A Systematic Review of Randomized Trials of Artesunate for Severe Malaria_Chinese Journal of Evidence-Based Medicine

Authors：

YUAN ZhiFang , SUN Xin , MENG Yue , JING YuanYuan , MAO Xiu ,  LI YouPing

Chinese Evidence-based Medicine Center, West China Hospital, Sichuan University, Chengdu 610041, China;

Corresponding author：

LI YouPing, Email: yzmylab@hotmail.com

Keywords：

Severe malaria; Artesunate; Quinine; Systematic Review; Randomized controlled trial

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Objective　 To investigate the effects of two formulations of artesunate, and to provide evidence for the WHO Model List of Essential Medicines.
Method s　We searched The Cochrane Library (2006, Issue 4), MEDLINE ( 1966 to 2007), EMbase (1988 to 2007), CBM (1978 to 2007), VIP (1989 to 2007) and CNKI (1994 to 2007). Randomised trials comparing the two formulations of artesunate with other drugs were eligible for inclusion. We applied the methods of The Cochrane Collaboration to assess the effects of artesunate, compared to placebo and active controls.
Results　 Eleven trials were included, of which 6 compared intravenous artesunate with intravenous quinine. The quality of each study was high, 6 out of the 11 studies were graded A according to the criteria of The Cochrane Collaboration. The other 5 were graded B. The meta-analysis suggested that the mortality rate was lower in the intravenous artesunate group than in the intravenous quinine group [RR 0.65, 95%CI (0.52, 0.80), P lt;0.0001]. Three trials compared intravenous artesunate with artemisinin suppositories. These trials generated similar estimates and confidence intervals for mortality rates, showing no significant difference between the two treatments [0.94 (0.35 to 2.56), 0.58 (0.19 to 1.74) and 2.00 (0.39 to 10.26)]. Two trials compared intravenous artesunate and intramuscular artesunate, and no significant difference in mortality rate was identified between the two treatment groups [RR 1.50, 95%CI 0.52 to 4.31]. Mortality rates were not statistically significantly different for intravenous artesunate compared to alternative drugs. No significant adverse drug reactions were observed.
Conclusions　 Artesunate is effective and safe in the treatment of severe malaria.

Citation： YUAN ZhiFang,SUN Xin,MENG Yue,JING YuanYuan,MAO Xiu,LI YouPing. A Systematic Review of Randomized Trials of Artesunate for Severe Malaria. Chinese Journal of Evidence-Based Medicine, 2007, 07(11): 794-801. doi: Copy

