Polymorphism of the Chloroquine Resistance Transporter (Crt), Dihydrofolate Reductase (dhfr) and Kelch13 Propeller (K13 Propeller) Genes of Plasmodium falciparum in Saliva and Urine in Malaria Patients
Identifieur interne : 000028 ( Hal/Checkpoint ); précédent : 000027; suivant : 000029Polymorphism of the Chloroquine Resistance Transporter (Crt), Dihydrofolate Reductase (dhfr) and Kelch13 Propeller (K13 Propeller) Genes of Plasmodium falciparum in Saliva and Urine in Malaria Patients
Auteurs : Olefongo Dagnogo [Côte d'Ivoire]Source :
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Abstract
Malaria is a parasitosis transmitted to humans by a protozoan belonging to the genus Plasmodium. Its management involves early diagnosis and prompt treatment with effective antimalarials. However, in Côte d'Ivoire as in other countries, the management of the disease faces resistance to most antimalarials. Antimalarial drug resistance surveillance and malaria diagnosis require blood collection. Blood collection, with its requirement for qualified personnel and biological risk associated with the use of needles, can lead to poor compliance when a repeat bioassay is required. To cover the need for diagnosis or antimalarial drug resistance surveillance, a non-invasive sampling method that can substitute blood collection is necessary.This thesis evaluated the performance of saliva and urine for detection of antimalarial drug resistance molecular markers by polymorphism study approach of these markers. Saliva and urine performance for antimalarial drug resistance molecular markers detection was evaluated by comparing genomic DNA amplification yield for Plasmodium falciparum extracted from urine, saliva and blood and pfcrt, pfdhfr and pfK13 propeller genes detectability in these biological products. The analysis identified saliva as the best alternative to blood for antimalarial drug resistance molecular markers studies.Antimalarial drug resistance molecular markers polymorphism study showed that the prevalence of genotypes conferring resistance to pyrimethamine (P), chloroquine (CQ) and artemisinin derivatives in 2015 reached comparable levels in the isolates from the three biological products (blood, urine and saliva). Prevalence of alleles associated with chloroquine chemoresistance represented by pfcrt gene Thr-76 decreased while that of the alleles associated with pyrimethamine chemoresistance represented by dhfr-ts gene mutation Asn-108 increased in Anonkoua-Kouté, Port-Bouet and Ayamé. No mutations of K13 propeller gene conferring resistance to artemisinin derivatives were observed as well in the three biological products (saliva, urine and blood) as on all study sites. The study showed that artemisinin-based combination therapies used for the first-line treatment of malaria in Côte d'Ivoire are still effective.
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Polymorphism of the Chloroquine Resistance Transporter (Crt), Dihydrofolate Reductase (dhfr) and Kelch13 Propeller (K13 Propeller) Genes of Plasmodium falciparum in Saliva and Urine in Malaria Patients</title><title xml:lang="fr">Polymorphisme des gènes Chloroquine Resistance Transporter (crt), dihydrofolate reductase (dhfr) et Kelch13 propeller (K13 propeller) de Plasmodium falciparum dans la salive et les urines chez le sujet atteint de paludisme</title><author><name sortKey="Dagnogo, Olefongo" sort="Dagnogo, Olefongo" uniqKey="Dagnogo O" first="Olefongo" last="Dagnogo">Olefongo Dagnogo</name><affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-484496" status="INCOMING"> <orgName>Université Félix Houphouët-Boigny d’Abidjan-Cocody</orgName> <orgName type="acronym">Université Félix Houphouët-Boigny d’Abidjan-Cocody</orgName> <desc> <address> <country key="CI"></country> </address> </desc> <listRelation> <relation active="#struct-484494" type="direct"></relation> </listRelation> <tutelles><tutelle active="#struct-484494" type="direct"><org type="institution" xml:id="struct-484494" status="INCOMING"> <orgName>Université Félix Houphouët-Boigny d’Abidjan-Cocody</orgName> <desc> <address> <country key="CI"></country> </address> </desc> </org></tutelle></tutelles></hal:affiliation><country>Côte d'Ivoire</country></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">HAL</idno><idno type="RBID">Hal:tel-02358468</idno><idno type="halId">tel-02358468</idno><idno type="halUri">https://tel.archives-ouvertes.fr/tel-02358468</idno><idno type="url">https://tel.archives-ouvertes.fr/tel-02358468</idno><date when="2018-03-23">2018-03-23</date><idno type="wicri:Area/Hal/Corpus">000192</idno><idno type="wicri:Area/Hal/Curation">000192</idno><idno type="wicri:Area/Hal/Checkpoint">000028</idno><idno