Should I take malaria prophylaxis (Malarone (atovaquone-proguanil), doxycycline, or Lariam (mefloquine)) if I'm traveling to a malaria-endemic region?

Should You Take Malaria Prophylaxis for Travel?

Yes, you should take malaria prophylaxis if traveling to a malaria-endemic region, with the specific medication choice depending on your destination's resistance patterns, trip duration, medical history, and tolerance for side effects.

Determining Your Need for Prophylaxis

The decision to take malaria prophylaxis depends entirely on whether you're traveling to a malaria-endemic area. Compliance with prophylaxis is essential—most malaria deaths occur in travelers who do not fully comply with their regimen 1.

Key Principles for All Prophylaxis Regimens

• Start chemoprophylaxis 1-2 weeks before departure to establish the habit and identify any intolerance before travel 1, 2
• Continue taking medication daily (or weekly, depending on the drug) throughout your stay in the endemic area 1, 2
• Most critically, continue prophylaxis for 4 weeks after leaving the malarious area to prevent infections that may be incubating 1
• No prophylactic regimen guarantees complete protection—mosquito bite prevention remains essential 2, 3

First-Line Medication Options

Atovaquone-Proguanil (Malarone)

Atovaquone-proguanil is the preferred first-line option for most short-term travelers due to its superior tolerability profile and convenient post-travel dosing 3, 4.

• Efficacy: 100% protection in clinical trials of non-immune travelers, effective against chloroquine-resistant and mefloquine-resistant strains 3
• Major advantage: Only requires 7 days of continuation after leaving the endemic area (versus 4 weeks for other agents) 3, 4
• Tolerability: Significantly fewer gastrointestinal and neuropsychiatric adverse events compared to alternatives 3, 5
• Dosing: 250/100 mg once daily for adults, weight-based dosing for children ≥11 kg 3
• Limitations: Expensive and not universally reimbursed; must be taken with food for adequate absorption 4
• Contraindications: Severe renal impairment (creatinine clearance <30 mL/min) 6

Doxycycline

Doxycycline is the preferred alternative for longer-term travel (>2 months), budget-conscious travelers, or those visiting mefloquine-resistant areas in Southeast Asia 1, 7.

• Efficacy: Highly effective against chloroquine-resistant and mefloquine-resistant P. falciparum 1
• Dosing: 100 mg once daily, starting 1-2 days before travel, continuing for 4 weeks after departure 7, 2
• Major side effect: Photosensitivity—avoid excessive sun exposure, use high-SPF sunscreen, and wear protective clothing 1, 7
• Other common side effects: Gastrointestinal upset, vaginal candidiasis in women 5
• Absolute contraindications: Pregnancy (causes fetal bone growth inhibition and tooth discoloration), children under 8 years, breastfeeding 7, 8
• Drug interactions: Phenytoin, carbamazepine, and barbiturates decrease doxycycline half-life, potentially requiring dose adjustment 1, 2

Mefloquine (Lariam)

Mefloquine should be reserved for specific situations: pregnancy (second/third trimester), young children requiring long-term prophylaxis, or when other options are contraindicated 1.

• Efficacy: Highly effective in areas with chloroquine resistance, 100% protection in clinical trials 3, 5
• Dosing: 250 mg weekly for adults, starting 1-2 weeks before travel, continuing for 4 weeks after departure 1
• Neuropsychiatric side effects: Anxiety, depression, insomnia, abnormal dreams, and rarely hallucinations or psychotic episodes occur in a significant proportion of users 1, 9, 5
  • 70% of neuropsychiatric effects occur within the first three doses 1
  • Absolute effect sizes versus atovaquone-proguanil: 13% versus 3% for insomnia, 14% versus 7% for abnormal dreams, 6% versus 1% for anxiety, 6% versus 1% for depressed mood 5
  • These side effects can persist for months or years after stopping mefloquine and may become permanent 9, 5
• Absolute contraindications: History of seizures, epilepsy, serious psychiatric disorder (including depression), liver impairment 1, 8, 9
• Relative contraindications: Activities requiring fine motor coordination or precision movements 1, 9

Special Populations

Pregnant Women

• Pregnant women are at particular risk of severe malaria and should avoid endemic areas if possible 1
• First choice: Mefloquine in second and third trimesters (safe, long track record) 1
• Alternative: Chloroquine plus proguanil in areas without resistance 1
• Contraindicated: Doxycycline (all trimesters), atovaquone-proguanil (insufficient safety data), mefloquine (first trimester) 7

Children

• For trips <2 weeks: Atovaquone-proguanil (weight-based dosing for children ≥11 kg) 3, 6
• For trips >2 months: Mefloquine (better compliance with weekly dosing) 6
• Avoid doxycycline in children <8 years due to permanent tooth discoloration and impaired bone growth 7

Patients with Depression or Psychiatric History

• Mefloquine is absolutely contraindicated in patients with any history of serious psychiatric disorder, including controlled depression 8, 9
• First choice: Doxycycline 8
• Alternative: Atovaquone-proguanil 8

Patients with Renal Impairment

• Severe renal impairment (CrCl <30 mL/min): Mefloquine or doxycycline (both hepatically metabolized) 1
• Moderate renal impairment: Adjust proguanil dose based on creatinine clearance 1
• Atovaquone-proguanil is contraindicated in severe renal impairment 6

Asplenic Patients

• Asplenic travelers are at particular risk of severe malaria and require meticulous adherence to both chemoprophylaxis and mosquito bite prevention measures 1

Essential Non-Pharmacologic Measures

Mosquito bite prevention is mandatory regardless of chemoprophylaxis choice 1, 2:

• Use DEET-containing insect repellents on exposed skin (follow manufacturer's recommendations, especially for children) 1
• Wear long-sleeved clothing and long trousers after sunset 1
• Sleep under insecticide-treated bed nets, properly tucked under the mattress 1
• Use electric mats to vaporize synthetic pyrethroids or burn mosquito coils overnight 1
• Consider impregnating clothing with permethrin 1
• Stay in well-screened or air-conditioned accommodations when possible 6

Critical Post-Travel Considerations

• Seek immediate medical evaluation for any fever or flu-like illness occurring within one year of returning from a malaria-endemic area 1
• Inform healthcare providers of your travel history, as breakthrough infections can occur with all prophylaxis regimens 1
• For travelers with prolonged exposure to P. vivax or P. ovale endemic areas, consider adding primaquine 30 mg base daily during the last 2 weeks of the 4-week post-exposure prophylaxis period to prevent relapses from dormant liver stages 1, 7
• Primaquine requires G6PD testing before use and is contraindicated in G6PD deficiency and pregnancy 10, 7

Common Pitfalls to Avoid

• Do not stop prophylaxis early—most infections occur in travelers who discontinue medication prematurely 1
• Do not rely solely on medication—mosquito bite prevention is equally important 2
• Do not take mefloquine if you have any psychiatric history, even if well-controlled 8, 9
• Do not assume you're protected after prophylaxis ends—malaria can present up to one year after exposure 1
• Do not take halofantrine or ketoconazole with mefloquine or within 15 weeks of stopping mefloquine due to potentially fatal cardiac complications 9