摘要
Background: Several artemisinin-based combination therapies (ACT) are available to treat uncomplicated malaria in Africa. The present study aimed to assess the ranking of their efficacy and tolerance. Methods: A database of randomized controlled trials was retrieved from published papers. Network meta-analysis was used to compare efficacy on day 28 and day 42 after initiation of treatment. Age covariate effect on treatment outcome was assessed, and a modeling approach to reduce heterogeneity among trials was evaluated under the hypothesis of consistency in a meta-regression. Safety and adverse events were compared among different ACTs. A Bayesian analysis was performed to implement the consistency models using WinBUGS software. The results were compared to those of the frequentist approach using the R software. Results: Eighty-one articles, in which a total of 15 different ACTs were tested in more than 36,000 patients, were included. On day 28, dihydroartemisinin-piperaquine (DHPP) was more effective than artemether-lumefantrine (AL) before (odds ratio [OR], 1.83;95% confidence interval [CI], 1.31 - 2.56) and after age-covariate adjustment (OR, 1.70;95% CI, 1.20 - 2.43). The result was similar on day 42. DHPP occupied the top rank. The risk of having cough, diarrhoea or headache post-treatment was significantly lower with DHPP than AL. Artesunate-mefloquine (ASMQ) was associated with a significantly lower prevalence of vomiting or nausea (OR, 0.80;95% CI, 0.48 - 1.30) and headache (OR, 0.53;95% CI, 0.40 - 0.68) compared to AL. On the contrary, vomiting and nausea occurred more frequently after fixed-dose artesunate-amodiaquine formulation (ASAQf) than with AL (OR, 1.45;95% CI, 1.18 - 1.78). The risk of anaemia was higher with ASAQf and co-blistered artesunate-amodiaquine (ASAQc) than with AL. There was no significant difference in risk of anaemia (P > 0.05) between AL and different formulations of ASAQ. Conclusions: Based on the available evidence, this study demonstrated the superiority of DHPP, followed by AL, among currently recommended ACTs in terms of efficacy and tolerance. Network meta-analysis could be an alternative analytical tool but needs more data input from therapeutic efficacy studies. The determination of the best available therapy requires data triangulation and data science.
Background: Several artemisinin-based combination therapies (ACT) are available to treat uncomplicated malaria in Africa. The present study aimed to assess the ranking of their efficacy and tolerance. Methods: A database of randomized controlled trials was retrieved from published papers. Network meta-analysis was used to compare efficacy on day 28 and day 42 after initiation of treatment. Age covariate effect on treatment outcome was assessed, and a modeling approach to reduce heterogeneity among trials was evaluated under the hypothesis of consistency in a meta-regression. Safety and adverse events were compared among different ACTs. A Bayesian analysis was performed to implement the consistency models using WinBUGS software. The results were compared to those of the frequentist approach using the R software. Results: Eighty-one articles, in which a total of 15 different ACTs were tested in more than 36,000 patients, were included. On day 28, dihydroartemisinin-piperaquine (DHPP) was more effective than artemether-lumefantrine (AL) before (odds ratio [OR], 1.83;95% confidence interval [CI], 1.31 - 2.56) and after age-covariate adjustment (OR, 1.70;95% CI, 1.20 - 2.43). The result was similar on day 42. DHPP occupied the top rank. The risk of having cough, diarrhoea or headache post-treatment was significantly lower with DHPP than AL. Artesunate-mefloquine (ASMQ) was associated with a significantly lower prevalence of vomiting or nausea (OR, 0.80;95% CI, 0.48 - 1.30) and headache (OR, 0.53;95% CI, 0.40 - 0.68) compared to AL. On the contrary, vomiting and nausea occurred more frequently after fixed-dose artesunate-amodiaquine formulation (ASAQf) than with AL (OR, 1.45;95% CI, 1.18 - 1.78). The risk of anaemia was higher with ASAQf and co-blistered artesunate-amodiaquine (ASAQc) than with AL. There was no significant difference in risk of anaemia (P > 0.05) between AL and different formulations of ASAQ. Conclusions: Based on the available evidence, this study demonstrated the superiority of DHPP, followed by AL, among currently recommended ACTs in terms of efficacy and tolerance. Network meta-analysis could be an alternative analytical tool but needs more data input from therapeutic efficacy studies. The determination of the best available therapy requires data triangulation and data science.
作者
Solange Whegang Youdom
Roméo Simeu Tchouenkou
Eugène-Patrice Ndong-Nguéma
Leonardo K. Basco
Solange Whegang Youdom;Roméo Simeu Tchouenkou;Eugène-Patrice Ndong-Nguéma;Leonardo K. Basco(Department of Public Health, Faculty of Medicine and Pharmaceutical Sciences, University of Dschang, Dschang, Cameroon;National Advanced School of Engineering, University of Yaounde I, Yaounde, Cameroon;Aix Marseille University, IRD, AP-HM, SSA, VITROME, Marseille, France;Institut Hospitalo-Universitaire (IHU)—Méditerranée Infection, Marseille, France)
