Volume 81, Issue 4
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645


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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  1. Coatney GR, 1963. Pitfalls in a discovery: the chronicle of chloroquine. Am J Trop Med Hyg 12: 121–128. [Google Scholar]
  2. Organization WH, 2001. The Use of Antimalarial Drugs. Report of a WHO Informal Consultation. Report WHO/CDS/RBM/2001.33. Geneva: Switzerland.
  3. Baird JK, Basri H, Purnomo, Bangs MJ, Subianto B, Patchen LC, Hoffman SL, 1991. Resistance to chloroquine by Plasmodium vivax in Irian Jaya, Indonesia. Am J Trop Med Hyg 44: 547–552. [Google Scholar]
  4. Rieckmann KH, Davis DR, Hutton DC, 1989. Plasmodium vivax resistance to chloroquine? Lancet 2: 1183–1184. [Google Scholar]
  5. Oh MD, Shin H, Shin D, Kim U, Lee S, Kim N, Choi MH, Chai JY, Choe K, 2001. Clinical features of vivax malaria. Am J Trop Med Hyg 65: 143–146. [Google Scholar]
  6. Feighner BH, Pak SI, Novakoski WL, Kelsey LL, Strickman D, 1998. Reemergence of Plasmodium vivax malaria in the republic of Korea. Emerg Infect Dis 4: 295–297. [Google Scholar]
  7. Park JW, Klein TA, Lee HC, Pacha LA, Ryu SH, Yeom JS, Moon SH, Kim TS, Chai JY, Oh MD, Choe KW, 2003. Vivax malaria: a continuing health threat to the Republic of Korea. Am J Trop Med Hyg 69: 159–167. [Google Scholar]
  8. Kim HC, Pacha LA, Lee WJ, Lee JK, Gaydos JC, Sames WJ, Lee HCS, Bradley K, Jeung GG, Tobler SK, Klein TA, 2009. Malaria in the Republic of Korea, 1993–2007. Variable related to reemergence and persistence of Plasmodium vivax among Korean populations and US Forces Korea. Mil Med 174: (in press). [Google Scholar]
  9. Klein TA, Pacha LA, Lee HCS, Kim HC, Lee WJ, Lee JK, Jeung GG, Sames WJ, Gaydos JC, 2009. Plasmodium vivax malaria among U.S. Forces Korea in the Republic of Korea, 1993–2007. Mil Med 174: 412–418. [Google Scholar]
  10. Yeom JS, Ryu SH, Oh S, Choi DH, Song KJ, Oh YH, Lee JH, Kim YA, Ahn SY, Yang HY, Cha JE, Park JW, 2005. Evaluation of anti-malarial effects of mass chemoprophylaxis in the Republic of Korea army. J Korean Med Sci 20: 707–712. [Google Scholar]
  11. Berliner RW, Earle DP, Taggart JV, Zubrod CG, Welch WJ, Conan NJ, Bauman E, Scudder ST, Shannon JA, 1948. Studies on the chemotherapy of the human malarias. VI. The physiological disposition, antimalarial activity, and toxicity of several derivatives of 4-aminoquinoline. J Clin Invest 27: 98–107. [Google Scholar]
  12. Baird JK, 2004. Chloroquine resistance in Plasmodium vivax. Antimicrob Agents Chemother 48: 4075–4083. [Google Scholar]
  13. Han ET, Lee DH, Park KD, Seok WS, Kim YS, Tsuboi T, Shin EH, Chai JY, 2006. Reemerging vivax malaria: changing patterns of annual incidence and control programs in the Republic of Korea. Korean J Parasitol 44: 285–294. [Google Scholar]
  14. Schuurkamp GJ, Spicer PE, Kereu RK, Bulungol PK, Rieckmann KH, 1992. Chloroquine-resistant Plasmodium vivax in Papua New Guinea. Trans R Soc Trop Med Hyg 86: 121–122. [Google Scholar]
  15. Bergqvist Y, Domeij-Nyberg B, 1983. Distribution of chloroquine and its metabolite desethyl-chloroquine in human blood cells and its implication for the quantitative determination of these compounds in serum and plasma. J Chromatogr 272: 137–148. [Google Scholar]
  16. Gustafsson LL, Walker O, Alvan G, Beermann B, Estevez F, Gleisner L, Lindstrom B, Sjoqvist F, 1983. Disposition of chloroquine in man after single intravenous and oral doses. Br J Clin Pharmacol 15: 471–479. [Google Scholar]
  17. Taylor WR, Doan HN, Nguyen DT, Tran TU, Fryauff DJ, Gomez-Saladin E, Kain KC, Le DC, Baird JK, 2000. Assessing drug sensitivity of Plasmodium vivax to halofantrine or choroquine in southern, central Vietnam using an extended 28-day in vivo test and polymerase chain reaction genotyping. Am J Trop Med Hyg 62: 693–697. [Google Scholar]
  18. Murphy GS, Basri H, Purnomo, Andersen EM, Bangs MJ, Mount DL, Gorden J, Lal AA, Purwokusumo AR, Harjosuwarno S, 1993. Vivax malaria resistant to treatment and prophylaxis with chloroquine. Lancet 341: 96–100. [Google Scholar]
  19. Baird JK, Leksana B, Masbar S, Suradi, Sutanihardja MA, Fryauff DJ, Subianto B, 1997. Whole blood chloroquine concentrations with Plasmodium vivax infection in Irian Jaya, Indonesia. Am J Trop Med Hyg 56: 618–620. [Google Scholar]
