The molecular basis of antimalarial drug resistance in Plasmodium vivax

Highlights

• Drug resistance is emerging in Plasmodium vivax, an important cause of malaria.

• The complex biology of P. vivax and the limited range of research tools make it difficult to identify drug resistance.

• The molecular mechanisms of drug resistance in P. vivax remain elusive.

• This review highlights the extent of drug resistance, the putative mechanisms of resistance and new technologies for the study of P. vivax drug resistance.

Abstract

Plasmodium vivax is the most geographically widespread cause of human malaria and is responsible for the majority of cases outside of the African continent. While great progress has been made towards eliminating human malaria, drug resistant parasite strains pose a threat towards continued progress. Resistance has arisen to multiple antimalarials in P. vivax, including to chloroquine, which is currently the first line therapy for P. vivax in most regions. Despite its importance, an understanding of the molecular mechanisms of drug resistance in this species remains elusive, in large part due to the complex biology of P. vivax and the lack of in vitro culture. In this review, we will cover the extent and challenges of measuring clinical and in vitro drug resistance in P. vivax. We will consider the roles of candidate drug resistance genes. We will highlight the development of molecular approaches for studying P. vivax biology that provide the opportunity to validate the role of putative drug resistance mutations as well as identify novel mechanisms of drug resistance in this understudied parasite. Validated molecular determinants and markers of drug resistance are essential for the rapid and cost-effective monitoring of drug resistance in P. vivax, and will be useful for optimizing drug regimens and for informing drug policy in control and elimination settings.