Travelers should start on chloroquine 1 to 2 weeks before entering an area without chloroquine resistance (strength of recommendation [SOR]: C, based on expert opinion). In areas with chloroquine-resistant Plasmodium falciparum, travelers will need to take atovaquone/proguanil, doxycycline, or primaquine 1 day before entering the area, or mefloquine 2 to 7 weeks before travel (SOR: B, based on prospective patient-oriented outcomes and expert opinion). Before prescribing medications, determine malaria risk and sensitivity of Plasmodium species by country at wwwn.cdc.gov/travel/yellowBookCh5- MalariaYellowFeverTable.aspx (SOR: C, based on patient-oriented expert opinion)

Clark, Steven L.

Crawford, Paul

Nichols, William

University of Missouri: MOspace

950	 vol 56, No 11 / November 2007  The Journal of family PracTiceCliniCal INquIrIes From the Family Physicians Inquiries Network		evidence-based answerclinical commentaryWhen	should	travelers		begin	malaria	prophylaxis?Travelers should start on chloroquine 1 to 2 weeks before entering an area without chloroquine resistance (strength of recommendation [sor]: c, based on expert opinion). In areas with chloroquine-resistant Plasmodium falciparum, travelers will need to take atovaquone/proguanil, doxycycline, or primaquine 1 day before entering the area, or mefloquine 2 to 7 weeks before travel (sor: B, based on prospective patient-oriented outcomes and expert opinion). before prescribing medications, determine malaria risk and sensitivity of Plasmodium species by country at wwwn.cdc.gov/travel/yellowbookCh5-malariaYellowFeverTable.aspx (sor: c, based on patient-oriented expert opinion).5 tips to help travelers avoid malariaDespite our best efforts, more than 10,000 American and european travelers contract malaria each year. Five clinical pointers are helpful in prescribing malaria prophylaxis and preventing malaria in travelers. 1. advise patients that they’ll need to get their antimalarials before they leave for their trip. The CDC recommends against the purchase of antimalarials while overseas because of concerns about product quality.  2. encourage patients to plan ahead. most local community pharmacies do not routinely stock antimalarials and must special order them. If a patient mentions an upcoming trip, advise them that they’ll need to allow an extra 2 weeks to obtain their medications.  3. consult 1 of 2 continuously updated Web sites prior to selecting a medication for malaria prophylaxis:  wwwn.cdc.gov/travel/destinationlist.aspx or www.who.int/ith/en.  start times vary from 1 day to several weeks prior to travel based on the medication selected. 4. encourage patients to spray clothing with permethrin prior to travel. Permethrin remains effective as a repellent even after months of clothing use and multiple washes.  5. encourage travelers to finish their medication after they return and to report unexplained fevers for up to 1 year after travel. Brian V. Reamy, MDuniformed services university, bethesda, mdz	 Evidence	summaryTravelers to malaria-endemic areas should avoid mosquito bites by using netting and repellents, and use chemo-prophylaxis to prevent infection. Although no drug regimen guar-antees protection against malaria, phy-sicians should prescribe 1 of several Steven l. Clark, MD  and Paul Crawford, MDEglin Air Force Base Family Medicine Residency,  Eglin Air Force Base, FlaWilliam nichols, MlSLibrarian, Eglin Regional Hospital,  Eglin Air Force Base, Flafast trackBefore selecting  a medication  for malaria  prophylaxis, go to:  z  wwwn.cdc.gov/travel/destinationList.aspx z  www.who.int/ith/enfast trackwww.jfponline.com  vol 56, No 11 / November 2007 951options based on the location of travel, the susceptibility of indigenous P falci-parum, and the side-effect profile.1 Timing	and	dosage	of	prophylactic	drugsProphylactic medications must be start-ed at different times before travel, but for some medications the optimal time to initiate treatment is unclear. Evi-dence-based recommendations2,3 with consideration for side-effect profiles are given in the TablE.In contrast to the pretreatment times for all other malarial prophylax-es, the generally accepted pretreatment time for mefloquine is 1 to 2 weeks be-fore entering a risk area. However, this may still be inadequate due to the drug’s long half-life, which results in a long delay in reaching therapeutic blood lev-els.4 The evidence indicates that meflo-quine should be started at least 2, and as many as 7, weeks before travel.The standard recommended dose of 250 mg/week of mefloquine “produces maximum steady-state plasma concen-trations of 1000 to 2000 mcg/L, which are reached only after 7 to 10 weeks.”4 One study of 293 children under the age of 5 years in Malawi found that plasma concentrations of mefloquine were be-low prophylactic level (500 mcg/mL) against P falciparum until the fourth to seventh week of once-weekly dosing (P<.0003).5 One way of reaching prophylactic levels earlier would be to give meflo-quine 250 mg daily for 3 days followed by 250 mg weekly.4 A safety study of 157 