Another risk to US travelers—malaria

Factors determining the need for,
 and selection of, chemoprophylaxis


When used properly, chemoprophylactic drugs are effective in preventing malaria (SOR: A). Atovaquone-proguanil achieves efficacy of 95% to 100%,¹⁷ while doxycycline, primaquine, and mefloquine are slightly less effective.^18-20 Chloroquine is effective in 6 regions of the tropics and subtropics where Plasmodium falciparum resistance has not developed. Select a drug based on your assessment of an individual’s level of risk according to the personal itinerary, trip duration and accommodations, cost of medication, tolerance for adverse effects, and other factors (eg, comorbidities, concurrent drug usage, pregnancy).

Location matters. The risk of malaria transmission can vary considerably not only between countries, but also regionally within countries and even between a city and its immediate surroundings. Therefore, select a chemoprophylactic agent based on the specific itinerary, planned activities, the potential for unforeseen additional excursions, and local Plasmodium resistance patterns. For example, chloroquine is effective only in the Caribbean, Central America, and some countries in the Middle East.²¹ Mefloquine resistance has been reported in parts of Cambodia, Thailand, Vietnam, Burma, China, and Laos.²¹

Children, pregnant women, the elderly, and immunocompromised patients are at highest risk for complicated and lethal cases of malaria.On its Travelers’ Health Web site (www.cdc.gov/travel), the Centers for Disease Control and Prevention (CDC) reports for each country 1) the risk of malaria transmission, 2) areas within the country that pose a risk, 3) evidence of Plasmodium drug resistance, 4) which Plasmodium species are active, and 5) which chemoprophylactic medications are recommended.²² Additional Web sites, either free or subscription-based, allow users to view this same information on maps, advise on where insect precautions alone are sufficiently protective, and provide information about the traveler’s risk of contracting other diseases (TABLE 1).

TABLE 1

Comparative adverse effects of antimalarial agents. A Cochrane Review on the tolerability of chemoprophylactic agents concluded that atovaquone-proguanil and doxycycline were better tolerated than mefloquine (SOR: B). Compared with mefloquine, atovaquone-proguanil led to fewer reports of any adverse effects (relative risk [RR]=0.72), gastrointestinal adverse effects (RR=0.54), and neuropsychiatric adverse events (RR= 0.49-0.86, depending on the studies).²³ Doxycycline users have reported fewer neuropsychiatric events (RR=0.84) than mefloquine users.²³ These are relatively small differences, and the authors point out that these figures are based on low-quality evidence. Additional research is likely to have an impact on the confidence in the estimate of effect and to ultimately change the estimate.

Mefloquine is contraindicated in travelers with seizures, active or recent history of depression, generalized anxiety disorder, psychosis, schizophrenia, or other psychiatric disorders. Compared with mefloquine, atovaquone-proguanil and doxycycline cause fewer neuropsychiatric adverse effects (such as vivid dreams, dizziness, anxiety, depression, visual disturbance, or seizures).²⁴ Caution is advised when prescribing chloroquine for patients with epilepsy because the medication has the potential to lower the seizure threshold.²⁵

Use caution when prescribing mefloquine for patients with cardiac conduction disturbances. Electrocardiogram alterations such as sinus bradycardia, first-degree AV block, prolongation of QTc intervals, and abnormal T wave changes have been reported.²⁶ Chloroquine can also prolong QTc intervals.²⁶

Safety in pregnancy and breastfeeding. Malaria in pregnancy is associated with increased rates of anemia, low birth weight, prematurity, intrauterine growth restriction, and infant mortality.²⁷ Chloroquine and mefloquine are considered safe during pregnancy and breastfeeding. Doxycycline has been associated with increased risk of harm to the fetus. Atovaquone-proguanil can be used in breastfeeding women if the child is ≥5 kg (≥11 lbs). Chemoprophylaxis taken by the mother while breastfeeding does not protect the infant from infection.

Dosing considerations. Mefloquine and chloroquine are dosed weekly; doxycycline and atovaquone-proguanil are taken daily.When considering chemoprophylaxis, check on Plasmodium resistance patterns in and around destinations and take into account drug adverse effects for those with comorbidities. Travelers staying in a malaria-endemic region for longer periods (months rather than weeks) often prefer the weekly rather than daily medications; however, this may not be possible due to the adverse-effect profile of mefloquine or to traveling in an area with known chloroquine resistance. Some individuals prefer the routine of taking a medication daily, since remembering to take a single dose on the same day each week can be challenging. Others may not want to carry a large number of pills and therefore prefer weekly dosing. Have patients take medications before the trip, to assess tolerability and to ensure adequate blood concentrations before exposure.