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
. 2019 Feb 1;4(1):26.
doi: 10.3390/tropicalmed4010026.

Resistance to Artemisinin Combination Therapies (ACTs): Do Not Forget the Partner Drug!

Affiliations
Review

Resistance to Artemisinin Combination Therapies (ACTs): Do Not Forget the Partner Drug!

Christian Nsanzabana. Trop Med Infect Dis. .

Abstract

Artemisinin-based combination therapies (ACTs) have become the mainstay for malaria treatment in almost all malaria endemic settings. Artemisinin derivatives are highly potent and fast acting antimalarials; but they have a short half-life and need to be combined with partner drugs with a longer half-life to clear the remaining parasites after a standard 3-day ACT regimen. When introduced, ACTs were highly efficacious and contributed to the steep decrease of malaria over the last decades. However, parasites with decreased susceptibility to artemisinins have emerged in the Greater Mekong Subregion (GMS), followed by ACTs' failure, due to both decreased susceptibility to artemisinin and partner drug resistance. Therefore, there is an urgent need to strengthen and expand current resistance surveillance systems beyond the GMS to track the emergence or spread of artemisinin resistance. Great attention has been paid to the spread of artemisinin resistance over the last five years, since molecular markers of decreased susceptibility to artemisinin in the GMS have been discovered. However, resistance to partner drugs is critical, as ACTs can still be effective against parasites with decreased susceptibility to artemisinins, when the latter are combined with a highly efficacious partner drug. This review outlines the different mechanisms of resistance and molecular markers associated with resistance to partner drugs for the currently used ACTs. Strategies to improve surveillance and potential solutions to extend the useful therapeutic lifespan of the currently available malaria medicines are proposed.

Keywords: antimalarial; artemisinin; drug; molecular marker; partner drug; resistance; surveillance.

PubMed Disclaimer

Conflict of interest statement

The author declares no conflict of interest.

Similar articles

Cited by

References

    1. Menard D., Dondorp A. Antimalarial Drug Resistance: A Threat to Malaria Elimination. Cold Spring Harb. Perspect. Med. 2017;7:a025619. doi: 10.1101/cshperspect.a025619. - DOI - PMC - PubMed
    1. Woodrow C.J., White N.J. The clinical impact of artemisinin resistance in Southeast Asia and the potential for future spread. FEMS Microbiol. Rev. 2017;41:34–48. doi: 10.1093/femsre/fuw037. - DOI - PMC - PubMed
    1. Ariey F., Witkowski B., Amaratunga C., Beghain J., Langlois A.-C., Khim N., Kim S., Duru V., Bouchier C., Ma L., et al. A molecular marker of artemisinin-resistant Plasmodium falciparum malaria. Nature. 2014;505:50–55. doi: 10.1038/nature12876. - DOI - PMC - PubMed
    1. Ménard D., Khim N., Beghain J., Adegnika A.A., Shafiul-Alam M., Amodu O., Rahim-Awab G., Barnadas C., Berry A., Boum Y., et al. A Worldwide Map of Plasmodium falciparum K13-Propeller Polymorphisms. N. Eng. J. Med. 2016;374:2453–2464. doi: 10.1056/NEJMoa1513137. - DOI - PMC - PubMed
    1. Das S., Saha B., Hati A.K., Roy S. Evidence of Artemisinin-Resistant Plasmodium falciparum Malaria in Eastern India. N. Engl. J. Med. 2018;379:1962–1964. doi: 10.1056/NEJMc1713777. - DOI - PubMed

LinkOut - more resources