Biological Resistance of Hydroxychloroquine for Plasmodium vivax Malaria in the Republic of Korea

Sei Won Lee Department of Internal Medicine, Armed Forces Capital Hospital, Seongnam, Republic of Korea; Department of Internal Medicine, The Armed Forces Ildong Hospital, Pocheon, Republic of Korea; Department of Laboratory Medicine, The Armed Forces Yangju Hospitial, Yangju, Republic of Korea; Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Division of Malaria and Parasitic Diseases, Korea Centers for Disease Control and Prevention, Seoul, Republic of Korea; Division of Parasite Diseases, Center for Disease Control and Prevention, Atlanta, Georgia; Force Health Protection and Preventive Medicine, 65th Medical Brigade, USAMEDDAC-Korea, Seoul, Republic of Korea; 5th Medical Detachment, 168th Multifunctional Medical Battalion, 65th Medical Brigade, Seoul, Republic of Korea; Department of Clinical Pathology, Armed Forces Byuck Je Hospital, Goyang, Republic of Korea; Chief of Professional Service, Armed Forces Seoul Hospital, Seoul, Republic of Korea

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Minhee Lee Department of Internal Medicine, Armed Forces Capital Hospital, Seongnam, Republic of Korea; Department of Internal Medicine, The Armed Forces Ildong Hospital, Pocheon, Republic of Korea; Department of Laboratory Medicine, The Armed Forces Yangju Hospitial, Yangju, Republic of Korea; Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Division of Malaria and Parasitic Diseases, Korea Centers for Disease Control and Prevention, Seoul, Republic of Korea; Division of Parasite Diseases, Center for Disease Control and Prevention, Atlanta, Georgia; Force Health Protection and Preventive Medicine, 65th Medical Brigade, USAMEDDAC-Korea, Seoul, Republic of Korea; 5th Medical Detachment, 168th Multifunctional Medical Battalion, 65th Medical Brigade, Seoul, Republic of Korea; Department of Clinical Pathology, Armed Forces Byuck Je Hospital, Goyang, Republic of Korea; Chief of Professional Service, Armed Forces Seoul Hospital, Seoul, Republic of Korea

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Dae Dong Lee Department of Internal Medicine, Armed Forces Capital Hospital, Seongnam, Republic of Korea; Department of Internal Medicine, The Armed Forces Ildong Hospital, Pocheon, Republic of Korea; Department of Laboratory Medicine, The Armed Forces Yangju Hospitial, Yangju, Republic of Korea; Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Division of Malaria and Parasitic Diseases, Korea Centers for Disease Control and Prevention, Seoul, Republic of Korea; Division of Parasite Diseases, Center for Disease Control and Prevention, Atlanta, Georgia; Force Health Protection and Preventive Medicine, 65th Medical Brigade, USAMEDDAC-Korea, Seoul, Republic of Korea; 5th Medical Detachment, 168th Multifunctional Medical Battalion, 65th Medical Brigade, Seoul, Republic of Korea; Department of Clinical Pathology, Armed Forces Byuck Je Hospital, Goyang, Republic of Korea; Chief of Professional Service, Armed Forces Seoul Hospital, Seoul, Republic of Korea

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Changsoo Kim Department of Internal Medicine, Armed Forces Capital Hospital, Seongnam, Republic of Korea; Department of Internal Medicine, The Armed Forces Ildong Hospital, Pocheon, Republic of Korea; Department of Laboratory Medicine, The Armed Forces Yangju Hospitial, Yangju, Republic of Korea; Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Division of Malaria and Parasitic Diseases, Korea Centers for Disease Control and Prevention, Seoul, Republic of Korea; Division of Parasite Diseases, Center for Disease Control and Prevention, Atlanta, Georgia; Force Health Protection and Preventive Medicine, 65th Medical Brigade, USAMEDDAC-Korea, Seoul, Republic of Korea; 5th Medical Detachment, 168th Multifunctional Medical Battalion, 65th Medical Brigade, Seoul, Republic of Korea; Department of Clinical Pathology, Armed Forces Byuck Je Hospital, Goyang, Republic of Korea; Chief of Professional Service, Armed Forces Seoul Hospital, Seoul, Republic of Korea

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Yeon-Joo Kim Department of Internal Medicine, Armed Forces Capital Hospital, Seongnam, Republic of Korea; Department of Internal Medicine, The Armed Forces Ildong Hospital, Pocheon, Republic of Korea; Department of Laboratory Medicine, The Armed Forces Yangju Hospitial, Yangju, Republic of Korea; Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Division of Malaria and Parasitic Diseases, Korea Centers for Disease Control and Prevention, Seoul, Republic of Korea; Division of Parasite Diseases, Center for Disease Control and Prevention, Atlanta, Georgia; Force Health Protection and Preventive Medicine, 65th Medical Brigade, USAMEDDAC-Korea, Seoul, Republic of Korea; 5th Medical Detachment, 168th Multifunctional Medical Battalion, 65th Medical Brigade, Seoul, Republic of Korea; Department of Clinical Pathology, Armed Forces Byuck Je Hospital, Goyang, Republic of Korea; Chief of Professional Service, Armed Forces Seoul Hospital, Seoul, Republic of Korea

