Publication:
Pharmacogenetic assessment of tafenoquine efficacy in patients with Plasmodium vivax malaria

Issued Date

2020-09-01

Resource Type

Article

ISSN

17446880

DOI

10.1097/FPC.0000000000000407

Other identifier(s)

2-s2.0-85089302162

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Mahidol University

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SCOPUS

Bibliographic Citation

Pharmacogenetics and genomics. Vol.30, No.7 (2020), 161-165

Suggested Citation

Pamela L. St Jean, Gavin C.K.W. Koh, John J. Breton, Fe E.J. Espino, Tran T. Hien, Srivicha Krudsood, Marcus V.G. Lacerda, Alejandro Llanos-Cuentas, Chanthap Lon, Rezika Mohammed, Chayadol S. Namaik-Larp, Dhelio B. Pereira, David L. Saunders, Ivan D. Velez, Daniel Yilma, Maria F. Villegas, Stephan Duparc, Justin A. Green Pharmacogenetic assessment of tafenoquine efficacy in patients with Plasmodium vivax malaria. Pharmacogenetics and genomics. Vol.30, No.7 (2020), 161-165. doi:10.1097/FPC.0000000000000407 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/57685

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Title

Pharmacogenetic assessment of tafenoquine efficacy in patients with Plasmodium vivax malaria

Author(s)

Pamela L. St Jean
 Gavin C.K.W. Koh
 John J. Breton
 Fe E.J. Espino
 Tran T. Hien
 Srivicha Krudsood
 Marcus V.G. Lacerda
 Alejandro Llanos-Cuentas
 Chanthap Lon
 Rezika Mohammed
 Chayadol S. Namaik-Larp
 Dhelio B. Pereira
 David L. Saunders
 Ivan D. Velez
 Daniel Yilma
 Maria F. Villegas
 Stephan Duparc
 Justin A. Green

Other Contributor(s)

Oxford University Clinical Research Unit
 GlaxoSmithKline, USA
 PAREXEL International
 University of Gondar
 Gokila
 Universidad Peruana Cayetano Heredia
 Jimma University
 Fundacao de Medicina Tropical do Amazonas
 Universidad de Antioquia
 GlaxoSmithKline plc.
 Armed Forces Research Institute of Medical Sciences, Thailand
 Mahidol University
 Centro de Investigaciones Clínicas
 Medicines for Malaria Venture
 Umphang Hospital
 Centro de Pesquisa em Medicina Tropical

Abstract

Plasmodium vivax has the largest geographic range of human malaria species and is challenging to manage and eradicate due to its ability to establish a dormant liver stage, the hypnozoite, which can reactivate leading to relapse. Until recently, the only treatment approved to kill hypnozoites was the 8-aminoquinoline, primaquine, requiring daily treatment for 14 days. Tafenoquine, an 8-aminoquinoline single-dose treatment with activity against P. vivax hypnozoites, has recently been approved by the US Food and Drug Administration and Australian Therapeutic Goods Administration for the radical cure of P. vivax malaria in patients 16 years and older. We conducted an exploratory pharmacogenetic analysis (GSK Study 208099) to assess the role of host genome-wide variation on tafenoquine efficacy in patients with P. vivax malaria using data from three GSK clinical trials, GATHER and DETECTIVE Part 1 and Part 2. Recurrence-free efficacy at 6 and 4 months and time to recurrence up to 6 months postdosing were analyzed in 438 P. vivax malaria patients treated with tafenoquine. Among the approximately 10.6 million host genetic variants analyzed, two signals reached genome-wide significance (P value ≤ 5 × 10). rs62103056, and variants in a chromosome 12 intergenic region, were associated with recurrence-free efficacy at 6 and 4 months, respectively. Neither of the signals has an obvious biological rationale and would need replication in an independent population. This is the first genome-wide association study to evaluate genetic influence on response to tafenoquine in P. vivax malaria.

Keyword(s)

Biochemistry, Genetics and Molecular Biology
 Medicine

Availability

URI

https://repository.li.mahidol.ac.th/handle/123456789/57685

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Scopus 2020