Prevalence of anti-malarial resistance genes in Dakar, Senegal from 2013 ă to 2014
Identifieur interne : 000196 ( Hal/Curation ); précédent : 000195; suivant : 000197Prevalence of anti-malarial resistance genes in Dakar, Senegal from 2013 ă to 2014
Auteurs : Agathe Boussaroque ; Bécaye Fall [Sénégal] ; Marylin Madamet [France] ; Khalifa Ababacar Wade ; Mansour Fall [Sénégal] ; Aminata Nakoulima [Sénégal] ; Khadidiatou Ba Fall ; Pierre Dionne [Sénégal] ; Nicolas Benoit [France] ; Bakary Diatta ; Yaya Diemé [Sénégal] ; Boubacar Wade [Sénégal] ; Bruno Pradines [France]Source :
- Malaria Journal [ 1475-2875 ] ; 2016-07.
Abstract
Background: To determine the impact of the introduction of ă artemisinin-based combination therapy (ACT) on parasite susceptibility, ă a molecular surveillance for antimalarial drug resistance was conducted ă on local isolates from the Hopital Principal de Dakar between November ă 2013 and January 2014 and between August 2014 and December 2014. ă Methods: The prevalence of genetic polymorphisms in antimalarial ă resistance genes (pfcrt, pfmdr1, pfdhfr and pfdhps) was evaluated in 103 ă isolates. ă Results: The chloroquine-resistant haplotypes CVIET and CVMET were ă identified in 31.4 and 3.9 % of the isolates, respectively. The ă frequency of the pfcrt K76T mutation was increased from 29.3 % in ă 2013-2014 to 43.2 % in 2014. The pfmdr1 N86Y and Y184F mutations were ă identified in 6.1 and 53.5 % of the isolates, respectively. The pfdhfr ă triple mutant (S108N, N51I and C59R) was detected in the majority of the ă isolates (82.3 %). The prevalence of quadruple mutants (pfdhfr S108N, ă N51I, C59R and pfdhps A437G) was 40.4 %. One isolate (1.1 %) harboured ă the pfdhps mutations A437G and K540E and the pfdhfr mutations S108N, ă N51I and C59R. ă Conclusions: Despite a decline in the prevalence of chloroquine ă resistance due to the official withdrawal of the drug and to the ă introduction of ACT, the spread of resistance to chloroquine has ă continued. Furthermore, susceptibility to amodiaquine may be decreased ă as a result of cross-resistance. The frequency of the pfmdr1 mutation ă N86Y declined while the Y184F mutation increased in prevalence, ă suggesting that selective pressure is acting on pfmdr1, leading to a ă high prevalence of mutations in these isolates and the lack of specific ă mutations. The 50.5 % prevalence of the pfmdr1 polymorphisms N86Y and ă Y184F suggests a decrease in lumefantrine susceptibility. Based on these ă results, intensive surveillance of ACT partner drugs must be conducted ă regularly in Senegal.
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DOI: 10.1186/s12936-016-1379-2
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<author><name sortKey="Madamet, Marylin" sort="Madamet, Marylin" uniqKey="Madamet M" first="Marylin" last="Madamet">Marylin Madamet</name>
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<country>France</country>
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<author><name sortKey="Wade, Khalifa Ababacar" sort="Wade, Khalifa Ababacar" uniqKey="Wade " first=" Khalifa Ababacar" last="Wade"> Khalifa Ababacar Wade</name>
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<country>Sénégal</country>
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<author><name sortKey="Nakoulima, Aminata" sort="Nakoulima, Aminata" uniqKey="Nakoulima A" first="Aminata" last="Nakoulima">Aminata Nakoulima</name>
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<author><name sortKey="Fall, Khadidiatou Ba" sort="Fall, Khadidiatou Ba" uniqKey="Fall " first=" Khadidiatou Ba" last="Fall"> Khadidiatou Ba Fall</name>
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<author><name sortKey="Dionne, Pierre" sort="Dionne, Pierre" uniqKey="Dionne P" first="Pierre" last="Dionne">Pierre Dionne</name>
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<country>Sénégal</country>
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<author><name sortKey="Benoit, Nicolas" sort="Benoit, Nicolas" uniqKey="Benoit N" first="Nicolas" last="Benoit">Nicolas Benoit</name>
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<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>
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</address>
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<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>
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</address>
<ref type="url">http://fr.ap-hm.fr/</ref>
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<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>
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</address>
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<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>
