Drug combination of amodiaquine and sulfadoxinepyrimethamine might offer the optimal treatment for malaria

Results of a randomised trial from Uganda in this week’s issue of THE LANCET suggest that the drug combination of amodiaquine and sulfadoxinepyrimethamine might offer the optimal treatment for malaria in terms of efficacy and cost-effectiveness in this region.

The study also shows that the drug combination of chloroquine and sulfadoxine-pyrimethamine—the recommended first-line treatment in Uganda—is far less effective than other drug combinations.

Philip Rosenthal (University of California San Francisco) and colleagues coordinated a clinical trial among young children (aged 6 months to 10 years) via a hospital in Kampala, Uganda. Around 400 children were randomly allocated one of three combinations: chloroquine+sulfadoxine-pyrimethamine, amodiaquine+sulfadoxine-pyrimethamine, or amodiaquine+artesunate. The latter two combinations were far more effective, with treatment failures below 10% at one month’s follow-up; by contrast, the failure rate of chloroquine+sulfadoxine-pyrimethamine was 35%.

Professor Rosenthal comments: “African countries are faced with a challenge. Escalating drug resistance has rendered chloroquine ineffective, but the best replacement for first-line antimalarial therapy has been unclear. Artemisinincontaining combination therapy has been strongly advocated for use in Africa, but limited clinical experience and the high cost of these regimens are important obstacles. In Kampala, amodiaquine+sulfadoxine-pyrimethamine currently offers a readily available, efficacious, and economical alternative...Although the lifespan of amodiaquine+sulfadoxine-pyrimethamine might be limited by resistance, this regimen could be appropriate for regions of Africa where resistance to the individual drugs remains low, as an interim policy pending introduction of artemisinin-containing combinations.”

Amir Attaran (University of Ottowa, Canada) states in an accompanying commentary (p 1922): “Rather than clinical efficacy trials, more urgently needed are clinical studies of the effectiveness of artemisinin-combination therapies in African field conditions, to monitor the success (or failure) of the implementation process. Also needed is pressure on the UK Department for International Development, the US Agency for International Development, and the World Bank, which purchase little, if any, artemisinin-combination therapy. The Senate and the General Accounting Office in the USA are now investigating USAID’s inaction, and other donors should expect similar probes unless they act proactively. Much has been achieved in 2004; neither science nor policy can afford to let up.”