-7805. Norma Roncal, Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, AP 4314, Lima 100, Peru, Telephone: 51-1-482-3903, Fax: 51-1-482-3404. Lucia Gerena, Walter Reed Army Institute of Research, Washington, DC 20307-5100, Fax: 301-319-9449. Coralith Garcia and Lely Solari, Universidad Peruana Cayetano Heredia, Av. Honorio Delgado 430, San Martin de Porras, Lima. Peru, Telephone: Phone 51-1-319000. Alan J. Magill, Walter Reed Army Institute of Research, Silver Spring MD 20910-7500, Telephone: 301-319-9959, Fax: 301-319-9585. Hiroji Kanbara: Institute of Tropical Medicine, Nagasaki University, Sakamoto 1-12-4, Nagasaki 852-8523, Japan, Telephone: 81-95-849-7838, Fax: 81-95-849-7805. E-mail: f0512{at}cc.nagasaki-u.ac.jp.

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