Geographically variable plasmodial drug resistance has become a major factor in malaria. The World Health Organization gives advice in its annually revised booklet, Vaccination Certificate Requirements and Health Advice for International Travel; and national bodies publish advice (e.g. British National Formulary) that applies particularly to their own residents. These or other appropriate sources ought to be consulted before specific advice is given. The following general principles apply:
• Chemoprophylaxis is part of a broader regimen and only ever gives relative protection; travellers should protect against bites by using mosquito nets and repellents and wearing well-covering clothing especially during high-risk times of day (after dusk).
• Mefloquine, chloroquine, proguanil, and pyrimethamine plus dapsone (Maloprim), alone or in combination are most commonly advised for prophylaxis regimens; and doxycycline for special cases (drug resistance or intolerance); primaquine is being re-evaluated.
• Effective chemoprophylaxis requires that there be a plasmodicidal concentration of drug in the blood when the first infected mosquito bites, and that it be sustained safely for long periods.
• The progressive rise in plasma concentration to steady state (after t'/2 x 5), sometimes attained only after weeks (consider mefloquine t'/2
21 days, chloroquine tl/2 50 days), allows that unwanted effects (that will impair compliance or be unsafe) may occur after a subject has entered a malarial area. Thus it is advised that prophylaxis be begun long enough before travel to reveal acute intolerance and to impress on the subject the importance of compliance (to relate drug-taking to a specific daily or weekly event).
• Prompt achievement of efficacy and safety by one (or two) doses is plainly important for those travellers who cannot wait on dosage schedules to deliver both only when steady-state blood concentrations are attained; the schedules must reflect this need.
• Prophylaxis should continue for at least 4 weeks after leaving an endemic area to kill parasites that are acquired about the time of departure, are still incubating in the liver and will develop into the erythrocyte phase. The traveller should be aware that any illness occurring within a year, and especially within 3 months, of return may be malaria.
• Chloroquine and proguanil may be used for periods of up to 5 years, and mefloquine for up to 1 or 2 years: expert advice should be taken by long-term travellers, especially those going to areas for which other prophylactic drugs are recommended.
• Naturally acquired immunity offers the most reliable protection for people living permanently in endemic areas (below). Repeated attacks of malaria confer partial immunity and the disease often becomes no more than an occasional inconvenience. Vaccines to confer active immunity are under development.
• The partially immune as a rule should not take a prophylactic. The reasoning is that immunity is sustained by the red cell cycle, loss of which through prophylaxis diminishes their resistance and leaves them highly vulnerable to the disease. There are however exceptions to this general advice and the partially immune may or should use a prophylactic:
— if it is virtually certain that they will never abandon its use,
— if they go to another malarial area where the strains of parasite may differ, during the last few months of pregnancy in areas where Plasmodium falciparum is prevalent,
— to avert the risk of miscarriage.
All these factors contribute to conventional advice to travellers.
Examples of standard regimens
• chloroquine 300 mg (base) once weekly (start one week before travel)
• proguanil 200 mg once daily (start 2-3 days before travel)
• chloroquine plus proguanil in the above doses
• mefloquine 250 mg once weekly (start one week, preferably 2-3 weeks, before travel).
For 'last minute' travellers. The standard regimens normally provide immediate protection but for special assurance a priming/loading dose may be considered, e.g. the standard prophylactic dose daily for 2-3 days (this has been suggested for mefloquine).
Drug interactions. Where subjects are already taking other drugs, e.g. antiepileptics, some cardiovascular drugs, it is desirable to start prophylaxis as much as 2-3 weeks in advance to establish safety.
Women living in endemic areas in which Plasmodium falciparum remains sensitive to chloroquine should take chloroquine prophylactically throughout pregnancy. Proguanil (an 'antifol', see below) may be taken for prophylaxis provided it is accompanied by folic acid 5 mg/d. Chloroquine may be used in full dose to treat chloroquine-sensitive infections. Quinine is the only widely available drug that is acceptable as suitable for treating chloroquine-resistant infections during pregnancy. Mefloquine is teratogenic in animals and a woman should avoid pregnancy whilst taking it, and for 3 months after; pyrimethamine plus dapsone (Maloprim) should not be given in the first trimester, but may be given in the second and third trimesters with a folate supplement.
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