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In vitro piperaquine susceptibility is not associated with the Plasmodium falciparum chloroquine resistance transporter gene

Identifieur interne : 000191 ( France/Analysis ); précédent : 000190; suivant : 000192

In vitro piperaquine susceptibility is not associated with the Plasmodium falciparum chloroquine resistance transporter gene

Auteurs : Aurélie Pascual [France] ; Marilyn Madamet [France] ; Lionel Bertaux [France] ; Rémy Amalvict [France] ; Nicolas Benoit [France] ; Dominique Travers [France] ; Julien Cren [France] ; Nicolas Taudon [France] ; Christophe Rogier [Madagascar] ; Daniel Parzy [France] ; Bruno Pradines [France]

Source :

RBID : Hal:inserm-00911243

Abstract

Background
Dihydroartemisinin-piperaquine is a new ACT that is administered as single daily dose for three days and has been demonstrated to be tolerated and highly effective for the treatment of uncomplicated Plasmodium falciparum malaria. Piperaquine was used alone to replace chloroquine as the first-line treatment for uncomplicated malaria in China in response to increasing chloroquine resistance in the 1970s. However, the rapid emergence of piperaquine-resistant strains that resulted in the cessation of its use in China in the 1980s, suggests that there is cross-resistance between piperaquine and chloroquine. Very few data are available on cross-resistance between piperaquine and chloroquine, and the data that do exist are often contradictory.
Methods
In total, 280 P. falciparum isolates, collected between April 2008 and June 2012 from patients hospitalized in France with imported malaria from a malaria-endemic country, were assessed ex vivo for piperaquine and chloroquine susceptibilities by using the standard 42-hour 3H-hypoxanthine uptake inhibition method. The chloroquine resistance-associated mutation K76T in pfcrt was also investigated for the 280 isolates.
Results
The IC50 for piperaquine ranged from 9.8 nM to 217.3 nM (mean = 81.3 nM. The IC50 for chloroquine ranged from 5.0 nM to 1,918 nM (mean = 83.6 nM. A significant but low correlation was observed between the Log IC50 values for piperaquine and chloroquine (r = 0.145, p < 0.001). However, the coefficient of determination of 0.021 indicates that only 2.1% of the variation in the response to piperaquine is explained by the variation in the response to chloroquine. The mean value for piperaquine was 74.0 nM in the Pfcrt K76 wild-type group (no = 125) and 87.7 nM in the 76 T mutant group (no = 155). This difference was not significant (p = 0.875, Mann Whitney U test).
Conclusions
The present work demonstrates that there was no cross-resistance between piperaquine and chloroquine among 280 P. falciparum isolates and that piperaquine susceptibility is not associated with pfcrt, the gene involved in chloroquine resistance. These results confirm the efficacy of piperaquine in association with dihydroartemisinin and support its use in areas in which parasites are resistant to chloroquine.


