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Meta-Analysis
. 2009 Jul 8;2009(3):CD007483.
doi: 10.1002/14651858.CD007483.pub2.

Artemisinin-based combination therapy for treating uncomplicated malaria

David Sinclair  1 , Babalwa Zani, Sarah Donegan, Piero Olliaro, Paul Garner
Affiliations
Meta-Analysis

Artemisinin-based combination therapy for treating uncomplicated malaria

David Sinclair et al. Cochrane Database Syst Rev. .

Abstract

Background: The World Health Organization recommends uncomplicated P. falciparum malaria is treated using Artemisinin-based Combination Therapy (ACT). This review aims to assist the decision making of malaria control programmes by providing an overview of the relative benefits and harms of the available options.

Objectives: To compare the effects of ACTs with other available ACT and non-ACT combinations for treating uncomplicated P. falciparum malaria.

Search strategy: We searched the Cochrane Infectious Diseases Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; EMBASE; LILACS, and the metaRegister of Controlled Trials (mRCT) to March 2009.

Selection criteria: Randomized head to head trials of ACTs in uncomplicated P. falciparum malaria.This review is limited to: dihydroartemisinin-piperaquine; artesunate plus mefloquine; artemether-lumefantrine (six doses); artesunate plus amodiaquine; artesunate plus sulfadoxine-pyrimethamine and amodiaquine plus sulfadoxine-pyrimethamine.

Data collection and analysis: Two authors independently assessed trials for eligibility and risk of bias, and extracted data. We analysed primary outcomes in line with the WHO 'Protocol for assessing and monitoring antimalarial drug efficacy' and compared drugs using risk ratios (RR) and 95% confidence intervals (CI). Secondary outcomes were effects on P. vivax, gametocytes, haemoglobin, and adverse events.

Main results: Fifty studies met the inclusion criteria. All five ACTs achieved PCR adjusted failure rates of < 10%, in line with WHO recommendations, at most study sites.Dihydroartemisinin-piperaquine performed well compared to the ACTs in current use (PCR adjusted treatment failure versus artesunate plus mefloquine in Asia; RR 0.39, 95% CI 0.19 to 0.79; three trials, 1062 participants; versus artemether-lumefantrine in Africa; RR 0.39, 95% CI 0.24 to 0.64; three trials, 1136 participants).ACTs were superior to amodiaquine plus sulfadoxine-pyrimethamine in East Africa (PCR adjusted treatment failure versus artemether-lumefantrine; RR 0.12, 95% CI 0.06 to 0.24; two trials, 618 participants; versus AS+AQ; RR 0.44, 95% CI 0.22 to 0.89; three trials, 1515 participants).Dihydroartemisinin-piperaquine (RR 0.32, 95% CI 0.24 to 0.43; four trials, 1442 participants) and artesunate plus mefloquine (RR 0.30, 95% CI 0.21 to 0.41; four trials, 1003 participants) were more effective than artemether-lumefantrine at reducing the incidence of P.vivax over 42 days follow up.

Authors' conclusions: Dihydroartemisinin-piperaquine is another effective first-line treatment for P. falciparum malaria.The performance of the non-ACT (amodiaquine plus sulfadoxine-pyrimethamine) falls below WHO recommendations for first-line therapy in parts of Africa.In areas where primaquine is not being used for radical cure of P. vivax, ACTs with long half-lives may provide some benefit.

PubMed Disclaimer

Conflict of interest statement

None known.

