Rationale:

• Currently recommended antimalarial drugs offer excellent protection against P. falciparum malaria when taken appropriately.
• Selection of an effective prophylactic regimen depends on patterns of drug resistance and other factors, some of which affect compliance: number of pills, dosing interval (i.e., daily vs. weekly), duration of travel, duration of pretravel and posttravel medication, cost, and tolerability of side effects.
• Lack of proper prophylaxis is associated with severe complications from malaria and death.

Evidence:

• A randomized, controlled trial comparing atovaquone-proguanil with mefloquine showed that both were completely effective in the prevention of malaria in 976 nonimmune travelers to Africa and South America (15).
• A randomized, placebo-controlled trial conducted in 272 Zambian immune persons showed prophylaxis success rates of 98% and 63% for atovaquone-proguanil and placebo, respectively (P<0.001) (16).
• A randomized, placebo-controlled trial conducted in 198 Kenyan immune persons showed prophylaxis success rates of 100% and 48% for atovaquone-proguanil and placebo, respectively (P<0.001) (17).
• One systematic review of five randomized clinical trials conducted in nonimmune travelers concluded that mefloquine is effective for the prevention of malaria (18).
• A randomized, placebo-controlled trial conducted in 204 Indonesian soldiers with limited immunity found 1 out of 67 cases of malaria with doxycycline prophylaxis, 0 out of 68 cases of malaria with mefloquine prophylaxis, and 53 out of 69 cases of malaria with placebo prophylaxis (19).
• A randomized, placebo-controlled trial in 152 Indonesian adults with limited immunity showed 96.3% protective efficacy of doxycycline against P. falciparum malaria relative to placebo (20).
• The CDC reported 4685 cases of imported malaria in Americans who traveled between 1992 to 2001. Of these, 19% received inappropriate prophylaxis (typically chloroquine in an area with chloroquine resistance) and 56% took no prophylaxis at all (21).
• Of 799 patients with imported malaria with onset of illness in 2002 and for whom prophylaxis information was available, 17% took inappropriate prophylaxis for the area visited, and 60% took no prophylaxis at all (22).
• One study showed that ineffective prophylaxis was primarily the result of inappropriate medical advice and that nearly all such malaria cases could have been avoided (23).
• From 1959 to 1987, there were 68 fatalities reported among U.S. travelers with P. falciparum infection. Of these 68 fatalities, 77% had not taken chemoprophylaxis, 13% took prophylaxis that was known at the time to be ineffective in the region they were visiting, and 6% had correct prophylaxis antimalarials but took them haphazardly (24).

Comments:

• The Medical Letter periodically publishes an update on antimalarial drugs (25).
• Once travelers reach their destination, they should be aware that local herbal and alternative remedies are unlikely to be effective, that locally produced antimalarials may be of poor quality or outright fakes, and that some apparently name-brand packages are fraudulent (26).
• Although pyrimethamine-sulfadoxine (Fansidar) and amodiaquine (Camoquine) have been marketed for malaria prophylaxis in the past, they are no longer approved for this indication due to an unacceptable risk of serious adverse events, including exfoliative dermatitis, hepatitis, and blood dyscrasias (27; 28; 29).
• Most antimalarial drugs (chloroquine, mefloquine, and doxycycline) are taken for 4 weeks after leaving a malarious area to ensure clearance of liver-stage P. falciparum parasites, against which these drugs have no (or questionable) activity. Atovaquone-proguanil is active against liver-stage P. falciparum; thus, this drug is taken for only 7 days after leaving a malarious area.
• Persons who travel at certain times of the year and to certain urban settings and tourist destinations in Southeast Asia and South and Central America may not require a prophylactic drug (30), although insect repellent measures may still be recommended to reduce the risk of acquiring other mosquito-borne diseases (e.g., bancroftian filariasis, dengue hemorrhagic fever) or of being bitten by chiggers, flies, fleas, or ticks.
• Pregnant women should refrain from travel to malarious areas if possible. Prophylaxis considerations for pregnant women are included in the table Chemoprophylaxis for Malaria.