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Resistance of Plasmodium falciparum field isolates to in-vitro artemether and point mutations of the SERCA-type PfATPase6
Artemisinin derivatives are an essential component of treatment against multidrug-resistant Plasmodium falciparum malaria. We aimed to investigate in-vitro resistance to artemisinin derivatives in field isolates. In-vitro susceptibility of 530 P falciparum isolates from three countries (Cambodia, Fr...
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Published in: | The Lancet (British edition) 2005-12, Vol.366 (9501), p.1960-3 |
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container_title | The Lancet (British edition) |
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creator | Jambou, Ronan Legrand, Eric Niang, Makhtar Khim, Nimol Lim, Pharath Volney, Béatrice Ekala, Marie Thérèse Bouchier, Christiane Esterre, Philippe Fandeur, Thierry Mercereau-Puijalon, Odile |
description | Artemisinin derivatives are an essential component of treatment against multidrug-resistant Plasmodium falciparum malaria. We aimed to investigate in-vitro resistance to artemisinin derivatives in field isolates. In-vitro susceptibility of 530 P falciparum isolates from three countries (Cambodia, French Guiana, and Senegal) with different artemisinin use was assessed with an isotopic microtest. Artemether IC50 up to 117 and 45 nmol/L was seen in French Guiana and Senegal, respectively. DNA sequencing in a subsample of 60 isolates lends support to SERCA-PfATPase6 as the target for artemisinins. The S769N PfATPase6 mutation, noted exclusively in French Guiana, was associated with raised (>30 nmol/L) artemether IC50s (p |
doi_str_mv | 10.1016/S0140-6736(05)67787-2 |
format | article |
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We aimed to investigate in-vitro resistance to artemisinin derivatives in field isolates. In-vitro susceptibility of 530 P falciparum isolates from three countries (Cambodia, French Guiana, and Senegal) with different artemisinin use was assessed with an isotopic microtest. Artemether IC50 up to 117 and 45 nmol/L was seen in French Guiana and Senegal, respectively. DNA sequencing in a subsample of 60 isolates lends support to SERCA-PfATPase6 as the target for artemisinins. The S769N PfATPase6 mutation, noted exclusively in French Guiana, was associated with raised (>30 nmol/L) artemether IC50s (p<0.0001, Mann-Whitney). All resistant isolates came from areas with uncontrolled use of artemisinin derivatives. 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We aimed to investigate in-vitro resistance to artemisinin derivatives in field isolates. In-vitro susceptibility of 530 P falciparum isolates from three countries (Cambodia, French Guiana, and Senegal) with different artemisinin use was assessed with an isotopic microtest. Artemether IC50 up to 117 and 45 nmol/L was seen in French Guiana and Senegal, respectively. DNA sequencing in a subsample of 60 isolates lends support to SERCA-PfATPase6 as the target for artemisinins. The S769N PfATPase6 mutation, noted exclusively in French Guiana, was associated with raised (>30 nmol/L) artemether IC50s (p<0.0001, Mann-Whitney). All resistant isolates came from areas with uncontrolled use of artemisinin derivatives. This rise in resistance indicates the need for increased vigilance and a coordinated and rapid deployment of drug combinations.</description><subject>Animals</subject><subject>Antimalarials</subject><subject>Artemisinins</subject><subject>Drug Resistance, Multiple</subject><subject>Genotype</subject><subject>Humans</subject><subject>Life Sciences</subject><subject>Microbiology and Parasitology</subject><subject>Parasitic Sensitivity Tests</subject><subject>Parasitology</subject><subject>Plasmodium falciparum</subject><subject>Point Mutation</subject><issn>0140-6736</issn><issn>1474-547X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><recordid>eNqVjT1rwzAURUVpadyPn1B4YzuofYplyR5NSMnQwSQZuplHLBMV2zKSHPC_bwKle6Z74B7uZexF4LtAoT52KCRypVP1itmb0jrXfHnDEiG15JnU37cs-VcW7CGEH0SUCrN7thAqXWaqyBM2b02wIdJwMOBaqDoKvWvs1ENL3cGO5C9oTdeADa6jaAJEB3bgJxu9A_LR9CYejQcaGhidHSL0U6Ro3RAuk-cOduvtquRxHg1UbbmvKBj1xO7OF8E8_-Uj45_r_WrDj9TVo7c9-bl2ZOtN-VWPFKKZfI2YFVjkxUmk1_q_n5NeVA</recordid><startdate>20051203</startdate><enddate>20051203</enddate><creator>Jambou, Ronan</creator><creator>Legrand, Eric</creator><creator>Niang, Makhtar</creator><creator>Khim, Nimol</creator><creator>Lim, Pharath</creator><creator>Volney, Béatrice</creator><creator>Ekala, Marie