Figures

1
1
Methodological quality summary: review authors' judgements about each methodological quality item for each included study.
2
2
Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.
3
3
How does Dihydroartemisinin‐piperaquine perform? Summary of primary outcome: Effectiveness: Total Failure (P. falciparum) PCR adjusted.
4
4
Olliaro‐Vaillant plot. Day 28 PCR adjusted treatment failure data for trials of DHA‐P against all comparators are presented in this plot. The horizontal red line represents the WHO standard of 10% treatment failure (PCR corrected). Plots below this line represent trials where DHA‐P performed to this standard. The vertical blue line represents no difference between the two drugs. Plots to the right of this line represent trials where DHA‐P performed better than the comparator drug, and plots to the left represent trials where the comparator drug performed better than DHA‐P.
5
5
How does Artesunate plus mefloquine perform? Summary of primary outcome: Effectiveness: Total Failure (P. falciparum) PCR adjusted.
6
6
Olliaro‐Vaillant plot. Day 28 PCR adjusted treatment failure data for trials of AS+MQ against all comparators are presented in this plot. The horizontal red line represents the WHO standard of 10% treatment failure (PCR corrected). Plots below this line represent trials where AS+MQ performed to this standard. The vertical blue line represents no difference between the two drugs. Plots to the right of this line represent trials where AS+MQ performed better than the comparator drug, and plots to the left represent trials where the comparator drug performed better than AS+MQ.
7
7
How does Artemether‐lumefantrine perform? Summary of primary outcome: Effectiveness: Total Failure (P. falciparum) Day PCR adjusted.
8
8
Olliaro‐Vaillant plot. Day 28 PCR adjusted treatment failure data for trials of AL6 against all comparators are presented in this plot. The horizontal red line represents the WHO standard of 10% treatment failure (PCR corrected). Plots below this line represent trials where AL6 performed to this standard. The vertical blue line represents no difference between the two drugs. Plots to the right of this line represent trials where AL6 performed better than the comparator drug, and plots to the left represent trials where the comparator drug performed better than AL6.
9
9
How does Artesunate plus amodiaquine perform? Summary of primary outcome: Effectiveness: Total Failure (P. falciparum) PCR adjusted.
10
10
Olliaro‐Vaillant plot. Day 28 PCR adjusted treatment failure data for trials of AS+AQ against all comparators are presented in this plot. The horizontal red line represents the WHO standard of 10% treatment failure (PCR corrected). Plots below this line represent trials where AS+AQ performed to this standard. The vertical blue line represents no difference between the two drugs. Plots to the right of this line represent trials where AS+AQ performed better than the comparator drug, and plots to the left represent trials where the comparator drug performed better than AS+AQ.
1.1
1.1. Analysis
Comparison 1 Dihydroartemisinin‐piperaquine vs Artesunate plus mefloquine, Outcome 1 Total Failure (P. falciparum) Day 63 PCR unadjusted.
1.2
1.2. Analysis
Comparison 1 Dihydroartemisinin‐piperaquine vs Artesunate plus mefloquine, Outcome 2 Total Failure (P. falciparum) Day 63 PCR adjusted.
1.3
1.3. Analysis
Comparison 1 Dihydroartemisinin‐piperaquine vs Artesunate plus mefloquine, Outcome 3 Total Failure (P. falciparum) Day 42 PCR unadjusted.
1.4
1.4. Analysis
Comparison 1 Dihydroartemisinin‐piperaquine vs Artesunate plus mefloquine, Outcome 4 Total Failure (P. falciparum) Day 42 PCR adjusted.
1.5
1.5. Analysis
Comparison 1 Dihydroartemisinin‐piperaquine vs Artesunate plus mefloquine, Outcome 5 Total Failure (P. falciparum) Day 28 PCR unadjusted.
1.6
1.6. Analysis
Comparison 1 Dihydroartemisinin‐piperaquine vs Artesunate plus mefloquine, Outcome 6 Total Failure (P. falciparum) Day 28 PCR adjusted.
1.7
1.7. Analysis
Comparison 1 Dihydroartemisinin‐piperaquine vs Artesunate plus mefloquine, Outcome 7 P. vivax parasitaemia.
1.8
1.8. Analysis
Comparison 1 Dihydroartemisinin‐piperaquine vs Artesunate plus mefloquine, Outcome 8 Gametocyte development (in those negative at baseline).
1.9
1.9. Analysis
Comparison 1 Dihydroartemisinin‐piperaquine vs Artesunate plus mefloquine, Outcome 9 Gametocytaemia carriage.
1.10
1.10. Analysis
Comparison 1 Dihydroartemisinin‐piperaquine vs Artesunate plus mefloquine, Outcome 10 Serious adverse events (including deaths).
1.11
1.11. Analysis
Comparison 1 Dihydroartemisinin‐piperaquine vs Artesunate plus mefloquine, Outcome 11 Early vomiting.
1.12
1.12. Analysis
Comparison 1 Dihydroartemisinin‐piperaquine vs Artesunate plus mefloquine, Outcome 12 Sensitivity analysis: Total Failure Day 63 PCR unadjusted.
1.13
1.13. Analysis
Comparison 1 Dihydroartemisinin‐piperaquine vs Artesunate plus mefloquine, Outcome 13 Sensitivity analysis: Total Failure Day 63 PCR adjusted.
2.1
2.1. Analysis
Comparison 2 Dihydroartemisinin‐piperaquine vs Artemether‐lumefantrine, Outcome 1 Total Failure (P. falciparum) Day 42 PCR unadjusted.
2.2
2.2. Analysis
Comparison 2 Dihydroartemisinin‐piperaquine vs Artemether‐lumefantrine, Outcome 2 Total Failure (P. falciparum) Day 42 PCR adjusted.
2.3
2.3. Analysis
Comparison 2 Dihydroartemisinin‐piperaquine vs Artemether‐lumefantrine, Outcome 3 Total Failure (P. falciparum) Day 28 PCR unadjusted.
2.4
2.4. Analysis
Comparison 2 Dihydroartemisinin‐piperaquine vs Artemether‐lumefantrine, Outcome 4 Total Failure (P. falciparum) Day 28 PCR adjusted.
2.5
2.5. Analysis
Comparison 2 Dihydroartemisinin‐piperaquine vs Artemether‐lumefantrine, Outcome 5 P. vivax parasitaemia.
2.6
2.6. Analysis
Comparison 2 Dihydroartemisinin‐piperaquine vs Artemether‐lumefantrine, Outcome 6 Gametocyte development (in those negative at baseline).
2.7
2.7. Analysis
Comparison 2 Dihydroartemisinin‐piperaquine vs Artemether‐lumefantrine, Outcome 7 Anaemia.
2.8
2.8. Analysis
Comparison 2 Dihydroartemisinin‐piperaquine vs Artemether‐lumefantrine, Outcome 8 Serious adverse events (including deaths).
2.9
2.9. Analysis
Comparison 2 Dihydroartemisinin‐piperaquine vs Artemether‐lumefantrine, Outcome 9 Early vomiting.
3.1
3.1. Analysis
Comparison 3 Dihydroartemisinin‐piperaquine vs Artesunate plus amodiaquine, Outcome 1 Total Failure (P. falciparum) Day 28 PCR unadjusted.
3.2
3.2. Analysis
