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Temporal trends of molecular markers associated with artemether-lumefantrine tolerance/resistance in Bagamoyo district, Tanzania

2013Journal article Open access
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dc.contributor.authorMalmberg, Maja
dc.contributor.authorNgasala, Billy
dc.contributor.authorFerreira, Pedro E.
dc.contributor.authorLarsson, Erik
dc.contributor.authorJovel, Irina
dc.contributor.authorHjalmarsson, Angelica
dc.contributor.authorPetzold, Max
dc.contributor.authorPremji, Zul
dc.contributor.authorGil, José Pedro
dc.contributor.authorBjorkman, Anders
dc.contributor.authorMartensson, Andreas
dc.date.accessioned2018-12-07T14:53:20Z
dc.date.available2018-12-07T14:53:20Z
dc.date.issued2013
dc.description.abstractBackground: Development and spread of Plasmodium falciparum resistance to artemisinin-based combination therapy (ACT) constitutes a major threat to recent global malaria control achievements. Surveillance of molecular markers could act as an early warning system of ACT-resistance before clinical treatment failures are apparent. The aim of this study was to analyse temporal trends of established genotypes associated with artemether-lumefantrine tolerance/resistance before and after its deployment as first-line treatment for uncomplicated malaria in Tanzania 2006. Methods: Single nucleotide polymorphisms in the P. falciparum multidrug resistance gene 1 (pfmdr1) N86Y, Y184F, D1246Y and P. falciparum chloroquine transporter gene (pfcrt) K76T were analysed from dried blood spots collected during six consecutive studies from children with uncomplicated P. falciparum malaria in Fukayosi village, Bagamoyo District, Tanzania, between 2004-2011. Results: There was a statistically significant yearly increase of pfmdr1 N86, 184F, D1246 and pfcrt K76 between 2006-2011 from 14% to 61% (yearly OR = 1.38 [95% CI 1.25-1.52] p < 0.0001), 14% to 35% (OR = 1.17 [95% CI 1.07-1.30] p = 0.001), 54% to 85% (OR = 1.21 [95% CI 1.03-1.42] p = 0.016) and 49% to 85% (OR = 1.33 [95% CI 1.17-1.51] p < 0.0001), respectively. Unlike for the pfmdr1 SNP, a significant increase of pfcrt K76 was observed already between 2004-2006, from 26% to 49% (OR = 1.68 [95% CI 1.17-2.40] p = 0.005). From 2006 to 2011 the pfmdr1 NFD haplotype increased from 10% to 37% (OR = 1.25 [95% CI 1.12-1.39] p < 0.0001), whereas the YYY haplotype decreased from 31% to 6% (OR = 0.73 [95% CI 0.56-0.98] p = 0.018). All 390 successfully analysed samples had one copy of the pfmdr1 gene. Conclusion: The temporal selection of molecular markers associated with artemether-lumefantrine tolerance/resistance may represent an early warning sign of impaired future drug efficacy. This calls for stringent surveillance of artemether-lumefantrine efficacy in Tanzania and emphasizes the importance of molecular surveillance as a complement to standard in vivo trials.
dc.description.sponsorshipSwedish Development Cooperation Agency-Department for Research Cooperation [AM: SIDA-SAREC 2009-193, BN: Bil-Tz 16/9875007059]; Swedish Civil Contingencies Agency [2010-7991]; Goljes foundation
dc.description.versioninfo:eu-repo/semantics/publishedVersion
dc.identifier.doi10.1186/1475-2875-12-103
dc.identifier.issn1475-2875
dc.identifier.urihttp://hdl.handle.net/10400.1/11463
dc.language.isoeng
dc.peerreviewedyes
dc.publisherBMC
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectPlasmodium-Falciparum malaria
dc.subjectIn-Vivo selection
dc.subjectCombination therapy
dc.subjectResistant malaria
dc.subjectWestern cambodia
dc.subjectPfmdr1 gene
dc.subjectArtemisinin
dc.subjectChloroquine
dc.subjectAfrica
dc.subjectParasites
dc.titleTemporal trends of molecular markers associated with artemether-lumefantrine tolerance/resistance in Bagamoyo district, Tanzania
dc.typejournal article
dspace.entity.typePublication
oaire.citation.startPage103
oaire.citation.titleMalaria Journal
oaire.citation.volume12
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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