Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2020 Nov 12:11:596697.
doi: 10.3389/fphar.2020.596697. eCollection 2020.

Safety and Efficacy of Adjunctive Therapy With Artesunate in the Treatment of Severe Malaria: A Systematic Review and Meta-Analysis

Yuanyuan Zou  1 , Fei Tuo  1 , Zhiqi Zhang  1 , Jiawen Guo  2 , Yueming Yuan  1   2 , Hongying Zhang  1 , Zhiyong Xu  2 , Ziyi Pan  1 , Yexiao Tang  1 , Changsheng Deng  1 , Nadia Julie  1 , Wanting Wu  1 , Wenfeng Guo  1 , Changqing Li  1 , Xinan Huang  1 , Qin Xu  1 , Jianping Song  1 , Qi Wang  1
Affiliations
Review

Safety and Efficacy of Adjunctive Therapy With Artesunate in the Treatment of Severe Malaria: A Systematic Review and Meta-Analysis

Yuanyuan Zou et al. Front Pharmacol. .

Abstract

Objective: The purpose of this meta-analysis of longitudinal studies is to determine the safety and efficacy of artesunate combined with other forms of adjunctive therapies for severe malaria. Methods: Following the PRISMA guidelines, we searched multiple databases with the search terms "artesunate" and "adjunctive therapy" and "severe malaria" in July 2020. If the search showed a randomized controlled trial, the study was included in this meta-analysis. The random-effects model was used to calculate the combined incidence rate and relative risk or risk difference. Results: This meta-analysis included nine longitudinal studies with 724 participants. We found that the mortality rates in the artesunate monotherapy group and the artesunate + adjuvant therapy group are similar (RD = -0.02, 95% confidence interval: -0.06-0.02). The incidence of adverse reactions in the artesunate monotherapy group and the artesunate + adjuvant therapy group was also similar. Conclusion: No significant differences in safety and efficacy were observed between the artesunate monotherapy group and the artesunate + adjuvant therapy group. Higher quality and rigorously designed randomized controlled studies are needed to validate our findings.

Keywords: artesunate; efficacy; meta-analysis; safety; severe malaria; systematic review.

PubMed Disclaimer

Figures

FIGURE 1
FIGURE 1
PRISMA flow chart.
FIGURE 2
FIGURE 2
Comparison of mortality rates in ATS monotherapy group and ATS + adjuvant therapy group.
FIGURE 3
FIGURE 3
Comparison of PCT levels in ATS monotherapy group and ATS + adjuvant therapy group.
FIGURE 4
FIGURE 4
Comparison of FCT levels in ATS monotherapy group and ATS + adjuvant therapy group.
FIGURE 5
FIGURE 5
Funnel chart of included trials.
FIGURE 6
FIGURE 6
Sensitivity analysis of included trials.
See this image and copyright information in PMC

References

    1. Anstey N. M., Weinberg J. B., Hassanali M. Y., Mwaikambo E. D., Manyenga D., Misukonis M. A., et al. (1996). Nitric oxide in tanzanian children with malaria: inverse relationship between malaria severity and nitric oxide production/nitric oxide synthase type 2 expression. J. Exp. Med. 184 (2), 557–567. 10.1084/jem.184.2.557. - DOI - PMC - PubMed
    1. Bangirana P., Conroy A. L., Opoka R. O., Hawkes M. T., Hermann L., Miller C., et al. (2018). Inhaled nitric oxide and cognition in pediatric severe malaria: A randomized double-blind placebo controlled trial. PLoS One 13 (1), e0191550 10.1371/journal.pone.0191550. - DOI - PMC - PubMed
    1. Charunwatthana P., Abul Faiz M., Ruangveerayut R., Maude R. J., Rahman M. R., Roberts L. J., et al. (2009). N-acetylcysteine as adjunctive treatment in severe malaria: a randomized, double-blinded placebo-controlled clinical trial. Crit. Care Med. 37 (2), 516–522. 10.1097/CCM.0b013e3181958dfd. - DOI - PMC - PubMed
    1. Erice C., Kain K. C. (2019). New insights into microvascular injury to inform enhanced diagnostics and therapeutics for severe malaria. Virulence 10 (1), 1034–1046. 10.1080/21505594.2019.1696621. - DOI - PMC - PubMed
    1. Evans S. G., Morrison D., Kaneko Y., Havlik I. (1998). The effect of curdlan sulphate on development in vitro of plasmodium falciparum. Trans. R. Soc. Trop. Med. Hyg. 92 (1), 87–89. 10.1016/S0035-9203(98)90969-5 - DOI - PubMed