Comparison 3 Dihydroartemisinin‐piperaquine vs Artesunate plus amodiaquine, Outcome 2 Total Failure (P. falciparum) Day 28 PCR adjusted.
3.3
3.3. Analysis
Comparison 3 Dihydroartemisinin‐piperaquine vs Artesunate plus amodiaquine, Outcome 3 Total Failure (P. falciparum) Day 42 PCR unadjusted.
3.4
3.4. Analysis
Comparison 3 Dihydroartemisinin‐piperaquine vs Artesunate plus amodiaquine, Outcome 4 Total Failure (P. falciparum) Day 42 PCR adjusted.
3.5
3.5. Analysis
Comparison 3 Dihydroartemisinin‐piperaquine vs Artesunate plus amodiaquine, Outcome 5 P. vivax parasitaemia.
3.6
3.6. Analysis
Comparison 3 Dihydroartemisinin‐piperaquine vs Artesunate plus amodiaquine, Outcome 6 Serious adverse events (including deaths).
3.7
3.7. Analysis
Comparison 3 Dihydroartemisinin‐piperaquine vs Artesunate plus amodiaquine, Outcome 7 Early vomiting.
4.1
4.1. Analysis
Comparison 4 Dihydroartemisinin‐piperaquine vs Artesunate plus sulfadoxine‐pyrimethamine, Outcome 1 Total Failure (P. falciparum) Day 42 PCR unadjusted.
4.2
4.2. Analysis
Comparison 4 Dihydroartemisinin‐piperaquine vs Artesunate plus sulfadoxine‐pyrimethamine, Outcome 2 Total Failure (P. falciparum) Day 42 PCR adjusted.
4.3
4.3. Analysis
Comparison 4 Dihydroartemisinin‐piperaquine vs Artesunate plus sulfadoxine‐pyrimethamine, Outcome 3 Total Failure (P. falciparum) Day 28 PCR unadjusted.
4.4
4.4. Analysis
Comparison 4 Dihydroartemisinin‐piperaquine vs Artesunate plus sulfadoxine‐pyrimethamine, Outcome 4 Total Failure (P. falciparum) Day 28 PCR adjusted.
4.5
4.5. Analysis
Comparison 4 Dihydroartemisinin‐piperaquine vs Artesunate plus sulfadoxine‐pyrimethamine, Outcome 5 P. vivax parasitaemia by day 42.
5.1
5.1. Analysis
Comparison 5 Dihydroartemisinin‐piperaquine vs Amodiaquine plus sulfadoxine‐pyrimethamine, Outcome 1 Total Failure (P. falciparum) Day 28 PCR unadjusted.
5.2
5.2. Analysis
Comparison 5 Dihydroartemisinin‐piperaquine vs Amodiaquine plus sulfadoxine‐pyrimethamine, Outcome 2 Total Failure (P. falciparum) Day 28 PCR adjusted.
5.3
5.3. Analysis
Comparison 5 Dihydroartemisinin‐piperaquine vs Amodiaquine plus sulfadoxine‐pyrimethamine, Outcome 3 Total Failure (P. falciparum) Day 42 PCR unadjusted.
5.4
5.4. Analysis
Comparison 5 Dihydroartemisinin‐piperaquine vs Amodiaquine plus sulfadoxine‐pyrimethamine, Outcome 4 Total Failure (P. falciparum) Day 42 PCR adjusted.
5.5
5.5. Analysis
Comparison 5 Dihydroartemisinin‐piperaquine vs Amodiaquine plus sulfadoxine‐pyrimethamine, Outcome 5 Gametocyte development.
5.6
5.6. Analysis
Comparison 5 Dihydroartemisinin‐piperaquine vs Amodiaquine plus sulfadoxine‐pyrimethamine, Outcome 6 Anaemia.
5.7
5.7. Analysis
Comparison 5 Dihydroartemisinin‐piperaquine vs Amodiaquine plus sulfadoxine‐pyrimethamine, Outcome 7 Early vomiting.
6.1
6.1. Analysis
Comparison 6 Artesunate plus mefloquine vs Artemether‐lumefantrine, Outcome 1 Total Failure (P. falciparum) Day 42 PCR unadjusted.
6.2
6.2. Analysis
Comparison 6 Artesunate plus mefloquine vs Artemether‐lumefantrine, Outcome 2 Total Failure (P. falciparum) Day 42 PCR adjusted.
6.3
6.3. Analysis
Comparison 6 Artesunate plus mefloquine vs Artemether‐lumefantrine, Outcome 3 Total Failure (P. falciparum) Day 28 PCR unadjusted.
6.4
6.4. Analysis
Comparison 6 Artesunate plus mefloquine vs Artemether‐lumefantrine, Outcome 4 Total Failure (P. falciparum) Day 28 PCR adjusted.
6.5
6.5. Analysis
Comparison 6 Artesunate plus mefloquine vs Artemether‐lumefantrine, Outcome 5 P. vivax parasitaemia.
6.6
6.6. Analysis
Comparison 6 Artesunate plus mefloquine vs Artemether‐lumefantrine, Outcome 6 Gametocyte development (in those negative at baseline).
6.7
6.7. Analysis
Comparison 6 Artesunate plus mefloquine vs Artemether‐lumefantrine, Outcome 7 Gametocyte carriage.
6.8
6.8. Analysis
Comparison 6 Artesunate plus mefloquine vs Artemether‐lumefantrine, Outcome 8 Serious adverse events (including deaths).
6.9
6.9. Analysis
Comparison 6 Artesunate plus mefloquine vs Artemether‐lumefantrine, Outcome 9 Early vomiting.
7.1
7.1. Analysis
Comparison 7 Artesunate plus mefloquine vs Artesunate plus amodiaquine, Outcome 1 Total Failure (P. falciparum) Day 28 PCR unadjusted.
7.2
7.2. Analysis
Comparison 7 Artesunate plus mefloquine vs Artesunate plus amodiaquine, Outcome 2 Total Failure (P. falciparum) Day 28 PCR adjusted.
7.3
7.3. Analysis
Comparison 7 Artesunate plus mefloquine vs Artesunate plus amodiaquine, Outcome 3 Gametocyte carriage.
8.1
8.1. Analysis
Comparison 8 Artesunate plus mefloquine vs Amodiaquine plus sulfadoxine‐pyrimethamine, Outcome 1 Total Failure (P. falciparum) Day 28 PCR unadjusted.
8.2
8.2. Analysis
Comparison 8 Artesunate plus mefloquine vs Amodiaquine plus sulfadoxine‐pyrimethamine, Outcome 2 Total Failure (P. falciparum) Day 28 PCR adjusted.
8.3
8.3. Analysis
Comparison 8 Artesunate plus mefloquine vs Amodiaquine plus sulfadoxine‐pyrimethamine, Outcome 3 Gametocyte carriage.
9.1
9.1. Analysis
Comparison 9 Artemether‐lumefantrine vs Artesunate plus amodiaquine, Outcome 1 Total Failure (P. falciparum) Day 28 PCR unadjusted.
9.2
9.2. Analysis
Comparison 9 Artemether‐lumefantrine vs Artesunate plus amodiaquine, Outcome 2 Total Failure (P. falciparum) Day 28 PCR adjusted.
9.3
9.3. Analysis
Comparison 9 Artemether‐lumefantrine vs Artesunate plus amodiaquine, Outcome 3 Gametocyte development.
9.4
9.4. Analysis
Comparison 9 Artemether‐lumefantrine vs Artesunate plus amodiaquine, Outcome 4 Gametocyte carriage.
9.5
9.5. Analysis
Comparison 9 Artemether‐lumefantrine vs Artesunate plus amodiaquine, Outcome 5 Anaemia.
9.6
9.6. Analysis
Comparison 9 Artemether‐lumefantrine vs Artesunate plus amodiaquine, Outcome 6 Proportion anaemic (Haemoglobin < 11 g/dl).
9.7
9.7. Analysis
Comparison 9 Artemether‐lumefantrine vs Artesunate plus amodiaquine, Outcome 7 Serious adverse events (including deaths).
9.8
9.8. Analysis
Comparison 9 Artemether‐lumefantrine vs Artesunate plus amodiaquine, Outcome 8 Early vomiting.
9.9
9.9. Analysis
Comparison 9 Artemether‐lumefantrine vs Artesunate plus amodiaquine, Outcome 9 Sensitivity analysis: Total Failure Day 28 PCR unadjusted.
9.10
9.10. Analysis
Comparison 9 Artemether‐lumefantrine vs Artesunate plus amodiaquine, Outcome 10 Sensitivity analysis: Total Failure Day 28 PCR adjusted.
10.1
10.1. Analysis
Comparison 10 Artemether‐lumefantrine vs Artesunate plus sulfadoxine‐pyrimethamine, Outcome 1 Total Failure (P. falciparum) Day 42 PCR unadjusted.
10.2
10.2. Analysis
Comparison 10 Artemether‐lumefantrine vs Artesunate plus sulfadoxine‐pyrimethamine, Outcome 2 Total Failure (P. falciparum) Day 42 PCR adjusted.
