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Prevalence of anti-malarial resistance genes in Dakar, Senegal from 2013 ă to 2014

Identifieur interne : 000116 ( France/Analysis ); précédent : 000115; suivant : 000117

Prevalence 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 :

RBID : Hal:hal-01466883

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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<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>
</TEI>
<affiliations>
<list>
<country>
<li>France</li>
<li>Sénégal</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>
<noCountry>
<name sortKey="Boussaroque, Agathe" sort="Boussaroque, Agathe" uniqKey="Boussaroque A" first="Agathe" last="Boussaroque">Agathe Boussaroque</name>
<name sortKey="Diatta, Bakary" sort="Diatta, Bakary" uniqKey="Diatta B" first="Bakary" last="Diatta">Bakary Diatta</name>
<name sortKey="Fall, Khadidiatou Ba" sort="Fall, Khadidiatou Ba" uniqKey="Fall " first=" Khadidiatou Ba" last="Fall"> Khadidiatou Ba Fall</name>
<name sortKey="Wade, Khalifa Ababacar" sort="Wade, Khalifa Ababacar" uniqKey="Wade " first=" Khalifa Ababacar" last="Wade"> Khalifa Ababacar Wade</name>
</noCountry>
<country name="Sénégal">
<noRegion>
<name sortKey="Fall, Becaye" sort="Fall, Becaye" uniqKey="Fall B" first="Bécaye" last="Fall">Bécaye Fall</name>
</noRegion>
<name sortKey="Dieme, Yaya" sort="Dieme, Yaya" uniqKey="Dieme Y" first="Yaya" last="Diemé">Yaya Diemé</name>
<name sortKey="Dionne, Pierre" sort="Dionne, Pierre" uniqKey="Dionne P" first="Pierre" last="Dionne">Pierre Dionne</name>
<name sortKey="Fall, Mansour" sort="Fall, Mansour" uniqKey="Fall M" first="Mansour" last="Fall">Mansour Fall</name>
<name sortKey="Nakoulima, Aminata" sort="Nakoulima, Aminata" uniqKey="Nakoulima A" first="Aminata" last="Nakoulima">Aminata Nakoulima</name>
<name sortKey="Wade, Boubacar" sort="Wade, Boubacar" uniqKey="Wade B" first="Boubacar" last="Wade">Boubacar Wade</name>
</country>
<country name="France">
<region name="Provence-Alpes-Côte d'Azur">
<name sortKey="Madamet, Marylin" sort="Madamet, Marylin" uniqKey="Madamet M" first="Marylin" last="Madamet">Marylin Madamet</name>
</region>
<name sortKey="Benoit, Nicolas" sort="Benoit, Nicolas" uniqKey="Benoit N" first="Nicolas" last="Benoit">Nicolas Benoit</name>
<name sortKey="Pradines, Bruno" sort="Pradines, Bruno" uniqKey="Pradines B" first="Bruno" last="Pradines">Bruno Pradines</name>
</country>
</tree>
</affiliations>
</record>

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