Infection by Plasmodium vivax poses unique challenges for diagnosis and treatment. Relatively low numbers of parasites in peripheral circulation may be difficult to confirm, and patients infected by dormant liver stages cannot be diagnosed before activation and the ensuing relapse. Radical cure thus requires
therapy aimed at both the blood stages of the parasite (blood schizontocidal) and prevention of subsequent relapses (hypnozoitocidal).
Chloroquine and
primaquine have been the companion
therapies of choice for the treatment of
vivax malaria since the 1950s. Confirmed resistance to
chloroquine occurs in much of the vivax endemic world and demands the investigation of alternative blood schizontocidal companions in radical cure. Such a shift in practice necessitates investigation of the safety and efficacy of
primaquine when administered with those
therapies, and the toxicity profile of such combination treatments, particularly in patients with
glucose-6-phosphate dehydrogenase deficiency. These clinical studies are confounded by the frequency and timing of relapse among strains of P. vivax, and potentially by differing susceptibilities to
primaquine. The inability to maintain this parasite in continuous in vitro culture greatly hinders new
drug discovery. Development of safe and effective
chemotherapies for
vivax malaria for the coming decades requires overcoming these challenges.