New antimalarials. A risk-benefit analysis

Although more than 40% of the world's population live in malaria endemic areas, there are only 6 available antimalarial drugs for the treatment of Plasmodium falciparum infections. Three of these have been developed in the last 20 years and are discussed in this review. Mefloquine is relatively well tolerated and has the advantage of a single day regimen. It has ideal properties for prophylactic use. However, although rare, serious adverse reactions do occur and the drug cannot be used in severe malaria. Resistance has already emerged in some parts of the world. Halofantrine is also well tolerated and has a rapid antimalarial activity. It is more expensive than other antimalarials and the existence of cross-resistance links its usefulness to the demise of mefloquine. The discovery of a potentially lethal cardiotoxicity associated with halofantrine casts a further shadow over its use. The artemisinin derivatives represent an exciting breakthrough in the treatment of malaria. They are cheap and have a very rapid action. They seem remarkably free from toxic adverse effects, although the neurotoxicity seen in animal studies with the liposoluble derivatives gives rise for concern. However, the lack of pharmacokinetic and toxicity data as yet preclude their approval by Western drug regulation authorities. All antimalarials are threatened by the emergence of parasite resistance. Combination therapy using mefloquine and an artemisinin derivative may provide a way in which resistance can be combated.