What is the recommended malaria vaccine regimen for individuals traveling to or living in areas where malaria is endemic, particularly for children and adults with varying risk factors and medical histories?

Malaria Vaccine Recommendations

The RTS,S/AS01 malaria vaccine (Mosquirix®) is recommended by WHO for children from 5 months of age living in regions with moderate to high Plasmodium falciparum transmission in sub-Saharan Africa, administered as a 4-dose schedule (3 initial doses at least 1 month apart, with a 4th dose 15-18 months after dose 3), and should be used alongside—not instead of—chemoprophylaxis and mosquito avoidance measures for travelers. 1

Vaccine Eligibility and Regimen

For Children in Endemic Areas

• Children aged 5 months and older living in malaria-endemic regions should receive RTS,S/AS01 according to a 4-dose schedule: doses 1-3 given at least 1 month apart, followed by a 4th dose 15-18 months after the 3rd dose. 2, 1

• An optional 5-dose schedule may be used in areas with highly seasonal malaria transmission to optimize protection during high-risk periods. 1

• The vaccine demonstrates greater efficacy in children (5-17 months at first vaccination) compared to younger infants, with protection against clinical malaria, severe malaria, and malaria hospitalization. 2, 1

• Large-scale pilot implementation in Africa confirms the vaccine has a favorable safety profile, can be delivered through routine national immunization programs, and substantially reduces severe malaria burden. 1

Critical Limitation for Travelers

• RTS,S/AS01 is NOT recommended for travelers (adults or children) visiting malaria-endemic areas, as it is designed specifically for children living continuously in endemic regions and provides only partial protection that wanes over time. 2

• The vaccine showed vaccine efficacy that waned over time, making it unsuitable as a standalone prevention strategy for short-term travelers. 2

Chemoprophylaxis for Travelers

For Chloroquine-Resistant Areas (Most of Africa, Madagascar)

• First-line options include atovaquone-proguanil, doxycycline, or mefloquine, as chloroquine resistance is widespread in Africa where 80% of imported U.S. malaria cases originate. 3, 4

• Atovaquone-proguanil: Start 1-2 days before travel, continue daily during travel, and for 7 days after departure—the shortest post-exposure duration of any regimen. 3

• Doxycycline 100 mg daily: Start 1-2 days before travel, continue daily during travel, and for 4 weeks after departure; contraindicated in pregnancy and children under 8 years. 5, 3

• Mefloquine 250 mg weekly: Start 1-2 weeks before travel, continue weekly during travel, and for 4 weeks after departure; avoid in patients with seizure history, psychiatric disorders, or those requiring precision movements. 5, 3

For Chloroquine-Sensitive Areas (Central America, Haiti, Dominican Republic)

• Chloroquine 500 mg base weekly is the prophylactic drug of choice: Start 1-2 weeks before travel, continue weekly during travel, and for 4 weeks after departure. 6, 7

• Hydroxychloroquine may be substituted for those who cannot tolerate chloroquine. 6

Special Populations

• Pregnant women should use chloroquine as the safest option and carry Fansidar for presumptive self-treatment if fever develops and medical care is unavailable. 5, 3

• Children under 15 kg should use chloroquine, as mefloquine and doxycycline are contraindicated. 5, 3

Essential Mosquito Protection Measures

All travelers must combine chemoprophylaxis with rigorous personal protection, as no antimalarial regimen guarantees complete protection. 6, 3

Behavioral Measures

• Remain in well-screened areas during evening and nighttime hours (dusk to dawn) when Anopheles mosquitoes feed most actively. 6, 7

• Sleep under mosquito nets, preferably permethrin-impregnated nets. 6

• Wear clothing that covers most of the body, especially during high-risk hours. 6, 7

Chemical Protection

• Apply DEET at 20-50% concentration to exposed skin—higher concentrations (up to 50%) provide longer protection and should be considered first choice. 6, 3

• Apply DEET sparingly only to exposed skin or clothing; avoid high-concentration products on children's skin, do not apply to children's hands (risk of eye/mouth contact), never use on wounds or irritated skin, and wash treated skin after coming indoors. 6, 3

• Apply permethrin (Permanone) to clothing for additional protection. 6, 7

• Use pyrethroid-containing sprays in living/sleeping areas during evening and nighttime hours. 7

Prevention of Relapsing Malaria

• Primaquine 30 mg base daily during the last 2 weeks of the 4-week post-exposure prophylaxis period prevents relapses of P. vivax and P. ovale for travelers with prolonged exposure in endemic areas (e.g., missionaries, Peace Corps volunteers). 5, 3

• Primaquine requires mandatory G6PD testing before use and is contraindicated in pregnancy and G6PD deficiency. 5, 3

• Most malarious areas worldwide (except Haiti) have at least one species of relapsing malaria, but primaquine is not indicated for all travelers—only those with prolonged exposure. 5

Critical Warnings

• Any fever or influenza-like symptoms during or after travel requires immediate medical evaluation with thick and thin malaria smears, as symptoms can develop as early as 8 days after exposure or as late as several months after leaving the malarious area, even after chemoprophylaxis has been discontinued. 6, 3, 4

• Among U.S. residents diagnosed with malaria, 71.7% had not taken malaria chemoprophylaxis during travel, highlighting the critical importance of adherence. 4

• Severe malaria occurred in approximately 14% of U.S. patients in 2017, with a mortality rate of 0.3%, emphasizing that delayed treatment can have serious or fatal consequences. 4

• Malaria can still be contracted despite perfect adherence to all preventive measures—no antimalarial regimen guarantees 100% protection. 6, 3