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Malar J. 2017 Jan 9;16(1):23. doi: 10.1186/s12936-016-1663-1.

Absence of in vivo selection for K13 mutations after artemether-lumefantrine treatment in Uganda.

Author information

1
Division of Malaria Research, Proteo-Science Center, Ehime University, 3 Bunkyo-cho, Matsuyama, Ehime, 790-8577, Japan.
2
Department of Molecular and Cellular Parasitology, School of Medicine, Juntendo University, Tokyo, 113-8421, Japan. tmita@juntendo.ac.jp.
3
Department of Molecular and Cellular Parasitology, School of Medicine, Juntendo University, Tokyo, 113-8421, Japan.
4
Department of International Affairs and Tropical Medicine, School of Medicine, Tokyo Women's Medical University, Tokyo, Japan.
5
Health Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Takamatsu, Japan.
6
St. Mary's Hospital LACOR, Gulu, Uganda.
7
Department of Molecular Protozoology, Research Institute for Microbial Diseases, Osaka University, Suita, Japan.
8
Med Biotech Laboratories, Kampala, Uganda.
9
Department of Biology, Faculty of Science, Gulu University, Gulu, Uganda.
10
Division of Malaria Research, Proteo-Science Center, Ehime University, 3 Bunkyo-cho, Matsuyama, Ehime, 790-8577, Japan. tsuboi.takafumi.mb@ehime-u.ac.jp.

Abstract

BACKGROUND:

Individual drug treatment may select resistant parasites in the human body, a process termed in vivo selection. Some single nucleotide polymorphisms in Plasmodium falciparum chloroquine-resistance transporter (pfcrt) and multidrug resistance gene 1 (pfmdr1) genes have been reportedly selected after artemether-lumefantrine treatment. However, there is a paucity of data regarding in vivo selection of P. falciparum Kelch propeller domain (pfkelch13) polymorphisms, responsible for artemisinin-resistance in Asia, and six putative background mutations for artemisinin resistance; D193Y in ferredoxin, T484I in multiple resistance protein 2, V127M in apicoplast ribosomal protein S10, I356T in pfcrt, V1157L in protein phosphatase and C1484F in phosphoinositide-binding protein.

METHODS:

Artemether-lumefantrine efficacy study with a follow-up period of 28 days was conducted in northern Uganda in 2014. The above-mentioned genotypes were comparatively analysed before drug administration and on days; 3, 7, and 28 days after treatment.

RESULTS:

In 61 individuals with successful follow-up, artemether-lumefantrine treatment regimen was very effective with PCR adjusted efficacy of 95.2%. Among 146 isolates obtained before treatment, wild-type alleles were observed in 98.6% of isolates in pfkelch13 and in all isolates in the six putative background genes except I356T in pfcrt, which had 2.4% of isolates as mixed infections. In vivo selection study revealed that all isolates detected in the follow-up period harboured wild type alleles in pfkelch13 and the six background genes.

CONCLUSION:

Mutations in pfkelch13 and the six background genes may not play an important role in the in vivo selection after artemether-lumefantrine treatment in Uganda. Different mechanisms might rather be associated with the existence of parasites after treatment.

KEYWORDS:

Artemether–lumefantrine; Drug resistance; In vivo selection; Plasmodium falciparum; Polymorphisms; pfkelch13

PMID:
28068997
PMCID:
PMC5223472
DOI:
10.1186/s12936-016-1663-1
[Indexed for MEDLINE]
Free PMC Article

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