Severe
malaria is a global problem, claiming at least 1 million lives annually. Few adequately powered clinical studies have been directed at improving the management of severe
malaria over the years, but this situation is slowly changing. The
antimalarial treatment of severe disease is being transformed by the development and deployment of the water-soluble
artemisinin derivative
artesunate. Parenteral
artesunate is now the treatment of choice in low-transmission areas and in the 2nd and 3rd trimesters of pregnancy, and research is underway into whether it should replace
quinine as the treatment of choice in African children. Development of good manufacturing practice (GMP) formulations should make parenteral
artesunate more widely available in the near future. The development of
artesunate suppositories offers another exciting prospect, the ability to treat patients with severe disease in remote rural settings, delaying the evolution of disease and buying them time to reach a health care facility. No adjunctive
therapy has been shown to improve the outcome of severe
malaria, but most studies have been underpowered. Future trials of interventions shown to be promising in pilot studies should be large and adequately powered. This will require multi-center designs and necessitate close collaboration between groups, as well as agreement on the research agenda. We suggest a list of candidate interventions for debate.