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Quinine Treatment Selects the pfnhe-1 ms4760-1 Polymorphism in Malian Patients with Falciparum Malaria

dc.contributor.authorKone, Aminatou
dc.contributor.authorMu, Jianbing
dc.contributor.authorMaiga, Hamma
dc.contributor.authorBeavogui, Abdoul H.
dc.contributor.authorYattara, Omar
dc.contributor.authorSagara, Issaka
dc.contributor.authorTekete, Mamadou M.
dc.contributor.authorTraore, Oumar B.
dc.contributor.authorDara, Antoine
dc.contributor.authorDama, Souleymane
dc.contributor.authorDiallo, Nouhoum
dc.contributor.authorKodio, Aly
dc.contributor.authorTraore, Aliou
dc.contributor.authorBjoerkman, Anders
dc.contributor.authorGil, José Pedro
dc.contributor.authorDoumbo, Ogobara K.
dc.contributor.authorWellems, Thomas E.
dc.contributor.authorDjimde, Abdoulaye A.
dc.date.accessioned2018-12-07T14:53:00Z
dc.date.available2018-12-07T14:53:00Z
dc.date.issued2013-02
dc.description.abstractBackground. The mechanism of Plasmodium falciparum resistance to quinine is not known. In vitro quantitative trait loci mapping suggests involvement of a predicted P. falciparum sodium-hydrogen exchanger (pfnhe-1) on chromosome 13. Methods. We conducted prospective quinine efficacy studies in 2 villages, Kolle and Faladie, Mali. Cases of clinical malaria requiring intravenous therapy were treated with standard doses of quinine and followed for 28 days. Treatment outcomes were classified using modified World Health Organization protocols. Molecular markers of parasite polymorphisms were used to distinguish recrudescent parasites from new infections. The prevalence of pfnhe-1 ms4760-1 among parasites before versus after quinine treatment was determined by direct sequencing. Results. Overall, 163 patients were enrolled and successfully followed. Without molecular correction, the mean adequate clinical and parasitological response (ACPR) was 50.3% (n = 163). After polymerase chain reaction correction to account for new infections, the corrected ACPR was 100%. The prevalence of ms4760-1 increased significantly, from 26.2% (n = 107) before quinine treatment to 46.3% (n = 54) after therapy (P = .01). In a control sulfadoxine-pyrimethamine study, the prevalence of ms4760-1 was similar before and after treatment. Conclusions. This study supports a role for pfnhe-1 in decreased susceptibility of P. falciparum to quinine in the field.
dc.description.sponsorshipHoward Hughes Medical Institute [55005502]; Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health; European and Developing Countries Clinical Trials Partnership [EDCTP IP_07_31060_002]
dc.description.versioninfo:eu-repo/semantics/publishedVersion
dc.identifier.doi10.1093/infdis/jis691
dc.identifier.issn0022-1899
dc.identifier.issn1537-6613
dc.identifier.urihttp://hdl.handle.net/10400.1/11304
dc.language.isoeng
dc.peerreviewedyes
dc.publisherOxford Univ Press Inc
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectIn-Vitro susceptibility
dc.subjectDrug-resistant malaria
dc.subjectPlasmodium-Falciparum
dc.subjectNa+/H+ exchanger
dc.subjectMicrosatellite variations
dc.subjectChloroquine resistance
dc.subjectAntimalarial-drugs
dc.subjectAssociation
dc.subjectResponses
dc.subjectEfficacy
dc.titleQuinine Treatment Selects the pfnhe-1 ms4760-1 Polymorphism in Malian Patients with Falciparum Malaria
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage527
oaire.citation.issue3
oaire.citation.startPage520
oaire.citation.titleJournal of Infectious Diseases
oaire.citation.volume207
person.familyNameGil
person.givenNameJosé Pedro
person.identifier.ciencia-idD01A-B30E-BCD5
person.identifier.orcid0000-0002-6107-9379
person.identifier.scopus-author-id7201625436
rcaap.rightsopenAccess
rcaap.typearticle
relation.isAuthorOfPublicationcb728715-0e4c-4ae5-9e21-b6a8f35a8313
relation.isAuthorOfPublication.latestForDiscoverycb728715-0e4c-4ae5-9e21-b6a8f35a8313

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