Chloroquine and mefloquine chemoresistance profiles are not related to the Circumsporozoite Protein (CSP) VK210 subtypes in field isolates of Plasmodium vivax from Manaus, Brazilian Amazon

Abstract

Background: The central repetitive region (CRR) of the P. vivax Circumsporozoite Surface Protein (CSP) is composed of a repetitive sequence that characterizes three variants: VK210, VK247, and P.vivax-like. An important issue is the possibility of differential response to treatment, depending on the parasite genotype. Objectives: To characterize the CSP variants in P. vivax isolates with different profiles of sensitivity to chloroquine and mefloquine, from individuals living in a Brazilian malariaendemic region. Methods: The determination of CSP variants was performed by sequencing, and the sensitivity of P. vivax isolates to chloroquine and mefloquine was determined by Deli-test. Findings: Five different allele sizes were amplified, but sequencing proved that all isolates were VK210 variant. However, great genetic diversity in CRR was observed, resulting in 10 different VK210 subtypes. The frequency of isolates with a resistance profile for chloroquine and mefloquine were 11.8% and 23.8%, respectively. No difference was observed in frequency of resistant isolates according to VK210 subtypes. Main conclusions: The VK210 variant is the most frequent in the studied region, and there is great genetic variability in the CRR of the P. vivax CSP. Moreover, VK210 subtypes do not seem to mark P. vivax populations with different antimalarial drug sensitivity profiles.