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CLEARANCE OF DRUG-RESISTANT PARASITES AS A MODEL FOR PROTECTIVE IMMUNITY IN PLASMODIUM FALCIPARUM MALARIA

ABDOULAYE A. DJIMDÉBandiagara Malaria Project, Malaria Research and Training Center, Department of Epidemiology of Parasitic Diseases, and Department of Hematology, Faculty of Medicine, Pharmacy and Dentistry, University of Bamako, Bamako, Mali; Wellcome Trust Centre for Human Genetics, Oxford University, Oxford, United Kingdom; Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland; Malaria Section, Center for Vaccine Development, University of Maryland, Baltimore, Maryland

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OGOBARA K. DOUMBOBandiagara Malaria Project, Malaria Research and Training Center, Department of Epidemiology of Parasitic Diseases, and Department of Hematology, Faculty of Medicine, Pharmacy and Dentistry, University of Bamako, Bamako, Mali; Wellcome Trust Centre for Human Genetics, Oxford University, Oxford, United Kingdom; Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland; Malaria Section, Center for Vaccine Development, University of Maryland, Baltimore, Maryland

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OUSMANE TRAOREBandiagara Malaria Project, Malaria Research and Training Center, Department of Epidemiology of Parasitic Diseases, and Department of Hematology, Faculty of Medicine, Pharmacy and Dentistry, University of Bamako, Bamako, Mali; Wellcome Trust Centre for Human Genetics, Oxford University, Oxford, United Kingdom; Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland; Malaria Section, Center for Vaccine Development, University of Maryland, Baltimore, Maryland

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ANDO B. GUINDOBandiagara Malaria Project, Malaria Research and Training Center, Department of Epidemiology of Parasitic Diseases, and Department of Hematology, Faculty of Medicine, Pharmacy and Dentistry, University of Bamako, Bamako, Mali; Wellcome Trust Centre for Human Genetics, Oxford University, Oxford, United Kingdom; Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland; Malaria Section, Center for Vaccine Development, University of Maryland, Baltimore, Maryland

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KASSOUM KAYENTAOBandiagara Malaria Project, Malaria Research and Training Center, Department of Epidemiology of Parasitic Diseases, and Department of Hematology, Faculty of Medicine, Pharmacy and Dentistry, University of Bamako, Bamako, Mali; Wellcome Trust Centre for Human Genetics, Oxford University, Oxford, United Kingdom; Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland; Malaria Section, Center for Vaccine Development, University of Maryland, Baltimore, Maryland

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YACOUBA DIOURTEBandiagara Malaria Project, Malaria Research and Training Center, Department of Epidemiology of Parasitic Diseases, and Department of Hematology, Faculty of Medicine, Pharmacy and Dentistry, University of Bamako, Bamako, Mali; Wellcome Trust Centre for Human Genetics, Oxford University, Oxford, United Kingdom; Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland; Malaria Section, Center for Vaccine Development, University of Maryland, Baltimore, Maryland

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SAFIATOU NIARE-DOUMBOBandiagara Malaria Project, Malaria Research and Training Center, Department of Epidemiology of Parasitic Diseases, and Department of Hematology, Faculty of Medicine, Pharmacy and Dentistry, University of Bamako, Bamako, Mali; Wellcome Trust Centre for Human Genetics, Oxford University, Oxford, United Kingdom; Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland; Malaria Section, Center for Vaccine Development, University of Maryland, Baltimore, Maryland

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DRISSA COULIBALYBandiagara Malaria Project, Malaria Research and Training Center, Department of Epidemiology of Parasitic Diseases, and Department of Hematology, Faculty of Medicine, Pharmacy and Dentistry, University of Bamako, Bamako, Mali; Wellcome Trust Centre for Human Genetics, Oxford University, Oxford, United Kingdom; Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland; Malaria Section, Center for Vaccine Development, University of Maryland, Baltimore, Maryland

