Research on malarial drugs for travelers

Oct 7 2009

A new review of existing research finds that a combination drug and the common antibiotic doxycycline allow travelers to fend off malaria with the fewest side effects in areas where the parasite is resistant to a widely accepted preventive treatment.

Another drug, mefloquine, has the most side effects, but it might be appropriate for people who already have taken it without problems, the review authors write.

Doctors must make decisions by relying on a variety of factors, and the review does not suggest that any one approach is better than another, said lead review author Dr. Frederique Jacquerioz, a researcher with Tulane University's Center for Evidence-based Global Health.

"The main message is that you have to take some malaria chemoprophylaxis [preventive treatment] if you go to an endemic area," she said. "It's one of the best preventive measures we have."

Malaria is present in more than 100 countries and is especially dangerous in many tropical countries. Travelers should be especially cautious when they go to more remote areas, Jacquerioz said.

"It really depends how you travel," she said. "If you stay in the capital in a four-star hotel and have air conditioning, you're really less at risk."

However, the situation is entirely different if you backpack in rural areas, she said.

An estimated 10,000 to 30,000 travelers develop malaria infections each year, according to the World Health Organization. Of those, researchers estimate that 150 will die.

The authors of the new review say the number of cases is skyrocketing due to increasing travel to tropical locales. In many cases, the preferred antimalarial drug, called chloroquine, does not work because the malaria parasite has developed resistance to it since the 1950s.

Jacquerioz and a colleague analyzed existing research to determine the possible risks of alternative medications.

They found eight studies, with 4,240 participants that fit their review criteria.

The review appears in the latest issue of The Cochrane Library, a publication of the Cochrane Collaboration, an international organization that evaluates medical research. Systematic reviews draw evidence-based conclusions about medical practice after considering both the content and quality of existing medical trials on a topic.

The review authors found that two medications — the combo drug atovaquone-proguanil and doxycycline — had about the same level of side effects, although researchers said the studies were not of high quality.

Compared to a third drug, mefloquine, atovaquone-proguanil had fewer gastrointestinal and neuropsychiatric side effects, which include nightmares and dizziness. Doxycycline also had fewer neuropsychiatric side effects.

The eight studies found no severe side effects — fatal, life threatening or requiring hospitalization — among those who took the drugs.

The researchers also looked beyond the review studies to examine medical literature for mentions of case reports of deaths associated with normal use of the drugs. There were no reports of deaths connected to any of the drugs except mefloquine, which had a connection to 22 deaths, including five suicides.

The researchers caution that the number could be artificially high because publicity over the drug's safety might make it more likely that individuals are linking the deaths to the medication.

"There is a big controversy about whether we should use [the drug] or not, and in which populations," Jacquerioz said.

The review, she said, does not provide data on safety to support or oppose mefloquine's use.

Dr. Andrea Boggild of Toronto General Hospital's Tropical Disease Unit said mefloquine is appropriate in some cases, although it does indeed cause nightmares, insomnia and irritability.

"It is important to remember that severe neuropsychiatric adverse events are rare and probably occur on the order of one in 6,000 to one in 10,000 people taking mefloquine," Boggild said. "In people who have previously taken mefloquine and tolerated it, there is no reason not to use it."

The drug is inexpensive, easy to take and "an attractive choice for many, many travelers," Boggild said. The drug's price is between that of generic doxycycline, at about $10 to $15 for the required doses for a 14-day trip, and atovaquone-proguanil at $110 to $120.

Both Jacquerioz and Boggild emphasized the importance of getting professional advice before going on a trip to a potentially dangerous area.

"Travelers, whether they are going for business, tourism, missionary work or to visit friends and relatives, should seek pre-travel advice from a dedicated travel medicine specialist," Boggild said. "They should be aware that no antimalarial drug is 100 percent effective at preventing malaria, and medical attention should be sought immediately if fever develops in the risk area while traveling or after a person returns home."

http://www.cochrane.org