Artemisinin resistance is a major threat to malaria control efforts. Resistance is characterized by an increase in the Plasmodium falciparum 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 IC50in ARS1 when compared with parental strain PA after 72 h of 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.

Induction of high tolerance to artemisinin by sub-lethal administration: A new in vitro model of P. falciparum / De Lucia, Serena; Tsamesidis, Ioannis; Pau, Maria Carmina; Kesely, Kristina R.; Pantaleo, Antonella; Turrini, Francesco. - In: PLOS ONE. - ISSN 1932-6203. - 13:1(2018), p. e0191084. [10.1371/journal.pone.0191084]

Induction of high tolerance to artemisinin by sub-lethal administration: A new in vitro model of P. falciparum

Pau, Maria Carmina
Membro del Collaboration Group
;
Pantaleo, Antonella
Membro del Collaboration Group
;
2018-01-01

Abstract

Artemisinin resistance is a major threat to malaria control efforts. Resistance is characterized by an increase in the Plasmodium falciparum 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 IC50in ARS1 when compared with parental strain PA after 72 h of 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.
2018
Induction of high tolerance to artemisinin by sub-lethal administration: A new in vitro model of P. falciparum / De Lucia, Serena; Tsamesidis, Ioannis; Pau, Maria Carmina; Kesely, Kristina R.; Pantaleo, Antonella; Turrini, Francesco. - In: PLOS ONE. - ISSN 1932-6203. - 13:1(2018), p. e0191084. [10.1371/journal.pone.0191084]
File in questo prodotto:
File Dimensione Formato  
De Lucia Plos One 2018.pdf

accesso aperto

Descrizione: Articolo in rivista
Tipologia: Versione editoriale (versione finale pubblicata)
Licenza: Creative commons
Dimensione 5.91 MB
Formato Adobe PDF
5.91 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11388/202258
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 14
  • ???jsp.display-item.citation.isi??? 16
social impact