The prevention and treatment of Plasmodium vivax malaria

Summary points

• The worldwide burden of Plasmodium vivax malaria has more than halved from an estimated 17.3 to 6.5 million cases between 2010 and 2019. This resulted from increased deployment of conventional malaria control measures (rapid diagnostic tests, effective antimalarial treatment, vector control) and significant global investment in malaria elimination. There is no generally available P. vivax vaccine, nor is there likely to be one in the near future.
• The latest-generation RDTs used for P. vivax diagnosis have sensitivities comparable to microscopy. Ultrasensitive PCR methods which can detect parasite densities as low as 28/ml have revealed a much higher prevalence of asymptomatic P. vivax infection in malaria endemic regions than previously estimated.
• Chloroquine remains an effective schizonticide for vivax malaria, except in Indonesia, Sabah and Papua New Guinea where there is high-level chloroquine resistance. Artemisinin combination therapies are effective alternative schizonticides that unify the treatment of all malarias. Relapses contribute significantly to the burden of P. vivax infections. Prevention of relapse requires “radical cure” with an 8-aminoquinoline (primaquine daily for 7 to 14 days, or single-dose tafenoquine). These drugs cause oxidant haemolysis in G6PD deficiency, so safe use requires G6PD testing. Overall, the risks of primaquine haemolysis have been overemphasised and the benefits of relapse prevention underappreciated.
• Qualitative screening tests for G6PD deficiency (detecting <30% normal enzyme activity) are adequate for screening before giving primaquine for radical cure, but a quantitative point of care G6PD test to detect <70% normal enzyme activity is needed for tafenoquine.
• Radical curative efficacy depends on the total 8-aminoquinoline dose given; higher primaquine doses (7 mg base/kg rather than 3.5 mg base/kg) are required in parts of Southeast Asia and Oceania. The currently recommended dose of tafenoquine (300 mg) is sub-optimal. In low transmission settings, elimination of vivax malaria is possible with current tools.