Publications

OBJECTIVES

To compare the efficacy and safety of artemisinin combination therapies for the treatment of uncomplicated falciparum malaria in Uganda.

DESIGN

Randomized single-blind controlled trial.

SETTING

Tororo, Uganda, an area of high-level malaria transmission.

PARTICIPANTS

Children aged one to ten years with confirmed uncomplicated P. falciparum malaria.

INTERVENTIONS

Amodiaquine + artesunate or artemether-lumefantrine.

OUTCOME MEASURES

Risks of recurrent symptomatic malaria and recurrent parasitemia at 28 days, unadjusted and adjusted by genotyping to distinguish recrudescences and new infections.

RESULTS

Of 408 participants enrolled, 403 with unadjusted efficacy outcomes were included in the per-protocol analysis. Both treatment regimens were highly efficacious; no recrudescences occurred in patients treated with amodiaquine + artesunate, and only two occurred in those treated with artemether-lumefantrine. However, recurrent malaria due to new infections was common. The unadjusted risk of recurrent symptomatic malaria was significantly lower for participants treated with artemether-lumefantrine than for those treated with amodiaquine + artesunate (27% versus 42%, risk difference 15%, 95% CI 5.9%-24.2%). Similar results were seen for the risk of recurrent parasitemia (51% artemether-lumefantrine versus 66% amodiaquine + artesunate, risk difference 16%, 95% CI 6.2%-25.2%). Amodiaquine + artesunate and artemether-lumefantrine were both well-tolerated. Serious adverse events were uncommon with both regimens.

CONCLUSIONS

Amodiaquine + artesunate and artemether-lumefantrine were both highly efficacious for treatment of uncomplicated malaria. However, in this holoendemic area, despite the excellent performance of both regimens in terms of efficacy, many patients experienced recurrent parasitemia due to new infections. Artemether-lumefantrine was superior to amodiaquine + artesunate for prevention of new infections. To maximize the benefit of artemisinin combination therapy in Africa, treatment should be integrated with strategies to prevent malaria transmission. The impact of frequent repeated therapy on the efficacy, safety, and cost-effectiveness of new artemisinin regimens should be further investigated.

The decrease in the rate at which novel medical products are reaching the market, despite major scientific achievements and investment that might have predicted otherwise, is causing much concern. Although this 'pipeline problem' has often been discussed in the context of drug development, it is also crucial to examine the unique characteristics of the pipeline for biomarkers and diagnostics. Here, we characterize the pipeline problem for biomarkers and diagnostics, and consider what steps could be taken to solve it.