The problem of antimalarial resistance and its implications for drug discovery

Expert Opin Drug Discov. 2024 Feb;19(2):209-224. doi: 10.1080/17460441.2023.2284820. Epub 2024 Feb 1.

Abstract

Introduction: Malaria remains a devastating infectious disease with hundreds of thousands of casualties each year. Antimalarial drug resistance has been a threat to malaria control and elimination for many decades and is still of concern today. Despite the continued effectiveness of current first-line treatments, namely artemisinin-based combination therapies, the emergence of drug-resistant parasites in Southeast Asia and even more alarmingly the occurrence of resistance mutations in Africa is of great concern and requires immediate attention.

Areas covered: A comprehensive overview of the mechanisms underlying the acquisition of drug resistance in Plasmodium falciparum is given. Understanding these processes provides valuable insights that can be harnessed for the development and selection of novel antimalarials with reduced resistance potential. Additionally, strategies to mitigate resistance to antimalarial compounds on the short term by using approved drugs are discussed.

Expert opinion: While employing strategies that utilize already approved drugs may offer a prompt and cost-effective approach to counter antimalarial drug resistance, it is crucial to recognize that only continuous efforts into the development of novel antimalarial drugs can ensure the successful treatment of malaria in the future. Incorporating resistance propensity assessment during this developmental process will increase the likelihood of effective and enduring malaria treatments.

Keywords: Plasmodium falciparum; antimalarial drug discovery; antimalarial drug resistance; artemisinin-based combination therapies; irresistibles.

Publication types

  • Review

MeSH terms

  • Antimalarials* / pharmacology
  • Drug Discovery
  • Drug Resistance / genetics
  • Humans
  • Malaria* / drug therapy
  • Plasmodium falciparum

Substances

  • Antimalarials