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01.12.2017 | Research | Ausgabe 1/2017 Open Access

Malaria Journal 1/2017

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

Malaria Journal > Ausgabe 1/2017
Betty Balikagala, Toshihiro Mita, Mie Ikeda, Miki Sakurai, Shouki Yatsushiro, Nobuyuki Takahashi, Shin-Ichiro Tachibana, Mary Auma, Edward H. Ntege, Daisuke Ito, Eizo Takashima, Nirianne Marie Q. Palacpac, Thomas G. Egwang, Joseph Okello Onen, Masatoshi Kataoka, Eisaku Kimura, Toshihiro Horii, Takafumi Tsuboi
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​s12936-016-1663-1) contains supplementary material, which is available to authorized users.
Joseph Okello Onen deceased on 15 September 2015



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.


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.


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.


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.
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