The Medical Letter on Drugs and Therapeutics
Prevention of Malaria
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Many patients planning to travel seek advice about prevention of malaria.1 No drug is 100% effective for this indication; travelers should be told to take other protective measures as well. Malaria in pregnancy is particularly serious for both mother and fetus; prophylaxis is indicated if travel cannot be avoided. Countries with a risk of malaria are listed in the table on page 102. Some countries with endemic malaria transmission may not have malaria in the most frequently visited major cities and rural tourist resorts.

CHLOROQUINE-SENSITIVE MALARIA — Chloroquine is the drug of choice for prevention of malaria in the few areas that still have only chloroquine-sensitive malaria: Central America (west of the Panama Canal Zone), Paraguay, northern Argentina, Mexico, Haiti, the Dominican Republic, North and South Korea, Armenia, Georgia and some countries in the Middle East (chloroquine resistance has been reported in Iran, Yemen, Oman, and Saudi Arabia). In rural areas of China where malaria occurs, it is generally chloroquine sensitive. Only Hainan and Yunnan provinces have chloroquine resistance.

CHLOROQUINE-RESISTANT MALARIA — Three drugs with similar efficacy, listed with their dosages in the table on page 101, are available in the US for prevention of chloroquine-resistant malaria. Malarone, a fixed-dose combination of atovaquone and proguanil taken once daily, is generally the best tolerated.2 It can cause gastrointestinal (GI) disturbances and has been associated with Stevens- Johnson syndrome.3 Atovaquone/proquanil should not be given to patients with severe renal impairment (CrCl <30 mL/min).

Mefloquine has the advantage of once-a-week dosing, but it is contraindicated in patients with a history of depression, anxiety, psychosis, schizophrenia or other major psychiatric disorders, and also in those with a history of seizures or cardiac conduction abnormalities. Dizziness, headache, insomnia and disturbing dreams are the most common CNS adverse effects. The drug’s adverse effects in children are similar to those in adults.4 If a patient develops anxiety, depression, restlessness or confusion while taking mefloquine, it should be stopped. The drug should not be given together with quinine, quinidine or halofantrine due to potential prolongation of the QT interval; caution is required when using these drugs to treat patients who have taken mefloquine prophylaxis. Mefloquine can be given to patients taking beta-blockers if they do not have an underlying arrhythmia.

Doxycycline, which frequently causes GI disturbances and can cause photosensitivity and vaginitis, offers an inexpensive once-daily alternative for travelers ≥8 years old who are not pregnant. Taking the drug with food may ameliorate GI upset. Doxycycline should not be taken concurrently with antacids, oral iron or bismuth salts.

For patients unable to take other antimalarial drugs, several studies have shown that daily primaquine phosphate begun one day before departure and continued until 3-7 days after leaving the malarious area can provide effective prophylaxis against chloroquine-resistant Plasmodium falciparum and P. vivax.5 Primaquine can cause hemolytic anemia in patients with glucose-6-phosphate dehydrogenase (G-6-PD) deficiency, which is most common in African, Asian, and Mediterranean peoples. Travelers should be screened for G-6-PD deficiency before treatment. Primaquine should be taken with food to reduce GI effects. The drug should not be used during pregnancy.

MEFLOQUINE-RESISTANT MALARIA — Doxycycline or atovaquone/proguanil are recommended for prophylaxis against mefloquine-resistant malaria, which occurs in the malarious areas of Thailand and in the areas of Myanmar and Cambodia that border on Thailand.

PREVENTION OF RELAPSE — For travelers with a high risk of infection with P. vivax and P. ovale, such as those with prolonged stay in regions where these species are highly endemic, which includes almost all areas where malaria is found (except Haiti and the Dominican Republic), some Medical Letter consultants add “terminal prophylaxis” with primaquine phosphate. Others prefer to rely on surveillance to detect cases.

PROTECTION AGAINST MOSQUITO BITES — To minimize insect bites, travelers should wear light-colored, long-sleeved shirts, pants, socks and covered shoes. They should sleep in screened areas and avoid going out after sunset when the mosquitoes that transmit malaria are most active. Dusk and dawn are the peak biting times.