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<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>
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<author><name sortKey="Diatta, Bakary" sort="Diatta, Bakary" uniqKey="Diatta B" first="Bakary" last="Diatta">Bakary Diatta</name>
</author>
<author><name sortKey="Dieme, Yaya" sort="Dieme, Yaya" uniqKey="Dieme Y" first="Yaya" last="Diemé">Yaya Diemé</name>
<affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-214449" status="INCOMING"> <orgName>Laboratoire d'étude de la chimiosensibilité du paludisme</orgName>
<desc> <address> <addrLine>Rte de la Corniche Est, Dakar</addrLine>
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<desc> <address> <addrLine> 1, avenue Nelson Mandéla - B.P. 3006 - DAKAR (Sénégal)</addrLine>
<country key="SN"></country>
</address>
<ref type="url">http://www.hopitalprincipal.sn/</ref>
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<tutelle active="#struct-352262" type="direct"><org type="institution" xml:id="struct-352262" status="INCOMING"> <orgName>Fédération des laboratoires</orgName>
<desc> <address> <country key="FR"></country>
</address>
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</hal:affiliation>
<country>Sénégal</country>
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</author>
<author><name sortKey="Wade, Boubacar" sort="Wade, Boubacar" uniqKey="Wade B" first="Boubacar" last="Wade">Boubacar Wade</name>
<affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-214459" status="INCOMING"> <orgName>Chefferie</orgName>
<desc> <address> <addrLine>Rte de la Corniche Est, Dakar</addrLine>
<country key="SN"></country>
</address>
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<tutelles><tutelle active="#struct-338318" type="direct"><org type="institution" xml:id="struct-338318" status="VALID"> <orgName>Hôpital Principal de Dakar</orgName>
<desc> <address> <addrLine> 1, avenue Nelson Mandéla - B.P. 3006 - DAKAR (Sénégal)</addrLine>
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</address>
<ref type="url">http://www.hopitalprincipal.sn/</ref>
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</org>
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</hal:affiliation>
<country>Sénégal</country>
</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-199392" status="OLD"> <idno type="IdRef">123037891</idno>
<idno type="RNSR">200817431S</idno>
<orgName>Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes</orgName>
<orgName type="acronym">URMITE</orgName>
<date type="start">2008-01-01</date>
<date type="end">2017-12-31</date>
<desc> <address> <addrLine>27 Bd Jean Moulin 13385 MARSEILLE Cedex 5</addrLine>
<country key="FR"></country>
</address>
<ref type="url">http://www.mediterranee-infection.com/</ref>
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<orgName type="acronym">IRD</orgName>
<desc> <address> <addrLine>SiègeLe Sextant 44, bd de DunkerqueCS 9000913572 Marseille cedex 02</addrLine>
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</address>
<ref type="url">http://www.ird.fr/</ref>
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<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>
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<orgName>Institut National de la Santé et de la Recherche Médicale</orgName>
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<date type="end">2011-12-31</date>
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</address>
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<desc> <address> <country key="FR"></country>
</address>
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<orgName>Centre National de la Recherche Scientifique</orgName>
<orgName type="acronym">CNRS</orgName>
<date type="start">1939-10-19</date>
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</address>
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</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>
</analytic>
<idno type="DOI">10.1186/s12936-016-1379-2</idno>
<series><title level="j">Malaria Journal</title>
<idno type="ISSN">1475-2875</idno>
<imprint><date type="datePub">2016-07</date>
