Malaria is a major cause of illness and death in many of the world's poorest countries. It is spread from person to person by the bite of mosquitoes infected with a microorganism called Plasmodium. The Plasmodium species P. falciparum is the most common cause of malaria worldwide and causes the majority of deaths. Uncomplicated malaria is the mild form of the disease which, if left untreated, can progress rapidly to become life threatening. The drugs traditionally used to treat uncomplicated malaria have become ineffective in many parts of the world due to the development of drug resistance.

The World Health Organization now recommends Artemisinin-based Combination Therapy (ACTs) for treating uncomplicated malaria. The ACTs combine an artemisinin-derivative (a relatively new group of drugs which are very effective) with another longer-lasting drug to try and reduce the risk of further resistance developing.

This review summarizes the relative benefits and harms of the four ACTs in common use, one relatively new ACT (dihydroartemisinin plus piperaquine), and one combination which does not contain an artemisinin derivative but remains in use in some African countries (amodiaquine plus sulfadoxine-pyrimethamine).

All five ACTs were shown to be highly effective at treating P. falciparum in most places where they have been studied. However, there were several trials where ACTs had high levels of treatment failure, which emphasises the need to continue to monitor their performance.

The new ACT, dihydroartemisinin plus piperaquine, was shown to be at least as effective as the ACTs currently in widespread use in Asia and Africa, and represents another option for malaria treatment.

ACTs were shown to be more effective than amodiaquine plus sulfadoxine-pyrimethamine in countries from East Africa which probably represents high levels of resistance, to both drugs in this combination, in this region.

The second most common form of malaria, P. vivax, can also be treated with ACTs but requires additional treatment to cure the patient completely. This is because the P. vivax parasite can lie dormant in the liver for months or years before becoming active again. ACTs where the partner drug has a long duration of action may help to delay these relapses.

The ACTs seem to be relatively safe with few serious side effects. Minor side effects are more common but can be difficult to distinguish from the symptoms of malaria itself. Fifty trials were included in this review but did not include the most vulnerable populations; pregnant women and young infants (age < six months).