type="wicri:explorRef" wicri:stream="Hal" wicri:step="Checkpoint">000028</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Polymorphism of the Chloroquine Resistance Transporter (Crt), Dihydrofolate Reductase (dhfr) and Kelch13 Propeller (K13 Propeller) Genes of Plasmodium falciparum in Saliva and Urine in Malaria Patients</title><title xml:lang="fr">Polymorphisme des gènes Chloroquine Resistance Transporter (crt), dihydrofolate reductase (dhfr) et Kelch13 propeller (K13 propeller) de Plasmodium falciparum dans la salive et les urines chez le sujet atteint de paludisme</title><author><name sortKey="Dagnogo, Olefongo" sort="Dagnogo, Olefongo" uniqKey="Dagnogo O" first="Olefongo" last="Dagnogo">Olefongo Dagnogo</name><affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-484496" status="INCOMING"> <orgName>Université Félix Houphouët-Boigny d’Abidjan-Cocody</orgName> <orgName type="acronym">Université Félix Houphouët-Boigny d’Abidjan-Cocody</orgName> <desc> <address> <country key="CI"></country> </address> </desc> <listRelation> <relation active="#struct-484494" type="direct"></relation> </listRelation> <tutelles><tutelle active="#struct-484494" type="direct"><org type="institution" xml:id="struct-484494" status="INCOMING"> <orgName>Université Félix Houphouët-Boigny d’Abidjan-Cocody</orgName> <desc> <address> <country key="CI"></country> </address> </desc> </org></tutelle></tutelles></hal:affiliation><country>Côte d'Ivoire</country></affiliation></author></analytic></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="mix" xml:lang="en"><term>Plasmodium falciparum</term><term>molecular diagnosis</term><term>pfK13 propeller</term><term>pfcrt</term><term>pfdhfr</term><term>polymorphism</term><term>saliva</term><term>urine</term></keywords><keywords scheme="mix" xml:lang="fr"><term>Plasmodium falciparum</term><term>diagnostic moléculaire</term><term>pfK13 propeller</term><term>pfcrt</term><term>pfdhfr</term><term>salive</term><term>urine</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"> <p>Malaria is a parasitosis transmitted to humans by a protozoan belonging to the genus Plasmodium. Its management involves early diagnosis and prompt treatment with effective antimalarials. However, in Côte d'Ivoire as in other countries, the management of the disease faces resistance to most antimalarials. Antimalarial drug resistance surveillance and malaria diagnosis require blood collection. Blood collection, with its requirement for qualified personnel and biological risk associated with the use of needles, can lead to poor compliance when a repeat bioassay is required. To cover the need for diagnosis or antimalarial drug resistance surveillance, a non-invasive sampling method that can substitute blood collection is necessary.This thesis evaluated the performance of saliva and urine for detection of antimalarial drug resistance molecular markers by polymorphism study approach of these markers. Saliva and urine performance for antimalarial drug resistance molecular markers detection was evaluated by comparing genomic DNA amplification yield for Plasmodium falciparum extracted from urine, saliva and blood and pfcrt, pfdhfr and pfK13 propeller genes detectability in these biological products. The analysis identified saliva as the best alternative to blood for antimalarial drug resistance molecular markers studies.Antimalarial drug resistance molecular markers polymorphism study showed that the prevalence of genotypes conferring resistance to pyrimethamine (P), chloroquine (CQ) and artemisinin derivatives in 2015 reached comparable levels in the isolates from the three biological products (blood, urine and saliva). Prevalence of alleles associated with chloroquine chemoresistance represented by pfcrt gene Thr-76 decreased while that of the alleles associated with pyrimethamine chemoresistance represented by dhfr-ts gene mutation Asn-108 increased in Anonkoua-Kouté, Port-Bouet and Ayamé. No mutations of K13 propeller gene conferring resistance to artemisinin derivatives were observed as well in the three biological products (saliva, urine and blood) as on all study sites. The study showed that artemisinin-based combination therapies used for the first-line treatment of malaria in Côte d'Ivoire are still effective.