Chloroquine and mefloquine resistance 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 Plasmodium vivax circumsporozoite surface protein (CSP) is composed of a repetitive sequence that is characterised by three variants: VK210, VK247 and P. vivax -like. The most important challenge in the treatment of P. vivax infection is the possibility of differential response based on the parasite genotype. OBJECTIVES To characterise the CSP variants in P. vivax isolates from individuals residing in a malaria-endemic region in Brazil and to profile these variants based on sensitivity to chloroquine and mefloquine. METHODS The CSP variants were determined by sequencing and the sensitivity of the P. vivax isolates to chloroquine and mefloquine was determined by Deli-test. FINDINGS Although five different allele sizes were amplified, the sequencing results showed that all of the isolates belonged to the VK210 variant. However, we observed substantial genetic diversity in the CRR, resulting in the identification of 10 different VK210 subtypes. The frequency of isolates that were resistant to chloroquine and mefloquine was 11.8 and 23.8%, respectively. However, we did not observe any difference in the frequency of the resistant isolates belonging to the VK210 subtypes. MAIN CONCLUSION The VK210 variant is the most frequently observed in the studied region and there is significant genetic variability in the CRR of the P. vivax CSP. Moreover, the antimalarial drug sensitivity profiles of the isolates does not seem to be related to the VK210 subtypes.

Genetic polymorphism and natural selection of circumsporozoite protein in Myanmar Plasmodium vivax

“…Among the three PvCSP allelic variants, only two allelic variants, VK210 and VK247, were identified in P. vivax isolates from Myanmar analysed in this study. The VK210 was the dominant allele occurring in 83.6% of Myanmar PvCSP population, which is consistent with previous studies reporting that VK210 is the most common allelic variant in the PvCSP populations from Iran, India, China, Brazil, Thailand, Bangladesh, and Azerbaijan [22][23][24][25][26][27][28][29][30]. Meanwhile, VK247 was more prevalent in certain regions of Colombia [31].…”

Genetic polymorphism and natural selection of circumsporozoite protein in Myanmar Plasmodium vivax

“…Among the three pvcsp allelic variants, only two allelic variants, VK210 and VK247, were identi ed in P. vivax isolates from Myanmar analysed in this study. The VK210 was the dominant allele occurring in 83.6% of Myanmar pvcsp population, which is consistent with previous studies reporting that VK210 is the most common allelic variant in the pvcsp populations from Iran, India, China, Brazil, Thailand, Bangladesh, and Azerbaijan [23][24][25][26][27][28][29][30][31]. Meanwhile, VK247 was more prevalent in certain regions of Colombia [32].…”

Balancing selection and high genetic diversity of Plasmodium vivax circumsporozoite central region in parasites from Brazilian Amazon and Rio de Janeiro Atlantic Forest

“…On the other hand, the allotype 3, considered a T-helper cell epitope, revealed an “excess” of nonsynonymous substitutions in the great majority of the samples. The low Sal-1 allotype 3 frequency has already been reported in China [ 63 ], Mexico [ 69 ], Sudan [ 61 ], and also in Brazil [ 27 , 28 , 71 ]. Thus, it is reasonable to speculate that such nonsynonymous polymorphisms are not essential for P .…”