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Increased primaquine total dose prevents Plasmodium vivax relapses in patients with impaired CYP2D6 activity: report of three cases

August 18, 2021 - 16:20 -- Open Access
Anielle de Pina-Costa, Ana Carolina Rios Silvino, Edwiges Motta dos Santos, Renata Saraiva Pedro, José Moreira, Gabriela Liseth Umana, Ana Danielle Tavares da Silva, Otília Helena Lupi da Rosa Santos, Karina Medeiros de Deus Henriques, Cláudio Tadeu Daniel-Ribeiro, Patrícia Brasil, Tais Nobrega Sousa and André M. Siqueira
Malaria Journal 2021 20:341, 14 August 2021

The relapsing nature of Plasmodium vivax infection is a major barrier to its control and elimination. Factors such as adequate dosing, adherence, drug quality, and pharmacogenetics can impact the effectiveness of radical cure of P. vivax and need to be adequately evaluated. CYP2D6 pathway mediates the activation of primaquine (primaquine) into an active metabolite(s) in hepatocytes, and impaired activity has been linked to a higher risk of relapse.

Not Open Access | Impact of CYP2D6 Genetic Variation on Radical Cure of Plasmodium vivax Malaria

June 1, 2021 - 15:45 -- NOT Open Access
Suarez-Kurtz G
Clin Pharmacol Ther. 2021 May 27

Plasmodium vivax is the most widespread human malaria parasite, with 2.5 billion people at risk of infection worlwide. P. vivax forms liver hypnozoites which trigger further symptomatic episodes (relapses) weeks or months after the initial episode. Radical cure of vivax malaria requires hypnozoitocide therapy to prevent relapses. The two FDA-approved hypnozoiticides for human use, primaquine and tafenoquine, are pro-drugs, that require in vivo conversion into metabolites with redox activity. This mini-review focuses on the association between CYP2D6-mediated hydroxylation and hypnozoiticide efficacy of primaquine and tafenoquine.

The association of CYP2D6 gene polymorphisms in the full-length coding region with higher recurrence rate of vivax malaria in Yunnan Province, China

March 24, 2021 - 14:40 -- Open Access
Herong Huang, Ying Dong, Yanchun Xu, Yan Deng, Canglin Zhang, Shuping Liu, Mengni Chen and Yan Liu
Malaria Journal 2021 20:160, 20 March 2021

Accumulating evidence suggest that compromised CYP2D6 enzyme activity caused by gene mutation could contribute to primaquine failure for the radical cure of vivax malaria. The current study aims to preliminarily reveal the association between the recurrence of vivax malaria in Yunnan Province and CYP2D6 gene mutation by analysing polymorphisms in the entire coding region of human CYP2D6 gene.

NOT Open Access | Novel insights into Plasmodium vivax therapeutic failure: CYP2D6 activity and time of exposure to malaria modulate the risk of recurrence

March 9, 2020 - 14:21 -- NOT Open Access
Silvino ACR, Kano FS, Costa MA, Fontes CJF, Soares IS, Brito CFA, Carvalho LH, Sousa TN
Antimicrob Agents Chemother. 2020 Mar 2. pii: AAC.02056-19

Plasmodium vivax relapse is one of the major causes of sustained global malaria transmission. Primaquine (PQ) is the only commercial drug available to prevent relapses, and its efficacy is dependent on metabolic activation by cytochrome P450 2D6 (CYP2D6). Impaired CYP2D6 function, caused by allelic polymorphisms, leads to the therapeutic failure of PQ as a radical cure for P. vivax malaria.

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