Details:

Alternative Title:
Emerg Infect Dis
Personal Author:
Ménard, Sandie ; Ben Haddou, Tanila ; Ramadani, Arba Pramundita ; Ariey, Frédéric ; Iriart, Xavier ; ... More +
Ménard, Sandie ; Ben Haddou, Tanila ; Ramadani, Arba Pramundita ; Ariey, Frédéric ; Iriart, Xavier ; Beghain, Johann ; Bouchier, Christiane ; Witkowski, Benoit ; Berry, Antoine ; Mercereau-Puijalon, Odile ; Benoit-Vical, Françoise Less -
Description:
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.
Subject:
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Antimalarials
Artemisinins
Drug Tolerance
Humans
Malaria
Malaria, Falciparum
Research

Source:
Emerg Infect Dis. 21(10):1733-1741
Pubmed ID:
26401601
Pubmed Central ID:
PMC4593447
Document Type:
Journal Article
Collection(s):
Emerging Infectious Diseases
Main Document Checksum:
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urn:sha256:2cc4d0041c8b8574068057ced2dddd4e0c3f14e9e0b6a3b753bdc83030f26a17
File Type:

Supporting Files

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