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To Avert Malaria, Some Travelers Say "Make Mine Malarone"

For those at risk of contracting malaria from a bite like this, Malarone may be a preferable—though more costly—alternative to Lariam.

Anxiety attacks, hallucinations, paranoia, suicidal urges: these are among the rare severe side effects that some users ascribe to Lariam (mefloquine), the longtime first-choice antimalarial drug recommended for protecting travelers who visit regions where this parasitic disease is endemic. In recent years, more and more travelers have added their voices to the rising chorus of concerns over the purported side effects of this drug. Now, however, those travelers can consider the drug Malarone as a new option for prophylaxis, one that apparently causes few side effects.

"I think Malarone is an excellent drug," says Jay Keystone, a travel health expert at the University of Toronto. "It appears to be safe, effective, and well-tolerated and can be stopped a week after return." While Malarone's side effect profile appears to be very good, only long-term use in tens of thousands of people will verify its apparent safety, he adds. Moreover, although Malarone may supersede Lariam as the drug of choice among many business and leisure travelers, its comparatively high cost leaves room for Lariam and other malaria prophylactic agents.

The U.S. Food and Drug Administration approved Malarone in July 2000 for both the treatment and prevention of malaria, a move that offers travelers an alternative to Lariam and doxycycline, the only other agents approved for malaria prophylaxis. Malarone combines avotaquone and proguanil, two drugs that when used separately act weakly against malaria parasites. But when used together, they effectively attack the parasites at both the liver and blood stages of their life cycle.

However, it was not until late last year that public health officials at the U.S. Centers for Disease Control and Prevention (CDC) in Atlanta, Ga., began revising their malaria prophylaxis recommendations—which had long cited Lariam as the "drug of choice"—to include Malarone. Outstanding concerns were whether Malarone could effectively protect individuals with malaria-naive immune systems and whether it is effective against Plasmodium vivax as well as P. falciparum. "Once we had the efficacy data in hand—which is what we were waiting for—we were then comfortable that [Malarone] is a viable drug for prophylaxis in U.S. citizens," says Rick Steketee, chief of the CDC's malaria epidemiology branch.

Those data come from a trial in Indonesia completed last year showing that Malarone is effective in protecting individuals who had not already been exposed against malaria caused by either P. falciparum or P. vivax malaria. These findings were announced during the 49th annual meeting of the American Society for Tropical Medicine and Hygiene, held 29 October-2 November in Houston, Tex.

Previous trials on Malarone were conducted among individuals in Africa, where there is no P. vivax but high likelihood for exposure to P. falciparum, says Kevin Baird of the U.S. Naval Medical Research Unit in Jakarta, Indonesia, part of the team that conducted the latest study. "The Indonesia trial filled in the missing data, demonstrating good safety, tolerance, and efficacy."

Among 297 participants receiving either Malarone or a placebo, only three in the experimental group contracted malaria, compared to 37 cases among those receiving a placebo. Malarone achieved an efficacy level of 95% in preventing P. falciparum infection and 81% in preventing P. vivax infection. Only one individual receiving the drug dropped out due to an adverse event, a rash.

These findings could help to ease a controversy that grew up around the continuing use of Lariam as the chief agent for preventing malaria. The latter drug had come under fire following reports about its neuropsychological side effects. Prophylaxis with Lariam appears to cause moderate to severe effects in about 3% of users, Keystone notes. "In the past few years, the media has picked up on Lariam adverse events and given exaggerated reports about this `horrible' drug," he says. "A significant amount of public concern has been raised about Lariam, so people hesitate to use it."

Steketee notes that several controlled studies were unable to document a statistically significant higher rate of adverse side effects associated with Lariam than with a placebo. Therefore, CDC officials have not dropped the drug from the list of those recommended for preventing malaria. In effect, "CDC is saying Lariam equals doxycycline equals Malarone," Keystone says.

With this revision of CDC's long-standing drug-of-choice policy, the burden now shifts to individual travel clinics and organizations to determine which drug to prescribe, a decision complicated by concerns over Lariam's safety and Malarone's cost. According to a small survey, the average cost of malaria prophylaxis for a two-week trip would be $34 for doxycycline, $74 for Lariam, and $127 for Malarone—even though the first two drugs must be taken three weeks longer than Malarone at the end of a trip, he points out.

Cost issues are vexing organizations, such as the U.S. Peace Corps, which are considering whether to adopt their own drug-of-choice policy, Steketee notes. Although Malarone may be more costly to the Peace Corps, some volunteers may object to a policy that favors Lariam.

"I think for the short-term traveler who can afford it, [Malarone] will likely replace Lariam," Keystone says. But for travelers planning extended stays, Malarone may prove financially out of reach.

Christine Stencel
Christine Stencel is a communications manager and science writer at ASM.