</p> </div></front></TEI><hal api="V3"> <titleStmt> <title xml:lang="en">Polymorphism of the Chloroquine Resistance Transporter (Crt), Dihydrofolate Reductase (dhfr) and Kelch13 Propeller (K13 Propeller) Genes of Plasmodium falciparum in Saliva and Urine in Malaria Patients</title> <title xml:lang="fr">Polymorphisme des gènes Chloroquine Resistance Transporter (crt), dihydrofolate reductase (dhfr) et Kelch13 propeller (K13 propeller) de Plasmodium falciparum dans la salive et les urines chez le sujet atteint de paludisme</title> <author role="aut"> <persName> <forename type="first">Olefongo</forename> <surname>Dagnogo</surname> </persName> <email type="md5">c4bd2534dc2aa708bb0f5f398a5054a7</email> <email type="domain">yahoo.fr</email> <idno type="halauthorid">11646728</idno> <orgName ref="#struct-218070"></orgName> <affiliation ref="#struct-484496"></affiliation> </author> <editor role="depositor"> <persName> <forename>Joseph</forename> <surname>Djaman</surname> </persName> <email type="md5">ab2e55ab6b1e5f430a6ad79da8b17fa0</email> <email type="domain">pasteur.ci</email> </editor> </titleStmt> <editionStmt> <edition n="v1" type="current"> <date type="whenSubmitted">2019-11-12 00:33:17</date> <date type="whenModified">2019-11-15 15:21:52</date> <date type="whenReleased">2019-11-15 15:21:52</date> <date type="whenProduced">2018-03-23</date> <date type="whenEndEmbargoed">2019-11-12</date> <ref type="file" target="https://tel.archives-ouvertes.fr/tel-02358468/document"> <date notBefore="2019-11-12"></date> </ref> <ref type="file" subtype="author" n="1" target="https://tel.archives-ouvertes.fr/tel-02358468/file/Th%C3%A8se%20Dagnogo.pdf"> <date notBefore="2019-11-12"></date> </ref> </edition> <respStmt> <resp>contributor</resp> <name key="167956"> <persName> <forename>Joseph</forename> <surname>Djaman</surname> </persName> <email type="md5">ab2e55ab6b1e5f430a6ad79da8b17fa0</email> <email type="domain">pasteur.ci</email> </name> </respStmt> </editionStmt> <publicationStmt> <distributor>CCSD</distributor> <idno type="halId">tel-02358468</idno> <idno type="halUri">https://tel.archives-ouvertes.fr/tel-02358468</idno> <idno type="halBibtex">dagnogo:tel-02358468</idno> <idno type="halRefHtml">Sciences du Vivant [q-bio]. Université Félix Houphouët-Boigny, Abidjan, Côte d'Ivoire), 2018. Français</idno> <idno type="halRef">Sciences du Vivant [q-bio]. Université Félix Houphouët-Boigny, Abidjan, Côte d'Ivoire), 2018. Français</idno> </publicationStmt> <seriesStmt></seriesStmt> <notesStmt></notesStmt> <sourceDesc> <biblStruct> <analytic> <title xml:lang="en">Polymorphism of the Chloroquine Resistance Transporter (Crt), Dihydrofolate Reductase (dhfr) and Kelch13 Propeller (K13 Propeller) Genes of Plasmodium falciparum in Saliva and Urine in Malaria Patients</title> <title xml:lang="fr">Polymorphisme des gènes Chloroquine Resistance Transporter (crt), dihydrofolate reductase (dhfr) et Kelch13 propeller (K13 propeller) de Plasmodium falciparum dans la salive et les urines chez le sujet atteint de paludisme</title> <author role="aut"> <persName> <forename type="first">Olefongo</forename> <surname>Dagnogo</surname> </persName> <email type="md5">c4bd2534dc2aa708bb0f5f398a5054a7</email> <email type="domain">yahoo.fr</email> <idno type="halauthorid">11646728</idno> <orgName ref="#struct-218070"></orgName> <affiliation ref="#struct-484496"></affiliation> </author> </analytic> <monogr> <imprint> <date type="dateDefended">2018-03-23</date> </imprint> <authority type="institution">Université Félix Houphouët-Boigny, Abidjan, Côte d'Ivoire)</authority> <authority type="supervisor">Djaman Allico Joseph</authority> </monogr> </biblStruct> </sourceDesc> <profileDesc> <langUsage> <language ident="fr">French</language> </langUsage> <textClass> <keywords scheme="author"> <term xml:lang="en">Plasmodium falciparum</term> <term xml:lang="en">pfcrt</term> <term xml:lang="en">pfdhfr</term> <term xml:lang="en">pfK13 propeller</term> <term xml:lang="en">saliva</term> <term xml:lang="en">urine</term> <term xml:lang="en">polymorphism</term> <term xml:lang="en">molecular diagnosis</term> <term xml:lang="fr">Plasmodium falciparum</term> <term xml:lang="fr">pfcrt</term> <term xml:lang="fr">pfdhfr</term> <term xml:lang="fr">pfK13 propeller</term> <term xml:lang="fr">salive</term> <term xml:lang="fr">urine</term> <term xml:lang="fr">diagnostic moléculaire</term> </keywords> <classCode scheme="halDomain" n="sdv">Life Sciences [q-bio]</classCode> <classCode scheme="halDomain" n="sdv.mp">Life Sciences [q-bio]/Microbiology and Parasitology</classCode> <classCode scheme="halDomain" n="sdv.mp.par">Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology</classCode> <classCode scheme="halTypology" n="THESE">Theses</classCode> </textClass> <abstract xml:lang="en"> <p>Malaria is a parasitosis transmitted to humans by a protozoan belonging to the genus Plasmodium. Its management involves early diagnosis and prompt treatment with effective antimalarials. However, in Côte d'Ivoire as in other countries, the management of the disease faces resistance to most antimalarials. Antimalarial drug resistance surveillance and malaria diagnosis require blood collection. Blood collection, with its requirement for