期刊
MALARIA JOURNAL
卷 16, 期 -, 页码 -出版社
BMC
DOI: 10.1186/s12936-016-1663-1
关键词
In vivo selection; pfkelch13; Artemether-lumefantrine; Drug resistance; Polymorphisms; Plasmodium falciparum
资金
- JSPS KAKENHI, Japan [JP26240101, JP26253026, JP26670202, JP15H05276, JP16K15266]
- Global Health Innovative Technology Fund [G2013-105]
- Japan Agency for Medical Research and Development, AMED
- Strategic Promotion of International Cooperation to Accelerate Innovation in Africa by MEXT
- Grants-in-Aid for Scientific Research [16K08765] Funding Source: KAKEN
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.
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