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Review
. 2022 Sep 23:13:876282.
doi: 10.3389/fphar.2022.876282. eCollection 2022.

Artemisinin resistance and malaria elimination: Where are we now?

Borimas Hanboonkunupakarn  1   2 , Joel Tarning  2   3 , Sasithon Pukrittayakamee  1   2   4 , Kesinee Chotivanich  1   2   4
Affiliations
Review

Artemisinin resistance and malaria elimination: Where are we now?

Borimas Hanboonkunupakarn et al. Front Pharmacol. .

Abstract

The emergence of artemisinin resistance is a major obstacle to the global malaria eradication/elimination programs. Artemisinin is a very fast-acting antimalarial drug and is the most important drug in the treatment of severe and uncomplicated malaria. For the treatment of acute uncomplicated falciparum malaria, artemisinin derivatives are combined with long half-life partner drugs and widely used as artemisinin-based combination therapies (ACTs). Some ACTs have shown decreased efficacy in the Southeast Asian region. Fortunately, artemisinin has an excellent safety profile and resistant infections can still be treated successfully by modifying the ACT. This review describes the pharmacological properties of ACTs, mechanisms of artemisinin resistance and the potential changes needed in the treatment regimens to overcome resistance. The suggested ACT modifications are extension of the duration of the ACT course, alternating use of different ACT regimens, and addition of another antimalarial drug to the standard ACTs (Triple-ACT). Furthermore, a malaria vaccine (e.g., RTS,S vaccine) could be added to mass drug administration (MDA) campaigns to enhance the treatment efficacy and to prevent further artemisinin resistance development. This review concludes that artemisinin remains the most important antimalarial drug, despite the development of drug-resistant falciparum malaria.

Keywords: Plasmodium falciparum; artemisinin-based combination therapies; drug resistance; mechanism of resistance; pharmacodynamic; pharmacokinetics.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Pharmacokinetic-pharmacodynamic (PK-PD) principles of ACT treatment. The minimal inhibitory concentrations (MIC) is the lowest antimalarial drug concentration that will inhibit the visible growth of the parasites, resulting in parasite elimination at drug concentrations >MIC and parasite growth at drug concentrations
FIGURE 2
FIGURE 2
ACT-related elimination of a malaria infection, illustrating the impact of (A) starting parasitaemia and (B) rate of parasite decline on time to clearing an infection. The impact of parasitaemia (A) is illustrated assuming a 103-fold reduction in parasitaemia every parasite lifecycle of 48 h. The impact of parasite decline (B) is illustrated assuming an admission parasitaemia of 1010 parasites.
See this image and copyright information in PMC

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