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ABDOULAYE K. KONEBandiagara Malaria Project, Malaria Research and Training Center, Department of Epidemiology of Parasitic Diseases, and Department of Hematology, Faculty of Medicine, Pharmacy and Dentistry, University of Bamako, Bamako, Mali; Wellcome Trust Centre for Human Genetics, Oxford University, Oxford, United Kingdom; Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland; Malaria Section, Center for Vaccine Development, University of Maryland, Baltimore, Maryland

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YACOUBA CISSOKOBandiagara Malaria Project, Malaria Research and Training Center, Department of Epidemiology of Parasitic Diseases, and Department of Hematology, Faculty of Medicine, Pharmacy and Dentistry, University of Bamako, Bamako, Mali; Wellcome Trust Centre for Human Genetics, Oxford University, Oxford, United Kingdom; Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland; Malaria Section, Center for Vaccine Development, University of Maryland, Baltimore, Maryland

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MAMADOU TEKETEBandiagara Malaria Project, Malaria Research and Training Center, Department of Epidemiology of Parasitic Diseases, and Department of Hematology, Faculty of Medicine, Pharmacy and Dentistry, University of Bamako, Bamako, Mali; Wellcome Trust Centre for Human Genetics, Oxford University, Oxford, United Kingdom; Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland; Malaria Section, Center for Vaccine Development, University of Maryland, Baltimore, Maryland

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BAKARY FOFANABandiagara Malaria Project, Malaria Research and Training Center, Department of Epidemiology of Parasitic Diseases, and Department of Hematology, Faculty of Medicine, Pharmacy and Dentistry, University of Bamako, Bamako, Mali; Wellcome Trust Centre for Human Genetics, Oxford University, Oxford, United Kingdom; Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland; Malaria Section, Center for Vaccine Development, University of Maryland, Baltimore, Maryland

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ALASSANE DICKOBandiagara Malaria Project, Malaria Research and Training Center, Department of Epidemiology of Parasitic Diseases, and Department of Hematology, Faculty of Medicine, Pharmacy and Dentistry, University of Bamako, Bamako, Mali; Wellcome Trust Centre for Human Genetics, Oxford University, Oxford, United Kingdom; Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland; Malaria Section, Center for Vaccine Development, University of Maryland, Baltimore, Maryland

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DAPA A. DIALLOBandiagara Malaria Project, Malaria Research and Training Center, Department of Epidemiology of Parasitic Diseases, and Department of Hematology, Faculty of Medicine, Pharmacy and Dentistry, University of Bamako, Bamako, Mali; Wellcome Trust Centre for Human Genetics, Oxford University, Oxford, United Kingdom; Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland; Malaria Section, Center for Vaccine Development, University of Maryland, Baltimore, Maryland

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THOMAS E. WELLEMSBandiagara Malaria Project, Malaria Research and Training Center, Department of Epidemiology of Parasitic Diseases, and Department of Hematology, Faculty of Medicine, Pharmacy and Dentistry, University of Bamako, Bamako, Mali; Wellcome Trust Centre for Human Genetics, Oxford University, Oxford, United Kingdom; Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland; Malaria Section, Center for Vaccine Development, University of Maryland, Baltimore, Maryland

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DOMINIC KWIATKOWSKIBandiagara Malaria Project, Malaria Research and Training Center, Department of Epidemiology of Parasitic Diseases, and Department of Hematology, Faculty of Medicine, Pharmacy and Dentistry, University of Bamako, Bamako, Mali; Wellcome Trust Centre for Human Genetics, Oxford University, Oxford, United Kingdom; Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland; Malaria Section, Center for Vaccine Development, University of Maryland, Baltimore, Maryland

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CHRISTOPHER V. PLOWEBandiagara Malaria Project, Malaria Research and Training Center, Department of Epidemiology of Parasitic Diseases, and Department of Hematology, Faculty of Medicine, Pharmacy and Dentistry, University of Bamako, Bamako, Mali; Wellcome Trust Centre for Human Genetics, Oxford University, Oxford, United Kingdom; Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland; Malaria Section, Center for Vaccine Development, University of Maryland, Baltimore, Maryland

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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.

Author Notes

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@medicine.umaryland.edu.
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