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

被引：21

作者：

Balikagala, Betty ^{[1
]}

Mita, Toshihiro ^{[2
]}

Ikeda, Mie ^{[2
]}

Sakurai, Miki ^{[3
]}

Yatsushiro, Shouki ^{[4
]}

Takahashi, Nobuyuki ^{[3
]}

Tachibana, Shin-Ichiro ^{[2
]}

Auma, Mary ^{[5
]}

Ntege, Edward H. ^{[1
]}

Ito, Daisuke ^{[1
]}

Takashima, Eizo ^{[1
]}

Palacpac, Nirianne Marie Q. ^{[6
]}

Egwang, Thomas G. ^{[7
]}

Onen, Joseph Okello ^{[8
]}

Kataoka, Masatoshi ^{[4
]}

Kimura, Eisaku ^{[6
]}

Horii, Toshihiro ^{[6
]}

Tsuboi, Takafumi ^{[1
]}

机构：

[1] Ehime Univ, Div Malaria Res, Proteosci Ctr, 3 Bunkyo Cho, Matsuyama, Ehime 7908577, Japan

[2] Juntendo Univ, Sch Med, Dept Mol & Cellular Parasitol, Tokyo 1138421, Japan

[3] Tokyo Womens Med Univ, Sch Med, Dept Int Affairs & Trop Med, Tokyo, Japan

[4] Natl Inst Adv Ind Sci & Technol, Hlth Res Inst, Takamatsu, Kagawa, Japan

[5] St Marys Hosp LACOR, Gulu, Uganda

[6] Osaka Univ, Microbial Dis Res Inst, Dept Mol Protozool, Suita, Osaka, Japan

[7] Med Biotech Labs, Kampala, Uganda

[8] Gulu Univ, Dept Biol, Fac Sci, Gulu, Uganda

来源：

MALARIA JOURNAL | 2017年 / 16卷

关键词：

In vivo selection; pfkelch13; Artemether-lumefantrine; Drug resistance; Polymorphisms; Plasmodium falciparum; ARTEMISININ-COMBINATION THERAPY; PLASMODIUM-FALCIPARUM PARASITES; UNCOMPLICATED MALARIA; DIHYDROARTEMISININ-PIPERAQUINE; RESISTANT MALARIA; KENYAN CHILDREN; SPREAD; GENE; CLEARANCE; INFECTION;

D O I：

10.1186/s12936-016-1663-1

中图分类号：

R51 [传染病];

学科分类号：

100401 ;

摘要：

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.

引用

页数：11

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