Plasmodium falciparum K13 expression associated with parasite clearance during artemisinin-based combination therapy

BACKGROUND: Delayed parasite clearance and, consequently, reduced efficacy of artemisinin-based combination therapies have been linked with Plasmodium falciparum K13 gene SNPs in Southeast Asia. In Africa, significantly prolonged clearance has not yet been observed and the presently restricted variation in parasite clearance cannot be explained by K13 polymorphisms.OBJECTIVES: Our aim was to study the in vivo pfK13 transcriptional response in patients treated with artemether-lumefantrine and explore whether the pfk13 transcripts can explain the patients' parasite clearance outcomes.PATIENTS AND METHODS: A total of 47 Tanzanian children with microscopically confirmed uncomplicated P. falciparum malaria were hospitalized and received artemether-lumefantrine treatment (clinical trial ID: NCT00336375). RNA was extracted from venous blood samples collected before treatment initiation and at five more timepoints after treatment. cDNA was synthesized and pfk13 transcripts measured by real-time PCR.RESULTS: A wide range of pfk13 transcript variation was observed throughout all timepoints after artemether-lumefantrine treatment. Taking parasite clearance data together with the pfk13 transcripts profile, we observed a negative correlation inferring that pfk13 down-regulation is associated with longer parasite clearance time.CONCLUSIONS: The findings suggest that a reduced PfK13 transcriptional response may represent a first step towards artemisinin tolerance/resistance.

Ferreira, P E (författare)
Otienoburu, S D (författare)
Calçada, C (författare)
Ngasala, BillyUppsala universitet,Internationell barnhälsa och nutrition,Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania(Swepub:uu)bilng827 (författare)
Björkman, AKarolinska Institutet (författare)
Mårtensson, Andreas,1963-Uppsala universitet,Internationell barnhälsa och nutrition(Swepub:uu)andma331 (författare)
Gil, José PedroKarolinska Institutet,Uppsala universitet,Internationell barnhälsa och nutrition,Division of Pharmacogenetics, Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden;Center for Biodiversity, Functional & Integrative Genomics, Faculdade de Ciências, Universidade de Lisboa, Lisbon, Portugal(Swepub:uu)jospe411 (författare)
Veiga, M I (författare)
Uppsala universitetInternationell barnhälsa och nutrition (creator_code:org_t)

Ingår i:Journal of Antimicrobial Chemotherapy: Oxford University Press (OUP)74:7, s. 1890-18930305-74531460-2091

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