Malaria is the most important parasitic disease that you will face in most tropical and subtropical countries. A delay in diagnosis and treatment can have fatal consequences. If you plan to travel to a malarious region, there are five things you must do:

1. Estimate your risk of being exposed to malaria. You can find out from the Destinations section of this website if there is risk of malaria in the countries you will be visiting, what regions are most infected, and what type of malaria is most common.
    
2. Take measures to prevent insect bites. Use an insect repellent on your skin in conjunction with permethrin-treated clothing. A permethrin-treated mosquito net is often very useful. If you prevent mosquito bites, your risk of malaria is virtually eliminated.
    
3. Take a prophylactic drug. These are listed below. Drug prophylaxis is especially important in countries where there is the risk of falciparum malaria. Don't skip prescribed doses.
    
4. Know the symptoms of malaria.
    
5. Seek immediate medical treatment if symptoms of malaria occur. Always consider malaria if you develop a fever after being in a malarious area.

Virtually all cases of malaria can be prevented. Unfortunately, a high proportion of travelers who have acquired malaria most likely did not receive appropriate information on, or did not comply with, malaria prevention measures.

Chemoprophylaxis
Before departing for a malarious area, you and your doctor (or travel clinic specialist) should review your itinerary and decide if prophylaxis is indicated and which drug you should take. In general, drug prophylaxis is indicated if your risk of exposure will be moderate to high.

Factors determining your need for, and choice of, prophylaxis include (1) your itinerary; (2) the intensity and duration of your exposure to mosquito bites, especially those transmitting P. falciparum species of malaria parasites; (3) your own knowledge of malaria and its symptoms; (4) your ability to obtain rapid, qualified medical care should symptoms occur; (5) your medical history and personal health status; (6) your history of known drug allergies or known ability (or inability) to tolerate certain prophylactic drugs; (7) your use of other medications that may be incompatible with prophylactic drugs; (8) your age; and (9) your pregnancy status, if applicable.

The complexity of the situation is one reason why seeing a travel medicine specialist is advisable when exposure to malaria is likely.

Drugs Used to Prevent Malaria

Atovaquone/Proguanil (Malarone)
A combination of atovaquone (250 mg) and proguanil (100 mg) is the newest drug for the prevention and treatment of malaria. In multiple trials, atovaquone/proguanil (Malarone) has been shown to be 95-100% effective against chloroquine-resistant and multidrug-resistant strains of P. falciparum parasites, including those along the borders of Thailand and Vietnam. Atovaquone/proguanil (Malarone) only a short period of pre-exposure and postexposure dosing.

Adult dosage—One tablet, started 1-2 days before travel, taken daily during exposure, and for 7 days after leaving the malarious region.

Child dosage—Pediatric-strength tablet (25 mg proguanil with 62.5 mg atovaquone) is available. The dosage is based on weight: 10 kg-20 kg, 1 pediatric-strength tablet; 21-30 kg, 2 pediatric-strength tablets; 31-40 kg, 3 pediatric-strength tablets; and more than 40 kg, 1 adult-strength tablet.

Side effects—So far, atovaquone/proguanil (Malarone) has an enviable safety record, with no reports of serious adverse side effects. Patients with renal insufficiency, however, should not take atovaquone/proguanil but should instead choose either mefloquine or doxycycline. Most complaints include stomach upset, cough, and skin rash. Tablets should be taken with food or a milky drink at the same time each day. If vomiting occurs within 1 hour after dosing, a repeat dose should be taken.

Atovaquone/proguanil (Malarone) has not been adequately tested in pregnancy, and, therefore, its use cannot be recommended; however, neither component drug has shown teratogenic effects in animal models. The manufacturer suggests that the drug may be used cautiously if the potential benefit outweighs the potential risk to the fetus.

Chloroquine
For sensitive P. falciparum and P. vivax, chloroquine remains the drug of choice to prevent malaria. The standard doses are generally well tolerated and safe for pregnant women and children. Because of widespread resistance, however, the use of chloroquine against P. falciparum is limited to persons traveling in Central America, the Caribbean, and parts of the Middle East. While chloroquine remains effective against most strains of P. vivax, P. ovale, and P. malariae, resistance to P. vivax is increasing, particularly in the South Pacific, Southeast Asia, and parts of South America (Guyana).

