The preclinical discovery and development of rectal artesunate for the treatment of malaria in young children: a review of the evidence

Expert Opin Drug Discov. 2021 Jan;16(1):13-22. doi: 10.1080/17460441.2020.1804357. Epub 2020 Sep 14.

Abstract

Introduction: Plasmodium falciparum, the deadliest malaria parasite, kills hundreds of thousands of people per year, mainly young children in Sub-Saharan Africa. Artesunate suppositories are recommended as pre-referral malaria treatment in remote endemic areas for severely ill children to prevent progression of the disease and to provide extra time for patients until the definitive severe malaria treatment can be administered.

Areas covered: The authors provide an overview of the discovery of artesunate and its different formulations focusing on rectal administration, summarizing key studies concerning the pharmacokinetic, pharmacodynamic, safety, tolerability and efficacy of rectal artesunate leading to WHO recommendation and market authorization in Africa. In addition, studies on acceptance and adherence to rectal artesunate administration and the post-launch status are also covered.

Expert opinion: Efforts by ministries of health in malaria endemic countries together with international health organizations should establish and enforce guidelines to ensure the correct use of artesunate suppositories only as pre-referral medication in presumed severe malaria cases to minimize the risk of abuse as a monotherapy for treatment of uncomplicated malaria. The priority is to not jeopardize the efficacy of artesunate and to prevent resistance development against this valuable drug class in Africa.

Keywords: Plasmodium falciparum; Artesunate; pre-referral treatment; rectal artesunate; severe malaria; suppositories.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Administration, Rectal
  • Age Factors
  • Animals
  • Antimalarials / administration & dosage*
  • Antimalarials / adverse effects
  • Antimalarials / pharmacokinetics
  • Artesunate / administration & dosage*
  • Artesunate / adverse effects
  • Artesunate / pharmacokinetics
  • Child
  • Child, Preschool
  • Drug Development
  • Drug Evaluation, Preclinical
  • Humans
  • Malaria, Falciparum / drug therapy*
  • Malaria, Falciparum / parasitology
  • Plasmodium falciparum / drug effects
  • Plasmodium falciparum / isolation & purification
  • Severity of Illness Index
  • Suppositories

Substances

  • Antimalarials
  • Suppositories
  • Artesunate