Volume 93, Issue 3
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645



Long-term antimalarial chemoprophylaxis is currently used by deployed U.S. military personnel. Previous small, short-term efficacy studies have shown variable rates of side effects among patients taking various forms of chemoprophylaxis, though reliable safety and tolerability data on long-term use are limited. We conducted a survey of troops returning to Fort Drum, NY following a 12-month deployment to Operation Enduring Freedom, Afghanistan from 2006 to 2007. Of the 2,351 respondents, 95% reported taking at least one form of prophylaxis during their deployment, and 90% were deployed for > 10 months. Compliance with daily doxycycline was poor (60%) compared with 80% with weekly mefloquine (MQ). Adverse events (AEs) were reported by approximately 30% with both MQ and doxycycline, with 10% discontinuing doxycycline compared with 4% of MQ users. Only 6% and 31% of soldiers reported use of bed nets and skin repellents, respectively. Compliance with long-term malaria prophylaxis was poor, and there were substantial tolerability issues based on these anonymous survey results, though fewer with MQ than doxycycline. Given few long-term antimalarial chemoprophylaxis options, there is an unmet medical need for new antimalarials safe for long-term use.


Article metrics loading...

The graphs shown below represent data from March 2017
Loading full text...

Full text loading...



  1. Takafuki ET, Krikpatrick JW, Miller RN, Karwacki JJ, Kelley PW, Gray MR, McNeill KM, Timboe HL, Kane RE, Sanchez JL, , 1984. An efficacy trial of doxycycline chemoprophylaxis against leptospirosis. N Engl J Med 310: 497500.[Crossref] [Google Scholar]
  2. Pages F, Boutin JP, Meynard JB, Keundjian A, Ryfer S, Giurato L, Baudon D, , 2002. Tolerability of doxycycline monohydrate sald vs. chloroquine-proguanil in malaria prophylaxis. Trop Med Int Health 7: 919924.[Crossref] [Google Scholar]
  3. 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: 302030.[Crossref] [Google Scholar]
  4. Jarvinen A, Nykanen S, Paasiniemi L, Hirsjarvi-Lahti T, Mattila J, , 1995. Enteric coating reduces upper gastrointestinal adverse reactions to doxycycline. Clin Drug Investig 10: 323327.[Crossref] [Google Scholar]
  5. Malmborg AS, , 1984. Bioavailability of doxycycline monohydrate. A comparison with equivalent doses of doxycycline hydrochloride. Chemotherapy 30: 7680.[Crossref] [Google Scholar]
  6. Bryan JP, , 2006. Cost considerations of malaria chemoprophylaxis including use of primaquine for primary or terminal chemoprophylaxis. Am J Trop Med Hyg 75: 416420. [Google Scholar]
  7. 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 doxycline and mefloquine in malaria prophylaxis of the ISAF troops in Afghanistan. J Infect 51: 253258.[Crossref] [Google Scholar]
  8. Phillips MA, Kass RB, , 1996. User acceptability patterns for mefloquine and doxycline malaria prophylaxis. J Travel Med 3: 4045.[Crossref] [Google Scholar]
  9. Brisson M, Brisson P, , 2012. Compliance with antimalarial chemoprophylaxis in a combat zone. Am J Trop Med Hyg 86: 587590.[Crossref] [Google Scholar]
  10. Champel V, Jonville-Bera AP, Bera F, Autret E, , 1997. Esophageal involvement after tetracycline ingestion. Therapie 52: 587589. [Google Scholar]
  11. Ohrt C, Richie T, 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. Ann Intern Med 126: 963972.[Crossref] [Google Scholar]
  12. Michel R, Bardot S, Queyriaux B, Boutin JP, Touze JE, , 2010. Doxycycline-chloroquine vs. doxycycline-placebo for malaria prophylaxis in nonimmune soldiers: a double-blind randomized field trial in sub-Saharan Africa. Trans R Soc Trop Med Hyg 104: 290297.[Crossref] [Google Scholar]
  13. Tan KR, Magill AJ, Parise ME, Arquine PM, , 2011. Doxycycline for malaria chemoprophylaxis and treatment: report from the CDC expert meeting on malaria chemoprophylaxis. Am J Trop Med Hyg 84: 517531.[Crossref] [Google Scholar]
