Doxycycline for Malaria Chemoprophylaxis and Treatment: Report from the CDC Expert Meeting on Malaria Chemoprophylaxis

Kathrine R. Tan Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia; Walter Reed Army Institute for Research, Silver Spring, Maryland

Search for other papers by Kathrine R. Tan in
Current site
Google Scholar
PubMed
Close
,
Alan J. Magill Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia; Walter Reed Army Institute for Research, Silver Spring, Maryland

Search for other papers by Alan J. Magill in
Current site
Google Scholar
PubMed
Close
,
Monica E. Parise Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia; Walter Reed Army Institute for Research, Silver Spring, Maryland

Search for other papers by Monica E. Parise in
Current site
Google Scholar
PubMed
Close
, and
Paul M. Arguin Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia; Walter Reed Army Institute for Research, Silver Spring, Maryland

Search for other papers by Paul M. Arguin in
Current site
Google Scholar
PubMed
Close
Restricted access

Doxycycline, a synthetically derived tetracycline, is a partially efficacious causal prophylactic (liver stage of Plasmodium) drug and a slow acting blood schizontocidal agent highly effective for the prevention of malaria. When used in conjunction with a fast acting schizontocidal agent, it is also highly effective for malaria treatment. Doxycycline is especially useful as a prophylaxis in areas with chloroquine and multidrug-resistant Plasmodium falciparum malaria. Although not recommended for pregnant women and children < 8 years of age, severe adverse events are rarely reported for doxycycline. This report examines the evidence behind current recommendations for the use of doxycycline for malaria and summarizes the available literature on its safety and tolerability.

Author Notes

*Address correspondence to Kathrine R. Tan, Malaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, 4770 Buford Hwy MS F-22, Atlanta, GA 30341. E-mail: ktan@cdc.gov

Authors' addresses: Kathrine R. Tan and Paul M. Arguin, Malaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, GA, E-mails: ktan@cdc.gov and parguin@cdc.gov. Alan J. Magill, Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Silver Spring, MD, E-mail: alan.magill@us.army.mil. Monica E. Parise, Parasitic Diseases Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, GA, E-mail: mparise@cdc.gov.

  • 1.

    Centers for Disease Control and Prevention, 2009. CDC Health Information for International Travel 2010. Atlanta, GA: Elsevier.

  • 2.

    Griffith KS, Lewis LS, Mali S, Parise ME, 2007. Treatment of malaria in the United States: a systematic review. JAMA 297: 22642277.

  • 3.

    2008. Tetracyclines. McEvoy G, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, Inc.

  • 4.

    Rieckmann KH, McNamara JV, Willerson D, Kass L, Frischer J, Carson PE, 1971. Effects of tetracycline against chloroquineresistant and cloroquine-sensitive Plasmodium falcuparum. Am J Trop Med Hyg 20: 811815.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5.

    Clyde DF, DuPont HL, Hornick RB, 1971. Antimalarial effects of tetracyclines in man. J Trop Med Hyg 74: 238242.

  • 6.

    Colwell EJ, Hickman RL, Intraprasert R, Tirabutana C, 1972. Minocycline and tetracycline treatment of acute falciparum malaria in Thailand. Am J Trop Med Hyg 21: 144149.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7.

    Colwell EJ, Hickman RL, Kosakal S, 1972. Tetracycline treatment of chloroquine-resistant falciparum malaria in Thailand. JAMA 220: 684686.

  • 8.

    Willerson RK Jr, Carson PE, Frischer H, 1972. Effects of minocycline against chloroquine-resistant falciparum malaria. Am J Trop Med Hyg 21: 857862.

  • 9.

    Lacy CF, Armstrong LL, Goldmann MP, Leonard LL, 2006. Lexi Comp's Drug Information Handbook. Hudson, OH: Lexi Comp.

  • 10.

    Andersen SL, Oloo AJ, Gordon DM, Ragama OB, Aleman GM, Berman JD, Tang DB, Dunne MW, Shanks GD, 1998. Successful double-blinded, randomized, placebo-controlled field trial of azithromycin and doxycycline as prophylaxis for malaria in western Kenya. Clin Infect Dis 26: 146150.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11.

    Weiss WR, Oloo AJ, Johnson A, Koech D, Hoffman SL, 1995. Daily primaquine is effective for prophylaxis against falciparum malaria in Kenya: comparison with mefloquine, doxycycline, and chloroquine plus proguanil. J Infect Dis 171: 15691575.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12.

    Baudon D, Martet G, Pascal B, Bernard J, Keundjian A, Laroche R, 1999. Efficacy of daily antimalarial chemoprophylaxis in tropical Africa using either doxycycline or chloroquine-proguanil; a study conducted in 1996 in the French Army. Trans R Soc Trop Med Hyg 93: 302303.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13.