healthy US Marine volunteers showed that preloading achieves pro-phylactic blood levels of mefloquine by the third day while weekly me-floquine is subprophylactic until the fifth week.4 While a study of the long-term use of mefloquine in 421 healthy Peace Corps volunteers has shown it to be safe,6 clinical trials and case reports in-dicate that a loading dose of mefloquine is associated with adverse drug events, which include neuropsychiatric and gastrointestinal symptoms.4,7Evidence-based	recommendations	for	prevention	of	malaria2–3,8Drug usage aDulT Dose TreaTmenT scheDuleatovaquone/ Prophylaxis in areas  1 tablet orally each day  Daily from 1 day prior to entry proguanil with chloroquine-resistant or  (250 mg atovaquone and  until 7 days after leaving Contraindicated  mefloquine-resistant P falciparum 100 mg proguanil  in pregnancy  hydrochloride)chloroquine  Prophylaxis only in areas with  300 mg base (500 mg salt) Weekly from 2 weeks prior to entry   chloroquine-sensitive P falciparum orally, once/week until 4 weeks after leaving (take on     the same day of the week)Doxycycline  Prophylaxis in areas  100 mg orally, daily Daily from 1 day prior to entry Contraindicated  with chloroquine-resistant or  until 4 weeks after leaving  in children <8  mefloquine-resistant P falciparum   years of age and  pregnant womenmefloquine  Prophylaxis in areas with 228 mg base (250 mg salt) Weekly from 2–7 weeks before entry   chloroquine-resistant P falciparum orally, once/week until 4 weeks after leaving     (take on the same day of the week)Primaquine An option for prophylaxis  30 mg base (52.6 mg salt)  Daily from 1 day prior to entry until  in special circumstances orally, daily 7 days after leavingtaBleEncourage  patients to spray clothing with  permethrin  before travel.  It remains an effective repellent even after  multiple washesMalaria prophylaxisRecommendations	from	othersThe World health organization (WHO) states that “weekly mefloquine should be started at least 1 week, but preferably 2–3 weeks before departure, to achieve higher pre-travel blood levels and to al-low side effects to be detected before travel so that possible alternatives can be considered.”8 centers for Disease control and Prevention recommendations integrate recommendations from WHO and Cochrane.   nacknowledgmentsThe opinions and assertions contained herein are the private views of the authors and not to be construed as official, or as reflecting the views of the us Air Force medical service or the us Air Force at large.references 1.  Chen lH, Keystone Js. New strategies for the pre-vention of malaria in travelers. Infect Dis Clin North Am 2005; 19:185–210.  2.  Physicians’ Desk Reference. 61st ed. montvale, NJ: Thomson; 2007:2786.  3.  Parise m, barber A, mali s. Prevention of specific infectious diseases—malaria. In Arguin Pm, Ko-zarsky Pe, Navin AW (eds), Health Information for International Travel 2005–2006. Atlanta, Ga: us Department of Health and Human services, Pub-lic Health service, Centers for Disease Control and Prevention; 2007. Available at: wwwn.cdc.gov/travel/yellowbookCh4-malaria.aspx. Accessed on october 11, 2007. 4.  boudreau e, schuster b, sanchez J, et al. Toler-ability of prophylactic lariam regimens. Trop Med Parasitol 1993; 44:257–265. 5.  slutsker lm, Khoromana Co, Payne D, et al. meflo-quine therapy for Plasmodium falciparum malaria in children under 5 years of age in malawi: in vivo/in vitro efficacy and correlation of drug concentration with parasitological outcome. Bull World Health Or-gan 1990; 68:53–59.  6.  lobel Ho, miani m, eng T, et al. long-term malaria prophylaxis with weekly mefloquine. Lancet 1993; 341:848–51.  7.  schlagenhauf P. mefloquine for malaria chemopro-phylaxis 1992-1998: a review. J Travel Med 1999; 6:122–133. 8.  International Travel and Health 2005. Chapter 7: malaria. Geneva: World Health organization; 2005. Available at: whqlibdoc.who.int/publica-tions/2005/9241580364_chap7.pdf. Accessed on october 11, 2007.CliniCal INquIrIesCMEEvidence-Based PracticeThe compleTe  eBp 2007 compilaTionEvidence-Based Practice:  The 2007, Volume 10 CompilationComplete Volume 9 Collection Evidence-based medicine froma team you trust — published byand for family physiciansEvery month, family physicians from around the country collaborate to independently bring you Evidence-Based Practice, free from the bias of  pharmaceutical industry support. We’ve compiled all the 2007 issues into one convenient reference manual, complete with a study guide.WhaT’s inside:n Transforming Practice n In The News n Focused Topic Updatesn HelpDesk Answers n Drug Profile n Topics in Maternity Care n Behavioral Health Mattersn Patient EducationRelevant, Timely, evidence-Based:  all from one reliable sourceBrought to you by your friends atFamily Physicians Inquiries NetworkPhone: 573-256-2066, email: ebp@fpin.orgor click on the “subscribe now” link  at www.ebponline.netAVAILABLE IN DECEMBER 2007—PREORDER YOUR COPY TODAY!  

When should travelers begin malaria prophylaxis?

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