  14. Nevin RL, Pietrusiak PP, Caci JB, , 2008. Prevalence of contraindications to mefloquine use among USA military personnel deployed to Afghanistan. Malar J 7: 30.[Crossref] [Google Scholar]
  15. Kircik LH, , 2010. Doxycycline and minocycline for the management of acne: a review of efficacy and safety with emphasis on clinical implications. J Drugs Dermatol 9: 14071411. [Google Scholar]
  16. Kitchener SJ, Nasveld PE, Gregory RM, Edstein MD, , 2005. Mefloquine and doxycycline malaria prophylaxis in Australian soldiers in East Timor. Med J Aust 182: 168171. [Google Scholar]
  17. Sochantha T, Van Bortel W, Savonnaroth S, Marcotty T, Speybroeck N, Coosemans M, , 2010. Personal protection by long-lasting insecticidal hammocks against the bites of forest malaria vectors. Trop Med Int Health TM IH 15: 336341.[Crossref] [Google Scholar]
  18. Soto J, Medina F, Dember N, Berman J, , 1995. Efficacy of permethrin-impregnated uniforms in the prevention of malaria and leishmaniasis in Colombian soldiers. Clin Infect Dis 21: 599602.[Crossref] [Google Scholar]
  19. Wallace M, Sharp T, Smoak B, Iriye C, Rozmajzl P, Thornton SA, Batchelor R, Magill AJ, Lobel HO, Longer CF, Burans JP, , 1996. Malaria among United States troops in Somalia. Am J Med 100: 4955.[Crossref] [Google Scholar]
  20. Schlagenhauf P, Tschopp A, Johnson R, Nothdurft HD, Beck B, Schwartz E, Herold M, Krebs B, Veit O, Allwinn R, Steffen R, , 2003. Tolerability of malaria chemoprophylaxis in non-immune travellers to sub-Saharan Africa: multicentre, randomized, double blind, four arm study. BMJ 2003: 10781083.[Crossref] [Google Scholar]
  21. Office of the Assistant Secretary of Defense for Health Affairs, 2009. Memorandum: Policy Memorandum on the Use of Mefloquine (Lariam) in Malaria Prophylaxis. Available at: http://www.pdhealth.mil/malaria.asp. Accessed February 10, 2015. [Google Scholar]
  22. Resseguier N, Machault V, Ollivier L, Orlandi-Pradines E, Texier G, Pradines B, Gaudart J, Buguet A, Tourette-Turgis C, Rogier C, , 2010. Determinants of compliance with malaria chemoprophylaxis among French soldiers during missions in inter-tropical Africa. Malar J 9: 41.[Crossref] [Google Scholar]
  23. Faulde MK, Hoffmann R, Fazilat KM, Hoerauf A, , 2007. Malaria reemergence in northern Afghanistan. Emerg Infect Dis 13: 14021404.[Crossref] [Google Scholar]
  24. Brooker S, Leslie T, Kolaczinski K, Mohsen E, Mehboob N, Saleheen S, Khudonazarov J, Freeman T, Clements A, Rowland M, Kolaczinski J, , 2006. Spatial Epidemiology of Plasmodium vivax, Afghanistan. Emerg Infect Dis 12: 16001602.[Crossref] [Google Scholar]
  25. Leary KJ, Riel MA, Roy MJ, Cantilena LR, Bi D, Brater DC, van de Pol C, Pruett K, Kerr C, Veazey JM, Beboso R, Ohrt CA, , 2009. Randomized, double-blind, safety and tolerability study to assess the ophthalmic and renal effects of tafenoquine 200 mg weekly versus placebo for 6 months in healthy volunteers. Am J Trop Med Hyg 81: 356362. [Google Scholar]
  26. Dow GS, McCarthy WF, Reid M, Smith B, Tang D, Shanks GD, , 2014. A retrospective analysis of the protective efficacy of tafenoquine and mefloquine as prophylactic anti-malarials in non-immune individuals during deployment to a malaria-endemic area. Malar J 13: 49.[Crossref] [Google Scholar]
  27. Kersgard CM, Hickey PW, , 2013. Adult malaria chemoprophylaxis prescribing patterns in the military health system from 2007–2011. Am J Trop Med Hyg 89: 317325.[Crossref] [Google Scholar]
  28. Korhonen C, Peterson K, Bruder C, Jung P, , 2007. Self-reported adverse events associated with antimalarial chemoprophylaxis in Peace Corps volunteers. Am J Prev Med 33: 194199.[Crossref] [Google Scholar]
  29. Grahnén A, Olsson B, Johansson G, Eckernäs S-Å, , 1994. Doxycycline carrageenate—an improved formulation providing more reliable absorption and plasma concentrations at high gastric pH than doxycycline monohydrate. European Journal of Clinical Pharmacology 46: 143146.[Crossref] [Google Scholar]

Data & Media loading...

  • Received : 27 Mar 2015
  • Accepted : 02 May 2015
  • Published online : 02 Sep 2015

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error