Development of artemisinin resistance in malaria therapy. (August 2019)

• Record Type: Journal Article
• Authors: Naß, Janine; Efferth, Thomas
• Is Part Of: Pharmacological research. Volume 146(2019)
• Publication Date: 2019-08
• Subjects: ABC ATP-binding cassette -- ACT artemisinin-based combination therapy -- ARM-LU artemether-lumefantrine combination therapy -- AQ amodiaquine -- ARE arteether -- ARM artemether -- arps10 apicoplast ribosomal protein S10 -- ARS artemisinin -- ART artesunate -- atg18 autophagy-related gene 18 -- CQ chloroquine -- DEAQ desethylamodiaquine -- DHA dihydroartemisinin -- ER endoplasmic reticulum -- ERAR Emergency Response to Artemisinin Resistance -- fd ferredoxin -- fp2 falcipain-2 -- KEL1 drug-resistant lineages with mutation in kelch13 -- MQ mefloquine -- LU lumefrantrine -- PfATP6 sarcoplasmic reticulum Ca2+ ATPase -- PfCRT Plasmodium falciparum chloroquine resistance transporter -- PfMDR1 Plasmodium falciparum multidrug resistance gene 1 -- PfMRP1/2 Plasmodium falciparum multidrug resistance-related protein ½ -- PfPEMP1 Plasmodium falciparum erythrocyte membrane protein 1 -- PI3P phosphatidylinositol-3-phosphate -- PLA1 phospholipase A1 -- PP piperaquine -- PY pyrimethamine -- PROSC Plasmodium reactive oxidative stress complex -- QN quinine -- ROS reactive oxygen species -- SaMARA Surveillance and Monitoring of Antimalarial Resistance in Africa -- SU sulfadoxine -- TRiC TCP-1 ring complex -- UPR unfolded protein response -- WHO World Health Organization; Malaria -- Resistance -- Mutation -- Artemisinin -- Artemisinin combination therapy; Pharmacology -- Periodicals; Pharmacology -- Periodicals; Research -- Periodicals; Médicaments -- Recherche -- Périodiques; Pharmacologie -- Périodiques; 615.105
• DOI: 10.1016/j.phrs.2019.104275
• Languages: English
• ISSNs: 1043-6618

Abstract

Graphical abstract: Abstract: Malaria affects 200 million people worldwide. Today, the most successful treatments are artemisinin-based combination therapies (ACT). Resistance has already been described for the elder anti-malarials chloroquine, sulfadoxine–pyrimethamine and mefloquine. Unfortunately, over the last few years there has also been an emerging resistance to the successfully used drug artemisinin, especially in African and Asian countries. A systematic PubMed literature research was conducted for studies published between January 2002 and December 2018. Despite ACTs continue to be first line treatment, the number of studies is rising reporting on artemisinin resistance mutations. Most publications reported on kelch13 mutations (45 studies), the second most frequent mutations were found in pfmdr1 (32 studies). PfATPase6 mutations have been mainly studied in Asian countries (4 of 6 studies). Bearing this in mind, there is a pressing need to further examine the role and spread of mutations conferring artemisinin resistance. A further decline of treatment efficacy could result in increased rates of malaria-related deaths.