What are the medication options for malaria prophylaxis?

Malaria Prophylaxis Medication Options

Primary Medication Choices by Geographic Resistance Pattern

For areas with chloroquine-resistant P. falciparum (most of sub-Saharan Africa and Southeast Asia), atovaquone-proguanil or mefloquine are first-line options, while chloroquine alone (300 mg base weekly) remains effective only in areas without resistance such as Haiti. 1, 2

First-Line Options for Chloroquine-Resistant Areas

• Atovaquone-proguanil (Malarone): 250 mg/100 mg daily, started 1-2 days before travel, continued daily during travel, and for only 7 days after leaving the malarious area 1, 3, 4

  • This shorter post-travel duration is possible because both components are active against liver-stage parasites, providing causal prophylaxis 4
  • Efficacy is 95-100% against chloroquine-resistant P. falciparum 4
  • Must be taken with food or a milky drink to ensure adequate absorption 3
  • Generally better tolerated than alternatives, with significantly fewer gastrointestinal adverse events than chloroquine-proguanil and fewer neuropsychiatric events than mefloquine 4, 5

• Mefloquine: 250 mg weekly, started 1-2 weeks before travel, continued weekly during travel, and for 4 weeks after departure 1

  • Equally effective as atovaquone-proguanil with 100% efficacy in clinical trials 4
  • Critical contraindications: history of seizures, epilepsy, serious psychiatric disorders, or cardiac conduction abnormalities 6, 1
  • Neuropsychiatric side effects occur in approximately 0.01% of users, with 70% occurring within the first three doses 6, 1
  • Should not be used by those requiring fine motor coordination (e.g., pilots) 6

• Doxycycline: 100 mg daily, started 1-2 days before travel, continued daily during travel, and for 4 weeks after departure 7, 1

  • Preferred alternative for mefloquine-resistant areas in East Asia 6, 7
  • Absolute contraindications: pregnancy, nursing mothers, and children under 8 years of age 6, 7, 8
  • Risk of photosensitivity reactions—patients must avoid excessive sun exposure and use UVA-blocking sunscreens 6, 7
  • Take in the evening with food to minimize gastrointestinal side effects 6

For Chloroquine-Sensitive Areas

• Chloroquine: 300 mg base weekly, started 1-2 weeks before travel, continued weekly during travel, and for 4 weeks after departure 1

  • Excellent safety record with rare serious adverse reactions at prophylactic doses 6, 9
  • Minor side effects include gastrointestinal upset, headache, and pruritus, but rarely require discontinuation 6
  • Retinopathy risk only with prolonged use exceeding 6 years of cumulative weekly prophylaxis—periodic ophthalmologic exams recommended beyond this duration 6
  • May exacerbate psoriasis 6, 8

• Chloroquine plus proguanil: Chloroquine 300 mg base weekly plus proguanil 200 mg daily provides substantial (though not complete) protection in areas of limited chloroquine resistance 6

  • Proguanil rarely causes adverse reactions; reported side effects include nausea, vomiting, and mouth ulcers 6
  • This combination has fewer neuropsychiatric side effects than mefloquine 6

Special Population Considerations

Pregnant Women

• Chloroquine and proguanil have the longest safety record in pregnancy and are the preferred options 1
• Mefloquine can be used in the second and third trimesters 1
• Doxycycline is absolutely contraindicated throughout pregnancy 7, 1
• Pregnant women should avoid travel to endemic areas if possible, as falciparum malaria carries higher risk of death and serious complications in this population 1, 3

Children

• Atovaquone-proguanil: Can be used in children ≥5 kg with weight-based dosing; tablets may be crushed and mixed with condensed milk or food 10, 3
• Mefloquine: Contraindicated in children <15 kg; alternative for those >15 kg but avoid if history of seizures or psychiatric disorders 6, 10
• Doxycycline: Absolutely contraindicated in children <8 years of age 6, 10
• Chloroquine: Safe at any age with careful weight-based dosing; tablets can be pulverized and mixed with food, or suspension forms are available overseas 6, 10
• Pediatric doses must be calculated carefully according to body weight 10
• Critical safety warning: Overdose of antimalarials can be fatal—store in childproof containers out of reach of children 6

Patients with Renal Impairment

• Doxycycline can be used safely as it is metabolized and excreted through the liver rather than kidneys 7

Prevention of Relapsing Malaria

• Primaquine is indicated for travelers with prolonged exposure to P. vivax or P. ovale to prevent relapses from dormant liver-stage parasites 1
• Administered during the last 2 weeks of the 4-week post-exposure prophylaxis period 1
• Mandatory screening: G6PD deficiency must be ruled out before primaquine use, as it can cause severe hemolysis in deficient individuals 6

Critical Non-Pharmacologic Measures

• No chemoprophylactic regimen provides 100% protection—mosquito avoidance is essential 1, 3
• Apply DEET-containing insect repellents to exposed skin 6, 1
• Wear long-sleeved clothing and long trousers after sunset 6, 10, 1
• Use bed nets treated with permethrin 10
• Use pyrethrum-containing flying-insect spray in living and sleeping areas 1

Essential Compliance and Safety Warnings

• Most malaria deaths occur in travelers who do not fully comply with prophylaxis regimens 6, 1
• Start prophylaxis 1-2 weeks before travel (except doxycycline and atovaquone-proguanil which can start 1-2 days before) to establish habit and ensure tolerability 6, 10, 1
• Continue prophylaxis for the full duration after leaving endemic areas—4 weeks for most agents, 7 days for atovaquone-proguanil 1, 3
• Any fever or flu-like illness within one year of travel to a malarious area requires emergency evaluation for malaria, even with appropriate prophylaxis 1, 2
• Breakthrough infections can occur on all regimens 1, 3
• If prophylaxis is discontinued prematurely, consult a healthcare professional regarding alternative forms of prophylaxis 3