What are the pros and cons of taking antimalarial (malaria prevention) medication?

Antimalarial Prophylaxis: Pros and Cons

Taking antimalarial medication for malaria prevention significantly reduces your risk of a potentially life-threatening infection, but the choice of agent must balance efficacy against side effects, with no regimen providing 100% protection. 1

Major Benefits of Antimalarial Prophylaxis

Life-Saving Protection

• Antimalarials provide substantial protection against malaria, which can progress to severe disease syndromes with fatal outcomes, particularly from P. falciparum in sub-Saharan Africa and Southeast Asia 1, 2
• Most malaria deaths occur in travelers who do not fully comply with prophylaxis regimens, emphasizing that taking medication is far safer than the alternative 3, 1

Proven Efficacy by Agent

• Atovaquone-proguanil and mefloquine are first-line options for chloroquine-resistant areas (most of sub-Saharan Africa and Southeast Asia), providing the highest level of protection 1
• Primaquine offers unique causal prophylaxis by targeting pre-erythrocytic stages, preventing both primary attacks and relapses of P. vivax, with studies showing only 5.7% developed malaria compared to 52-53% with other agents 4, 2
• Chloroquine combined with proguanil provides substantial protection in areas with limited chloroquine resistance, with serious side effects being rare and deaths almost unknown 3

Significant Drawbacks and Risks

Neuropsychiatric Effects (Primarily Mefloquine)

• Mefloquine carries a significant risk of neuropsychiatric side effects including anxiety, depression, sleep disturbances, nightmares, hallucinations, and in rare cases, overt psychotic attacks or convulsions 3, 5
• These effects occur early in use (70% from the first three doses), with severe effects occurring in 0.01% of users, though British experience suggests higher frequency 3
• Dizziness, vertigo, tinnitus, hearing impairment, and loss of balance may continue for months or years after discontinuation and may be permanent in some cases 5
• Mefloquine is absolutely contraindicated in those with history of seizures, epilepsy, serious psychiatric disorders, or cardiac conduction abnormalities 1, 5

Gastrointestinal and Minor Side Effects

• Chloroquine/proguanil causes mouth ulcers, gastrointestinal upsets, occasional skin eruptions, and worsening of psoriasis, though these are more common than with other regimens 3, 6
• Vomiting occurs in 3% of mefloquine users during prophylaxis 5
• Atovaquone-proguanil has good tolerability but gastrointestinal upset can occur 6

Doxycycline-Specific Issues

• Photosensitization is uncommon but sometimes severe and prolonged, requiring avoidance of excessive sun exposure 3
• Absolutely contraindicated in children <8 years of age and throughout pregnancy 1, 7
• Requires daily dosing (versus weekly for other agents), which may reduce compliance 7

Rare but Serious Hematologic Risks

• Cases of agranulocytosis and aplastic anemia have been reported with antimalarials 5
• Maloprim (pyrimethamine-dapsone) has a low therapeutic ratio with risk of agranulocytosis if adult dose exceeds one tablet weekly 3

Primaquine Limitations

• G6PD deficiency must be ruled out before primaquine use, as it can cause severe hemolysis in deficient individuals 1
• This requires pre-travel testing, adding complexity to prophylaxis planning 1

Critical Compliance Requirements

Timing and Duration

• Start chemoprophylaxis 1-2 weeks before departure to establish habit and ensure adequate blood levels 3, 1
• Continue for 4 weeks after leaving the endemic area to prevent infections acquired near the end of travel 3, 8
• Doxycycline can begin 1-2 days before travel but still requires 4 weeks post-exposure 7

Monitoring for Long-Term Use

• Periodic ophthalmologic examinations are recommended for hydroxychloroquine/chloroquine use exceeding 6 years cumulative prophylaxis 8, 5
• Periodic liver function tests and neuropsychiatric evaluations should be performed for prolonged mefloquine use 5

Essential Non-Pharmacologic Measures

No chemoprophylactic regimen provides 100% protection, making mosquito avoidance essential 1, 8:

• Apply DEET-containing insect repellents to exposed skin 1
• Wear long-sleeved clothing and long trousers after sunset 1
• Use bed nets treated with permethrin 1
• Apply pyrethrum-containing flying-insect spray in living and sleeping areas 1

Special Population Considerations

Pregnancy

• Chloroquine and proguanil are preferred options due to their long safety record in pregnancy 1
• Mefloquine can be used in second and third trimesters 3
• Doxycycline is absolutely contraindicated throughout pregnancy 1

Children

• Atovaquone-proguanil is recommended for children ≥5 kg with weight-based dosing 1
• Mefloquine is contraindicated in children <15 kg 1, 7
• Doxycycline is absolutely contraindicated in children <8 years 1, 7

Renal Impairment

• Doxycycline can be used safely as it is metabolized and excreted through the liver 1
• Proguanil requires dose adjustment based on creatinine clearance 3

Critical Warning Signs

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. Breakthrough infections can occur despite compliance, and delayed diagnosis significantly increases mortality risk 1, 7.