10.3
10.3. Analysis
Comparison 10 Artemether‐lumefantrine vs Artesunate plus sulfadoxine‐pyrimethamine, Outcome 3 Total Failure (P. falciparum) Day 28 PCR unadjusted.
10.4
10.4. Analysis
Comparison 10 Artemether‐lumefantrine vs Artesunate plus sulfadoxine‐pyrimethamine, Outcome 4 Total Failure (P. falciparum) Day 28 PCR adjusted.
10.5
10.5. Analysis
Comparison 10 Artemether‐lumefantrine vs Artesunate plus sulfadoxine‐pyrimethamine, Outcome 5 P. vivax parasitaemia.
10.6
10.6. Analysis
Comparison 10 Artemether‐lumefantrine vs Artesunate plus sulfadoxine‐pyrimethamine, Outcome 6 Sensitivity analysis Total Failure Day 28 PCR unadjusted.
10.7
10.7. Analysis
Comparison 10 Artemether‐lumefantrine vs Artesunate plus sulfadoxine‐pyrimethamine, Outcome 7 Sensitivity analysis: Total Failure Day 28 PCR adjusted.
11.1
11.1. Analysis
Comparison 11 Artemether‐lumefantrine vs Amodiaquine plus sulfadoxine‐pyrimethamine, Outcome 1 Total Failure (P. falciparum) Day 28 PCR unadjusted.
11.2
11.2. Analysis
Comparison 11 Artemether‐lumefantrine vs Amodiaquine plus sulfadoxine‐pyrimethamine, Outcome 2 Total Failure (P. falciparum) Day 28 PCR adjusted.
11.3
11.3. Analysis
Comparison 11 Artemether‐lumefantrine vs Amodiaquine plus sulfadoxine‐pyrimethamine, Outcome 3 Total Failure (P. falciparum) Day 42 PCR unadjusted.
11.4
11.4. Analysis
Comparison 11 Artemether‐lumefantrine vs Amodiaquine plus sulfadoxine‐pyrimethamine, Outcome 4 Total Failure (P. falciparum) Day 42 PCR adjusted.
11.5
11.5. Analysis
Comparison 11 Artemether‐lumefantrine vs Amodiaquine plus sulfadoxine‐pyrimethamine, Outcome 5 Gametocyte carriage.
11.6
11.6. Analysis
Comparison 11 Artemether‐lumefantrine vs Amodiaquine plus sulfadoxine‐pyrimethamine, Outcome 6 Gametocyte development (in those negative at baseline).
11.7
11.7. Analysis
Comparison 11 Artemether‐lumefantrine vs Amodiaquine plus sulfadoxine‐pyrimethamine, Outcome 7 Anaemia.
11.8
11.8. Analysis
Comparison 11 Artemether‐lumefantrine vs Amodiaquine plus sulfadoxine‐pyrimethamine, Outcome 8 Serious adverse events (including deaths).
11.9
11.9. Analysis
Comparison 11 Artemether‐lumefantrine vs Amodiaquine plus sulfadoxine‐pyrimethamine, Outcome 9 Early vomiting.
12.1
12.1. Analysis
Comparison 12 Artesunate plus amodiaquine vs Artesunate plus sulfadoxine‐pyrimethamine, Outcome 1 Total Failure (P. falciparum) Day 28 PCR unadjusted.
12.2
12.2. Analysis
Comparison 12 Artesunate plus amodiaquine vs Artesunate plus sulfadoxine‐pyrimethamine, Outcome 2 Total Failure (P. falciparum) Day 28 PCR adjusted.
12.3
12.3. Analysis
Comparison 12 Artesunate plus amodiaquine vs Artesunate plus sulfadoxine‐pyrimethamine, Outcome 3 Gametocyte carriage.
12.4
12.4. Analysis
Comparison 12 Artesunate plus amodiaquine vs Artesunate plus sulfadoxine‐pyrimethamine, Outcome 4 Proportion of participants with anaemia.
12.5
12.5. Analysis
Comparison 12 Artesunate plus amodiaquine vs Artesunate plus sulfadoxine‐pyrimethamine, Outcome 5 Serious adverse events (including deaths).
13.1
13.1. Analysis
Comparison 13 Artesunate plus amodiaquine vs Amodiaquine plus sulfadoxine‐pyrimethamine, Outcome 1 Total Failure (P. falciparum) Day 28 PCR unadjusted.
13.2
13.2. Analysis
Comparison 13 Artesunate plus amodiaquine vs Amodiaquine plus sulfadoxine‐pyrimethamine, Outcome 2 Total Failure (P. falciparum) Day 28 PCR adjusted.
13.3
13.3. Analysis
Comparison 13 Artesunate plus amodiaquine vs Amodiaquine plus sulfadoxine‐pyrimethamine, Outcome 3 Gametocyte development.
13.4
13.4. Analysis
Comparison 13 Artesunate plus amodiaquine vs Amodiaquine plus sulfadoxine‐pyrimethamine, Outcome 4 Gametocyte carriage.
13.5
13.5. Analysis
Comparison 13 Artesunate plus amodiaquine vs Amodiaquine plus sulfadoxine‐pyrimethamine, Outcome 5 Anaemia.
13.6
13.6. Analysis
Comparison 13 Artesunate plus amodiaquine vs Amodiaquine plus sulfadoxine‐pyrimethamine, Outcome 6 Serious adverse events (including deaths).
14.1
14.1. Analysis
Comparison 14 Dihydroartemisinin‐piperaquine dose analysis: 3 dose vs 4 dose regimen, Outcome 1 Total Failure PCR unadjusted.
14.2
14.2. Analysis
Comparison 14 Dihydroartemisinin‐piperaquine dose analysis: 3 dose vs 4 dose regimen, Outcome 2 Total Failure PCR adjusted.
15.1
15.1. Analysis
Comparison 15 Dihydroartemisinin‐piperaquine dose analysis (versus Artesunate plus mefloquine), Outcome 1 Total Failure Day 63 PCR unadjusted.
15.2
15.2. Analysis
Comparison 15 Dihydroartemisinin‐piperaquine dose analysis (versus Artesunate plus mefloquine), Outcome 2 Total Failure Day 63 PCR adjusted.
15.3
15.3. Analysis
Comparison 15 Dihydroartemisinin‐piperaquine dose analysis (versus Artesunate plus mefloquine), Outcome 3 Total Failure Day 42 PCR unadjusted.
15.4
15.4. Analysis
Comparison 15 Dihydroartemisinin‐piperaquine dose analysis (versus Artesunate plus mefloquine), Outcome 4 Total Failure Day 42 PCR adjusted.
15.5
15.5. Analysis
Comparison 15 Dihydroartemisinin‐piperaquine dose analysis (versus Artesunate plus mefloquine), Outcome 5 Total Failure Day 28 PCR unadjusted.
15.6
15.6. Analysis
Comparison 15 Dihydroartemisinin‐piperaquine dose analysis (versus Artesunate plus mefloquine), Outcome 6 Total Failure Day 28 PCR adjusted.
16.1
16.1. Analysis
Comparison 16 Artesunate Mefloquine dose analysis: FDC versus split dose regimen, Outcome 1 Total Failure Day 63 PCR unadjusted.
16.2
16.2. Analysis
Comparison 16 Artesunate Mefloquine dose analysis: FDC versus split dose regimen, Outcome 2 Total Failure Day 63 PCR adjusted.
17.1
17.1. Analysis
Comparison 17 Artesunate plus mefloquine dose analysis (versus Dihydroartemisinin‐piperaquine), Outcome 1 Total Failure Day 63 PCR adjusted.
17.2
17.2. Analysis
Comparison 17 Artesunate plus mefloquine dose analysis (versus Dihydroartemisinin‐piperaquine), Outcome 2 Total Failure Day 28 PCR adjusted.
18.1
18.1. Analysis
Comparison 18 How does Dihydroartemisinin‐piperaquine perform?, Outcome 1 Effectiveness: Total Failure (P. falciparum) PCR adjusted.
19.1
19.1. Analysis
Comparison 19 How does Artesunate plus mefloquine perform?, Outcome 1 Effectiveness: Total Failure (P. falciparum) PCR adjusted.
20.1
20.1. Analysis
Comparison 20 How does Artemether‐lumefantrine perform?, Outcome 1 Effectiveness: Total Failure (P. falciparum) Day PCR adjusted.
21.1
21.1. Analysis
Comparison 21 How does Artesunate plus amodiaquine perform?, Outcome 1 Effectiveness: Total Failure (P. falciparum) PCR adjusted.
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Update of

