Atovaquone + proguanil: new preparation. Second-line antimalarial combination.

(1) Quinine, halofantrine and mefloquine are effective treatments for most cases of uncomplicated Plasmodium falciparum malaria. (2) The choice of drug for prevention of P. falciparum malaria in highly endemic regions depends on the risk of chloroquine resistance, and possibly mefloquine resistance. The reference treatments are the chloroquine + proguanil combination, and mefloquine. (3) Marketing authorisation has been granted in France for the atovaquone + proguanil combination, in curative and preventive treatment of P. falciparum malaria. (4) The efficacy of the atovaquone + proguanil combination in uncomplicated malaria is similar to that of other treatments. Some strains of malaria seem to have reduced sensitivity. (5) The atovaquone + proguanil combination is also effective as prophylaxis, but there are no clinical trials showing whether it is equivalent to or better than other preventive treatments in non immune travellers. (6) According to the French licensing terms, atovaquone + proguanil prophylaxis can be stopped 7 days after leaving an endemic area, rather than 3-4 weeks with other drugs. This recommendation is based on weak evidence: mainly on theoretical arguments and on the absence of clinical malaria in some patients with evidence of P. falciparum infection. (7) The atovaquone + proguanil combination is less effective against other Plasmodium species (P. malariae, P. ovale and P. vivax). Chloroquine remains the reference treatment for these forms of malaria, which do not carry a risk of serious complications. (8) There were few adverse events in people taking the atovaquone + proguanil combination during clinical trials. During curative treatment, this combination caused more nausea and vomiting than reference treatments, while, in the prophylactic setting, it had slightly fewer adverse effects than the chloroquine + proguanil combination or mefloquine alone. But the drop out rate was not significantly different between treatment groups. (9) Atovaquone should be taken with food, to improve absorption. (10) The atovaquone + proguanil combination is expensive and is not refunded in France. In contrast, curative treatment with quinine is cheap, and is fully refunded. (11) Mefloquine and quinine remain the treatments of choice for uncomplicated malaria where there is chloroquine resistance. The atovaquone + proguanil combination is useful if mefloquine and quinine are contraindicated; unlike halofantrine, this combination does not carry the risk of serious drug interactions. In the prophylactic setting, the lack of experience with atovaquone means it should only be used as a second line option, after mefloquine, for short-term prophylaxis in areas with a high prevalence of chloroquine resistance.