What are the recommended medications and dosing regimens for malaria prophylaxis in international travelers?

Malaria Prophylaxis for International Travel

Primary Recommendation by Geographic Risk

For areas with chloroquine-resistant P. falciparum, mefloquine 250 mg weekly is the first-line prophylaxis, started 1-2 weeks before travel and continued for 4 weeks after leaving the malarious area. 1 For travelers who cannot tolerate mefloquine or have contraindications, doxycycline 100 mg daily is the preferred alternative, started 1-2 days before travel and continued for 4 weeks after departure. 1, 2

For areas without chloroquine resistance, chloroquine alone (300 mg base weekly) remains effective and should be started 1-2 weeks before travel and continued for 4 weeks after leaving. 1, 3

Specific Dosing Regimens

Mefloquine (First-Line for Chloroquine-Resistant Areas)

• Adults: 250 mg (one tablet) weekly, starting 1 week before travel 4
• Pediatric patients >45 kg: One 250 mg tablet weekly 4
• Pediatric patients 30-45 kg: 3/4 tablet weekly 4
• Pediatric patients 20-30 kg: 1/2 tablet weekly 4
• Continue weekly during travel and for 4 additional weeks after leaving the endemic area 1, 4
• Take after the main meal with at least 8 oz (240 mL) of water 4

Doxycycline (Alternative for Chloroquine-Resistant Areas)

• Adults: 100 mg daily 2
• Pediatric patients >8 years and <45 kg: 2 mg/kg daily (up to adult dose) 2
• Pediatric patients ≥45 kg: 100 mg daily 2
• Start 1-2 days before travel (shorter lead time than other agents) 1, 2
• Continue daily during travel and for 4 weeks after leaving 1, 2
• Administer with adequate fluid and food to reduce esophageal irritation 2

Chloroquine (For Non-Resistant Areas)

• Adults: 300 mg base (500 mg salt) weekly 1
• Start 1-2 weeks before travel 1
• Continue weekly during travel and for 4 weeks after leaving 1
• Can be taken with meals or in divided twice-weekly doses if side effects occur 1

Special Populations

Pregnant Women

Pregnant women are at particular risk of severe malaria and should avoid endemic areas if possible. 1 When travel is unavoidable:

• Chloroquine and proguanil have a long safety record in pregnancy and are the preferred agents 1
• Mefloquine can be used in the second and third trimesters 1
• Doxycycline is contraindicated throughout pregnancy 5

Children

• Doxycycline is contraindicated in children under 8 years of age 6
• For children unable to take mefloquine or doxycycline, especially those under 15 kg, chloroquine is recommended 1
• Mefloquine tablets may be crushed and suspended in water, milk, or other beverage for children unable to swallow whole 4

Renal Impairment

• Mefloquine and doxycycline can be used without dose adjustment in renal failure, including dialysis patients, as they are metabolized and excreted through the liver 1, 5
• Proguanil requires dose reduction based on creatinine clearance 1

Asplenic Patients

Asplenic travelers are at particular risk of severe malaria and require meticulous precautions against mosquito bites and strict compliance with chemoprophylaxis 1

Critical Contraindications and Precautions

Mefloquine

• Contraindicated in patients with history of convulsions, epilepsy, or serious psychiatric disorders 1, 3
• Neuropsychiatric side effects occur in approximately 0.01% (severe), with 70% occurring within the first three doses 1
• Unsuitable for those with liver impairment 1
• Should not be used for self-treatment due to frequency of side effects, especially dizziness 1

Doxycycline

• Photosensitization risk: Avoid excessive sun exposure 1, 6, 5
• Drug interactions with phenytoin, carbamazepine, and barbiturates shorten doxycycline half-life; theoretically requiring dose increase, though limited clinical experience exists 1
• Contraindicated in pregnancy and lactation 6, 5

Prevention of Relapsing Malaria (P. vivax and P. ovale)

Primaquine is indicated for travelers with prolonged exposure (e.g., missionaries, Peace Corps volunteers) to prevent relapses from liver-stage parasites that can persist for up to 4 years. 1 Primaquine is administered during the last 2 weeks of the 4-week post-exposure prophylaxis period. 1 This is particularly important as mefloquine does not eliminate hepatic-phase parasites. 4

Essential Non-Pharmacologic Measures

Compliance with mosquito avoidance is critical, as most malaria deaths occur in travelers who do not fully comply with prophylaxis regimens. 1, 6, 3 Key protective measures include:

• Use DEET-containing insect repellents on exposed skin 6, 3
• Wear long-sleeved clothing and long trousers after sunset 6, 3
• Use pyrethrum-containing flying-insect spray in living and sleeping areas 6, 3
• Consider permethrin-treated clothing and mosquito nets 6, 3

Critical Pitfalls to Avoid

• No prophylactic regimen provides 100% protection against malaria 3
• Any fever or flu-like illness within one year of travel to a malarious area requires emergency evaluation for malaria 1
• Starting prophylaxis 1-2 weeks before travel (except doxycycline) allows assessment of tolerability and ensures adequate drug levels 1
• Breakthrough infections occur on all regimens; prompt medical evaluation is essential if symptoms develop 1, 3
• Travelers using chloroquine in resistant areas should carry standby treatment (though Fansidar is no longer recommended due to agranulocytosis risk) 1