Abstract

Plasmodium vivax malaria remained a significant global health burden, affecting approximately 14.3 million 
individuals annually, with its unique dormant hypnozoite stage in the liver presenting substantial challenges for 
complete parasite eradication. The persistent reactivation of these hypnozoites led to recurrent infections that 
compromised patient outcomes and sustained transmission cycles in endemic regions. Primaquine represented the 
only widely available medication capable of targeting hypnozoites for radical cure, yet its use was complicated by 
the risk of potentially life-threatening hemolytic anemia in individuals with glucose-6-phosphate dehydrogenase 
(G6PD) deficiency, an inherited enzymopathy affecting over 400 million people worldwide. This comprehensive 
review examined the biochemical mechanisms underlying primaquine efficacy and G6PD-related toxicity, evaluated 
current diagnostic strategies for G6PD screening, and analyzed the clinical evidence supporting various treatment 
regimens for relapse prevention. A systematic synthesis of peer-reviewed literature published between 2010 and 
2025 was conducted to assess diagnostic accuracy, safety profiles, and therapeutic outcomes. Recent advances in 
point-of-care testing technologies and standardized dosing protocols have substantially improved the risk-benefit 
balance of primaquine administration. Implementation of appropriate G6PD screening before treatment can enable 
safe radical cure while minimizing hemolytic complications, though access to reliable diagnostics remains limited in 
resource-constrained settings where P. vivax is most prevalent