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

• Published in: Malaria Journal
• Main Authors: 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, André M. Siqueira
• Format: Article in Journal/Newspaper
• Language: English
• Published: BMC 2021
• Subjects: Plasmodium vivax; Relapses; CYP2D6; Primaquine; Radical cure; Arctic medicine. Tropical medicine; RC955-962; Infectious and parasitic diseases; RC109-216; Arctic
• Online Access: https://doi.org/10.1186/s12936-021-03869-x; https://doaj.org/article/7d5e7ecc972b45aa8ef5c1e69c464f3a

Abstract Background 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. Cases presentation Three patients diagnosed with P. vivax malaria presented repeated relapses after being initially treated with chloroquine (25 mg/kg) and primaquine (3.5 mg/kg in 14 days) at a non-endemic travel clinic. Recurring episodes were subsequently treated with a higher dose of primaquine (7 mg/kg in 14 days), which prevented further relapses in two patients. However, one patient still presented two episodes after a higher primaquine dose and was prescribed 300 mg of chloroquine weekly to prevent further episodes. Impaired CYP2D6 function was observed in all of them. Conclusion Lack of response to primaquine was associated with impaired CYP2D6 activity in three patients presenting multiple relapses followed in a non-endemic setting. Higher primaquine dosage was safe and effectively prevented relapses in two patients and should be further investigated as an option in Latin America. It is crucial to investigate the factors associated with unsuccessful radical cures and alternative therapeutic options.