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Residents of malaria-endemic areas sometimes spontaneously clear Plasmodium falciparum infection without drug treatment, implying an important role for host factors such as immunity in this clearance. Host factors may also contribute to clearance of parasites resistant to a treatment drug. Chloroquine resistance is caused by point mutations in P. falciparum chloroquine resistance transporter (pfcrt) gene. We investigated the clearance of malaria parasites carrying the key chloroquine resistance-conferring PfCRT mutation K76T in patients treated with chloroquine. We found that the ability to clear these resistant parasites is strongly dependent on age (the best surrogate for protective immunity in endemic areas), suggesting that host immunity plays a critical role in the clearance of resistant P. falciparum infections. Age-adjusted comparison of subjects able to clear resistant parasites and those unable to do so provides a new phenotype for identifying host immune and genetic factors responsible for protective immunity against malaria.
Received November 4, 2002. Accepted for publication May 29, 2003.
Acknowledgments: We thank the following individuals for their contribution to this work: Chiaka Diakité, Robert Gwadz, Richard Sakai, Akouni Dougnon, Ibrahim Ouologuem, Idrissa Cisse, Dramane Coulibaly, Fassoro Camara, Drissa Camara, and Gana Camara; the directors of the Bandiagara and Mopti Health Centers and Mopti Regional Malaria Control Program; the Bandiagara Traditional Healers Association; and the residents of Mopti, Bandiagara, and Kolle.
Financial support: This study was supported by contract no. N01-AI-85346 from the National Institutes of Health (NIH), the UNDP/ World Bank/World Health Organization TDR/Multilateral Initiative on Malaria grant no. 980152, and by the U.S. Agency for International Development (USAID) through its Health and Human Resources Analysis for Africa Program and direct support from the USAID Mission, Bamako for development of the Malaria Research and Training Center. Abdoulaye A. Djimdé is supported by an NIH Research Fellowship and a United Nations Development Program/ World Bank/World Health Organization Special Program for Research and Training in Tropical Diseases Research Training Grant. Additional support for the group of Ogobara K. Doumbo at the Malaria Research and Training Center came from NIH grant no. 5P50AI39469 and the International Atomic Energy Agency.
Authors’ addresses: Abdoulaye A. Djimdé, Ogobara K. Doumbo, Ousmane Traoré, Ando B. Guindo, Kassoum Kayentao, Yacouba Diourté, Safiotou Niaré-Doumbo, Drissa Coulibaly, Abdoulaye K. Koné, Yacouba Cissoko, Mamadou Theketé, Bakary Fofana, Alassane Dicko, and Dapa A. Diallo, Malaria Research and Training Center, Faculty of Medicine, Pharmacy and Dentistry, University of Bamako, Point G, BP 1805, Bamako, Mali. Thomas E. Wellems, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 4, Room 126, Bethesda MD 20892. Dominic Kwiatkowski, University Department of Paediatrics, John Radcliffe Hospital, Oxford OX3 9DU and Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN, United Kingdom. Christopher V. Plowe, Malaria Section, Center for Vaccine Development, University of Maryland School of Medicine, 685 West Baltimore Street, HSF 480, Baltimore MD 21044.
Reprint requests: Christopher V. Plowe, Malaria Section, Center for Vaccine Development, University of Maryland School of Medicine, 685 West Baltimore Street, HSF 480, Baltimore MD 21044, Telephone: 1-410-706-5328, Fax: 1-410-706-6205, E-mail: cplowe{at}medicine.umaryland.edu.
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