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Plasmodium falciparum population dynamics during the early phase of anti-malarial drug treatment in Tanzanian children with acute uncomplicated malaria

2011-12Journal article Open access
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dc.contributor.authorCarlsson, Anja M.
dc.contributor.authorNgasala, Billy E.
dc.contributor.authorDahlstrom, Sabina
dc.contributor.authorMembi, Christopher
dc.contributor.authorVeiga, Maria Isabel
dc.contributor.authorRombo, Lars
dc.contributor.authorAbdulla, Salim
dc.contributor.authorPremji, Zul
dc.contributor.authorGil, J. P.
dc.contributor.authorBjorkman, Anders
dc.contributor.authorMartensson, Andreas
dc.date.accessioned2018-12-07T14:52:54Z
dc.date.available2018-12-07T14:52:54Z
dc.date.issued2011-12
dc.description.abstractBackground: This study aimed to explore Plasmodium falciparum population dynamics during the early phase of anti-malarial drug treatment with artemisinin-based combination therapy in children with clinical malaria in a high transmission area in Africa. Methods: A total of 50 children aged 1-10 years with acute uncomplicated P. falciparum malaria in Bagamoyo District, Tanzania, were enrolled. Participants were hospitalized and received supervised standard treatment with artemether-lumefantrine according to body weight in six doses over 3 days. Blood samples were collected 11 times, i.e. at time of diagnosis (-2 h) and 0, 2, 4, 8, 16, 24, 36, 48, 60 and 72 h after initiation of treatment. Parasite population dynamics were assessed using nested polymerase chain reaction (PCR)-genotyping of merozoite surface protein (msp) 1 and 2. Results: PCR-analyses from nine sequential blood samples collected after initiation of treatment identified 20 and 21 additional genotypes in 15/50 (30%) and 14/50 (28%) children with msp1 and msp2, respectively, non-detectable in the pre-treatment samples (-2 and 0 h combined). Some 15/20 (75%) and 14/21 (67%) of these genotypes were identified within 24 h, whereas 17/20 (85%) and 19/21 (90%) within 48 h for msp1 and msp2, respectively. The genotype profile was diverse, and varied considerably over time both within and between patients, molecular markers and their respective families. Conclusion: PCR analyses from multiple blood samples collected during the early treatment phase revealed a complex picture of parasite sub-populations. This underlines the importance of interpreting PCR-outcomes with caution and suggests that the present use of PCR-adjustment from paired blood samples in anti-malarial drug trials may overestimate assessment of drug efficacy in high transmission areas in Africa. The study is registered at http://www.clinicaltrials.gov with identifier NCT00336375.
dc.description.sponsorshipSwedish Development Cooperation Agency (SIDA-SAREC) [SWE 2003-278]; R&D-Unit, Sormland Count Council, Sweden [82090]; Golje's Foundation; Irma and Arvid Larsson-Rost's Foundation; Anders Otto Sward's Foundation
dc.description.versioninfo:eu-repo/semantics/publishedVersion
dc.identifier.doihttps://doi.org/10.1186/1475-2875-10-380
dc.identifier.issn1475-2875
dc.identifier.urihttp://hdl.handle.net/10400.1/11258
dc.language.isoeng
dc.peerreviewedyes
dc.publisherBiomed Central
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectAsymptomatic children
dc.subjectPcr
dc.subjectRecrudescence
dc.subjectReinfection
dc.subjectGenotype
dc.subjectMsp1
dc.subjectPlasmodium falciparum
dc.subjectParasite population dynamics
dc.subjectArtemether-lumefantrine
dc.subjectAntimalarial drug trials
dc.titlePlasmodium falciparum population dynamics during the early phase of anti-malarial drug treatment in Tanzanian children with acute uncomplicated malaria
dc.typejournal article
dspace.entity.typePublication
oaire.citation.startPage380
oaire.citation.titleMalaria Journal
oaire.citation.volume10
person.familyNameVeiga
person.familyNameGil
person.givenNameMaria Isabel
person.givenNameJosé Pedro
person.identifier.ciencia-id271C-6028-9C6B
person.identifier.ciencia-idD01A-B30E-BCD5
person.identifier.orcid0000-0002-2205-8102
person.identifier.orcid0000-0002-6107-9379
person.identifier.ridH-9922-2018
person.identifier.scopus-author-id12767840900
person.identifier.scopus-author-id7201625436
rcaap.rightsopenAccess
rcaap.typearticle
relation.isAuthorOfPublication76e56d6c-a7cb-4b41-8ad7-0e480b31ed41
relation.isAuthorOfPublicationcb728715-0e4c-4ae5-9e21-b6a8f35a8313
relation.isAuthorOfPublication.latestForDiscovery76e56d6c-a7cb-4b41-8ad7-0e480b31ed41

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