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

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.

Received February 23, 2009. Accepted for publication July 16, 2009.

Acknowledgments: We thank Major General Rock-Kwon Kim, Commanding General, and Colonel Taikseo Nam, Chief, Health Operation Division, Armed Forces Medical Command, for their support in coordinating the hyroxychloroquine resistance study. We also thank Dr. Joel Gaydos, Armed Forces Health Surveillance Center (AFHSC), Global Emerging Infections Surveillance and Response Systems (GEIS) for his support in conducting this work.

Financial support: Funding for portions of this work was provided by the AFHSC, GEIS, Silver Spring, MD, and the National Center for Military Intelligence, Fort Detrick, MD.

^* Address correspondence to Inho Park, Chief of Professional Service, Armed Forces Seoul Hospital, Sokyuk-dong 165, Chongno-Gu, Seoul, 110-200, Republic of Korea. E-mail: park.afmc{at}gmail.com

Authors’ addresses: Sei Won Lee, Department of Internal Medicine, Armed Forces Capital Hospital, San 13-4, Yul-dong, Bundang-gu, Seongnam-si, Gyeonggi-do 463-040, Republic of Korea, Tel: 82-31-725-6037, Fax: 82-2-706-0987, E-mail: desire31{at}medimail.co.kr. Minhee Lee, Department of Internal Medicine, The Armed Forces Ildong Hospital, Hwahyeon-ri, Hwahyeon-myeon, Pocheon-si, Gyeonggi-do 487-840, Republic of Korea, Tel: 82-31-531-0803, Fax: 82-31-532-0804. Dae Dong Lee, Department of Laboratory Medicine, The Armed Forces Yangju Hospitial, 49-1 Yongam-ri, Eunhyun-myon, Yangju 482-863, Republic of Korea, Tel: 82-31-863-1319, Fax: 82-31-863-6465. Changsoo Kim, Department of Preventive Medicine, Yonsei University College of Medicine, 250 Seongsanro, Seodaemungu, Seoul 120-752, Republic of Korea, Tel: 82-2-2228-1880, Fax: 82-2-392-8133. Yeon-Joo Kim, Division of Malaria and Parasitic Diseases, Korea Centers for Disease Control and Prevention, Tongil-ro 194, Eunpyung-gu, Seoul 122-701, Republic of Korea, Tel: 82-2-380-2941, Fax: 82-2-380-1560. Jung-Yeon Kim, Division of Malaria and Parasitic Diseases, National Institute of Health, Korea Centers for Diseases Control and Prevention, Tong-Il Lo 194, Eun-pyeong Gu, Seoul 122-701, Republic of Korea, Tel: 82-2-380-2183, Fax: 82-2-380-1560. Michael D. Green and Henry Nettey, Center for Disease Control and Prevention, 1600 Clifton Road, Mailstop F12, Atlanta, GA 30333, Tel: 770-488-4039, Fax: 770-488-4108. Terry A. Klein, Force Health Protection and Preventive Medicine, 65th Medical Brigade, USAMEDDAC-Korea, Unit 15281, APO AP 96205-5281 USA, Tel: 82-2-7916-3025, Fax: 82-2-7916-3028. Heung Chul Kim, 5th Medical Detachment, 168th Multifunctional Medical Battalion, 65th Medical Brigade, Unit 15247, APO AP 96205-5247 USA, Tel: 82-2-7915-1500, Fax: 82-2-7915-4920. Dong Hoon Ko, Department of Internal Medicine, Armed Forces Capital Hospital, San 13-4, Yul-dong, Bundang-gu, Seongnam-si, Gyeonggi-do 463-040, Republic of Korea, Tel: 82-31-725-6291, Fax: 82-31-706-0987. Hyungsuk Kim, Department of Clinical Pathology, Armed Forces Byuck Je Hospital, Byuck Je Dong, Deckyang-gu Goyang 412-779, Republic of Korea, Tel: 82-31-981-1787, Fax: 82-31-964-9902. Inho Park, Chief of Professional Service, Armed Forces Seoul Hospital, Sokyuk-dong 165, Chongno-Gu, Seoul, 110-200, Republic of Korea, Tel: 82-2-397-3710, Fax: 82-2-397-3999.