Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2838327 | Trends in Molecular Medicine | 2015 | 13 Pages |
Plasmodium vivax is the most widespread human malaria parasite, but has received much less attention than Plasmodium falciparum during the past 50 years of research. Plasmodium vivax was historically seen as causing only benign disease, but this view has recently changed, with increased recognition of the burden of vivax malaria, as well as numerous case reports of severe malaria or death caused by this parasite. The complexity of P. vivax biology is characteristic of specific features of the parasite, and recent years have seen major progress in our understanding of this complexity. In this review, we analyze the latest advances in the field, describing the constraints that the unique features of P. vivax place on drug treatments aimed at controlling or eliminating it.
TrendsThe cell tropism of Plasmodium vivax is narrower than previously thought, being restricted to young reticulocytes displaying high levels of CD71 expression, and rendering the establishment of continuous in vitro parasite cultures difficult.Primaquine, the only licensed antihypnozoite drug capable of preventing relapses of P. vivax malaria, may cause acute hemolysis in G6PD-deficient patients and its efficacy is also compromised by CYP2D6 polymorphisms, an enzyme that normally transforms the drug into its active metabolites in humans.Failure of chloroquine treatment for P. vivax infections is no longer limited to the Papua-Indonesia area and is prevalent in many endemic areas, including Southeast Asia and South America. However, the mechanisms of drug resistance in vivax remain unknown.Despite the lack of in vitro culture methods for P. vivax, short-term cultures established with ex vivo parasites and reticulocyte-rich preparations from human cord blood can be used to evaluate the efficacy of blood-stage parasite vaccines.Humanized mouse models and in vitro hepatocyte cultures are paving the way for P. vivax liver-stage drug and vaccine discovery.