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Jung-Yeon Kim Department of Internal Medicine, Armed Forces Capital Hospital, Seongnam, Republic of Korea; Department of Internal Medicine, The Armed Forces Ildong Hospital, Pocheon, Republic of Korea; Department of Laboratory Medicine, The Armed Forces Yangju Hospitial, Yangju, Republic of Korea; Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Division of Malaria and Parasitic Diseases, Korea Centers for Disease Control and Prevention, Seoul, Republic of Korea; Division of Parasite Diseases, Center for Disease Control and Prevention, Atlanta, Georgia; Force Health Protection and Preventive Medicine, 65th Medical Brigade, USAMEDDAC-Korea, Seoul, Republic of Korea; 5th Medical Detachment, 168th Multifunctional Medical Battalion, 65th Medical Brigade, Seoul, Republic of Korea; Department of Clinical Pathology, Armed Forces Byuck Je Hospital, Goyang, Republic of Korea; Chief of Professional Service, Armed Forces Seoul Hospital, Seoul, Republic of Korea

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Michael D. Green Department of Internal Medicine, Armed Forces Capital Hospital, Seongnam, Republic of Korea; Department of Internal Medicine, The Armed Forces Ildong Hospital, Pocheon, Republic of Korea; Department of Laboratory Medicine, The Armed Forces Yangju Hospitial, Yangju, Republic of Korea; Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Division of Malaria and Parasitic Diseases, Korea Centers for Disease Control and Prevention, Seoul, Republic of Korea; Division of Parasite Diseases, Center for Disease Control and Prevention, Atlanta, Georgia; Force Health Protection and Preventive Medicine, 65th Medical Brigade, USAMEDDAC-Korea, Seoul, Republic of Korea; 5th Medical Detachment, 168th Multifunctional Medical Battalion, 65th Medical Brigade, Seoul, Republic of Korea; Department of Clinical Pathology, Armed Forces Byuck Je Hospital, Goyang, Republic of Korea; Chief of Professional Service, Armed Forces Seoul Hospital, Seoul, Republic of Korea

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Terry A. Klein Department of Internal Medicine, Armed Forces Capital Hospital, Seongnam, Republic of Korea; Department of Internal Medicine, The Armed Forces Ildong Hospital, Pocheon, Republic of Korea; Department of Laboratory Medicine, The Armed Forces Yangju Hospitial, Yangju, Republic of Korea; Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Division of Malaria and Parasitic Diseases, Korea Centers for Disease Control and Prevention, Seoul, Republic of Korea; Division of Parasite Diseases, Center for Disease Control and Prevention, Atlanta, Georgia; Force Health Protection and Preventive Medicine, 65th Medical Brigade, USAMEDDAC-Korea, Seoul, Republic of Korea; 5th Medical Detachment, 168th Multifunctional Medical Battalion, 65th Medical Brigade, Seoul, Republic of Korea; Department of Clinical Pathology, Armed Forces Byuck Je Hospital, Goyang, Republic of Korea; Chief of Professional Service, Armed Forces Seoul Hospital, Seoul, Republic of Korea

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Heung Chul Kim Department of Internal Medicine, Armed Forces Capital Hospital, Seongnam, Republic of Korea; Department of Internal Medicine, The Armed Forces Ildong Hospital, Pocheon, Republic of Korea; Department of Laboratory Medicine, The Armed Forces Yangju Hospitial, Yangju, Republic of Korea; Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Division of Malaria and Parasitic Diseases, Korea Centers for Disease Control and Prevention, Seoul, Republic of Korea; Division of Parasite Diseases, Center for Disease Control and Prevention, Atlanta, Georgia; Force Health Protection and Preventive Medicine, 65th Medical Brigade, USAMEDDAC-Korea, Seoul, Republic of Korea; 5th Medical Detachment, 168th Multifunctional Medical Battalion, 65th Medical Brigade, Seoul, Republic of Korea; Department of Clinical Pathology, Armed Forces Byuck Je Hospital, Goyang, Republic of Korea; Chief of Professional Service, Armed Forces Seoul Hospital, Seoul, Republic of Korea

