EVIDENCE-BASED ANSWER
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/yellowBookCh5MalariaYellowFeverTable.aspx (SOR: C, based on patient-oriented expert opinion).
Clinical commentary
5 tips to help travelers avoid malaria
Brian V. Reamy, MD
Uniformed Services University, Bethesda, Md
Despite 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.
Evidence summary
Travelers to malaria-endemic areas should avoid mosquito bites by using netting and repellents, and use chemoprophylaxis to prevent infection.
Although no drug regimen guarantees protection against malaria, physicians should prescribe 1 of several options based on the location of travel, the susceptibility of indigenous P falciparum, and the side-effect profile.1
Timing and dosage of prophylactic drugs
Prophylactic medications must be started at different times before travel, but for some medications the optimal time to initiate treatment is unclear. Evidence-based recommendations2,3 with consideration for side-effect profiles are given in the TABLE.
In contrast to the pretreatment times for all other malarial prophylaxes, the generally accepted pretreatment time for mefloquine is 1 to 2 weeks before 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 levels.4 The evidence indicates that mefloquine 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 concentrations 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 below 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 mefloquine 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 prophylactic blood levels of mefloquine by the third day while weekly mefloquine is subprophylactic until the fifth week.4