Rationale:

• Malaria can be fatal in travelers.
• Treatment delay increases morbidity and mortality of malaria.
• Self-treatment by travelers is likely to be safe, effective, and potentially life-saving.

Evidence:

• Although there is much data showing the safety of treating returned travelers with antimalarial drugs, there are few studies indicating that stand-by treatment is effective in travelers (147).
• No randomized, controlled clinical trials have been performed, or are likely to be performed, due to the high morbidity and mortality of untreated or inappropriately treated malaria in nonimmune persons. For example, self-treatment with sulfadoxine-pyrimethamine has failed in Kenya, which is an area with widespread sulfadoxine-pyrimethamine-resistant parasites (148).
• The Medical Letter discusses atovaquone-proguanil treatment for malaria (149).

Comments:

• The CDC recommends atovaquone-proguanil as the drug of choice for stand-by treatment of malaria, provided the individual is not taking atovaquone-proguanil as chemoprophylaxis (Health Information for International Travel 2003-2004). It is important to note, however, that rare initial treatment failures and recrudescence of drug-resistant parasites (4 weeks posttreatment) have been reported with atovaquone-proguanil (see Comments under treating uncomplicated P. falciparum).
• The combination of artemether and lumefantrine, which has been registered in Europe but not in the U.S., is available in many malaria-endemic countries and has been recommended as emergency stand-by therapy for travelers. Lumefantrine does not cause significant QTc prolongation and can be safely administered to individuals who are already taking mefloquine prophylaxis. A randomized, placebo-controlled, double-blind crossover study showed that a single oral dose of artemether-lumefantrine (80 mg/480 mg) did not cause QTc prolongation. In contrast, a single oral dose of halofantrine (500 mg) caused significant QTc prolongation in 13 of 13 healthy men. The length of QTc prolongation increased with increasing plasma concentration of halofantrine (150). A monograph describing artemether-lumefantrine is available from the drug company.
• The CDC does not recommend halofantrine (widely available outside of the U.S.) for stand-by treatment due to the risk of arrhythmias (some fatal) even when used at appropriate treatment doses in individuals without a history of pre-existing cardiac problems or prior/concurrent use of related antimalarial drugs (e.g., mefloquine) (Health Information for International Travel 2003-2004).