Thérèse</creator><creator>Bouchier, Christiane</creator><creator>Esterre, Philippe</creator><creator>Fandeur, Thierry</creator><creator>Mercereau-Puijalon, Odile</creator><general>Elsevier</general><scope>1XC</scope><orcidid>https://orcid.org/0000-0003-3549-1543</orcidid><orcidid>https://orcid.org/0000-0003-3549-1543</orcidid></search><sort><creationdate>20051203</creationdate><title>Resistance of Plasmodium falciparum field isolates to in-vitro artemether and point mutations of the SERCA-type PfATPase6</title><author>Jambou, Ronan ; Legrand, Eric ; Niang, Makhtar ; Khim, Nimol ; Lim, Pharath ; Volney, Béatrice ; Ekala, Marie Thérèse ; Bouchier, Christiane ; Esterre, Philippe ; Fandeur, Thierry ; Mercereau-Puijalon, Odile</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-hal_primary_oai_HAL_pasteur_00590989v13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Animals</topic><topic>Antimalarials</topic><topic>Artemisinins</topic><topic>Drug Resistance, Multiple</topic><topic>Genotype</topic><topic>Humans</topic><topic>Life Sciences</topic><topic>Microbiology and Parasitology</topic><topic>Parasitic Sensitivity Tests</topic><topic>Parasitology</topic><topic>Plasmodium falciparum</topic><topic>Point Mutation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jambou, Ronan</creatorcontrib><creatorcontrib>Legrand, Eric</creatorcontrib><creatorcontrib>Niang, Makhtar</creatorcontrib><creatorcontrib>Khim, Nimol</creatorcontrib><creatorcontrib>Lim, Pharath</creatorcontrib><creatorcontrib>Volney, Béatrice</creatorcontrib><creatorcontrib>Ekala, Marie Thérèse</creatorcontrib><creatorcontrib>Bouchier, Christiane</creatorcontrib><creatorcontrib>Esterre, Philippe</creatorcontrib><creatorcontrib>Fandeur, Thierry</creatorcontrib><creatorcontrib>Mercereau-Puijalon, Odile</creatorcontrib><collection>Hyper Article en Ligne (HAL)</collection><jtitle>The Lancet (British edition)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jambou, Ronan</au><au>Legrand, Eric</au><au>Niang, Makhtar</au><au>Khim, Nimol</au><au>Lim, Pharath</au><au>Volney, Béatrice</au><au>Ekala, Marie Thérèse</au><au>Bouchier, Christiane</au><au>Esterre, Philippe</au><au>Fandeur, Thierry</au><au>Mercereau-Puijalon, Odile</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Resistance of Plasmodium falciparum field isolates to in-vitro artemether and point mutations of the SERCA-type PfATPase6</atitle><jtitle>The Lancet (British edition)</jtitle><date>2005-12-03</date><risdate>2005</risdate><volume>366</volume><issue>9501</issue><spage>1960</spage><epage>3</epage><pages>1960-3</pages><issn>0140-6736</issn><eissn>1474-547X</eissn><abstract>Artemisinin derivatives are an essential component of treatment against multidrug-resistant Plasmodium falciparum malaria. We aimed to investigate in-vitro resistance to artemisinin derivatives in field isolates. In-vitro susceptibility of 530 P falciparum isolates from three countries (Cambodia, French Guiana, and Senegal) with different artemisinin use was assessed with an isotopic microtest. Artemether IC50 up to 117 and 45 nmol/L was seen in French Guiana and Senegal, respectively. DNA sequencing in a subsample of 60 isolates lends support to SERCA-PfATPase6 as the target for artemisinins. The S769N PfATPase6 mutation, noted exclusively in French Guiana, was associated with raised (>30 nmol/L) artemether IC50s (p<0.0001, Mann-Whitney). All resistant isolates came from areas with uncontrolled use of artemisinin derivatives. This rise in resistance indicates the need for increased vigilance and a coordinated and rapid deployment of drug combinations.</abstract><pub>Elsevier</pub><pmid>16325698</pmid><doi>10.1016/S0140-6736(05)67787-2</doi><orcidid>https://orcid.org/0000-0003-3549-1543</orcidid><orcidid>https://orcid.org/0000-0003-3549-1543</orcidid></addata></record> |
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subjects | Animals Antimalarials Artemisinins Drug Resistance, Multiple Genotype Humans Life Sciences Microbiology and Parasitology Parasitic Sensitivity Tests Parasitology Plasmodium falciparum Point Mutation |
title | Resistance of Plasmodium falciparum field isolates to in-vitro artemether and point mutations of the SERCA-type PfATPase6 |
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