The global public health significance of Plasmodium vivax.

Plasmodium vivax occurs globally and thrives in both temperate and tropical climates. Here, we review the evidence of the biological limits of its contemporary distribution and the global population at risk (PAR) of the disease within endemic countries. We also review the most recent evidence for the endemic level of transmission within its range and discuss the implications for burden of disease assessments. Finally, the evidence-base for defining the contemporary distribution and PAR of P. vivax are discussed alongside a description of the vectors of human malaria within the limits of risk. This information along with recent data documenting the severe morbid and fatal consequences of P. vivax infection indicates that the public health significance of P. vivax is likely to have been seriously underestimated.

Diagnosis and treatment of Plasmodium vivax malaria.

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.