Artesunate Better Than Quinine for Severe Falciparum Malaria

Parenteral quinine, usually administered with another antimalarial drug, has long been the mainstay for treating severe falciparum malaria. To assess whether it remains the drug of choice, investigators conducted a multicenter, randomized trial comparing intravenous artesunate with intravenous quinine. Patients >2 years old who were hospitalized with severe falciparum malaria were enrolled at study sites in Bangladesh, Myanmar, India, and Indonesia. Following the initial, intravenous doses, medication was administered orally if patients could take pills. The study medication was given for a total of 7 days and, except in children aged <8 years and pregnant women, was combined with oral doxycycline. In-hospital death was the primary endpoint. Although the aim had been to enroll 2000 patients, the trial was stopped early (after 1461 were randomized), based on an interim analysis.

Overall, in-hospital mortality was 35% lower with artesunate than with quinine. Among blood-smear–positive patients, mortality was 15% for the artesunate group and 23% for the quinine group. For children (n=202), mortality was nonsignificantly lower with artesunate than with quinine treatment (5% vs. 11%). Among patients with hyperparasitemia (n=229), the treatment effect was significantly greater (23% mortality with artesunate vs. 53% with quinine). Quinine was associated with

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hypoglycemia in 3% (probably an underestimation, because glucose levels were not routinely monitored).

Comment: Quinine has a narrow therapeutic ratio and significant toxicity. Because quinine is unavailable in the U.S., parenteral quinidine is substituted, but this regimen requires cardiac monitoring. The current findings indicate that artesunate saves more lives than does quinine and should become the treatment of choice for severe falciparum malaria in adults. Unfortunately, this drug is also currently unavailable in the U.S. Some of the reasons for the lack of access to parenteral quinine and artesunate in the U.S. were reviewed in a recent perspective by Magill and Panosian.

— Mary E. Wilson, MD