1.	Zhou ZY, editor-in-chief. Handbook of Materia Medica. 2nd ed. Beijing: Jin Yong Publishing House, 1992. 526-527.
2.	Liu GJ. The application of bio-statistical method in Evidence-based Medicine. In: Li YP, Editor-in-Chief. Evidence-based Medicine. Beijing: Higher Education Press, 2003. 50-66.
3.	Disease information. http://www.who.int/tdr/diseases/malaria/diseaseinfo.htm.
4.	2006 Guidelines for the treatment of malaria. http://www.who.int/malaria/docs/TreatmentGuidelines2006.pdf.
5.	周自永, 主编. 新编常用药物手册. 第2版. 北京: 金庸出版社, 1992. 526-527.
6.	What is the best treatment against malaria?http://www.who.int/features/qa/26/en/index.html.
7.	McIntosh HM, Olliaro P. Artemisinin derivatives for treating severe malaria. Cochrane Database Syst Rev, 2000, (2): CD000527.
8.	Jones KL, Donegan S, Lalloo DG. Artesunate versus quinine for treating severe malaria. Cochrane Database of Systematic Reviews 2007, Issue 4. Art. No.: CD005967. DOI: 10.1002/14651858.CD005967.pub2.
9.	Tjitra E, Suprianto S, Dyer M, et al. Field Evaluation of the ICT Malaria P.f/P.v immunochromatographic test for detection of Plasmodium falciparum and Plasmodium vivax in patients with a presumptive clinical diagnosis of Malaria in eastern indonesia. J Clin Microbiol, 1999, 37: 2412-2417.
10.	World Health Organization. Severe and complicated malaria (World Health Organization Malaria Action Programme). Trans R Soc Trop Med Hyg,1986,80(Suppl):3-50.
11.	Warrell DA, Molyneux ME, Beales PF. Severe and complicated malaria. Trans R Soc Trop Med Hyg, 1990, 84(suppl 2):1-65.
12.	Turato G, Zuin R, Monti S. Celluar and structual changes in peripheral airways of subjects with severe COPD. Eur Respir J, 2001, 91: 662.
13.	Cochrane Reviewer, Handbook 4.2. The Cochrane Collaboration, 2006.
14.	Schulz KF, Chalmers I, Hayes RJ. Empirical evidence of bias. JAMA, 1995, 273: 408 - 421.
15.	刘关键. 统计学方法在循证医学中的应用. 见: 李幼平, 主编. 循证医学. 第1版. 北京: 高等教育出版社, 2003. 49-57.
16.	Karunajeewa, HA, Reeder J, Lorry K, et al. Artesunate suppositories versus intramuscular artemether for treatment of severe malaria in children in Papua New Guinea. Antimicrob Agents Chemother, 2006, 50(3): 968-974.
17.	Dondorp A, Nosten F, Stepniewska K, et al. Artesunate versus quinine for treatment of severe falciparum malaria: A randomised trial. Lancet, 2005, 366: 717-725.
18.	Hien TT, Phu NH, Mai NT, et al. An open randomized comparison of intravenous and intramuscular artesunate in severe falciparum malaria. Trans R Soc Trop Med Hyg, 1992, 86(6): 584-585.
19.	Haroon N, Amichandwala K, Solu MG. Comparative efficacy of quinine and artesunate in the treatment of severe malaria: a randomized controlled trial. JK Science, 2005, 7: 32-35.
20.	Hien TT, Arnold K, Vinh H, et al. Comparison of artemisinin suppositories with intravenous artesunate and intravenous quinine in the treatment of cerebral malaria. Trans R Soc Trop Med Hyg, 1992, 86(6): 582-583.
21.	Cao XT, Bethell DB, Pham TP, et al. Comparison of artemisinin suppositories, intramuscular artesunate and intravenous quinine for the treatment of severe childhood malaria. Trans R Soc Trop Med Hyg, 1997, 91(3): 335-342.
22.	Goka BQ, Adabayeri V, Ofori-Adjei E, et al. Comparison of chloroquine with artesunate in the treatment of cerebral malaria in Ghanaian children. J Trop Pediatr, 2001, 47(3): 165-169.
23.	Nealon C, Dzeing A, Müller-Römer U, et al. Intramuscular bioavailability and clinical efficacy of artesunate in gabonese children with severe malaria. Antimicrob Agents Chemother, 2002, 46(12): 3933-3939.
24.	Newton PN, Angus BJ, Chierakul W, et al. Randomized comparison of artesunate and quinine in the treatment of severe falciparum malaria. Clin Infect Dis, 2003, 37(1): 7-16.
25.	Ha V, Nguyen NH, Tran TB, et al. Severe and complicated malaria treated with artemisinin, artesunate or artemether in Viet Nam. Trans R Soc Trop Med Hyg, 1997, 91(4): 465-467..
26.	Mohanty AK, Rath BK, Mohanty R, et al. Randomized control trial of quinine and artesunate in complicated malaria. Indian J Pediatr, 2004, 71(4): 291-295.
27.	Peter B. Bloland.Drug resistance in malaria. http://www.who.int/csr/resources/publications/drugresist/malaria.pdf.
28.	Pradines B. Antimicrobial agents and chemotherapy. Trop Med Parasitol, 1999, 43(2): 418 - 420.

