Primaquine compliance

Photo: Cristina Donini

Primaquine is administered orally once a day for 14 days. This lengthy treatment course affects compliance resulting in lower efficacy in real world settings than what has been reported in clinical trials.

Results from several studies show that the efficacy of primaquine in patients who are either not supervised, or partially supervised, is 3 to 4 times lower.1,2,3 In some settings, compliance can be as low as 30% when the patient is not supervised.1

The efficacy of the treatment course can diminish when patients miss as few as 3 doses.1 What complicates the issue is that during the treatment course, typical malaria symptoms such as fever may disappear when the blood stage infection is cleared. This false sense of relief from the disease may deter patients from continuing with the treatment. However, the entire treatment course is required to adequately clear all parasites in the liver (hypnozoites).

A randomized study in which patients who had P. vivax malaria either received primaquine via directly observed therapy (DOT) or self-administered therapy (SAT) revealed that DOT patients were about 6 times less likely to experience the reappearance of P. vivax malaria in comparison to SAT patients after a 90-day follow-up period.2 The study showed that a reason for the re-emergence of P. vivax malaria among SAT patients was that patients did not adhere to the indicated primaquine dosage. The study suggests that if primaquine would be administered to patients by DOT, it would enhance overall effectiveness. DOT, however requires a higher level of health resource utilization.2 Moreover, the current international guidelines for administering primaquine do not endorse DOT.4 

The lack of compliance to primaquine treatment reduces the value that patients can derive from the intervention. This has significant public health implications at the global level. P. vivax relapse limits the gains made towards malaria elimination in many countries. New interventions are urgently required to address this.