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Molecular Markers of Sulfadoxine-Pyrimethamine Resistance in Samples from Children with Uncomplicated Plasmodium falciparum at Three Sites in Angola in 2019

dc.contributor.authorRosillo, Stefano R.
dc.contributor.authorDimbu, Pedro Rafael
dc.contributor.authorCândido, Ana Luisa M.
dc.contributor.authorOh, Je Hoon Michael
dc.contributor.authorFerreira, Carolina Miguel
dc.contributor.authorAndrade, Benjamin Nieto
dc.contributor.authorLabuda, Sarah
dc.contributor.authorHorth, Roberta
dc.contributor.authorKelley, Julia
dc.contributor.authorMorais, Joana F.M.
dc.contributor.authorFortes, Filomeno
dc.contributor.authorMartins, José Franco
dc.contributor.authorTalundzic, Eldin
dc.contributor.authorPluciński, Mateusz M.
dc.contributor.institutionIndividual Health Care (IHC)
dc.contributor.institutionGlobal Health and Tropical Medicine (GHTM)
dc.contributor.institutionInstituto de Higiene e Medicina Tropical (IHMT)
dc.contributor.pblAmerican Society for Microbiology
dc.date.accessioned2023-07-11T22:21:13Z
dc.date.available2023-07-11T22:21:13Z
dc.date.issued2023-04
dc.descriptionFunding Information: The study was funded by the U.S. President’s Malaria Initiative and the Advanced Molecular Detection program at CDC. Funding Information: We thank all study staff and participants, Venceslau Mambi Pelenda, José Bumba da Cunha, Oliveira Kiatoko, Felismina Caquece, Luzala Elisabeth Armando Garcia, Djos Kialanda, Garcia Pembele, Domingos Jandondo, and Belmira José Bondo. The findings and conclusions in this report are those of the author(s) and do not necessarily represent the official position of the U.S. Centers for Disease Control and Prevention or the U.S. Agency for International Development. The study was funded by the U.S. President’s Malaria Initiative and the Advanced Molecular Detection program at CDC. P.R.D., C.M.F., B.N.A., S.L., R.H., J.F.M.M., F.F., J.F.M., and M.M.P. designed and participated in the specimen collection. P.R.D., A.L.M.C., S.R.R., and J.K. performed the laboratory analysis. P.R.D., A.L.M.C., J.K., S.R.R., J.-H.M.O., and E.T. analyzed the sequencing data. S.R.R. and M.M.P. wrote the manuscript. All authors read and approved the final version of the manuscript. Publisher Copyright: Copyright © 2023 Rosillo et al.
dc.description.abstractSulfadoxine-pyrimethamine (SP) is used for prevention of malaria in pregnant women in Angola. We sequenced the Plasmodium falciparum dihydrofolate reductase (pfdhfr) and dihydropteroate synthase (pfdhps) genes, implicated in SP resistance, in samples collected during a 2019 study of artemisinin-based combination therapy efficacy in Benguela, Lunda Sul, and Zaire provinces. A total of 90 day 0 and day of failure samples were individually sequenced, while 508 day 0 samples from participants without recurrent parasitemia were pooled after DNA extraction into 61 pools. The N51I, C59R, and S108N pfdhfr mutations and A437G pfdhps mutations were present at high proportions in all provinces (weighted allele frequencies, 62% to 100%). The K540E pfdhps mutation was present at lower proportions (10% to 14%). The A581G pfdhps mutation was only observed in Zaire, at a 4.6% estimated prevalence. The I431V and A613S mutations were also only observed in Zaire, at a prevalence of 2.8% to 2.9%. The most common (27% to 66%) reconstructed haplotype in all three provinces was the canonical quadruple pfdhfr pfdhps mutant. The canonical quintuple mutant was absent in Lunda Sul and Benguela and present in 7.9% of samples in Zaire. A single canonical sextuple (2.6%) mutant was observed in Zaire Province. Proportions of the pfdhps K540E and A581G mutations were well below the World Health Organization thresholds for meaningful SP resistance (prevalence of 95% for K540E and 10% for A581G). Samples from therapeutic efficacy studies represent a convenient source of samples for monitoring SP resistance markers.en
dc.description.versionpublishersversion
dc.description.versionpublished
dc.format.extent9
dc.format.extent731723
dc.identifier.doi10.1128/aac.01601-22
dc.identifier.issn0066-4804
dc.identifier.otherPURE: 64215533
dc.identifier.otherPURE UUID: ee9484af-530e-4a72-ae68-ee284cdd886b
dc.identifier.otherScopus: 85152970343
dc.identifier.otherPubMed: 36916920
dc.identifier.otherPubMedCentral: PMC10112138
dc.identifier.otherWOS: WOS:000949583000001
dc.identifier.urihttp://hdl.handle.net/10362/155095
dc.identifier.urlhttps://www.scopus.com/pages/publications/85152970343
dc.language.isoeng
dc.peerreviewedyes
dc.subjectdhfr
dc.subjectdhps
dc.subjectsurveillance
dc.subjectR Medicine
dc.subjectRJ Pediatrics
dc.subjectQR Microbiology
dc.subjectQH426 Genetics
dc.subjectPharmacology
dc.subjectPharmacology (medical)
dc.subjectInfectious Diseases
dc.subjectParasitology
dc.subjectMolecular Biology
dc.subjectSDG 3 - Good Health and Well-being
dc.titleMolecular Markers of Sulfadoxine-Pyrimethamine Resistance in Samples from Children with Uncomplicated Plasmodium falciparum at Three Sites in Angola in 2019en
dc.typejournal article
degois.publication.issue4
degois.publication.titleAntimicrobial Agents and Chemotherapy
degois.publication.volume67
dspace.entity.typePublication
rcaap.rightsopenAccess

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