1. Zhou ZY, editor-in-chief. Handbook of Materia Medica. 2nd ed. Beijing: Jin Yong Publishing House, 1992. 526-527.
2. Liu GJ. The application of bio-statistical method in Evidence-based Medicine. In: Li YP, Editor-in-Chief. Evidence-based Medicine. Beijing: Higher Education Press, 2003. 50-66.
3. Disease information. http://www.who.int/tdr/diseases/malaria/diseaseinfo.htm.
4. 2006 Guidelines for the treatment of malaria. http://www.who.int/malaria/docs/TreatmentGuidelines2006.pdf.
5. 周自永, 主编. 新编常用药物手册. 第2版. 北京: 金庸出版社, 1992. 526-527.
6. What is the best treatment against malaria?http://www.who.int/features/qa/26/en/index.html.
7. McIntosh HM, Olliaro P. Artemisinin derivatives for treating severe malaria. Cochrane Database Syst Rev, 2000, (2): CD000527.
8. Jones KL, Donegan S, Lalloo DG. Artesunate versus quinine for treating severe malaria. Cochrane Database of Systematic Reviews 2007, Issue 4. Art. No.: CD005967. DOI: 10.1002/14651858.CD005967.pub2.
9. Tjitra E, Suprianto S, Dyer M, et al. Field Evaluation of the ICT Malaria P.f/P.v immunochromatographic test for detection of Plasmodium falciparum and Plasmodium vivax in patients with a presumptive clinical diagnosis of Malaria in eastern indonesia. J Clin Microbiol, 1999, 37: 2412-2417.
10. World Health Organization. Severe and complicated malaria (World Health Organization Malaria Action Programme). Trans R Soc Trop Med Hyg,1986,80(Suppl):3-50.
11. Warrell DA, Molyneux ME, Beales PF. Severe and complicated malaria. Trans R Soc Trop Med Hyg, 1990, 84(suppl 2):1-65.
12. Turato G, Zuin R, Monti S. Celluar and structual changes in peripheral airways of subjects with severe COPD. Eur Respir J, 2001, 91: 662.
13. Cochrane Reviewer, Handbook 4.2. The Cochrane Collaboration, 2006.
14. Schulz KF, Chalmers I, Hayes RJ. Empirical evidence of bias. JAMA, 1995, 273: 408 - 421.
15. 刘关键. 统计学方法在循证医学中的应用. 见: 李幼平, 主编. 循证医学. 第1版. 北京: 高等教育出版社, 2003. 49-57.
16. Karunajeewa, HA, Reeder J, Lorry K, et al. Artesunate suppositories versus intramuscular artemether for treatment of severe malaria in children in Papua New Guinea. Antimicrob Agents Chemother, 2006, 50(3): 968-974.
17. Dondorp A, Nosten F, Stepniewska K, et al. Artesunate versus quinine for treatment of severe falciparum malaria: A randomised trial. Lancet, 2005, 366: 717-725.
18. Hien TT, Phu NH, Mai NT, et al. An open randomized comparison of intravenous and intramuscular artesunate in severe falciparum malaria. Trans R Soc Trop Med Hyg, 1992, 86(6): 584-585.
19. Haroon N, Amichandwala K, Solu MG. Comparative efficacy of quinine and artesunate in the treatment of severe malaria: a randomized controlled trial. JK Science, 2005, 7: 32-35.
20. Hien TT, Arnold K, Vinh H, et al. Comparison of artemisinin suppositories with intravenous artesunate and intravenous quinine in the treatment of cerebral malaria. Trans R Soc Trop Med Hyg, 1992, 86(6): 582-583.
21. Cao XT, Bethell DB, Pham TP, et al. Comparison of artemisinin suppositories, intramuscular artesunate and intravenous quinine for the treatment of severe childhood malaria. Trans R Soc Trop Med Hyg, 1997, 91(3): 335-342.
22. Goka BQ, Adabayeri V, Ofori-Adjei E, et al. Comparison of chloroquine with artesunate in the treatment of cerebral malaria in Ghanaian children. J Trop Pediatr, 2001, 47(3): 165-169.
23. Nealon C, Dzeing A, Müller-Römer U, et al. Intramuscular bioavailability and clinical efficacy of artesunate in gabonese children with severe malaria. Antimicrob Agents Chemother, 2002, 46(12): 3933-3939.
24. Newton PN, Angus BJ, Chierakul W, et al. Randomized comparison of artesunate and quinine in the treatment of severe falciparum malaria. Clin Infect Dis, 2003, 37(1): 7-16.
25. Ha V, Nguyen NH, Tran TB, et al. Severe and complicated malaria treated with artemisinin, artesunate or artemether in Viet Nam. Trans R Soc Trop Med Hyg, 1997, 91(4): 465-467..
26. Mohanty AK, Rath BK, Mohanty R, et al. Randomized control trial of quinine and artesunate in complicated malaria. Indian J Pediatr, 2004, 71(4): 291-295.
27. Peter B. Bloland.Drug resistance in malaria. http://www.who.int/csr/resources/publications/drugresist/malaria.pdf.
28. Pradines B. Antimicrobial agents and chemotherapy. Trop Med Parasitol, 1999, 43(2): 418 - 420.

Chinese Journal of Evidence-Based Medicine

A Systematic Review of Randomized Trials of Artesunate for Severe Malaria

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