Induction of Multidrug Tolerance in Plasmodium falciparum by Extended Artemisinin Pressure.
Emerg Infect Dis
; 21(10): 1733-41, 2015 Oct.
Article
de En
| MEDLINE
| ID: mdl-26401601
ABSTRACT
Plasmodium falciparum resistance to artemisinin derivatives in Southeast Asia threatens global malaria control strategies. Whether delayed parasite clearance, which exposes larger parasite numbers to artemisinins for longer times, selects higher-grade resistance remains unexplored. We investigated whether long-lasting artemisinin pressure selects a novel multidrug-tolerance profile. Although 50% inhibitory concentrations for 10 antimalarial drugs tested were unchanged, drug-tolerant parasites showed higher recrudescence rates for endoperoxides, quinolones, and an antifolate, including partner drugs of recommended combination therapies, but remained susceptible to atovaquone. Moreover, the age range of intraerythrocytic stages able to resist artemisinin was extended to older ring forms and trophozoites. Multidrug tolerance results from drug-induced quiescence, which enables parasites to survive exposure to unrelated antimalarial drugs that inhibit a variety of metabolic pathways. This novel resistance pattern should be urgently monitored in the field because this pattern is not detected by current assays and represents a major threat to antimalarial drug policy.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Plasmodium falciparum
/
Paludisme à Plasmodium falciparum
/
Artémisinines
/
Tolérance aux médicaments
/
Paludisme
/
Antipaludiques
Limites:
Humans
Pays/Région comme sujet:
Asia
Langue:
En
Journal:
Emerg Infect Dis
Sujet du journal:
DOENCAS TRANSMISSIVEIS
Année:
2015
Type de document:
Article