TY - JOUR
T1 - Molecular insights into artemisinin resistance in Plasmodium falciparum
T2 - An updated review
AU - Azmi, Wihda Aisarul
AU - Rizki, Andita Fitri Mutiara
AU - Djuardi, Yenny
AU - Artika, I. Made
AU - Siregar, Josephine Elizabeth
N1 - Funding Information:
We thank John Acton for his assistance at the manuscript stage.
Publisher Copyright:
© 2023
PY - 2023/8
Y1 - 2023/8
N2 - Malaria still poses a major burden on human health around the world, especially in endemic areas. Plasmodium resistance to several antimalarial drugs has been one of the major hindrances in control of malaria. Thus, the World Health Organization recommended artemisinin-based combination therapy (ACT) as a front-line treatment for malaria. The emergence of parasites resistant to artemisinin, along with resistant to ACT partner drugs, has led to ACT treatment failure. The artemisinin resistance is mostly related to the mutations in the propeller domain of the kelch13 (k13) gene that encodes protein Kelch13 (K13). The K13 protein has an important role in parasite reaction to oxidative stress. The most widely spread mutation in K13, with the highest degree of resistance, is a C580Y mutation. Other mutations, which are already identified as markers of artemisinin resistance, are R539T, I543T, and Y493H. The objective of this review is to provide current molecular insights into artemisinin resistance in Plasmodium falciparum. The trending use of artemisinin beyond its antimalarial effect is described. Immediate challenges and future research directions are discussed. Better understanding of the molecular mechanisms underlying artemisinin resistance will accelerate implementation of scientific findings to solve problems with malarial infection.
AB - Malaria still poses a major burden on human health around the world, especially in endemic areas. Plasmodium resistance to several antimalarial drugs has been one of the major hindrances in control of malaria. Thus, the World Health Organization recommended artemisinin-based combination therapy (ACT) as a front-line treatment for malaria. The emergence of parasites resistant to artemisinin, along with resistant to ACT partner drugs, has led to ACT treatment failure. The artemisinin resistance is mostly related to the mutations in the propeller domain of the kelch13 (k13) gene that encodes protein Kelch13 (K13). The K13 protein has an important role in parasite reaction to oxidative stress. The most widely spread mutation in K13, with the highest degree of resistance, is a C580Y mutation. Other mutations, which are already identified as markers of artemisinin resistance, are R539T, I543T, and Y493H. The objective of this review is to provide current molecular insights into artemisinin resistance in Plasmodium falciparum. The trending use of artemisinin beyond its antimalarial effect is described. Immediate challenges and future research directions are discussed. Better understanding of the molecular mechanisms underlying artemisinin resistance will accelerate implementation of scientific findings to solve problems with malarial infection.
KW - Artemisinin
KW - Artemisinin resistance
KW - Artemisinin-based combination therapy
KW - K13
KW - Molecular marker
KW - Plasmodium falciparum
UR - http://www.scopus.com/inward/record.url?scp=85161297143&partnerID=8YFLogxK
U2 - 10.1016/j.meegid.2023.105460
DO - 10.1016/j.meegid.2023.105460
M3 - Review article
C2 - 37269964
AN - SCOPUS:85161297143
SN - 1567-1348
VL - 112
JO - Infection, Genetics and Evolution
JF - Infection, Genetics and Evolution
M1 - 105460
ER -
