A shorter course for anti-relapse therapy against vivax malaria.

14 Sep 2019
Rosenthal PJ

Although Plasmodium falciparum causes the greatest number of global malaria infections and deaths, the impact of infection with Plasmodium vivax, the dominant human malaria parasite outside of Africa, is large, with an estimated 7·4 million cases in 2017.

A particular challenge with P vivax infection is hypnozoites: dormant liver-stage parasites that are not eliminated by standard antimalarial treatments. Hypnozoites do not cause clinical illness, but without therapy that targets them, P vivax infections will commonly relapse, with recurrent symptomatic blood-stage infections weeks to months after the primary infection. By enabling recurrent episodes of malaria and ongoing transmission, P vivax relapses contribute substantially to the burden of malaria and make malaria eradication more difficult.

Standard therapy to eliminate P vivax hypnozoites is primaquine administered daily for 2 weeks, beginning soon after initiation of primary therapy to eliminate asexual parasites. Primaquine is generally well tolerated, but achieving compliance with a 2-week regimen is difficult. Furthermore, primaquine has dose-dependent toxicity in those with glucose-6-phosphate dehydrogenase (G6PD) deficiency, the most common human enzymopathy, with the potential for lethal haemolysis.

Recommendations for primaquine to treat P vivax infection with or without prior G6PD testing vary around the world, but because of low expectations for full compliance, cost concerns, high risks of reinfection, and the difficulty of testing for G6PD deficiency prior to therapy, most patients presenting with P vivax infection do not receive anti-relapse therapy.