    Ohrt C, Richie TL, Widjaja H, Shanks GD, Fitriadi J, Fryauff DJ, Handschin J, Tang D, Sandjaja B, Tjitra E, Hadiarso L, Watt G, Wignall FS, 1997. Mefloquine compared with doxycycline for the prophylaxis of malaria in Indonesian soldiers. A randomized, double-blind, placebo-controlled trial. Ann Intern Med 126: 963972.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14.

    Pang L, Limsomwong N, Singharaj P, 1988. Prophylactic treatment of vivax and falciparum malaria with low-dose doxycycline. J Infect Dis 158: 11241127.

  • 15.

    Pang LW, Limsomwong N, Boudreau EF, Singharaj P, 1987. Doxycycline prophylaxis for falciparum malaria. Lancet 1: 11611164.

  • 16.

    Rieckmann KH, Yeo AE, Davis DR, Hutton DC, Wheatley PF, Simpson R, 1993. Recent military experience with malaria chemoprophylaxis. Med J Aust 158: 446449

  • 17.

    Watanasook C, Singharaj P, Suriyamongkol V, Karwacki JJ, Shanks D, Phintuyothin P, Pilungkasa S, Wasuwat P, 1989. Malaria prophylaxis with doxycycline in soldiers deployed to the Thai-Kampuchean border. Southeast Asian J Trop Med Public Health 20: 6164.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18.

    Taylor WR, Richie TL, Fryauff DJ, Picarima H, Ohrt C, Tang D, Braitman D, Murphy GS, Widjaja H, Tjitra E, Ganjar A, Jones TR, Basri H, Berman J, 1999. Malaria prophylaxis using azithromycin: a double-blind, placebo-controlled trial in Irian Jaya, Indonesia. Clin Infect Dis 28: 7481.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19.

    Sanchez JL, DeFraites RF, Sharp TW, Hanson RK, 1993. Mefloquine or doxycycline prophylaxis in US troops in Somalia. Lancet 341: 10211022.

  • 20.

    Shamiss A, Atar E, Zohar L, Cain Y, 1996. Mefloquine versus doxycycline for malaria prophylaxis in intermittent exposure of Israeli Air Force aircrew in Rwanda. Aviat Space Environ Med 67: 872873.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21.

    Shanks GD, Roessler P, Edstein MD, Rieckmann KH, 1995. Doxycycline for malaria prophylaxis in Australian soldiers deployed to United Nations missions in Somalia and Cambodia. Mil Med 160: 443445.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22.

    Shanks GD, Barnett A, Edstein MD, Rieckmann KH, 1995. Effectiveness of doxycycline combined with primaquine for malaria prophylaxis. Med J Aust 162: 306307, 309–310.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23.

    Shmuklarsky MJ, Boudreau EF, Pang LW, Smith JI, Schneider I, Fleckenstein L, Abdelrahim MM, Canfield CJ, Schuster B, 1994. Failure of doxycycline as a causal prophylactic agent against Plasmodium falciparum malaria in healthy nonimmune volunteers. Ann Intern Med 120: 294299.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24.

    Willerson D, Rieckmann KH, Carson PE, Frischer H, 1972. Effects of minocycline against chloroquine-resistant falciparum malaria. Am J Trop Med Hyg 21: 857862.

  • 25.

    Clyde DF, 1974. Treatment of drug-resistant malaria in man. Bull World Health Organ 50: 243249.

  • 26.

    Taylor WR, Widjaja H, Richie TL, Basri H, Ohrt C, Tjitra Taufik E, Jones TR, Kain KC, Hoffman SL, 2001. Chloroquine/doxycycline combination versus chloroquine alone, and doxycycline alone for the treatment of Plasmodium falciparum and Plasmodium vivax malaria in northeastern Irian Jaya, Indonesia. Am J Trop Med Hyg 64: 223228.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 27.

    Ponnampalam JT, 1981. Doxycycline in the treatment of falciparum malaria among aborigine children in West Malaysia. Trans R Soc Trop Med Hyg 75: 372377.

  • 28.

    Alecrim MG, Lacerda MV, Mourao MP, Alecrim WD, Padilha A, Cardoso BS, Boulos M, 2006. Successful treatment of Plasmodium falciparum malaria with a six-doxe regimen of artemether-lumefantrine versus quinine-doxycycline in the Western Amazon regioni of Brazil. Am J Trop Med Hyg 74: 2025.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 29.

    Ejaz A, Haqnawaz Z, Hussain Z, Butt R, Awan ZI, Bux H, 2007. Treatment of uncomplicated Plasmodium falciparum malaria with quinine-doxycycline combination therapy. J Pak Med Assoc 57: 502505.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 30.