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<front><div type="abstract" xml:lang="en"> <p>Background: To determine the impact of the introduction of ă artemisinin-based combination therapy (ACT) on parasite susceptibility, ă a molecular surveillance for antimalarial drug resistance was conducted ă on local isolates from the Hopital Principal de Dakar between November ă 2013 and January 2014 and between August 2014 and December 2014. ă Methods: The prevalence of genetic polymorphisms in antimalarial ă resistance genes (pfcrt, pfmdr1, pfdhfr and pfdhps) was evaluated in 103 ă isolates. ă Results: The chloroquine-resistant haplotypes CVIET and CVMET were ă identified in 31.4 and 3.9 % of the isolates, respectively. The ă frequency of the pfcrt K76T mutation was increased from 29.3 % in ă 2013-2014 to 43.2 % in 2014. The pfmdr1 N86Y and Y184F mutations were ă identified in 6.1 and 53.5 % of the isolates, respectively. The pfdhfr ă triple mutant (S108N, N51I and C59R) was detected in the majority of the ă isolates (82.3 %). The prevalence of quadruple mutants (pfdhfr S108N, ă N51I, C59R and pfdhps A437G) was 40.4 %. One isolate (1.1 %) harboured ă the pfdhps mutations A437G and K540E and the pfdhfr mutations S108N, ă N51I and C59R. ă Conclusions: Despite a decline in the prevalence of chloroquine ă resistance due to the official withdrawal of the drug and to the ă introduction of ACT, the spread of resistance to chloroquine has ă continued. Furthermore, susceptibility to amodiaquine may be decreased ă as a result of cross-resistance. The frequency of the pfmdr1 mutation ă N86Y declined while the Y184F mutation increased in prevalence, ă suggesting that selective pressure is acting on pfmdr1, leading to a ă high prevalence of mutations in these isolates and the lack of specific ă mutations. The 50.5 % prevalence of the pfmdr1 polymorphisms N86Y and ă Y184F suggests a decrease in lumefantrine susceptibility. Based on these ă results, intensive surveillance of ACT partner drugs must be conducted ă regularly in Senegal.</p>
</div>
</front>
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<hal api="V3"> <titleStmt> <title xml:lang="en">Prevalence of anti-malarial resistance genes in Dakar, Senegal from 2013 ă to 2014</title>
<author role="aut"> <persName> <forename type="first">Agathe</forename>
<surname>Boussaroque</surname>
</persName>
<idno type="halauthorid">1481809</idno>
</author>
<author role="aut"> <persName> <forename type="first">Bécaye</forename>
<surname>Fall</surname>
</persName>
<idno type="halauthorid">861065</idno>
<affiliation ref="#struct-214449"></affiliation>
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<author role="aut"> <persName> <forename type="first">Marylin</forename>
<surname>Madamet</surname>
</persName>
<idno type="halauthorid">1474687</idno>
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<author role="aut"> <persName> <forename type="first">ă Khalifa Ababacar</forename>
<surname>Wade</surname>
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<surname>Nakoulima</surname>
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<author role="aut"> <persName> <forename type="first">ă Khadidiatou Ba</forename>
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<author role="aut"> <persName> <forename type="first">Pierre</forename>
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<author role="aut"> <persName> <forename type="first">Nicolas</forename>
<surname>Benoit</surname>
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<author role="aut"> <persName> <forename type="first">Bakary ă</forename>
<surname>Diatta</surname>
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<idno type="halauthorid">1488180</idno>
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<author role="aut"> <persName> <forename type="first">Yaya</forename>
<surname>Diemé</surname>
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<author role="aut"> <persName> <forename type="first">Bruno</forename>
<surname>Pradines</surname>
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<date type="whenModified">2019-10-11 01:21:21</date>
<date type="whenReleased">2017-02-13 18:27:12</date>
<date type="whenProduced">2016-07</date>
<ref type="externalLink" target="https://malariajournal.biomedcentral.com/track/pdf/10.1186/s12936-016-1379-2"></ref>
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<idno type="stamp" n="UNIV-AMU">Aix Marseille Université</idno>
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<sourceDesc> <biblStruct> <analytic> <title xml:lang="en">Prevalence of anti-malarial resistance genes in Dakar, Senegal from 2013 ă to 2014</title>
<author role="aut"> <persName> <forename type="first">Agathe</forename>
<surname>Boussaroque</surname>
</persName>
<idno type="halauthorid">1481809</idno>
</author>
<author role="aut"> <persName> <forename type="first">Bécaye</forename>
<surname>Fall</surname>
</persName>
<idno type="halauthorid">861065</idno>
<affiliation ref="#struct-214449"></affiliation>
</author>
<author role="aut"> <persName> <forename type="first">Marylin</forename>
<surname>Madamet</surname>
</persName>
<idno type="halauthorid">1474687</idno>
<affiliation ref="#struct-199392"></affiliation>
</author>
<author role="aut"> <persName> <forename type="first">ă Khalifa Ababacar</forename>