  • doi: 10.1002/14651858.CD007483

References

References to studies included in this review

Adjei 2006 GHA {published data only}
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Ashley 2003a THA {published and unpublished data}
    1. Ashley EA, Krudsood S, Phaiphun L, Srivilairit S, McGready R, Leowattana W, et al. Randomized, controlled dose‐optimization studies of dihydroartemisinin‐piperaquine for the treatment of uncomplicated multidrug‐resistant falciparum malaria in Thailand. Journal of Infectious Diseases 2004; Vol. 190, issue 10:1773‐82. - PubMed
Ashley 2003b THA {published and unpublished data}
    1. Ashley EA, Krudsood S, Phaiphun L, Srivilairit S, McGready R, Leowattana W, et al. Randomized, controlled dose‐optimization studies of dihydroartemisinin‐piperaquine for the treatment of uncomplicated multidrug‐resistant falciparum malaria in Thailand. Journal of Infectious Diseases 2004;190(10):1773‐82. - PubMed
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    1. Ashley EA, McGready R, Hutagalung R, Phaiphun L, Slight T, Proux S, et al. A randomized, controlled study of a simple, once‐daily regimen of dihydroartemisinin‐piperaquine for the treatment of uncomplicated, multidrug‐resistant falciparum malaria. Clinical Infectious Diseases 2005; Vol. 41, issue 4:425‐32. - PubMed
Ashley 2005 THA {published and unpublished data}
    1. Ashley EA, Lwin K, McGready R, Simon WH, Phaiphun L, Proux S, et al. An open label randomized comparison of mefloquine–artesunate as separate tablets vs. a new co‐formulatedcombination for the treatment of uncomplicated multidrug‐resistant falciparum malaria in Thailand. Tropical Medicine and International Health 2006;11(11):1653‐60. - PubMed
Bonnet 2004 GIN {published and unpublished data}
    1. Bonnet M, Roper C, Felix M, Coulibaly L, Kankolongo GM, Guthmann JP. Efficacy of antimalarial treatment in Guinea: in vivo study of two artemisinin combination therapies in Dabola and molecular markers of resistance to sulphadoxine‐pyrimethamine in N'Zerekore. Malaria Journal 2007; Vol. 6:54. - PMC - PubMed
Bousema 2004 KEN {published and unpublished data}
    1. Bousema JT, Schneider P, Gouagna LC, Drakeley CJ, Tostmann A, Houben R, et al. Moderate Effect of Artemisinin‐Based Combination Therapy on Transmission of Plasmodium falciparum. Journal of Infectious Diseases 2006; Vol. 193, issue 8:1151‐9. - PubMed
Bukirwa 2005 UGA {published data only}
    1. Bukirwa H, Yeka A, Kamya MR, Talisuna A, Banek K, Bakyaita N, et al. Artemisinin combination therapies for treatment of uncomplicated malaria in Uganda. PLoS Clinical Trials 2006; Vol. 1, issue 1:e7. - PMC - PubMed
Djimde 2004 MLI {published and unpublished data}
    1. Djimde AA, Fofana B, Sagara I, Sidibe B, Toure S, Dembele D, et al. Efficacy, Safety, and Selection of Molecular Markers of Drug Resistance by Two ACTs in Mali. American Journal of Tropical Medicine and Hygiene 2008; Vol. 78, issue 3:455‐61. - PubMed
Dorsey 2006 UGA {published and unpublished data}
    1. Dorsey G, Staedke S, Clark TD, Njama‐Meya D, Nzarubara B, Maiteki‐Sebuguzi C, et al. Combination therapy for uncomplicated falciparum malaria in Ugandan children: a randomized trial. JAMA 2007; Vol. 297, issue 20:2210‐9. - PubMed
Falade 2005 NGA {published data only}
    1. Falade CO, Ogundele AO, Yusuf BO, Ademowo OG, Ladipo SM. High efficacy of two artemisinin‐based combinations (artemether‐lumefantrine and artesunate plus amodiaquine) for acute uncomplicated malaria in Ibadan, Nigeria. Tropical Medicine and International Health 2008;13(5):635‐643. - PubMed
Fanello 2004 RWA {published data only}
    1. Fanello CI, Karema C, Doren W, Overmeir C, Ngamije D, D'Alessandro U. A randomised trial to assess the safety and efficacy of artemether‐lumefantrine (Coartem) for the treatment of uncomplicated Plasmodium falciparum malaria in Rwanda. Transactions of the Royal Society of Tropical Medicine and Hygiene 2007; Vol. 101, issue 4:344‐50. - PubMed
Faye 2003 SEN {published and unpublished data}
    1. Faye B, Ndiaye JL, Ndiaye D, Dieng Y, Faye O, Gaye O. Efficacy and tolerability of four antimalarial combinations in the treatment of uncomplicated Plasmodium falciparum malaria in Senegal. Malaria Journal 2007; Vol. 6, issue 1:80. - PMC - PubMed
Grande 2005 PER {published data only}
    1. Grande T, Bernasconi A, Erhart A, Gamboa D, Casapia M, Delgado C, et al. A randomised controlled trial to assess the efficacy of dihydroartemisinin‐piperaquine for the treatment of uncomplicated falciparum malaria in Peru. PLoS ONE 2007; Vol. 2, issue 10:e1101. - PMC - PubMed
Guthmann 2003 AGO {published and unpublished data}
    1. Guthmann JP, Ampuero J, Fortes F, Overmeir C, Gaboulaud V, Tobback S, et al. Antimalarial efficacy of chloroquine, amodiaquine, sulfadoxine‐pyrimethamine, and the combinations of amodiaquine + artesunate and sulfadoxine‐pyrimethamine + artesunate in Huambo and Bie provinces, central Angola. Trans R Soc Trop Med Hyg 2005; Vol. 99, issue 7:485‐92. - PubMed
Guthmann 2004 AGO {published data only}
    1. Guthmann JP, Cohuet S, Rigutto C, Fortes F, Saraiva N, Kiguli J, et al. High efficacy of two artemisinin‐based combinations (artesunate + amodiaquine and artemether + lumefantrine) in Caala, Central Angola. American Journal of Tropical Medicine and Hygiene 2006; Vol. 75, issue 1:143‐5. - PubMed
Hamour 2003 SDN {published data only}
    1. Hamour S, Melaku Y, Keus K, Wambugu J, Atkin S, Montgomery J, et al. Malaria in the Nuba Mountains of Sudan: baseline genotypic resistance and efficacy of the artesunate plus sulfadoxine‐pyrimethamine and artesunate plus amodiaquine combinations. Transactions of the Royal Society of Tropical Medicine and Hygiene 2005; Vol. 99, issue 7:548‐54. - PubMed
Hasugian 2005 IDN {published and unpublished data}
    1. Hasugian AR, Purba HL, Kenangalem E, Wuwung RM, Ebsworth EP, Maristela R, et al. Dihydroartemisinin‐piperaquine versus artesunate‐amodiaquine: superior efficacy and posttreatment prophylaxis against multidrug‐resistant Plasmodium falciparum and Plasmodium vivax malaria. Clinical Infectious Diseases 2007; Vol. 44, issue 8:1067‐74. - PMC - PubMed
Hutagalung 2002 THA {published data only}
    1. Hutagalung R, Paiphun L, Ashley EA, McGready R, Brockman A, Thwai KL, et al. A randomized trial of artemether‐lumefantrine versus mefloquine‐artesunate for the treatment of uncomplicated multi‐drug resistant Plasmodium falciparum on the western border of Thailand. Malaria Journal 2005; Vol. 4:46. - PMC - PubMed
Janssens 2003 KHM {published data only}
    1. Janssens B, Herp M, Goubert L, Chan S, Uong S, Nong S, et al. A randomized open study to assess the efficacy and tolerability of dihydroartemisinin‐piperaquine for the treatment of uncomplicated falciparum malaria in Cambodia. Tropical Medicine and International Health 2007; Vol. 12, issue 2:251‐9. - PubMed
Kamya 2006 UGA {published data only}
    1. Kamya MR, Yeka A, Bukirwa H, Lugemwa M, Rwakimari JB, Staedke SG, et al. Artemether‐lumefantrine versus dihydroartemisinin‐piperaquine for treatment of malaria: a randomized trial. PLoS Clinical Trials 2007; Vol. 2, issue 5:e20. - PMC - PubMed
Karema 2004 RWA {published and unpublished data}
    1. Karema C, Fanello CI, Overmeir C, Geertruyden JP, Doren W, Ngamije D, et al. Safety and efficacy of dihydroartemisinin/piperaquine (Artekin) for the treatment of uncomplicated Plasmodium falciparum malaria in Rwandan children. Transactions of the Royal Society of Tropical Medicine and Hygiene 2006; Vol. 100, issue 12:1105‐11. - PubMed
Karunajeewa 2007 PNG {published data only}
    1. Karunajeewa HA, Mueller I, Senn M, Lin E, Law I, Gomorrai PS, et al. A trial of combination antimalarial therapies in children from Papua New Guinea. New England Journal of Medicine 2008;359(24):2545‐57. - PubMed
Kayentao 2006 MLI {published data only}
    1. Kayentao K, Maiga H, Newman RD, McMorrow ML, Hoppe A, Yattara O, et al. Artemisinin‐based combinations versus amodiaquine plus sulphadoxine‐pyrimethamine for the treatment of uncomplicated malaria in Faladje, Mali. Malaria Journal 2009;8:5. - PMC - PubMed
Kobbe 2007 GHA {published data only}
    1. Kobbe R, Klein P, Adjei S, Amemasor S, Thompson WN, Heidemann H, et al. A randomized trial on effectiveness of artemether‐lumefantrine versus artesunate plus amodiaquine for unsupervised treatment of uncomplicated Plasmodium falciparum malaria in Ghanaian children. Malaria Journal 2008;7:261. - PMC - PubMed
Koram 2003 GHA {published data only}
    1. Koram KA, Abuaku B, Duah N, Quashie N. Comparative efficacy of antimalarial drugs including ACTs in the treatment of uncomplicated malaria among children under 5 years in Ghana. Acta Tropica 2005; Vol. 95, issue 3:194‐203. - PubMed