Adult dosage—500 mg salt (300 mg base) once weekly, beginning 1 week before and continuing 4 weeks after leaving the malarious area.

Child dosage—8.3 mg/kg salt (5 mg/kg base) once weekly, up to a maximum adult dose of 500 mg salt/week.

Side effects—Chloroquine is generally well tolerated and is safe for children and pregnant women. Taking chloroquine with meals can usually control gastrointestinal side effects, such as nausea. Dizziness, headache, blurred vision, and itching may also occur, but these symptoms will rarely require you to stop taking the drug.

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Doxycycline
Doxycycline is a tetracycline derivative that has the advantage of being more than 90% effective against chloroquine-resistant falciparum malaria, including the falciparum malaria found along the borders of Thailand.

Adult dosage—100 mg daily. Doxycycline should be started 1 to 2 days prior to exposure. It must be continued daily in malarious areas and for 4 weeks after departure from the malarious area.

Child dosage (for children older than 8 years of age)—2 mg per kg of body weight per day up to the adult dose of 100 mg daily.

Side effects—Most travelers tolerate doxycycline well, but nausea, vomiting, and heartburn can occur. Doxycycline should be swallowed in the upright position with sufficient liquid or food to ensure complete passage of the tablet into the stomach. Doxycycline can cause phototoxicity, which is an exaggerated sunburn reaction to strong sunlight. The risk can be reduced by avoiding prolonged, direct exposure to the sun, wearing a hat, and using a broad-spectrum sunscreen. Women may develop a vaginal yeast infection and should carry a self-treatment dose of an antifungal agent such as fluconazole (Diflucan).

Doxycycline is contraindicated for pregnant women and children under the age of 8.

Mefloquine
Mefloquine (Lariam) is recommended for both short- and long-term travel to countries where there is chloroquine-resistant P. falciparum. The drug is also highly effective against P. vivax, P. ovale, and P. malariae. In western Cambodia and along the border areas of Thailand, however, the incidence of mefloquine-resistant P. falciparum is as high as 50%, and prophylaxis with Malarone (atovaquone/proguanil) or doxycycline is recommended.

Adult dosage—250 mg (1 tablet) once weekly during travel in malarious areas and for 4 weeks after leaving such areas. Mefloquine should be started at least 1 week prior to departure.

Child dosage—Children: 5-14 kg, 1/8 tablet weekly; 15-19 kg, 1/4 tablet weekly; 20-30 kg, 1/2 tablet weekly; 31-45 kg, 3/4 tablet weekly; and >45 kg, 1 tablet weekly. Less than 5 kg, a proportionately lower dose should be given.

Side effects—Mefloquine (Lariam) in prophylactic doses is generally well tolerated, but about 25% of users report mild-to-moderate side effects—strange dreams, insomnia, nausea, dizziness, and weakness. Neuropsychological side effects (anxiety, depression, agitation, nightmares) that are severe enough to require discontinuation of the drug occur in about 3% of users; severe neuropsychiatric side effects (psychosis, seizures) are extremely rare. Splitting the weekly dose and taking one-half tablet twice weekly may reduce side effects. Taking the drug with food lessens upset stomach.

Mefloquine is now considered safe for prophylaxis during pregnancy (and, by extension, also safe for infants). The drug is contraindicated for patients with a history of epilepsy or seizures, serious psychiatric illness, or cardiac conduction disturbances associated with an arrhythmia.

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Factors That Influence Antimalarial Prophylactic Drug Choice

N/A (not available)
*Cost based on average wholesale price as of August 2001
†Cost of generic doxycycline
Note: Table lists drugs in alphabetical order.

Major Contraindications for Antimalarial Prophylactic Drugs

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An Alternative Drug for Malaria Prevention
Primaquine has long been used for the treatment of relapsing malaria, but in the last decade it has been reexamined for malaria prevention. When adults take a daily dose of 30 mg (or 0.5 mg/kg per day for children), an effectiveness of 85-95% against P. falciparum (as well as P. vivax and P. ovale) has been demonstrated. Like atovaquone/proguanil, prophylactic primaquine should be started 1 day before exposure, taken daily during exposure, and for 7 days post-exposure.

