Therapeutic failure of primaquine and need for new medicines in radical cure of Plasmodium vivax

• Primaquine has been the drug of choice for the prevention of P. vivax relapse.
• Primaquine resistance is unclear and confounded with treatment failure.
• Tafenoquine is the most studied drug in replacing primaquine.
• Availability, adherence, and rational use of primaquine can improve its effectiveness.

Primaquine has been the drug of choice for the prevention of Plasmodium vivax relapse for more than 60 years. Primaquine tolerant strain of P. vivax was identified in 1944. Significant mortality and disease burden of P. vivax calls for the need of new drugs. Primaquine resistance is a complex issue, as the mechanism of resistance is not clear. Direct evidence of resistance to primaquine by hypnozoites has not yet been shown. There are some reports detailing risk of primaquine resistance in specific regions, but the overall distribution of primaquine resistance in P. vivax-infected people is largely unknown. Confounding factors contribute to treatment failures; such as inadequate doses, inappropriate dosing intervals, risk of reinfection, combinations with blood schizontocidals, and compliance. Therefore, primaquine resistance needs to be addressed along with additional important confounding factors. Tafenoquine is the most studied drug in replacing primaquine for the radical cure of P. vivax malaria. It has comparable efficacy with primaquine. The potential advantage of tafenoquine is better compliance with a single dose regimen. Rational use of primaquine can secure its effectiveness, but it is essential in the future to have better or similar alternatives to treat P. vivax.