    White NJ, 1997. Assessment of the pharmacodynamic properties of antimalarial drugs in vivo. Antimicrob Agents Chemother 41: 14131422.

  • 31.

    Handfield-Jones RP, 1949. Chloroquine, proguanil, mepacrine and quinine in the treatment of malaria caused by Plasmodium falciparum. Ann Trop Med Parasitol 43: 345348.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 32.

    Watt G, Loesuttivibool L, Shanks GD, Boundreau EF, Brown AE, Pavanand K, Webster HK, Wechgritaya S, 1992. Quinine with tetracycline for the treatment of drug-resistant falciparum malaria in Thailand. Am J Trop Med Hyg 47: 108111.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 33.

    Reacher M, Campbell CC, Freeman J, Doberstyn EB, Brandling-Bennett AD, 1981. Drug therapy for Plasmodium falciparum malaria resistant to pyrimethamine-sulfadoxine (Fansidar). A study of alternate regimens in Eastern Thailand, 1980. Lancet 2: 10661069.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 34.

    Looareesuwan S, Vanijanonta S, Viravan C, Wilairatana P, Charoenlarp P, Lasserre R, Canfield C, Kyle DE, Webster HK, 1994. Randomized trial of mefloquine-tetracycline and quinine-tetracycline for acute uncomplicated falciparum malaria. Acta Trop 57: 4753.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 35.

    Karbwang J, Molunto P, Bunnag D, Harinasuta T, 1991. Plasma quinine levels in patients with falciparum malaria when given alone or in combination with tetracycline with or without primaquine. Southeast Asian J Trop Med Public Health 22: 7276.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 36.

    2008. Vibramycin. Physicians' Desk Reference. Montvale, NJ: Thomson PDR.

  • 37.

    Maibach H, 1991. Second-generation tetracyclines, a dermatologic overview: clinical uses and pharmacology. Cutis 48: 411417.

  • 38.

    Leyden JJ, 1985. Absorption of minocycline hydrochloride and tetracycline hydrochloride. Effect of food, milk, and iron. J Am Acad Dermatol 12: 308312.

  • 39.

    Meyer FP, Specht H, Quednow B, Walther H, 1989. Influence of milk on the bioavailability of doxycycline–new aspects. Infection 17: 245246.

  • 40.

    2002. Product Information: vibramycin brand of doxycycline monohydrate. New York: Pfizer.

  • 41.

    2003. Tetracyclines (Systemic). Group UDE, ed. USP DI Drug Information for the Health Care Provider. Greenwood Village, CO: Micromedex, Inc.

  • 42.

    Cunha BA, Comer JB, Jonas M, 1982. The tetracyclines. Med Clin North Am 66: 293302.

  • 43.

    Whelton A, Schach von Wittenau M, Twomey TM, Walker WG, Bianchine JR, 1974. Doxycycline pharmacokinetics in the absence of renal function. Kidney Int 5: 365371.

  • 44.

    Binh V, Chinh N, Thanh N, Cuong B, Quang N, Dai B, Travers T, Edstein M, 2009. Sex affects the steady-state pharmacokinetics of primaquine but not doxycycline in healthy subjects. Am J Trop Med Hyg 81: 747753.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 45.

    Marussig M, Motard A, Renia L, Baccam D, Lebras J, Charmot G, Mazier D, 1993. Activity of doxycycline against preerythrocytic malaria. J Infect Dis 168: 16031604.

  • 46.

    Dahl EL, Shock JL, Shenai BR, Gut J, DeRisi JL, Rosenthal PJ, 2006. Tetracyclines specifically target the apicoplast of the malaria parasite P. falciparum. Antimicrob Agents Chemother 50: 31243131.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 47.

    Budimulja AS, Syafruddin Tapchaisri P, Wilairat P, Marzuki S, 1997. The sensitivity of Plasmodium protein synthesis to prokaryotic ribosomal inhibitors. Mol Biochem Parasitol 84: 137141.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 48.

    Hill DR, Baird JK, Parise ME, Lewis LS, Ryan ET, Magill AJ, 2006. Primaquine: report from CDC expert meeting on malaria chemoprophylaxis I. Am J Trop Med Hyg 75: 402415.

  • 49.

    Pukrittayakamee S, Imwong M, Singhasivanon P, Stepniewska K, Day N, White N, 2008. Effects of different antimalarial drugs on gametocyte carriage in P. vivax malaria. Am J Trop Med Hyg 79: 378384.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 50.

    Wein S, Maynadier M, Tran Van Ba C, Cerdan R, Peyrottes S, Fraisse L, Vial H, 2010. Reliability of antimalarial sensitivity tests depends on drug mechanisms of action. J Clin Microbiol 48: 16511660.

    • PubMed
    • Search Google Scholar