Because primaquine is capable of causing severe hemolytic anemia, a G-6-PD enzyme-screening test is required before using this drug. Primaquine is contraindicated in pregnant women.

At this time, primaquine is not routinely recommended, but some physicians prescribe it for the traveler who cannot tolerate mefloquine or doxycycline. It has the advantage of being relatively inexpensive, compared to Malarone.

Recommendations for Prophylaxis of Malaria
The best choice of prophylactic drug depends on many factors, such as destination (Is there drug-resistant P. falciparum?), duration of travel, dosing schedule (Will there be a problem with compliance?), possible side effects, cost, and other factors.

• Atovaquone/proguanil (Malarone): This is considered the drug of choice for travelers taking relatively brief trips to chloroquine-resistant areas because of its favorable safety profile and its short period of pre-exposure and postexposure dosing. The dosing schedule is ideal for frequent travelers, for travelers who depart on short notice, and for those who live in the tropics and have repeated short exposures outside urban areas.
   
• Chloroquine (Aralen): The best choice for areas with chloroquine-sensitive malaria. This includes Mexico and Central America, the Caribbean, and parts of the Middle East.
   
• Doxycycline (Doryx, Vibramycin): This drug is an option for travel to chloroquine-resistant areas. Doxycycline is dosed daily and gives >90% protection against P. falciparum, even in areas with multidrug-resistant strains. It is an effective alternative for travelers who are unable to tolerate atovaquone/proguanil or mefloquine or for travelers who are concerned about the cost of prophylaxis.
   
• Mefloquine (Lariam): Mefloquine, if tolerated, may be preferable for long-term travel (>2-3 weeks) because of its lower cost (compared to atovaquone/proguanil) and weekly, rather than daily, dosing schedule.
   
• Primaquine: Although it is not FDA-approved for prophylaxis, its off-label use may be appropriate for some travelers or those who are intolerant of the other drugs.

Malaria Prophylaxis According to Geographic Area¹

¹In Central America, South America, and Southeast Asia, travelers are generally at risk only in rural areas during evening and nighttime hours. In sub-Saharan Africa and Oceania, malaria is often transmitted in both urban and rural areas.
²Atovaquone/proguanil can be carried for use as emergency treatment in remote areas if malaria is suspected in travelers not using this drug for prophylaxis and not having access to medical care in 24-48 hours.
³Off-label use. Requires G-6-PD enzyme-screening test.
⁴A combination of proguanil and a sulfonamide is an alternative for travelers in Thailand unable to take doxycycline or atovaquone/proguanil. Dosage: proguanil, 200 mg daily, plus either sulfisoxazole, 75 mg/kg daily, or sulfamethoxazole, 1500 mg daily. Mefloquine resistance is common along the Thai/Myanmar and Thai/Cambodian borders.

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Standby Treatment
Is chemoprophylaxis always necessary? The answer is almost always yes in areas with falciparum malaria, but less compelling where the main risk is vivax malaria. A few European countries are considering a change in their efforts to prevent malaria. Realizing that malaria is extremely rare in travelers to some areas, they are now moving toward "standby therapy" instead of continuous chemoprophylaxis for travelers to most parts of Central and South America as well as parts of Asia. Travelers qualifying for "standby therapy" should:

• be well-informed and educated;
   
• consult with a travel medicine expert and be provided with doses of the standby drug to carry with them (i.e., not given a prescription for the medication); and
   
• be advised to seek prompt medical diagnosis and treatment in case of illness.

Travelers who are supplied with standby treatment must have precise instructions regarding how to recognize malarial symptoms, how to take the medication, and warnings about adverse effects from the medication. However, while such advice appears to be straightforward and logical, there are potential problems, including the following:

• Noncompliance with the advice to consult a medical professional within 24 hours of taking the standby medication, especially if the traveler feels better.
   
• Overdiagnosis of malaria by physicians in endemic countries.
   
• The inadvertent use of the malaria standby medication for other illnesses, such as travelers' diarrhea.
   
• Adverse side effects from some of the drugs presently available for standby treatment (e.g., quinine, mefloquine). One agent, halofantrine, is no longer used; it has been associated with several fatalities.

Click here for more information on Malaria.

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