Malaria Chemoprophylaxis and Travel Immunizations

to the editor: The article on pretravel consultation by Drs. Bazemore and Huntington presents a broad overview of the role of family physicians in preparing patients for safe travel. However, the article contains some important errors and omissions.

Regarding malaria chemoprophylaxis, the article indicates that atovaquone/proguanil (Malarone) is not recommended for children weighing less than 24 lb (11 kg). The Centers for Disease Control and Prevention (CDC) has advised that this drug is safe to use in children weighing as little as 11 lb (5 kg) in a dosage of one half of a pediatric pill per day.¹ The pill may be crushed and mixed with formula or food.

Although chloroquine (Aralen) is rapidly absorbed, its extensive sequestration in body organs necessitates more than a single dose to achieve therapeutic levels. The drug should be started one to two weeks—not one to two days—before exposure to chloroquine-sensitive malaria. This also provides a window of time before traveling to assess how well the drug is tolerated. Similarly, mefloquine (formerly Lariam) requires multiple doses to achieve therapeutic levels. Relative resistance to mefloquine is not unusual, and subtherapeutic drug levels are not only potentially ineffective, but may add to selective pressure for resistance. Some physicians advocate a loading dose of 250 mg per day for three days, followed by 250 mg per week during exposure and for one month after exposure. No matter how the loading dose is administered, one tablet one to two days before exposure is not sufficient.²

The information presented on doxycycline is correct, but an important consideration is that patients may travel to areas endemic for leptospirosis and rickettsial infections. Both of these infections are effectively prevented with doxycycline.

The authors describe the mouse brain–derived Japanese encephalitis vaccine (Je-vax), which is no longer being produced and has limited availability. It is available only for pediatric use. Ixiaro is a new Japanese encephalitis vaccine that appears to have fewer adverse effects. It is approved for use in patients 17 years and older, and is given as two doses spaced 28 days apart.³

According to the CDC, a booster dose of the meningococcal polysaccharide vaccine (Menomune) should be given every five years if the patient received the first dose after 10 years of age. It is licensed for use in patients two years and older. However, Menomune has been largely supplanted by the meningococcal conjugated vaccine (Menactra) because of its longer duration of protection. Menactra is licensed for use in patients two to 55 years of age. Menomune is the preferred form in pregnant women who are at risk of meningitis.⁴

The tuberculosis (bacillus Calmette-Guérin) vaccine is rarely given in the United States, but it may be appropriate in young children traveling to high-risk locations. It is often required for school entry in other parts of the world. When it is used in the United States, it is given via a multipuncture device, not intradermally.⁵

in reply: We appreciate Dr. Jones' interest and helpful comments. The pediatric dosing limitation for atovaquone/proguanil (Malarone) cited in our article references the approved package insert at the time the manuscript was submitted. Although the Centers for Disease Control and Prevention (CDC) recommends using this drug in children weighing less than 24 lb (11 kg), this use is currently off-label. We also appreciate Dr. Jones' pointing out a typographical error in the recommended initiation point for prophylactic chloroquine (Aralen) and mefloquine (formerly Lariam) use, which is indeed one to two weeks—not days—in advance of travel.

We also agree that Ixiaro, which was not yet approved at the time of our manuscript's publication, is now the preferred pretravel vaccination for Japanese encephalitis. We appreciate the details provided by Dr. Jones on meningococcal conjugate and bacillus Calmette-Guérin (BCG) vaccines, a full discussion of which was not possible because of space limitations. The footnotes in Table 4 of our article regarding both of these drugs came from the manufacturer's package inserts. Reports by the Canada Communicable Disease Report and the Morbidity and Mortality Weekly Report (MMWR) note that the BCG vaccine may be rendered intradermally or subcutaneously.^1,2 The MMWR states, “BCG vaccinations are usually administered by the intradermal method, and reactions…can be expected after vaccination. …Higher rates of local reactions may result from using subcutaneous injection in comparison with reactions from intradermal injection.” ² Travel practitioners rendering evidence-based advice will discover occasional disagreement among recommendations from the CDC, drug manufacturers, proprietary decision-support tools, and practices in other developed nations.