AJTMH Transactions of the Royal Society of Tropical Medicine and Hygiene
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Am. J. Trop. Med. Hyg., 69(2), 2003, pp. 184-187
Copyright © 2003 by The American Society of Tropical Medicine and Hygiene

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SHORT REPORT: ASSOCIATION BETWEEN CHLOROQUINE AND AMODIAQUINE RESISTANCE AND ALLELIC VARIATION IN THE PLASMODIUM FALCIPARUM MULTIPLE DRUG RESISTANCE 1 GENE AND THE CHLOROQUINE RESISTANCE TRANSPORTER GENE IN ISOLATES FROM THE UPPER NILE IN SOUTHERN SUDAN

EDWIN O. OCHONG’, INGRID V. F. VAN DEN BROEK, KEES KEUS, AND ALEXIS NZILA
Kenya Medical Research Institute, Wellcome Trust Collaborative Program, Médecins sans Frontières-Holland, South Sudan Section, Nairobi, Kenya; Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool, United Kingdom

 

ABSTRACT

Amodiaquine, a 4-aminoquinoline compound, is being considered as an alternative to chloroquine and pyrimethamine/sulfadoxine where resistance in Plasmodium falciparum to both drugs has been selected. Although amodiaquine is more potent than chloroquine, its effectiveness is reduced in areas where chloroquine resistance is high. We report an association of the P. falciparum chloroquine resistance transporter (pfcrt) gene and the P. falciparum multiple drug resistance 1 (pfmdr1) gene, two chloroquine resistance markers, with chloroquine and amodiaquine efficacy in vivo in southern Sudan. The data show that the allele of the pfcrt gene with a lysine to threonine change at codon 76 is strongly associated with both chloroquine and amodiaquine resistance. No such association was observed with the pfmdr1 gene.

Received February 10, 2003. Accepted for publication May 12, 2003.

Acknowledgments: We thank the malaria laboratory staff and clinic workers in Lankien, Sudan for their unremitting assistance in the project, as well as the local authorities for their cooperation, and the Nuer community in southern Sudan for participation in the study. We also thank the staff of the Médecins sans Frontières-Holland South Sudan Section and the Médecins sans Frontières-Holland headquarters in Amsterdam for advice, and Professor C. Sibley for advice during the PCR/genotyping studies.

Financial support: This work was supported by the National Institutes of Health (Fogarty International grant TW 01186) and the Wellcome Trust of Great Britain (grant no. 056769). Alexis Nzila was supported by the Wellcome Trust.

Authors’ addresses: Edwin O. Ochong’, Kenya Medical Research Institute, Wellcome Trust Collaborative Program, PO Box 43640, 00100 GPO, Nairobi, Kenya. Ingrid. V.F. van den Broek and Kees Keus, Médecins sans Frontières-Holland, South Sudan Section, PO Box 4064, Nairobi, Kenya. Alexis Nzila, Kenya Medical Research Institute, Wellcome Trust Collaborative Program, PO Box 43640, 00100 GPO, Nairobi, Kenya and Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool L69 3BX, United Kingdom, Telephone: 254-2-271-0672, Fax: 254-2-271-1673, E-mail: anzila{at}wtnairobi.mimcom.net.




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