Url:
DOI: 10.1186/1475-2875-12-431


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Hal:inserm-00911243

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<name sortKey="Parzy, Daniel" sort="Parzy, Daniel" uniqKey="Parzy D" first="Daniel" last="Parzy">Daniel Parzy</name>
<affiliation wicri:level="1">
<hal:affiliation type="laboratory" xml:id="struct-220808" status="OLD">
<idno type="RNSR">200817410U</idno>
<orgName>Infections Parasitaires : Transmission, Physiopathologie et Thérapeutiques</orgName>
<orgName type="acronym">IP-TPT</orgName>
<date type="start">2008-01-01</date>
<date type="end">2017-12-31</date>
<desc>
<address>
<addrLine>Faculté de Pharmacie27 bd Jean Moulin CS 3006413385 Marseille </addrLine>
<country key="FR"></country>
</address>
<ref type="url">http://pharmacie.univ-amu.fr/umr-md3</ref>
</desc>
<listRelation>
<relation name="UMR MD3" active="#struct-300092" type="direct"></relation>
<relation name="UMR MD3" active="#struct-300073" type="direct"></relation>
<relation name="UMR MD3" active="#struct-198056" type="direct"></relation>
<relation name="UMR MD3" active="#struct-67872" type="direct"></relation>
</listRelation>
<tutelles>
<tutelle name="UMR MD3" active="#struct-300092" type="direct">
<org type="institution" xml:id="struct-300092" status="VALID">
<orgName>Service de Santé des Armées</orgName>
<desc>
<address>
<country key="FR"></country>
</address>
</desc>
</org>
</tutelle>
<tutelle name="UMR MD3" active="#struct-300073" type="direct">
<org type="institution" xml:id="struct-300073" status="VALID">
<orgName>Assistance Publique - Hôpitaux de Marseille</orgName>
<orgName type="acronym">APHM</orgName>
<desc>
<address>
<addrLine>Direction générale AP-HM80, rue Brochier13 354 Marseille Cedex 5</addrLine>
<country key="FR"></country>
</address>
<ref type="url">http://fr.ap-hm.fr/</ref>
</desc>
</org>
</tutelle>
<tutelle name="UMR MD3" active="#struct-198056" type="direct">
<org type="institution" xml:id="struct-198056" status="VALID">
<idno type="IdRef">15863621X</idno>
<idno type="ISNI">0000 0001 2176 4817</idno>
<orgName>Aix Marseille Université</orgName>
<orgName type="acronym">AMU</orgName>
<date type="start">2012-01-01</date>
<desc>
<address>
<addrLine>Aix-Marseille UniversitéJardins du Pharo58 Boulevard Charles Livon13284 Marseille cedex 7</addrLine>
<country key="FR"></country>
</address>
<ref type="url">http://www.univ-amu.fr/</ref>
</desc>
</org>
</tutelle>
<tutelle name="UMR MD3" active="#struct-67872" type="direct">
<org type="institution" xml:id="struct-67872" status="VALID">
<orgName>Institut de Recherche pour le Développement</orgName>
<orgName type="acronym">IRD</orgName>
<desc>
<address>
<addrLine>SiègeLe Sextant 44, bd de DunkerqueCS 9000913572 Marseille cedex 02</addrLine>
<country key="FR"></country>
</address>
<ref type="url">http://www.ird.fr/</ref>
</desc>
</org>
</tutelle>
</tutelles>
</hal:affiliation>
<country>France</country>
<placeName>
<settlement type="city">Marseille</settlement>
<region type="region" nuts="2">Provence-Alpes-Côte d'Azur</region>
</placeName>
<orgName type="university">Université d'Aix-Marseille</orgName>
</affiliation>
</author>
<author>
<name sortKey="Pradines, Bruno" sort="Pradines, Bruno" uniqKey="Pradines B" first="Bruno" last="Pradines">Bruno Pradines</name>
<affiliation wicri:level="1">
<hal:affiliation type="laboratory" xml:id="struct-237933" status="INCOMING">
<orgName>Unité de Parasitologie</orgName>
<desc>
<address>
<addrLine>Département d'Infectiologie de Terrain - 34 boulevard Laveran 13013 Marseille</addrLine>
<country key="FR"></country>
</address>
</desc>
<listRelation>
<relation active="#struct-507058" type="direct"></relation>
</listRelation>
<tutelles>
<tutelle active="#struct-507058" type="direct">
<org type="institution" xml:id="struct-507058" status="VALID">
<orgName>Institut de Recherche Biomédicale des Armées</orgName>
<orgName type="acronym">IRBA</orgName>
<desc>
<address>
<addrLine>Brétigny-sur-Orge</addrLine>
<country key="FR"></country>
</address>
<ref type="url">https://www.defense.gouv.fr/sante/notre-expertise/recherche-biomedicale/recherche-biomedicale</ref>
</desc>
</org>
</tutelle>
</tutelles>
</hal:affiliation>
<country>France</country>
</affiliation>
</author>
</analytic>
<idno type="DOI">10.1186/1475-2875-12-431</idno>
<series>
<title level="j">Malaria Journal</title>
