Artemisinin resistance is a major threat to malaria control efforts.Resistance is characterized by an increase in the Plasmodium falciparum eeboo coupons parasite clearance half-life following treatment with artemisinin-based combination therapies (ACTs) and an increase in the percentage of surviving parasites.The remarkably short blood half-life of artemisinin derivatives may contribute to drug-resistance, possibly through factors including sub-lethal plasma concentrations and inadequate exposure.
Here we selected for a new strain of artemisinin resistant parasites, termed the artemisinin resistant strain 1 (ARS1), by treating P.falciparum Palo Alto (PA) cultures with sub-lethal concentrations of dihydroartemisinin (DHA).The resistance phenotype was maintained for over 1 year through monthly maintenance treatments with low doses of 2.
5 nM DHA.There was a moderate increase in the DHA IC50 in ARS1 when compared with parental strain PA after 72 h of animed aniflex complete drug exposure (from 0.68 nM to 2 nM DHA).
In addition, ARS1 survived treatment physiologically relevant DHA concentrations (700 nM) observed in patients.Furthermore, we confirmed a lack of cross-resistance against a panel of antimalarials commonly used as partner drugs in ACTs.Finally, ARS1 did not contain Pfk13 propeller domain mutations associated with ART resistance in the Greater Mekong Region.
With a stable growth rate, ARS1 represents a valuable tool for the development of new antimalarial compounds and studies to further elucidate the mechanisms of ART resistance.