SAN DIEGO – A very small insect causes more than 1 million deaths each year, and in some countries, ranks second only to HIV/AIDS in associated mortality rates.

But malaria doesn’t just affect people who live in endemic regions, Dr. Loren Miller said at the annual meeting of the American College of Physicians. Americans who travel to those countries for business or pleasure are also at risk, and should discuss malaria prophylaxis with their health care providers.

Mosquito-borne malaria is now resistant to prophylactic chloroquine and mefloquine in some areas, but other drugs such as the combination atovaquone/proguanil are available.

Prophylaxis is generally very safe and extremely effective, but choosing the right agent is key, said Dr. Miller, director of the infection control program at Harbor-UCLA Medical Center, Torrance, Calif. Two of the most common agents – chloroquine and mefloquine – are no longer effective in many parts of Mexico, Central and South America, the Middle East, sub-Saharan Africa, India, and Southeast Asia.

In chloroquine-susceptible regions, the drug is a good choice, but still has limitations. "It has to be started 1-2 weeks before travel, so it’s not useful in people who come to the travel clinic and tell you they’re leaving in a few days," Dr. Miller said. The drug also has to be continued for a month after travel. It’s generally well tolerated, although it can exacerbate psoriasis.

Mefloquine can also be an option in countries of susceptible malaria strains. It too, must be started well in advance of travel [1-3 weeks] and continued for 4 weeks afterward. Adverse effects include the rare possibility of psychiatric symptoms, and exacerbation of seizure disorders and cardiac conduction abnormalities. "The lay press really has it in for this drug," he added. "There have been anecdotal reports of patients having hallucinations after getting it, and patients may come to you having read about this in a travel magazine. But in my experience, these are very rare."

The combination of atovaquone/proguanil is another option. "This can be started just 1 day before travel and it has to be continued for 7 days afterward. It’s very well tolerated, although contraindicated in those with a creatinine clearance of less than 30 mL/minute."

The drug is very expensive, running about $56 per week and, like all antimalarials, isn’t usually covered by insurance.

"The poor man’s alternative is doxycycline," Dr. Miller said. This must be started 1-2 weeks early and continued 2-4 weeks after travel. "This drug can cause photosensitivity, which you need to talk about because these people are going to tropical areas – and it can cause vaginal candidiasis."

Many experts consider primaquine to be a second-line agent. It’s most effective against Plasmodium vivax. A glucose-6-phosphate dehydrogenase deficiency test is necessary for blacks, Asians, and patients of Mediterranean descent, because the drug can cause acute hemolysis in deficient patients. "Since this test takes a while to come back, primaquine is not recommended for patients who want to travel soon," Dr. Miller said.

Immigrants who want to return to their native countries might claim they don’t need malarial prophylaxis because of exposure during childhood. Two studies have come to different conclusions about this idea, Dr. Miller said.

A 2005 study compared 99 Europeans traveling to malaria-endemic regions with 252 Africans returning home to such areas. The immigrants had lived in Europe for an average of 4 or more years. "Of those who contracted malaria, the Africans had lower mean parasite densities, less severe disease, and accelerated parasite clearance," Dr. Miller said (Am. J. Trop. Med. Hyg. 2005;72:21-25).

The second study, conducted in 2004, found no significant clinical differences between 93 immigrants returning to malaria-endemic countries and 167 to nonendemic countries. Of those who contracted the disease, "There was a trend toward less ICU admission in the previously exposed group, but it wasn’t significant (4% vs. 11%). So clearly, these people can get malaria, they can go to the ICU for it, and if they are in the ICU, there is a chance of dying from it. If someone is returning to an endemic area, I would absolutely recommend prophylaxis" (QJM 2004;10:645-9).

Dr. Miller divides his vaccination protocol into three parts, according to destination. "If they’re going to Central America, the Caribbean or the mid-East, they get chloroquine. If they’re going to the area of the Thai-Burma border, they get atovaquone/proguanil or doxycycline. If they’re going anywhere else, they get mefloquine or, if they can’t take that, either doxycycline or atovaquone/proguanil."

The Centers for Disease Control and Prevention’s Yellow Book notes which antimalarials are effective in any given country. For that resource, go to www.cdc.gov/travel.

Dr. Miller reported having financial relationships with Pfizer, Cubist Pharmaceuticals, GlaxoSmithKline, and Merck. He has been a consultant with Theravance.

Malaria Prophylaxis: Destination Designates Drug