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Henry Nettey Department of Internal Medicine, Armed Forces Capital Hospital, Seongnam, Republic of Korea; Department of Internal Medicine, The Armed Forces Ildong Hospital, Pocheon, Republic of Korea; Department of Laboratory Medicine, The Armed Forces Yangju Hospitial, Yangju, Republic of Korea; Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Division of Malaria and Parasitic Diseases, Korea Centers for Disease Control and Prevention, Seoul, Republic of Korea; Division of Parasite Diseases, Center for Disease Control and Prevention, Atlanta, Georgia; Force Health Protection and Preventive Medicine, 65th Medical Brigade, USAMEDDAC-Korea, Seoul, Republic of Korea; 5th Medical Detachment, 168th Multifunctional Medical Battalion, 65th Medical Brigade, Seoul, Republic of Korea; Department of Clinical Pathology, Armed Forces Byuck Je Hospital, Goyang, Republic of Korea; Chief of Professional Service, Armed Forces Seoul Hospital, Seoul, Republic of Korea

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Dong Hoon Ko Department of Internal Medicine, Armed Forces Capital Hospital, Seongnam, Republic of Korea; Department of Internal Medicine, The Armed Forces Ildong Hospital, Pocheon, Republic of Korea; Department of Laboratory Medicine, The Armed Forces Yangju Hospitial, Yangju, Republic of Korea; Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Division of Malaria and Parasitic Diseases, Korea Centers for Disease Control and Prevention, Seoul, Republic of Korea; Division of Parasite Diseases, Center for Disease Control and Prevention, Atlanta, Georgia; Force Health Protection and Preventive Medicine, 65th Medical Brigade, USAMEDDAC-Korea, Seoul, Republic of Korea; 5th Medical Detachment, 168th Multifunctional Medical Battalion, 65th Medical Brigade, Seoul, Republic of Korea; Department of Clinical Pathology, Armed Forces Byuck Je Hospital, Goyang, Republic of Korea; Chief of Professional Service, Armed Forces Seoul Hospital, Seoul, Republic of Korea

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Hyungsuk Kim Department of Internal Medicine, Armed Forces Capital Hospital, Seongnam, Republic of Korea; Department of Internal Medicine, The Armed Forces Ildong Hospital, Pocheon, Republic of Korea; Department of Laboratory Medicine, The Armed Forces Yangju Hospitial, Yangju, Republic of Korea; Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Division of Malaria and Parasitic Diseases, Korea Centers for Disease Control and Prevention, Seoul, Republic of Korea; Division of Parasite Diseases, Center for Disease Control and Prevention, Atlanta, Georgia; Force Health Protection and Preventive Medicine, 65th Medical Brigade, USAMEDDAC-Korea, Seoul, Republic of Korea; 5th Medical Detachment, 168th Multifunctional Medical Battalion, 65th Medical Brigade, Seoul, Republic of Korea; Department of Clinical Pathology, Armed Forces Byuck Je Hospital, Goyang, Republic of Korea; Chief of Professional Service, Armed Forces Seoul Hospital, Seoul, Republic of Korea

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Inho Park Department of Internal Medicine, Armed Forces Capital Hospital, Seongnam, Republic of Korea; Department of Internal Medicine, The Armed Forces Ildong Hospital, Pocheon, Republic of Korea; Department of Laboratory Medicine, The Armed Forces Yangju Hospitial, Yangju, Republic of Korea; Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Division of Malaria and Parasitic Diseases, Korea Centers for Disease Control and Prevention, Seoul, Republic of Korea; Division of Parasite Diseases, Center for Disease Control and Prevention, Atlanta, Georgia; Force Health Protection and Preventive Medicine, 65th Medical Brigade, USAMEDDAC-Korea, Seoul, Republic of Korea; 5th Medical Detachment, 168th Multifunctional Medical Battalion, 65th Medical Brigade, Seoul, Republic of Korea; Department of Clinical Pathology, Armed Forces Byuck Je Hospital, Goyang, Republic of Korea; Chief of Professional Service, Armed Forces Seoul Hospital, Seoul, Republic of Korea

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The Republic of Korea (ROK) Army instituted a vivax malaria chemoprophylaxis program (hydroxychloroquine [HCQ] 400 mg per week) in 1997 that was expanded to nearly 200,000 soldiers by 2007, raising concerns for the emergence of drug-resistant vivax malaria. Therefore, a study of whole blood HCQ concentrations for all malaria patients admitted to four ROK Army hospitals was conducted from June through September 2007. For all 142 vivax malaria patients enrolled, fevers returned to normal by Day 3 post-treatment and all thin blood films were negative for parasites by Day 7. Pre-treatment whole blood concentrations of HCQ for 14 patients were > 100 ng/mL. Eight of the patients were enrolled in the ROK Army chemoprophylaxis program that reported taking HCQ as directed, with the last pill taken ≥ 4 days before diagnosis. Although there was no evidence of clinical resistance, chemoprophylaxis data indicates the biological resistance or tolerance to HCQ in ROK.

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