Elsevier

The Lancet

Volume 369, Issue 9560, 10–16 February 2007, Pages 491-498
The Lancet

Articles
Artemether-lumefantrine versus amodiaquine plus sulfadoxine-pyrimethamine for uncomplicated falciparum malaria in Burkina Faso: a randomised non-inferiority trial

https://doi.org/10.1016/S0140-6736(07)60236-0Get rights and content

Summary

Background

Artemisinin-based combination regimens are widely advocated for malarial treatment, but other effective regimens might be cheaper and more readily available. Our aim was to compare the risk of recurrent parasitaemia in patients given artemether-lumefantrine with that in those given amodiaquine plus sulfadoxine-pyrimethamine for uncomplicated malaria.

Methods

We enrolled 521 patients aged 6 months or older with uncomplicated falciparum malaria in Bobo-Dioulasso, Burkina Faso. Patients were randomly assigned to receive standard doses of either artemether-lumefantrine (261) or amodiaquine plus sulfadoxine-pyrimethamine (260) for 3 days. Primary endpoints were the risks of treatment failure within 28 days, either unadjusted or adjusted by genotyping to distinguish recrudescence from new infection. The study is registered at controlled-trials.gov with the identifier ISRCTN54261005.

Findings

Of enrolled patients, 478 (92%) completed the 28-day study. The risk of recurrent symptomatic malaria was lowest in the group given amodiaquine plus sulfadoxine-pyrimethamine (1·7% vs 10·2%; risk difference 8·5%; 95% CI 4·3–12·6; p=0·0001); as was the risk of recurrent parasitaemia (4·7% vs 15·1%; 10·4%; 5·1–15·6; p=0·0002). Nearly all recurrences were due to new infections. Recrudescences were four late treatment failures with artemether-lumefantrine and one early treatment failure with amodiaquine plus sulfadoxine-pyrimethamine. Both regimens were safe and well tolerated, with pruritus more common with amodiaquine plus sulfadoxine-pyrimethamine than with artemether-lumefantrine. Each regimen selected for new isolates with mutations that have been associated with decreased drug susceptibility.

Interpretation

Amodiaquine plus sulfadoxine-pyrimethamine was more effective than was artemether-lumefantrine for the treatment of uncomplicated malaria. For regions of Africa where amodiaquine plus sulfadoxine-pyrimethamine continues to be effective, this less expensive and more available regimen should be considered as an alternative to blanket recommendations for artemisinin-based combination treatment for malaria.

Introduction

Antimalarial drug resistance is a severe and growing problem in Africa.1 As older monotherapy regimens become less effective, a consensus has emerged for the use of combination treatments for malaria.2 Artemisinin-based combination treatments have proved very effective against malaria in Asia and Africa,2, 3 and most countries in Africa have now changed their national regimens to incorporate artemisinin-based combination regimens as first-line treatment for uncomplicated malaria.4

However, the implementation of artemisinin-based combination therapy has its difficulties. First, these regimens are much more expensive than previous treatments. Although funding for antimalarial treatment in Africa has been increased, available resources might not be adequate to fund all the necessary treatments. Second, supplies of artemisinin derivatives, although growing, remain inadequate for the estimated 1 billion malaria treatments given each year in Africa.5 Third, artemisinin-based combination treatments have not yet been widely studied in all epidemiological settings in Africa, and might not be as successful in high transmission regions as in other areas.

Antimalarial combination regimens that do not contain an artemisinin derivative remain of interest, since they can be much less expensive and they offer an alternative treatment if artemisinin use remains restricted by cost, supply, unexpected toxic effects, or a combination of such factors. The non-artemisinin combination treatment that has been best studied is amodiaquine with sulfadoxine-pyrimethamine. This regimen combines two inexpensive and readily available drugs, and has proved to be particularly effective in regions of Africa with low levels of resistance to each component, such as much of west Africa.6, 7

Amodiaquine plus sulfadoxine-pyrimethamine has been shown to lower the risk of new infections after treatment compared with artemisinin-based regimens, presumably because of the long half-lives of sulfadoxine-pyrimethamine and amodiaquine or its derivatives.8 However, the benefits of any long-acting drug might be offset if it is selected for parasites with mutations that confer resistance to important antimalarial agents.9, 10, 11, 12, 13

Several countries in west Africa, including Burkina Faso, have changed their recommended first-line treatment for uncomplicated malaria to the artemisinin-based combination regimen, artemether-lumefantrine.4 However, few studies from Africa,14 and none from west Africa, have compared artemether-lumefantrine with non-artemisinin combination treatment. Our aim was to assess the efficacy of artemether-lumefantrine compared with amodiaquine plus sulfadoxine-pyrimethamine for treatment of patients with uncomplicated malaria in Burkina Faso.

Section snippets

Participants

The study was based in Bobo-Dioulasso, a city of about 450 000 inhabitants in western Burkina Faso, where malaria is holoendemic and transmission peaks during the rainy season (May to October). Patients were recruited from three government health centres (Colsama, Sarfalao, and Ouezzinville).

All patients who presented between August, 2005, and December, 2005, with high temperature or history of recent fever were referred to health-centre laboratories for initial screening of a thick blood smear

Results

Figure 1 shows that of the patients randomly assigned to a treatment group, 27 (5%) were excluded from enrolment either because they vomited their first dose of treatment twice or they had parasitaemias with densities that were outside of the inclusion criteria. Therefore, 521 patients were enrolled in the study. After 28 days of follow-up, 478 enrolled patients (92%) completed the study (figure 1). Table 1 shows the baseline characteristics of these study participants.

Table 2 shows results for

Discussion

We have shown that both artemether-lumefantrine and amodiaquine plus sulfadoxine-pyrimethamine were effective for clearance of uncomplicated malaria infections. However, in high transmission settings characteristic of much of sub-Saharan Africa, effects of therapy on subsequent infections should also be considered. Indeed, recurrent illnesses due to recrudescence and those caused by new infections are generally clinically indistinguishable.8 Therefore, the effects of treatment on the overall

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