<surname>Wade</surname>
</persName>
<idno type="halauthorid">1488178</idno>
</author>
<author role="aut"> <persName> <forename type="first">Mansour</forename>
<surname>Fall</surname>
</persName>
<idno type="halauthorid">1237779</idno>
<affiliation ref="#struct-440279"></affiliation>
</author>
<author role="aut"> <persName> <forename type="first">Aminata</forename>
<surname>Nakoulima</surname>
</persName>
<idno type="halauthorid">1237780</idno>
<affiliation ref="#struct-224319"></affiliation>
</author>
<author role="aut"> <persName> <forename type="first">ă Khadidiatou Ba</forename>
<surname>Fall</surname>
</persName>
<idno type="halauthorid">1488179</idno>
</author>
<author role="aut"> <persName> <forename type="first">Pierre</forename>
<surname>Dionne</surname>
</persName>
<idno type="halauthorid">1237781</idno>
<affiliation ref="#struct-440281"></affiliation>
</author>
<author role="aut"> <persName> <forename type="first">Nicolas</forename>
<surname>Benoit</surname>
</persName>
<idno type="halauthorid">1239205</idno>
<affiliation ref="#struct-220808"></affiliation>
<affiliation ref="#struct-199392"></affiliation>
<affiliation ref="#struct-440791"></affiliation>
</author>
<author role="aut"> <persName> <forename type="first">Bakary ă</forename>
<surname>Diatta</surname>
</persName>
<idno type="halauthorid">1488180</idno>
</author>
<author role="aut"> <persName> <forename type="first">Yaya</forename>
<surname>Diemé</surname>
</persName>
<idno type="halauthorid">1237782</idno>
<affiliation ref="#struct-214449"></affiliation>
</author>
<author role="aut"> <persName> <forename type="first">Boubacar</forename>
<surname>Wade</surname>
</persName>
<idno type="halauthorid">861074</idno>
<affiliation ref="#struct-214459"></affiliation>
</author>
<author role="aut"> <persName> <forename type="first">Bruno</forename>
<surname>Pradines</surname>
</persName>
<idno type="halauthorid">120627</idno>
<affiliation ref="#struct-199392"></affiliation>
<affiliation ref="#struct-343238"></affiliation>
</author>
</analytic>
<monogr> <idno type="halJournalId" status="VALID">1704</idno>
<idno type="issn">1475-2875</idno>
<title level="j">Malaria Journal</title>
<imprint> <publisher>BioMed Central</publisher>
<biblScope unit="volume">15</biblScope>
<date type="datePub">2016-07</date>
</imprint>
</monogr>
<idno type="doi">10.1186/s12936-016-1379-2</idno>
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<profileDesc> <langUsage> <language ident="en">English</language>
</langUsage>
<textClass> <classCode scheme="halDomain" n="sdv.mhep.mi">Life Sciences [q-bio]/Human health and pathology/Infectious diseases</classCode>
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<abstract xml:lang="en"> <p>Background: To determine the impact of the introduction of ă artemisinin-based combination therapy (ACT) on parasite susceptibility, ă a molecular surveillance for antimalarial drug resistance was conducted ă on local isolates from the Hopital Principal de Dakar between November ă 2013 and January 2014 and between August 2014 and December 2014. ă Methods: The prevalence of genetic polymorphisms in antimalarial ă resistance genes (pfcrt, pfmdr1, pfdhfr and pfdhps) was evaluated in 103 ă isolates. ă Results: The chloroquine-resistant haplotypes CVIET and CVMET were ă identified in 31.4 and 3.9 % of the isolates, respectively. The ă frequency of the pfcrt K76T mutation was increased from 29.3 % in ă 2013-2014 to 43.2 % in 2014. The pfmdr1 N86Y and Y184F mutations were ă identified in 6.1 and 53.5 % of the isolates, respectively. The pfdhfr ă triple mutant (S108N, N51I and C59R) was detected in the majority of the ă isolates (82.3 %). The prevalence of quadruple mutants (pfdhfr S108N, ă N51I, C59R and pfdhps A437G) was 40.4 %. One isolate (1.1 %) harboured ă the pfdhps mutations A437G and K540E and the pfdhfr mutations S108N, ă N51I and C59R. ă Conclusions: Despite a decline in the prevalence of chloroquine ă resistance due to the official withdrawal of the drug and to the ă introduction of ACT, the spread of resistance to chloroquine has ă continued. Furthermore, susceptibility to amodiaquine may be decreased ă as a result of cross-resistance. The frequency of the pfmdr1 mutation ă N86Y declined while the Y184F mutation increased in prevalence, ă suggesting that selective pressure is acting on pfmdr1, leading to a ă high prevalence of mutations in these isolates and the lack of specific ă mutations. The 50.5 % prevalence of the pfmdr1 polymorphisms N86Y and ă Y184F suggests a decrease in lumefantrine susceptibility. Based on these ă results, intensive surveillance of ACT partner drugs must be conducted ă regularly in Senegal.</p>
</abstract>
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