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
. 2021 Oct 1;34(5):432-439.
doi: 10.1097/QCO.0000000000000766.

Artemisinin and multidrug-resistant Plasmodium falciparum - a threat for malaria control and elimination

Mehul Dhorda  1   2 , Chanaki Amaratunga  1   2 , Arjen M Dondorp  1   2
Affiliations
Review

Artemisinin and multidrug-resistant Plasmodium falciparum - a threat for malaria control and elimination

Mehul Dhorda et al. Curr Opin Infect Dis. .

Abstract

Purpose of review: Artemisinin-based combination therapies (ACTs) are globally the first-line treatment for uncomplicated falciparum malaria and new compounds will not be available within the next few years. Artemisinin-resistant Plasmodium falciparum emerged over a decade ago in the Greater Mekong Subregion (GMS) and, compounded by ACT partner drug resistance, has caused significant ACT treatment failure. This review provides an update on the epidemiology, and mechanisms of artemisinin resistance and approaches to counter multidrug-resistant falciparum malaria.

Recent findings: An aggressive malaria elimination programme in the GMS has helped prevent the spread of drug resistance to neighbouring countries. However, parasites carrying artemisinin resistance-associated mutations in the P. falciparum Kelch13 gene (pfk13) have now emerged independently in multiple locations elsewhere in Asia, Africa and South America. Notably, artemisinin-resistant infections with parasites carrying the pfk13 R561H mutation have emerged and spread in Rwanda.

Summary: Enhancing the geographic coverage of surveillance for resistance will be key to ensure prompt detection of emerging resistance in order to implement effective countermeasures without delay. Treatment strategies designed to prevent the emergence and spread of multidrug resistance must be considered, including deployment of triple drug combination therapies and multiple first-line therapies.

PubMed Disclaimer

Conflict of interest statement

M.D., C.A. are coordinators and A.D. is the PI of the Development of Triple Artemisinin-based Combination Therapies (DeTACT) project, funded by the Foreign, Commonwealth and Development Office of the UK Government. A.D. chaired the Novartis Malaria Advisory Council from January until May 2021.

Figures

Box 1
Box 1
no caption available
FIGURE 1
FIGURE 1
Circular cascade of events leading to increased transmission, cases and deaths due to antimalarial drug resistance.
FIGURE 2
FIGURE 2
Spread of pfk13 haplotypes across the Greater Mekong Subregion. The long <i>pfk13</i> C580Y haplotype that emerged in 2008 spread from its origin in western Cambodia to Thailand, Laos and Viet Nam. The blue arrows depict a single <i>pfk13</i> F446I haplotype that probably originated in northern Myanmar. Adapted from [▪▪].
See this image and copyright information in PMC

References

    1. Bhatt S, Weiss DJ, Cameron E, et al. . The effect of malaria control on Plasmodium falciparum in Africa between 2000 and 2015. Nature 2015; 526:207–211. - PMC - PubMed
    1. Nosten F, White NJ. Artemisinin-based combination treatment of falciparum malaria. Am J Trop Med Hyg 2007; 77: 6 Suppl: 181–192. - PubMed
    1. Nosten F, Luxemburger C, ter Kuile FO, et al. . Treatment of multidrug-resistant Plasmodium falciparum malaria with 3-day artesunate-mefloquine combination. J Infect Dis 1994; 170:971–977. - PubMed
    1. World Health Organization. Guidelines for the treatment of malaria. Geneva, Switzerland: World Health Organization; 2006.
    1. White NJ, Hien TT, Nosten FH. A brief history of qinghaosu. Trends Parasitol 2015; 31:607–610. - PMC - PubMed

Publication types

MeSH terms