qualified personnel and biological risk associated with the use of needles, can lead to poor compliance when a repeat bioassay is required. To cover the need for diagnosis or antimalarial drug resistance surveillance, a non-invasive sampling method that can substitute blood collection is necessary.This thesis evaluated the performance of saliva and urine for detection of antimalarial drug resistance molecular markers by polymorphism study approach of these markers. Saliva and urine performance for antimalarial drug resistance molecular markers detection was evaluated by comparing genomic DNA amplification yield for Plasmodium falciparum extracted from urine, saliva and blood and pfcrt, pfdhfr and pfK13 propeller genes detectability in these biological products. The analysis identified saliva as the best alternative to blood for antimalarial drug resistance molecular markers studies.Antimalarial drug resistance molecular markers polymorphism study showed that the prevalence of genotypes conferring resistance to pyrimethamine (P), chloroquine (CQ) and artemisinin derivatives in 2015 reached comparable levels in the isolates from the three biological products (blood, urine and saliva). Prevalence of alleles associated with chloroquine chemoresistance represented by pfcrt gene Thr-76 decreased while that of the alleles associated with pyrimethamine chemoresistance represented by dhfr-ts gene mutation Asn-108 increased in Anonkoua-Kouté, Port-Bouet and Ayamé. No mutations of K13 propeller gene conferring resistance to artemisinin derivatives were observed as well in the three biological products (saliva, urine and blood) as on all study sites. The study showed that artemisinin-based combination therapies used for the first-line treatment of malaria in Côte d'Ivoire are still effective.</p> </abstract> <abstract xml:lang="fr"> <p>Le paludisme est une parasitose transmise à l’homme par un protozoaire appartenant au genre Plasmodium. Sa prise en charge implique un diagnostic précoce et le traitement rapide au moyen d'antipaludiques efficaces. Cependant, en Côte d'Ivoire comme dans d'autres pays, la prise en charge de la maladie se heurte à la résistance à la plupart des antipaludiques. La surveillance de la résistance aux antipaludiques ainsi que le diagnostic du paludisme nécessitent un prélèvement de sang. La prise de sang, avec son exigence de personnel qualifié et le risque biologique lié à l'inévitable utilisation des aiguilles, peut entraîner une mauvaise observance lorsqu'une répétition du test biologique est nécessaire. Pour couvrir les besoins de diagnostic ou de surveillance de résistance aux antipaludiques, une méthode de prélèvement non invasive qui peut se substituer à la collecte d'échantillons de sang est nécessaire. Cette thèse a évalué les performances de la salive et l'urine pour la détection des marqueurs moléculaires de résistance de Plasmodium falciparum aux antipaludiques par une approche d'étude du polymorphisme de ces marqueurs. L'évaluation de la performance de la salive et l'urine pour la détection des marqueurs moléculaires de résistance aux antipaludiques a été faite en comparant les taux d'amplification de l'ADN génomique de P. falciparum extrait à partir des urines, la salive et le sang et les taux de détectabilité des gènes pfcrt, pfdhfr et pfK13 propeller dans ces produits biologiques. L'analyse a permis d'identifier la salive comme meilleure alternative au sang pour l'étude des marqueurs moléculaires de résistance aux antipaludiques. L'étude du polymorphisme des marqueurs moléculaires de résistance aux antipaludiques a montré que les prévalences des génotypes conférant la résistance à la pyréméthamine (P), à la chloroquine (CQ) et aux dérivés d'artémisinine en 2015 ont atteint des niveaux comparables dans les isolats issus des trois produits biologiques (sang, urine et salive). La prévalence des allèles associés à la chimiorésistance de la chloroquine représentés par la mutation Thr-76 du gène pfcrt a baissé tandis que celle des allèles associés à la chimiorésistance de la pyriméthamine représentés par la mutation Asn-108 du gène pfdhfr-ts a augmenté à Anonkoua-Kouté, Port-Bouët et Ayamé. Aucune mutation des allèles mutants du gène K13 propeller conférant la résistance aux dérivés d'artémisinine n'a été observée aussi bien dans les trois produits biologiques (salive, urine et sang) que sur l'ensemble des sites d'étude.L'étude a ainsi montré que les combinaisons thérapeutiques à base d'artémisinine utilisées pour le traitement de première ligne du paludisme en Côte d'Ivoire sont toujours efficaces.</p> </abstract> </profileDesc> </hal></record>Pour manipuler ce document sous Unix (Dilib)
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