Lefevre 1999 THA {published data only}
    1. Lefevre G, Looareesuwan S, Treeprasertsuk S, Krudsood S, Silachamroon U, Gathmann I, et al. A clinical and pharmacokinetic trial of six doses of artemether‐ lumefantrine for multidrug‐resistant Plasmodium falciparum malaria in Thailand. American Journal of Tropical Medicine and Hygiene 2001; Vol. 64, issue 5‐6:247‐56. - PubMed
Martensson 2003 TZA {published data only}
    1. Martensson A, Stromberg J, Sisowath C, Msellem MI, Gil JP, Montgomery SM, et al. Efficacy of artesunate plus amodiaquine versus that of artemether‐lumefantrine for the treatment of uncomplicated childhood Plasmodium falciparum malaria in Zanzibar, Tanzania. Clinical Infectious Diseases 2005; Vol. 41, issue 8:1079‐86. - PubMed
Mayxay 2003 LAO {published and unpublished data}
    1. Mayxay M, Khanthavong M, Lindegardh N, Keola S, Barends M, Pongvongsa T, et al. Randomized comparison of chloroquine plus sulfadoxine‐pyrimethamine versus artesunate plus mefloquine versus artemether‐lumefantrine in the treatment of uncomplicated falciparum malaria in the Lao People's Democratic Republic. Clinical Infectious Diseases 2004; Vol. 39, issue 8:1139‐47. - PubMed
Mayxay 2004 LAO {published and unpublished data}
    1. Mayxay M, Thongpraseuth V, Khanthavong M, Lindegardh N, Barends M, Keola S, et al. An open, randomized comparison of artesunate plus mefloquine vs. dihydroartemisinin‐piperaquine for the treatment of uncomplicated Plasmodium falciparum malaria in the Lao People's Democratic Republic (Laos). Tropical Medicine and International Health 2006; Vol. 11, issue 8:1157‐65. - PubMed
Menard 2006 MDG {published data only}
    1. Menard D, Andrianina NN, Ramiandrasoa Z, Randriamanantena A, Rasoarilalao N, Jahevitra M, et al. Randomized clinical trial of artemisinin versus non‐artemisinin combination therapy for uncomplicated falciparum malaria in Madagascar. Malaria Journal 2007; Vol. 6:65. - PMC - PubMed
Mens 2007 KEN {published data only}
    1. Mens PF, Sawa P, Amsterdam SM, Versteeg I, Omar SA, Schallig HD, et al. A randomized trial to monitor the efficacy and effectiveness by QT‐NASBA of artemether‐lumefantrine versus dihydroartemisinin‐piperaquine for treatment and transmission control of uncomplicated Plasmodium falciparum malaria in western Kenya. Malaria Journal 2008;7(237):Doi:10.1186/1475‐2875‐7‐237. - PMC - PubMed
Mukhtar 2005 SDN {published data only}
    1. Mukhtar EA, Gadalla NB, El‐Zaki SE, Mukhtar I, Mansour FA, Babiker A, et al. A comparative study on the efficacy of artesunate plus sulphadoxine/pyrimethamine versus artemether‐lumefantrine in eastern Sudan. Malaria Journal 2007; Vol. 6:92. - PMC - PubMed
Mutabingwa 2004 TZA {published data only}
    1. Mutabingwa TK, Anthony D, Heller A, Hallett R, Ahmed J, Drakeley C, et al. Amodiaquine alone, amodiaquine+sulfadoxine‐pyrimethamine, amodiaquine+artesunate, and artemether‐lumefantrine for outpatient treatment of malaria in Tanzanian children: a four‐arm randomised effectiveness trial. Lancet 2005; Vol. 365, issue 9469:1474‐80. - PubMed
Owusu‐Agyei 2006 GHA {published data only}
    1. Owusu‐Agyei S, Asante KP, Owusu R, Adjuik M, Amenga‐Etego S, Dosoo DK, et al. An open label, randomised trial of artesunate+amodiaquine, artesunate+chlorproguanil‐dapsone and artemether‐lumefantrine for the treatment of uncomplicated malaria. PLoS ONE 2008;3(6):e2530. - PMC - PubMed
Ratcliff 2005 IDN {published and unpublished data}
    1. Ratcliff A, Siswantoro H, Kenangalem E, Maristela R, Wuwung RM, Laihad F, et al. Two fixed‐dose artemisinin combinations for drug‐resistant falciparum and vivax malaria in Papua, Indonesia: an open‐label randomised comparison. Lancet 2007; Vol. 369, issue 9563:757‐65. - PMC - PubMed
Sagara 2005b MLI {published and unpublished data}
    1. Sagara I, Diallo A, Kone M, Coulibaly M, Diawara SI, Guindo O, et al. A randomized trial of artesunate‐mefloquine versus artemether‐lumefantrine for treatment of uncomplicated Plasmodium falciparum malaria in Mali. American Journal of Tropical Medicine and Hygiene 2008;79(5):655‐61. - PubMed
Smithuis 2004 MMR {published data only}
    1. Smithuis F, Kyaw MK, Phe O, Aye KZ, Htet L, Barends M, et al. Efficacy and effectiveness of dihydroartemisinin‐piperaquine versus artesunate‐mefloquine in falciparum malaria: an open‐label randomised comparison. Lancet 2006; Vol. 367, issue 9528:2075‐85. - PubMed
Staedke 2003 UGA {published and unpublished data}
    1. Staedke SG, Mpimbaza A, Kamya MR, Nzarubara BK, Dorsey G, Rosenthal PJ. Combination treatments for uncomplicated falciparum malaria in Kampala, Uganda: randomised clinical trial. Lancet 2004; Vol. 364, issue 9449:1950‐7. - PubMed
Stohrer 2003 LAO {published data only}
    1. Stohrer JM, Dittrich S, Thongpaseuth V, Vanisaveth V, Phetsouvanh R, Phompida S, et al. Therapeutic efficacy of artemether‐lumefantrine and artesunate‐mefloquine for treatment of uncomplicated Plasmodium falciparum malaria in Luang Namtha Province, Lao People's Democratic Republic. Tropical Medicine and International Health 2004; Vol. 9, issue 11:1175‐83. - PubMed
Swarthout 2004 ZAR {published data only}
    1. Swarthout TD, Broek IV, Kayembe G, Montgomery J, Pota H, Roper C. Artesunate + amodiaquine and artesunate + sulphadoxine‐pyrimethamine for treatment of uncomplicated malaria in Democratic Republic of Congo: a clinical trial with determination of sulphadoxine and pyrimethamine‐resistant haplotypes. Tropical Medicine and International Health 2006; Vol. 11, issue 10:1503‐11. - PubMed
Tangpukdee 2005 THA {published data only}
    1. Tangpukdee N, Krudsood S, Thanachartwet W, Chalermrut K, Pengruksa C, Srivilairit S, et al. An open randomized clinical trial of Artekin vs artesunate‐mefloquine in the treatment of acute uncomplicated falciparum malaria. Southeast Asian Journal of Tropical Medicine and Public Health 2005; Vol. 36, issue 5:1085‐91. - PubMed
Tran 2002 VNM {published data only}
    1. Tran TH, Dolecek C, Pham PM, Nguyen TD, Nguyen TT, Le HT, et al. Dihydroartemisinin‐piperaquine against multidrug‐resistant Plasmodium falciparum malaria in Vietnam: randomised clinical trial. Lancet 2004; Vol. 363, issue 9402:18‐22. - PubMed
Van den Broek 2003a BGD {published and unpublished data}
    1. Broek IV, Maung UA, Peters A, Liem L, Kamal M, Rahman M, et al. Efficacy of chloroquine + sulfadoxine‐‐pyrimethamine, mefloquine + artesunate and artemether + lumefantrine combination therapies to treat Plasmodium falciparum malaria in the Chittagong Hill Tracts, Bangladesh. Transactions of the Royal Society of Tropical Medicine and Hygiene 2005; Vol. 99, issue 10:727‐35. - PubMed
Van den Broek 2004 ZAR {published and unpublished data}
    1. Broek I, Kitz C, Al Attas S, Libama F, Balasegaram M, Guthmann JP. Efficacy of three artemisinin combination therapies for the treatment of uncomplicated Plasmodium falciparum malaria in the Republic of Congo. Malaria Journal 2006; Vol. 5:113. - PMC - PubMed
Van Vugt 1998 THA {published data only}
    1. Vugt M, Looareesuwan S, Wilairatana P, McGready R, Villegas L, Gathmann I, et al. Artemether‐lumefantrine for the treatment of multidrug‐resistant falciparum malaria. Transactions of the Royal Society of Tropical Medicine and Hygiene 2000; Vol. 94, issue 5:545‐8. - PubMed
Yeka 2004 UGA {published and unpublished data}
    1. Yeka A, Banek K, Bakyaita N, Staedke SG, Kamya MR, Talisuna A, et al. Artemisinin versus nonartemisinin combination therapy for uncomplicated malaria: randomized clinical trials from four sites in Uganda. PLoS Medicine 2005; Vol. 2, issue 7:e190. - PMC - PubMed
Yeka 2007 UGA {published data only}
    1. Yeka A, Dorsey G, Kamya MR, Talisuna A, Lugemwa M, Rwakimari JB, et al. Artemether‐lumefantrine versus dihydroartemisinin‐piperaquine for treating uncomplicated malaria: a randomized trial to guide policy in Uganda. PLoS ONE 2008;3(6):e2390. - PMC - PubMed
Zongo 2005 BFA {published and unpublished data}
    1. Zongo I, Dorsey G, Rouamba N, Tinto H, Dokomajilar C, Guiguemde RT, et al. Artemether‐lumefantrine versus amodiaquine plus sulfadoxine‐pyrimethamine for uncomplicated falciparum malaria in Burkina Faso: a randomised non‐inferiority trial. Lancet 2007; Vol. 369, issue 9560:491‐8. - PubMed
Zongo 2007 BFA {published and unpublished data}
    1. Zongo I, Dorsey G, Rouamba N, Dokomajilar C, Sere Y, Rosenthal PJ, et al. Randomized comparison of amodiaquine plus sulfadoxine‐pyrimethamine, artemether‐lumefantrine, and dihydroartemisinin‐piperaquine for the treatment of uncomplicated Plasmodium falciparum malaria in Burkina Faso. Clinical Infectious Diseases 2007; Vol. 45, issue 11:1453‐61. - PubMed

