What medication is recommended for malaria prophylaxis (prevention) when traveling to areas with chloroquine-resistant or sensitive Plasmodium falciparum?

Malaria Prophylaxis for Travel

Primary Recommendation Based on Destination

For chloroquine-sensitive areas, use chloroquine 300 mg base weekly; for chloroquine-resistant regions, use atovaquone-proguanil, doxycycline 100 mg daily, or mefloquine 250 mg weekly as first-line options. 1, 2

Chloroquine-Sensitive Areas

• Chloroquine 300 mg base weekly is the drug of choice for areas without chloroquine resistance, such as parts of Central America west of the Panama Canal 3, 2, 4
• Start 1-2 weeks before travel, continue weekly during exposure, and for 4 weeks after leaving the endemic area 3, 1
• Hydroxychloroquine may be substituted if chloroquine causes gastrointestinal upset, as it is often better tolerated 3, 5

Chloroquine-Resistant Areas (Most of Sub-Saharan Africa, Southeast Asia)

Three first-line options exist, selected based on contraindications and side effect profiles:

Option 1: Atovaquone-Proguanil (Preferred for Tolerability)

• Most convenient regimen: Start 1-2 days before travel, continue daily during exposure, and for only 7 days after departure 1, 6
• Provides 95-100% protection against chloroquine-resistant P. falciparum 6
• Significantly fewer gastrointestinal adverse events than chloroquine-proguanil and fewer neuropsychiatric events than mefloquine 6, 7
• Must be taken with food to ensure adequate absorption 8
• More expensive than alternatives but superior adherence due to shorter post-travel duration 6

Option 2: Doxycycline 100 mg Daily

• Start 1-2 days before travel, continue daily during exposure, and for 4 weeks after departure 3, 1
• Effective alternative for mefloquine-resistant areas, particularly in East Asia 3, 2
• Contraindicated in pregnancy, lactation, and children <8 years 3, 2
• Photosensitivity can be severe and prolonged—counsel patients to avoid excessive sun exposure 3, 1
• Phenytoin, carbamazepine, and barbiturates shorten doxycycline half-life; theoretical need for dose increase 3

Option 3: Mefloquine 250 mg Weekly

• Start 1-2 weeks before travel, continue weekly during exposure, and for 4 weeks after departure 3, 1
• Highly effective against chloroquine-resistant P. falciparum 9, 6
• Neuropsychiatric side effects occur in 0.01%-higher frequency, with 70% occurring in the first three doses 3, 1
• Absolute contraindications: history of seizures, epilepsy, serious psychiatric disorders, or need for precision movements 3, 1, 2
• Never use mefloquine for self-treatment due to high frequency of dizziness at therapeutic doses 3
• Starting 1-2 weeks before travel allows assessment of tolerability before departure 3, 1

Special Populations

Pregnant Women

• Chloroquine is the safest option during pregnancy 3, 1
• Carry Fansidar (sulfadoxine-pyrimethamine) for presumptive self-treatment if fever develops and medical care is unavailable 3
• Continue weekly chloroquine after presumptive Fansidar treatment 3
• Mefloquine and doxycycline are contraindicated 3, 2

Children

• Children <15 kg should use chloroquine 3, 1
• Atovaquone-proguanil is effective in children ≥11 kg with weight-based dosing 6
• Doxycycline contraindicated in children <8 years 3, 2

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

• Primaquine 30 mg base daily during the last 2 weeks of the 4-week post-exposure prophylaxis period prevents relapses 3, 1
• Mandatory G6PD testing before primaquine use; absolutely contraindicated in G6PD deficiency and pregnancy 3, 1
• Generally indicated for prolonged exposure (missionaries, Peace Corps volunteers) rather than short-term travelers 3
• Chloroquine, mefloquine, and atovaquone-proguanil do not eliminate hepatic stages and cannot prevent relapses 4, 8

Critical Compliance and Safety Issues

Timing Pitfalls

• Most malaria deaths occur in travelers who do not fully comply with prophylaxis regimens 3, 1, 5
• Never stop prophylaxis early—continue for full 4 weeks post-exposure (except atovaquone-proguanil at 7 days) even if asymptomatic 1, 2
• Starting chloroquine/mefloquine 1-2 weeks before travel establishes habit formation and allows side effect assessment 3

Recognizing Prophylaxis Failure

• No prophylactic regimen provides 100% protection 2, 5
• Any fever during or after travel to endemic areas requires immediate medical evaluation with disclosure of travel history 3, 2
• P. vivax and P. ovale can relapse up to 4 years after exposure due to dormant liver stages 3, 2

Mosquito Avoidance Measures (Essential Adjunct)

• Remain in well-screened areas between dusk and dawn 3, 1
• Apply DEET-containing repellents to exposed skin (avoid high concentrations on children, never on wounds or irritated skin) 3, 1
• Wear long sleeves and pants after sunset 1
• Sleep under permethrin-treated bed nets 1
• Apply permethrin spray to clothing for additional protection 3, 1
• Use pyrethrum-containing flying-insect spray in living areas during evening hours 3