  20. Baird JK, Fryauff DJ, Basri H, Bangs MJ, Subianto B, Wiady I, Purnomo, Leksana B, Masbar S, Richie TL 1995. Primaquine for prophylaxis against malaria among nonimmune transmigrants in Irian Jaya, Indonesia. Am J Trop Med Hyg 52: 479–484. [Google Scholar]
  21. Fryauff DJ, Baird JK, Basri H, Sumawinata I, Purnomo, Richie TL, Ohrt CK, Mouzin E, Church CJ, Richards AL, 1995. Randomised placebo-controlled trial of primaquine for prophylaxis of falciparum and vivax malaria. Lancet 346: 1190–1193. [Google Scholar]
  22. Sumawinata IW, Bernadeta, Leksana B, Sutamihardja A, Purnomo, Subianto B, Sekartuti, Fryauff DJ, Baird JK, 2003. Very high risk of therapeutic failure with chloroquine for uncomplicated Plasmodium falciparum and P. vivax malaria in Indonesian Papua. Am J Trop Med Hyg 68: 416–420. [Google Scholar]
  23. Baird JK, Wiady I, Fryauff DJ, Sutanihardja MA, Leksana B, Widjaya H, Kysdarmanto, Subianto B, 1997. In vivo resistance to chloroquine by Plasmodium vivax and Plasmodium falciparum at Nabire, Irian Jaya, Indonesia. Am J Trop Med Hyg 56: 627–631. [Google Scholar]
  24. Hugosson E, Tarimo D, Troye-Blomberg M, Montgomery SM, Premji Z, Bjorkman A, 2003. Antipyretic, parasitologic, and immunologic effects of combining sulfadoxine/pyrimethamine with chloroquine or paracetamol for treating uncomplicated Plasmodium falciparum malaria. Am J Trop Med Hyg 69: 366–371. [Google Scholar]
  25. Baird JK, Leksana B, Masbar S, Fryauff DJ, Sutanihardja MA, Suradi, Wignall FS, Hoffman SL, 1997. Diagnosis of resistance to chloroquine by Plasmodium vivax: timing of recurrence and whole blood chloroquine levels. Am J Trop Med Hyg 56: 621–626. [Google Scholar]
  26. Lim CS, Kim YK, Lee KN, Kim MJ, Kim KH, Kim DS, Strickman D, 1999. Response to chloroquine of Plasmodium vivax among South Korean soldiers. Ann Trop Med Parasitol 93: 565–568. [Google Scholar]
  27. Goller JL, Jolley D, Ringwald P, Biggs BA, 2007. Regional differences in the response of Plasmodium vivax malaria to primaquine as anti-relapse therapy. Am J Trop Med Hyg 76: 203–207. [Google Scholar]
  28. Signorini L, Matteelli A, Castelnuovo F, Castelli F, Oladeji O, Carosi G, 1996. Short report: primaquine-tolerant Plasmodium vivax in an Italian traveler from Guatemala. Am J Trop Med Hyg 55: 472–473. [Google Scholar]
  29. Rombo L, Bjorkman A, Sego E, Ericsson O, 1986. Whole blood concentrations of chloroquine and desethylchloroquine during and after treatment of adult patients infected with Plasmodium vivax, P. ovale, or P. malariae. Trans R Soc Trop Med Hyg 80: 763–766. [Google Scholar]
  30. Touze JE, Debonne JM, Boutin JP, 2007. Current situation and future perspectives for malaria prophylaxis among travellers and military personnel. Bull Acad Natl Med 191: 1293–1302, discussion 1302–1303. [Google Scholar]
  31. Sonmez A, Harlak A, Kilic S, Polat Z, Hayat L, Keskin O, Dogru T, Yilmaz MI, Acikel CH, Kocar IH, 2005. The efficacy and tolerability of doxycycline and mefloquine in malaria prophylaxis of the ISAF troops in Afghanistan. J Infect 51: 253–258. [Google Scholar]
  32. Kofoed K, Petersen E, 2003. The efficacy of chemoprophylaxis against malaria with chloroquine plus proguanil, mefloquine, and atovaquone plus proguanil in travelers from Denmark. J Travel Med 10: 150–154. [Google Scholar]
  33. Kain KC, Harrington MA, Tennyson S, Keystone JS, 1998. Imported malaria: prospective analysis of problems in diagnosis and management. Clin Infect Dis 27: 142–149. [Google Scholar]
  34. Rombo L, Bergqvist Y, Hellgren U, 1987. Chloroquine and desethylchloroquine concentrations during regular long-term malaria prophylaxis. Bull World Health Organ 65: 879–883. [Google Scholar]
  35. Baird JK, Basri H, Subianto B, Fryauff DJ, McElroy PD, Leksana B, Richie TL, Masbar S, Wignall FS, Hoffman SL, 1995. Treatment of chloroquine-resistant Plasmodium vivax with chloroquine and primaquine or halofantrine. J Infect Dis 171: 1678–1682. [Google Scholar]

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  • Received : 23 Feb 2009
  • Accepted : 16 Jul 2009

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