Evaluation of Efficacy and Safety of Artemisinin Derivatives for Treatment of Severe Malaria: A Meta-Analysis Approach

Abstract

Despite progress in antimalarial management and intensive care, the prevalence of malaria is growing and the mortality rate is very high. Yet even with timely treatment of quinine in maximum doses, the death in patients of severe malaria is very high. The successive synthesis of artemether and artesunate has supplied highly successful substitutes to quinine. This systematic review and meta-analysis approach provides a comparative outcome analysis of Artemisinin derivatives (intervention) and other antimalarials (comparison) in the paediatric and adult population. From the year 1985 to the year 2015, studies were recognized using database searches, citation searches of selected articles. The electronic databases searched engines: Pubmed, Web of Science, Global Health, Medline and Cochrane review of Journals up to April 2015. We selected published randomized controlled clinical trials information comparing artemisinin derivatives and quinine for the management of severe malaria in adult and paediatric population as per WHO malaria treatment guideline, any gender, age group less than or greater than 15 years who were diagnosed with severe malaria. The primary outcome was efficacy in terms of parasite clearance time (PCT), Parasite clearance at D7 and D28 and fever clearance time (FCT). The secondary outcome was the mortality and adverse events. We measured 95% confidence interval by the using of REVMAN software version 5.3 for meta-analysis and summarized the collected data on the basis of characteristics of inclusion criteria of articles. We included total 33 RCTs, enrolling 8396 paediatric and adult patients who were suffering from severe malaria. Artemisinin and its derivatives showed mean parasite clearance time (PCT) (MD -8.50 hours, 95% CI -9.41 to -7.60) and mean fever clearance time (FCT) (MD -9.51 hours, 95% CI -11.22 to -7.81) P less than 0.00001 statistically significant as compared to quinine therapy. Artemisinin and its derivatives showed a statistically significant clearance of parasites when compared to quinine at Day 7 (OR 0.41, 95% CI 0.21, 0.81, random effect model, P=0.01). Overall artemisinin derivatives has shown more parasite clearance at D28 than quinine group (Odds ratio 0.54, 95% CI 0.23, 1.29, random effect model, P=0.17). We evaluated secondary outcomes mortality which showed artemisinin or its derivatives a statistically significant mortality reduction as compared to quinine. (Odds Ratio 0.77, 95% CI 0.67 to 0.89; 27 trials, 8396 participants) P=0.0002 and also showed a statistically significant reduction in the adverse events as compared with quinine (RR0.73, 95% CI 0.62 to 0.87) P=0.003. An overall positive result was found with artemisinin derivatives across all evaluated outcomes.