Abstract
BackgroundThe 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 presentationThree 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.ConclusionLack 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.
Highlights
The relapsing nature of Plasmodium vivax infection is a major barrier to its control and elimination
Lack of response to primaquine was associated with impaired cytochrome P450 2D6 (CYP2D6) activity in three patients pre‐ senting multiple relapses followed in a non-endemic setting
It was recently described that the cytochrome P450 2D6 (CYP2D6) pathway mediates the activation of primaquine into active phenolic metabolite(s) in hepatocytes [12, 13] and some genetic polymorphisms implied in reduced primaquine metabolism have been associated with a higher risk of relapse [14,15,16,17]
Summary
Lack of response to primaquine was associated with impaired CYP2D6 activity in three patients pre‐ senting 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
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