<idno type="ISSN">1475-2875</idno>
<imprint>
<date type="datePub">2013</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc>
<textClass></textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">
<p>Background
Dihydroartemisinin-piperaquine is a new ACT that is administered as single daily dose for three days and has been demonstrated to be tolerated and highly effective for the treatment of uncomplicated Plasmodium falciparum malaria. Piperaquine was used alone to replace chloroquine as the first-line treatment for uncomplicated malaria in China in response to increasing chloroquine resistance in the 1970s. However, the rapid emergence of piperaquine-resistant strains that resulted in the cessation of its use in China in the 1980s, suggests that there is cross-resistance between piperaquine and chloroquine. Very few data are available on cross-resistance between piperaquine and chloroquine, and the data that do exist are often contradictory.
Methods
In total, 280 P. falciparum isolates, collected between April 2008 and June 2012 from patients hospitalized in France with imported malaria from a malaria-endemic country, were assessed ex vivo for piperaquine and chloroquine susceptibilities by using the standard 42-hour 3H-hypoxanthine uptake inhibition method. The chloroquine resistance-associated mutation K76T in pfcrt was also investigated for the 280 isolates.
Results
The IC50 for piperaquine ranged from 9.8 nM to 217.3 nM (mean = 81.3 nM. The IC50 for chloroquine ranged from 5.0 nM to 1,918 nM (mean = 83.6 nM. A significant but low correlation was observed between the Log IC50 values for piperaquine and chloroquine (r = 0.145, p < 0.001). However, the coefficient of determination of 0.021 indicates that only 2.1% of the variation in the response to piperaquine is explained by the variation in the response to chloroquine. The mean value for piperaquine was 74.0 nM in the Pfcrt K76 wild-type group (no = 125) and 87.7 nM in the 76 T mutant group (no = 155). This difference was not significant (p = 0.875, Mann Whitney U test).
Conclusions
The present work demonstrates that there was no cross-resistance between piperaquine and chloroquine among 280 P. falciparum isolates and that piperaquine susceptibility is not associated with pfcrt, the gene involved in chloroquine resistance. These results confirm the efficacy of piperaquine in association with dihydroartemisinin and support its use in areas in which parasites are resistant to chloroquine.</p>
</div>
</front>
</TEI>
<affiliations>
<list>
<country>
<li>France</li>
<li>Madagascar</li>
</country>
<region>
<li>Provence-Alpes-Côte d'Azur</li>
</region>
<settlement>
<li>Marseille</li>
</settlement>
<orgName>
<li>Université d'Aix-Marseille</li>
</orgName>
</list>
<tree>
<country name="France">
<noRegion>
<name sortKey="Pascual, Aurelie" sort="Pascual, Aurelie" uniqKey="Pascual A" first="Aurélie" last="Pascual">Aurélie Pascual</name>
</noRegion>
<name sortKey="Amalvict, Remy" sort="Amalvict, Remy" uniqKey="Amalvict R" first="Rémy" last="Amalvict">Rémy Amalvict</name>
<name sortKey="Benoit, Nicolas" sort="Benoit, Nicolas" uniqKey="Benoit N" first="Nicolas" last="Benoit">Nicolas Benoit</name>
<name sortKey="Bertaux, Lionel" sort="Bertaux, Lionel" uniqKey="Bertaux L" first="Lionel" last="Bertaux">Lionel Bertaux</name>
<name sortKey="Cren, Julien" sort="Cren, Julien" uniqKey="Cren J" first="Julien" last="Cren">Julien Cren</name>
<name sortKey="Madamet, Marilyn" sort="Madamet, Marilyn" uniqKey="Madamet M" first="Marilyn" last="Madamet">Marilyn Madamet</name>
<name sortKey="Parzy, Daniel" sort="Parzy, Daniel" uniqKey="Parzy D" first="Daniel" last="Parzy">Daniel Parzy</name>
<name sortKey="Pradines, Bruno" sort="Pradines, Bruno" uniqKey="Pradines B" first="Bruno" last="Pradines">Bruno Pradines</name>
<name sortKey="Taudon, Nicolas" sort="Taudon, Nicolas" uniqKey="Taudon N" first="Nicolas" last="Taudon">Nicolas Taudon</name>
<name sortKey="Travers, Dominique" sort="Travers, Dominique" uniqKey="Travers D" first="Dominique" last="Travers">Dominique Travers</name>
</country>
<country name="Madagascar">
<noRegion>
<name sortKey="Rogier, Christophe" sort="Rogier, Christophe" uniqKey="Rogier C" first="Christophe" last="Rogier">Christophe Rogier</name>
</noRegion>
</country>
</tree>
</affiliations>
</record>

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