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Two antimalaria drugs are tolerated regimens in regions with resistance


In a review published in The Cochrane Library, researchers determined that atovaquone-proguanil and doxycycline were well tolerated by most travelers and are less likely than mefloquine to cause adverse neuropsychiatric outcomes.

Key Points

In a review published in The Cochrane Library, researchers determined that atovaquone-proguanil and doxycycline were well tolerated by most travelers and are less likely than mefloquine to cause adverse neuropsychiatric outcomes.

Plasmodium falciparum is responsible for the most severe form of malaria; and patients present with variable symptoms including spiking fever, chills, headache, muscular aching and weakness, vomiting, cough, and diarrhea. Unless the patient receives prompt diagnosis and treatment, the disease often progresses to circulatory and major organ failure, generalized convulsions, and death.

The preventive measures taken against malaria infection include barrier methods and chemoprophylaxis. Chloroquine is an effective prophylaxis in those regions in which P. falciparum has not developed resistance to the drug. In regions where resistance has developed, travelers will need to take newer and stronger regimens.

The researchers compared these agents to each other and to choroquine-proguanil (an older drug combination) and to primaquine (a candidate for chemoprophylaxis).

Atovaquone-proguanil (Malarone) in addition to being a suppressive drug is a causal hepatic stage agent; therefore, it need only be taken by the traveler for one week after leaving the malaria-endemic region.

Due to insufficient data, it is not recommended for pregnant women, but can be given to children of > 11-kg body weight. Doxycycline is an off-patent, once-daily, long-acting antimicrobial agent of the tetracycline class. It may be used by pregnant women, although data are insufficient as to its safety during the first trimester.

Because doxycycline is only effective in suppressing the blood stages of Plasmodium, it needs to be taken before, during, and 1-month after travel to a malaria-endemic region.

Mefloquine, like doxycycline, is an off-patent drug that may be used during the second and third trimesters of pregnancy. It is effective in suppressing the blood stages of the disease and, therefore, travelers need to follow the same guidelines as those taking doxycycline. However, its use remains controversial because of the neuropsychiatric character of the adverse events.

The authors report inconclusive evidence as to which drug is most effective. Likewise there was inclusive evidence as to which drug is safest in the study population.

They also note that primaquine has only modest activity against P. falciparum, although it is thought to protect against P. vivax infection.

Atovaquone-proguanil and doxycycline had a better tolerability profile than mefloquine, and all three drugs were better tolerated than chloroquine-proguanil.

Compared with mefloquine, atovaquone-proguanil users reported fewer of any adverse effect (risk ratio [RR] 0.72, 95% confidence intervals [CI] 0.6 to 0.85), gastrointestinal adverse effects (RR 0.54, 95% CI 0.42 to 0.7), neuropsychiatric adverse events (RR 0.86, 95% CI 0.75 to 0.99) and neuropsychiatric adverse effects (RR 0.84, 95% CI 0.38 to 0.63), and a better mood disturbance score (MD -7.20, 95% CI -10.79 to -3.61).

Doxycycline users had reported fewer neuropsychiatric events than mefloquine users (RR 0.84, 95% CI 0.73 to 0.96). For any of the outcomes, there was no difference between atovaquone-proguanil and doxycycline.

The authors report a number of limitations of their review. The selection criteria excluded placebo-controlled trials and also studies conducted on semi-immune populations. Also, the authors were unable in most cases to obtain additional data from authors of the studies under review.Adverse events were commonly reported for all of the drugs.

As the data did not provide evidence of comparative protective efficacy, the authors recommend that healthcare professionals when deciding whether to prescribe atovaquone-proguanil or doxycycline (or in exceptional cases, mefloquine) take into account factors such as cost, known contraindications, known rare serious adverse events, possible drug-drug interactions, ease of use, and travel itinerary.


Jacquerioz FA, Croft AM. Drugs for preventing malaria in travellers. Cochrane Database Sys Rev. 2009, Issue 4. Art. No.: CD006491. DOI: 10.1002/14651858.CD006491.pub2. Available at: http://www.cochrane.org/reviews/

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