Artemisinin antimalarials: preserving the "magic bullet"

The artemisinins are the most effective antimalarial drugs known. They possess a remarkably wide therapeutic index. These agents have been used in traditional Chinese herbal medicine for more then 2,000 years but were not subjected to scientific scrutiny until the 1970s. The first formal clinical trials of the artemisinins, and the development of methods for their industrial scale production, followed rapidly. A decade later, Chinese scientists shared their findings with the rest of the world; since then, a significant body of international trial evidence has confirmed these drugs to be far superior to any available alternative. In particular, they have the ability to rapidly kill a broad range of asexual parasite stages at safe concentrations that are consistently achievable via standard dosing regimens. As their half-life is very short, there was also thought to be a low risk of resistance. These discoveries conincided with the appearance and spread of resistance to all the other major classes of antimalarials. As a result, the artemisinins now form an essential element of recommended first-line antimalarial treatment regimens worldwide. To minimize risk of artemisinin resistance, they are recommended to be used to treat uncomplicated malaria in combination with other antimalarials as artemisinin combination therapies (ACTs). Their rollout has resulted in documented reductions in malaria prevalance in a number of African and Asian countries. Unfortunately, there are already worrisome early signs of artemisinin resistance appearing in Western Cambodia. If this resistance were to spread, it would be disastrous for malaria control efforts worldwide. The enormous challenge for the international community is how to avert this catastophe and preserve the effectiveness of this antimalarial "magic bullet"