Radical cure

Photo: Cristina Donini/MMV

What is P. vivax radical cure?

Radical cure requires the administration of a combination therapy (blood stage treatment in combination with liver stage treatment) to clear all parasites.

  • Blood stage treatment: Chloroquine, or in areas where chloroquine resistance is prevalent, artemisinin-based combination therapy (ACT) to clear blood stages.
  • Liver stage treatment: An 8-aminoquinoline, either primaquine or tafenoquine to clear hypnozoites in the liver.

At present, some patients with P. vivax malaria receive only chloroquine, leaving them vulnerable to repeated relapses. In many regions, a high proportion of P. vivax malaria prevalence can be attributed to relapses following activation of dormant hypnozoites, which contribute to onward transmission (see P. vivax relapses).

Expanded access to P. vivax radical cure is critical to reducing malaria burden and reaching malaria elimination targets.

Challenges for universal access to P. vivax radical cure

There are three main technical barriers to universal access of P. vivax radical cure.

Adherence:

The standard recommended regimen for primaquine, which clears hypnozoites in the liver, lasts for 14 days.1  Adherence to this regimen is difficult, especially when patients normally feel well following the 3-day course of chloroquine or an ACT. For this reason, it is often not prescribed. Tafenoquine, a single-dose 8-aminoquinoline, which was approved by the US FDA and Australian TGA in 2018, should improve adherence.

G6PD deficiency:

The use of primaquine or tafenoquine causes dose-dependent haemolysis in individuals with the enzyme disorder glucose-6-phosphate dehydrogenase deficiency (G6PD). G6PD-deficient individuals must be identified and excluded from 8-aminoquinoline therapy. Suitable point-of-care diagnostics to reliably identify G6PD-deficient patients at risk of haemolysis have been lacking, but new diagnostics are being developed to support tafenoquine deployment.

Contraindications:

The exclusion of a significant proportion of the population from access to radical cure due to contraindications to liver stage treatments undermines the potential for interrupting transmission caused by P. vivax relapse and achieving elimination . This remains a key objective for further drug and vaccine development.3