References to studies excluded from this review

Abacassamo 2002 MOZ {published data only}
    1. Abacassamo F, Enosse S, Aponte JJ, Gomez‐Olive FX, Quinto L, Mabunda S, et al. Efficacy of chloroquine, amodiaquine, sulphadoxine‐pyrimethamine and combination therapy with artesunate in Mozambican children with non‐complicated malaria. Tropical Medicine and International Health 2004; Vol. 9, issue 2:200‐8. - PubMed
Abuaku 2005 {published data only}
    1. Abuaku B, Koram K, Quashie N, Duah N. Efficacy of chloroquine, sulfadoxine‐pyrimethamine, amodiaquine + artesunate and artemether + lumefantrine in treating uncomplicated malaria in Ghana. Acta Tropica 2005;95 Suppl 1 [Abstracts from the 4th MIM Pan‐African Conference]:335.
Adjei 2005 {published data only}
    1. Adjei G, Goka B, Rodrigues O, Kitcher E, Badoe E, Alifrangis M, et al. Amodiaquine‐artesunate versus artemether‐lumefantrine: Efficacy and safety for single or repeat episodes of uncomplicated malaria in Ghanaian children. Acta Tropica 2005;95 Suppl 1 [Abstracts from the 4th MIM Pan‐African Conference]:38.
Bell 2008 {published data only}
    1. Bell DJ, Nyirongo SK, Mukaka M, Zijlstra EE, Plowe CV, Molyneux ME. Sulfadoxine‐pyrimethamine‐based combinations for malaria: a randomised blinded trial to compare efficacy, safety and selection of resistance in Malawi. PLoS ONE 2008;3(2):e1578. - PMC - PubMed
Blair 2006 {published data only}
    1. Blair S, Carmona‐Fonseca J, Pineros JG, Rios A, Alvarez T, Alvarez G, et al. Therapeutic efficacy test in malaria falciparum in Antioquia, Colombia. Malaria Journal 2006; Vol. 5:14. - PMC - PubMed
Denis 2006 {published data only}
    1. Denis MB, Tsuyuoka R, Lim P, Lindegardh N, Yi P, Top SN, et al. Efficacy of artemether‐lumefantrine for the treatment of uncomplicated falciparum malaria in northwest Cambodia. Tropical Medicine and International Health 2006; Vol. 11, issue 12:1800‐7. - PubMed
Dorsey 2002 {published data only}
    1. Dorsey G, Njama D, Kamya MR, Cattamanchi A, Kyabayinze D, Staedke SG, et al. Sulfadoxine/pyrimethamine alone or with amodiaquine or artesunate for treatment of uncomplicated malaria: a longitudinal randomised trial. Lancet 2002; Vol. 360, issue 9350:2031‐8. - PubMed
Dorsey‐G 2003 {published data only}
    1. Dorsey G, Vlahos J, Kamya MR, Staedke SG, Rosenthal PJ. Prevention of Increasing rates of treatment failure by combining sulfadoxine‐pyrimethamine with artesunate or amodiaquine for the sequential treatment of malaria. Journal of Infectious Diseases 2003; Vol. 188, issue 8:1231‐8. - PubMed
Fofana 2005 {published data only}
    1. Fofana B, Sidibe B, Dembele D, Toure S, Maiga H, Sagara I, et al. Comparison of the efficacy, safety and tolerability of three treatment regimens for uncomplicated P. falciparum malaria in Mali: artesunate+amodiaquine (3 days) versus artesunate (3 days) + sulfadoxine‐pyrimethamine (1 day) versus artesunate (5 days). Acta Tropica 2005;95 Suppl 1 [Abstracts from the 4th MIM Pan‐African Conference]:345‐6.
Ibrahium 2007 {published data only}
    1. Ibrahium AM, Kheir MM, Osman ME, Khalil IF, Alifrangis M, Elmardi KA, et al. Efficacies of artesunate plus either sulfadoxine‐pyrimethamine or amodiaquine, for the treatment of uncomplicated, Plasmodium falciparum malaria in eastern Sudan. Annals of Tropical Medicine and Parasitology 2007; Vol. 101, issue 1:15‐21. - PubMed
Jiao 1997 {published data only}
    1. Jiao XQ, Liu EY, Shan CQ, Shan CQ, Dal P, Gathmann I. A double‐blind comparative trial of benflumetol, a novel antimalarial, and CGP 56697, a combination of benflumetol and artemether, in the treatment of acute P. falciparum malaria in adults in China. Fifth International Conference on Travel Medicine Program and Abstracts. Geneva, 1997:Abstract 108.
Kabanywanyi 2007 {published data only}
    1. Kabanywanyi AM, Mwita A, Sumari D, Mandike R, Mugittu K, Abdulla S. Efficacy and safety of artemisinin‐based antimalarial in the treatment of uncomplicated malaria in children in southern Tanzania. Malaria Journal 2007; Vol. 6, issue 1:146. - PMC - PubMed
Massougbodji 2005 {published data only}
    1. Massougbodji A, Agbo K, Faye O, Guiguemde R, Kone M, Heidecker J, et al. Efficacy and safety of a combination of artsesunate/mefloquine, Artequin (TM), in African children and adults with uncomplicated P. falciparum malaria. Acta Tropica 2005;95 Suppl 1 [Abstracts from the 4th MIM Pan‐African Conference]:234‐5.
Meremikwu 2004 NGA {published data only}
    1. Meremikwu M, Alaribe A, Ejemot R, Oyo‐Ita A, Ekenjoku J, Nwachukwu C, et al. Artemether‐lumefantrine versus artesunate plus amodiaquine for treating uncomplicated childhood malaria in Nigeria: randomized controlled trial. Malaria Journal 2006; Vol. 5:43. - PMC - PubMed
Mockenhaupt 2005 {published data only}
    1. Mockenhaupt FP, Ehrhardt S, Dzisi SY, Teun Bousema J, Wassilew N, Schreiber J, et al. A randomized, placebo‐controlled, double‐blind trial on sulfadoxine‐pyrimethamine alone or combined with artesunate or amodiaquine in uncomplicated malaria. Tropical Medicine and International Health 2005; Vol. 10, issue 6:512‐20. - PubMed
Mohamed 2006 {published data only}
    1. Mohamed AO, Eltaib EH, Ahmed OA, Elamin SB, Malik EM. The efficacies of artesunate‐sulfadoxine‐pyrimethamine and artemether‐lumefantrine in the treatment of uncomplicated, Plasmodium falciparum malaria, in an area of low transmission in central Sudan. Annals of Tropical Medicine and Parasitology 2006; Vol. 100, issue 1:5‐10. - PubMed
