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Primary Care Corner with Geoffrey Modest MD: Malaria Prophylaxis Twice a Week With Atovaquone-proguanil?

7 Oct, 16 | by EBM

By Dr. Geoffrey Modest

Overall, the results are pretty miserable for medication adherence to malaria prophylaxis in long-term travelers to malaria-infested areas. A recent article found that twice-a-week prophylaxis with atovaquone – proguanil (Malarone) was very effective (see doi: 10.1093/jtm/taw064).


  • An observational study was conducted in two sites in West Africa: the jungle in Angola and a medical station in Equatorial Guinea.
  • Angola: 14 male expatriates, median age 24, working in the jungles of Angola for 16 months. During the first six months, all refused malaria prophylaxis, and eight developed malaria, 2 with severe cases. They then accepted twice weekly AP (atovaquone-proguanil), given through directly-observed therapy.
  • Equatorial Guinea: 108 medical staff and families (50% male, age range 1.5 to 71 with 28 < 12 years old, mean stay 19.5 months. 49 declined malaria prophylaxis, 40 received mefloquine, in 19 heard about the Angola experience and decided to take twice-weekly AP.
  • Overall, 122 people were included in the study. 63 did not take prophylaxis, 40 took mefloquine, and 33 took AP twice-weekly.


  • No prophylaxis: 16 cases of malaria: 11.7 per thousand person-months (1368 months at risk)
  • Mefloquine: two cases per 1000 person-months (983 months at risk)
  • AP twice-weekly: zero cases per 391 person-months (391 months at risk)
  • Either treatment was associated with a 20-fold decreased odds of malaria infection compared to no prophylaxis, OR = 0.05 (0.006 – 0.42), p= 0.006.


  • Malaria in general, and falciparum in particular, is a huge international problem, with ramifications for travelers:
    • 97 countries have continuing risk of malaria transmission. These countries are visited by more than 125 million international travelers per year
    • At least 10,000 cases of travel-associated malaria occur annually, mostly in those who did not take malaria chemoprophylaxis.
    • Malaria is still the leading cause of hospitalization in ill-returning febrile travelers
    • Malaria remains the leading cause of death from infectious diseases among travelers
    • Travel to sub-Saharan Africa has both a heavy burden of Plasmodium falciparum, as well as most deaths from malaria.
    • There are three approved options for malaria chemoprophylaxis in sub-Saharan Africa: mefloquine weekly, doxycycline daily, and AP daily.
  • Travelers spending more than a few weeks in a malarial zone often do not take prophylaxis. It was quite striking in this study that the 45% of the participants not taking prophylaxis were in fact medical personnel.
  • Although not formally studied, AP has the potential for long-term of prophylaxis given the long half-life of atovaquone of 50 to 84 hours, though proguanil is only 14 to 20 hours, with some suggestive data that weekly dosing may be adequate.
  • AP is in some ways the most appealing regimen, given its very low side effect profile vs. mefloquine or doxycycline, but is quite expensive. The weekly costs are approximately:  AP daily $50, mefloquine once a week $10, doxycycline daily $18.
  • This was not a large randomized controlled trial, but the numbers are quite impressive. I think at this point it is wise to recommend the standard approved treatments, but given the high likelihood for non-adherence, I personally will offer the option (as a second-tier option) of the twice-a-week AP therapy for those who are reluctant to take AP daily because of either cost (which then becomes $14/week and comparable to the other options), or concerns about effectiveness, or other concerns about taking daily medications.

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