Induction of Multidrug Tolerance in Plasmodium falciparum by Extended Artemisinin Pressure
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 w...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Centers for Disease Control and Prevention
2015-10-01
|
| Series: | Emerging Infectious Diseases |
| Subjects: | |
| Online Access: | https://wwwnc.cdc.gov/eid/article/21/10/15-0682_article |
| _version_ | 1811288738693644288 |
|---|---|
| author | Sandie Ménard Tanila Ben Haddou Arba Pramundita Ramadani Frédéric Ariey Xavier Iriart Johann Beghain Christiane Bouchier Benoit Witkowski Antoine Berry Odile Mercereau-Puijalon Françoise Benoit-Vical |
| author_facet | Sandie Ménard Tanila Ben Haddou Arba Pramundita Ramadani Frédéric Ariey Xavier Iriart Johann Beghain Christiane Bouchier Benoit Witkowski Antoine Berry Odile Mercereau-Puijalon Françoise Benoit-Vical |
| author_sort | Sandie Ménard |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-13T03:42:29Z |
| format | Article |
| id | doaj.art-5fad171e68444e7c8cce845eacc52d24 |
| institution | Directory Open Access Journal |
| issn | 1080-6040 1080-6059 |
| language | English |
| last_indexed | 2024-04-13T03:42:29Z |
| publishDate | 2015-10-01 |
| publisher | Centers for Disease Control and Prevention |
| record_format | Article |
| series | Emerging Infectious Diseases |
| spelling | doaj.art-5fad171e68444e7c8cce845eacc52d242022-12-22T03:04:06ZengCenters for Disease Control and PreventionEmerging Infectious Diseases1080-60401080-60592015-10-0121101733174110.3201/eid2110.150682Induction of Multidrug Tolerance in Plasmodium falciparum by Extended Artemisinin PressureSandie MénardTanila Ben HaddouArba Pramundita RamadaniFrédéric ArieyXavier IriartJohann BeghainChristiane BouchierBenoit WitkowskiAntoine BerryOdile Mercereau-PuijalonFrançoise Benoit-VicalPlasmodium 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.https://wwwnc.cdc.gov/eid/article/21/10/15-0682_articleartemisininPlasmodium falciparumparasitesmultidrug tolerancedrug pressureatovaquone |
| spellingShingle | Sandie Ménard Tanila Ben Haddou Arba Pramundita Ramadani Frédéric Ariey Xavier Iriart Johann Beghain Christiane Bouchier Benoit Witkowski Antoine Berry Odile Mercereau-Puijalon Françoise Benoit-Vical Induction of Multidrug Tolerance in Plasmodium falciparum by Extended Artemisinin Pressure Emerging Infectious Diseases artemisinin Plasmodium falciparum parasites multidrug tolerance drug pressure atovaquone |
| title | Induction of Multidrug Tolerance in Plasmodium falciparum by Extended Artemisinin Pressure |
| title_full | Induction of Multidrug Tolerance in Plasmodium falciparum by Extended Artemisinin Pressure |
| title_fullStr | Induction of Multidrug Tolerance in Plasmodium falciparum by Extended Artemisinin Pressure |
| title_full_unstemmed | Induction of Multidrug Tolerance in Plasmodium falciparum by Extended Artemisinin Pressure |
| title_short | Induction of Multidrug Tolerance in Plasmodium falciparum by Extended Artemisinin Pressure |
| title_sort | induction of multidrug tolerance in plasmodium falciparum by extended artemisinin pressure |
| topic | artemisinin Plasmodium falciparum parasites multidrug tolerance drug pressure atovaquone |
| url | https://wwwnc.cdc.gov/eid/article/21/10/15-0682_article |
| work_keys_str_mv | AT sandiemenard inductionofmultidrugtoleranceinplasmodiumfalciparumbyextendedartemisininpressure AT tanilabenhaddou inductionofmultidrugtoleranceinplasmodiumfalciparumbyextendedartemisininpressure AT arbapramunditaramadani inductionofmultidrugtoleranceinplasmodiumfalciparumbyextendedartemisininpressure AT fredericariey inductionofmultidrugtoleranceinplasmodiumfalciparumbyextendedartemisininpressure AT xavieririart inductionofmultidrugtoleranceinplasmodiumfalciparumbyextendedartemisininpressure AT johannbeghain inductionofmultidrugtoleranceinplasmodiumfalciparumbyextendedartemisininpressure AT christianebouchier inductionofmultidrugtoleranceinplasmodiumfalciparumbyextendedartemisininpressure AT benoitwitkowski inductionofmultidrugtoleranceinplasmodiumfalciparumbyextendedartemisininpressure AT antoineberry inductionofmultidrugtoleranceinplasmodiumfalciparumbyextendedartemisininpressure AT odilemercereaupuijalon inductionofmultidrugtoleranceinplasmodiumfalciparumbyextendedartemisininpressure AT francoisebenoitvical inductionofmultidrugtoleranceinplasmodiumfalciparumbyextendedartemisininpressure |