The most effective topical insect repellent is N, N-diethyl-m-toluamide (DEET).6,7 Applied on exposed skin, DEET repels mosquitoes, as well as ticks, chiggers, fleas, gnats and some flies. DEET is available in formulations of 5-40% and 100%. Concentrations of 30-35% are preferred by Medical Letter consultants; higher concentrations do not improve efficacy, but usually protect longer. A long-acting DEET formulation originally developed for the US Armed Forces (US Army Extended Duration Topical Insect and Arthropod Repellent – EDTIAR) containing 25-33% DEET (Ultrathon) can provide protection for 6-12 hours. DEET in concentrations of up to 50% is probably safe in children and infants >2 months old; it should not be used in infants <2 months old. One study found that applying DEET regularly during the second and third trimesters of pregnancy did not result in any adverse effects on the fetus.8 DEET may decrease the effectiveness of sunscreens; when they are used together, a sunscreen with a higher SPF should be used. Using a sunscreen and insect repellent together apparently does not reduce the effectiveness of the insect repellent.9

Picaridin is an insect repellent that has been available in Europe and Australia for many years. The 7% formulation (Cutter Advanced) currently sold in the US10 might be as effective against mosquitoes as low concentrations of DEET, but no data are available. Higher concentrations are sold in Europe and protect against mosquitoes for up to 8 hours.11-13

Permethrin (Duranon, Permanone, and others) is an insecticide available in liquid and spray form for use on clothing, mosquito nets, tents and sleeping bags for protection against mosquitoes. After application to clothing, it remains active for several weeks through multiple launderings. Using permethrin-impregnated mosquito nets while sleeping can be helpful when rooms are not screened or air-conditioned. If bednets or tents are immersed in the liquid, the effect can last for about 6 months. It can also be used in combination with DEET for increased protection.

CONCLUSION — No drug regimen guarantees protection against malaria. Insect repellents, insecticide impregnated bed nets and proper clothing are important adjuncts for malaria prophylaxis. Travelers to malarious areas should be reminded to seek medical attention if fever develops after they return.

1. LH Chen and JS Keystone. New strategies for the prevention of malaria in travelers. Infect Dis Clin North Am 2005; 19:185.

2. P Schlagenhauf et al. Tolerability of malaria chemoprophylaxis in non-immune travellers to sub-Saharan Africa: multicentre, randomised, double blind, four arm study. BMJ 2003; 327:1078.

3. M Emberger et al. Stevens-Johnson syndrome associated with Malarone antimalarial prophylaxis. Clin Infect Dis 2003; 37:e5.

4. TA Albright et al. Side effects of and compliance with malaria prophylaxis in children. J Travel Med 2002; 9:289.

5. JK Baird et al. Primaquine for prevention of malaria in travelers. Clin Infect Dis 2003; 37:1659.

6. Insect repellents. Med Lett Drugs Ther 2003; 45:41.

7. MS Fradin and JF Day. Comparative efficacy of insect repellents against mosquito bites. N Engl J Med 2002; 347:13.

8. R McGready et al. Safety of the insect repellent N, N-diethyl-mtoluamide (DEET) in pregnancy. Am J Trop Med Hyg 2001; 65:285.

9. ME Murphy et al. The effect of sunscreen on the efficacy of insect repellent: a clinical trial. J Am Acad Dermatol 2000; 43:219.

10. Picaridin – a new insect repellent. Med Lett Drugs Ther 2005; 47:46.

11. A Badolo et al. Evaluation of the sensitivity of Aedes aegypti and Anopheles gambiae complex mosquitoes to two insect repellents: DEET and KBR 3023. Trop Med Int Health 2004; 9:330.

12. SP Frances et al. Field evaluation of repellent formulations containing deet and picaridin against mosquitoes in Northern Territory, Australia. J Med Entomol 2004; 41:414.

13. C Costantini et al. Field evaluation of the efficacy and persistence of insect repellents DEET, IR3535, and KBR 3023 against Anopheles gambiae complex and other afrotropical vector mosquitoes. Trans R Soc Trop Med Hyg 2004; 98:644.

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