Mulenga 2006 {published data only}
    1. Mulenga M, Geertruyden JP, Mwananyanda L, Chalwe V, Moerman F, Chilengi R, et al. Safety and efficacy of lumefantrine‐artemether (Coartem(R)) for the treatment of uncomplicated Plasmodium falciparum malaria in Zambian adults. Malaria Journal 2006; Vol. 5, issue 1:73. - PMC - PubMed
Ndayiragije 2004 {published data only}
    1. Ndayiragije A, Niyungeko D, Karenzo J, Niyungeko E, Barutwanayo M, Ciza A, et al. Efficacy of therapeutic combinations with artemisinin derivatives in the treatment of non complicated malaria in Burundi.[Efficacite de combinaisons therapeutiques avec des derives de l'artemisinine dans le traitement de l'acces palustre non‐complique au Burundi]. Tropical Medicine and International Health 2004; Vol. 9, issue 6:673‐9. - PubMed
Ndiaye 2005 {published data only}
    1. Ndiaye P, Faye B, Ndiaye J, Ndiaye D, Diallo I, Seck P, et al. Efficacite et tolerance de l'association Artesunate plus Amodiaquine (Amonate®) versus Arthemether plus lumefantrine (Coartem®) six doses dans le traitement des acces palustres simples a Plasmodium falciparum au Senegal. Acta Tropica 2005;95 Suppl 1 [Abstracts from the 4th MIM Pan‐African Conference]:254‐5.
Obonyo 2007 {published data only}
    1. Obonyo CO, Juma EA, Ogutu BR, Vulule JM, Lau J. Amodiaquine combined with sulfadoxine/pyrimethamine versus artemisinin‐based combinations for the treatment of uncomplicated falciparum malaria in Africa: a meta‐analysis. Transactions of the Royal Society of Tropical Medicine and Hygiene 2007;101(2):117‐26. - PubMed
Okell 2008 {published data only}
    1. Okell LC, Drakeley CJ, Ghani AC, Bousema T, Sutherland CJ. Reduction of transmission from malaria patients by artemisinin combination therapies: A pooled analysis of six randomized trials. Malaria Journal 2008;7:125. - PMC - PubMed
Piola 2005 {published data only}
    1. Piola P, Fogg C, Bajunirwe F, Biraro S, Grandesso F, Ruzagira E, et al. Supervised versus unsupervised intake of six‐dose artemether‐lumefantrine for treatment of acute, uncomplicated Plasmodium falciparum malaria in Mbarara, Uganda: a randomised trial. Lancet 2005; Vol. 365, issue 9469:1467‐73. - PubMed
Rwagacondo 2003 {published data only}
    1. Rwagacondo CE, Niyitegeka F, Sarushi J, Karema C, Mugisha V, Dujardin JC, et al. Efficacy of amodiaquine alone and combined with sulfadoxine‐pyrimethamine and of sulfadoxine pyrimethamine combined with artesunate. American Journal of Tropical Medicine and Hygiene 2003; Vol. 68, issue 6:743‐7. - PubMed
Sagara 2006 {published data only}
    1. Sagara I, Dicko A, Djimde A, Guindo O, Kone M, Tolo Y, et al. A randomized trial of artesunate‐sulfamethoxypyrazine‐pyrimethamine versus artemether‐lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in Mali. American Journal of Tropical Medicine and Hygiene 2006; Vol. 75:630‐636. - PubMed
Sowunmi 2007a {published data only}
    1. Sowunmi A, Gbotosho GO, Adedeji AA, Tambo E, Fateye BA, Happi CT, et al. The effects of artemether‐lumefantrine vs amodiaquine‐sulfalene‐pyrimethamine on the hepatomegaly associated with Plasmodium falciparum malaria in children. Parasitology Research 2007; Vol. 100, issue 3:511‐7. - PubMed
Sowunmi 2007b {published data only}
    1. Sowunmi A, Gbotosho GO, Happi CT, Adedeji AA, Fehintola FA, Folarin OA, et al. Therapeutic efficacy and effects of artemether‐lumefantrine and amodiaquine‐sulfalene‐pyrimethamine on gametocyte carriage in children with uncomplicated Plasmodium falciparum malaria in Southwestern Nigeria. American Journal of Tropical Medicine and Hygiene 2007; Vol. 77, issue 2:235‐41. - PubMed
Tall 2005 {published data only}
    1. Tall A, Rabarijaona L, Bedja S, Rahamatou S, Ahmed O, Ratsimbasoa A, et al. Efficacy of artesunate + amodiaquine, artesunate + sulfadoxine‐pyrimethamine, chloroquine + sulfadoxine‐pyrimethamine in P.falciparum malaria in Comoros. Acta Tropica 2005;95 Suppl 1 [Abstracts from the 4th MIM Pan‐African Conference]:223‐4.
Tall 2007 {published data only}
    1. Tall A, Rabarijaona LP, Robert V, Bedja SA, Ariey F, Randrianarivelojosia M. Efficacy of artesunate plus amodiaquine, artesunate plus sulfadoxine‐pyrimethamine, and chloroquine plus sulfadoxine‐pyrimethamine in patients with uncomplicated Plasmodium falciparum in the Comoros Union. Acta Tropica 2007. - PubMed
Thapa 2007 {published data only}
    1. Thapa S, Hollander J, Linehan M, Cox‐Singh J, Bista MB, Thakur GD, et al. Comparison of artemether‐lumefantrine with sulfadoxine‐pyrimethamine for the treatment of uncomplicated Falciparum malaria in Eastern Nepal. American Journal of Tropical Medicine and Hygiene 2007; Vol. 77, issue 3:423‐30. - PubMed
Tranh 2009 {published data only}
    1. Thanh NX, Trung TN, Phong NC, Thien NX, Dai B, Dennis Shanks G, et al. Open label randomized comparison of dihydroartemisinin‐piperaquine and artesunate‐amodiaquine for the treatment of uncomplicated Plasmodium falciparum malaria in central Vietnam. Tropical Medicine and International Health 2009;14(5):1‐8. - PubMed
van den Broek 2005b {published data only}
    1. Broek I, Amsalu R, Balasegaram M, Hepple P, Alemu E, Hussein el B, et al. Efficacy of two artemisinin combination therapies for uncomplicated falciparum malaria in children under 5 years, Malakal, Upper Nile, Sudan. Malaria Journal 2005; Vol. 4, issue 1:14. - PMC - PubMed
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