Beyond pvmdr1 and pvcrt: search for diversity in new Plasmodium vivax genes potentially associated with antimalarial resistance

Drug resistance has been the hallmark of Plasmodium falciparum for over a century. This capability has allowed its expansion worldwide, particularly during the long period after the establishment of established resistance to chloroquine (CQ). P. vivax is the other species known to be able to evade antimalarial drugs. Drug resistance of P. vivax was initially described against antifolates, mediated by mutations in the pvdhfr and pvdhps genes, mirroring the mechanisms previously described in P. falciparum. Resistance to CQ also occurs, which is a growing threat, including in South America. The mechanisms involved show some differences in relation to P. falciparum. In P. vivax, the key gene appears to be pvmdr1, with pvcrt playing a secondary role here. Mixed infections with P. falciparum and P. vivax are treated worldwide with artemisinin combination therapy (ACT). P. vivax is thus frequently exposed to a number of ACTs in addition to CQ and primaquine. More importantly, the use of ACTs, in particular dihydroartemisinin-piperaquine (DHA-PPQ), has been proposed for the treatment of CQ-resistant P. vivax infections. Unfortunately, at least P. falciparum appears capable of rapidly developing resistance against this drug. This ability has been observed since the first experience of large-scale PQ administration in China in the early 1980s. In P. falciparum, the main mechanism of resistance to PPQ in Southeast Asia is the increase in gene copy number pfPM2 and pfPM3, which encode plasmepsins. The question remains whether P. vivax will follow a similar pattern.

Project details

Drug Resistance
Genetics and Genomics
P. vivax

Mar 2021 — Dec 2022

Brazil