Molecular epidemiology of Plasmodium vivax in Latin America: polymorphism and evolutionary relationships of the circumsporozoite gene

Abstract

BackgroundThe origins and dispersal of Plasmodium vivax to its current worldwide distribution remains controversial. Although progress on P. vivax genetics and genomics has been achieved worldwide, information concerning New World parasites remains fragmented and largely incomplete. More information on the genetic diversity in Latin America (LA) is needed to better explain current patterns of parasite dispersion and evolution.MethodsPlasmodium vivax circumsporozoite protein gene polymorphism was investigated using polymerase chain reaction amplification and restriction fragment length polymorphism (PCR-RFLP), and Sanger sequencing in isolates from the Pacific Ocean coast of Mexico, Nicaragua, and Peru. In conjunction with worldwide sequences retrieved from the Genbank, mismatch distribution analysis of central repeat region (CRR), frequency estimation of unique repeat types and phylogenetic analysis of the 3′ terminal region, were performed to obtain an integrative view of the genetic relationships between regional and worldwide isolates.ResultsFour RFLP subtypes, vk210a, b, c and d were identified in Southern Mexico and three subtypes vk210a, e and f in Nicaragua. The nucleotide sequences showed that Mexican vk210a and all Nicaraguan isolates were similar to other American parasites. In contrast, vk210b, c and d were less frequent, had a domain ANKKAEDA in their carboxyl end and clustered with Asian isolates. All vk247 isolates from Mexico and Peru had identical RFLP pattern. Their nucleotide sequences showed two copies of GGQAAGGNAANKKAGDAGA at the carboxyl end. Differences in mismatch distribution parameters of the CRR separate vk247 from most vk210 isolates. While vk247 isolates display a homogeneous pattern with no geographical clustering, vk210 isolates display a heterogeneous geographically clustered pattern which clearly separates LA from non-American isolates, except vk210b, c and d from Southern Mexico.ConclusionsThe presence of vk210a in Mexico and vk210e, f and g in Nicaragua are consistent with other previously reported LA isolates and reflect their circulation throughout the continent. The vk210b, c and d are novel genotypes in LA. Their genetic relationships and low variability within these vk210 and/or within the vk247 parasites in Southern Mexico suggest its recent introduction and/or recent expansion to this region. The global analysis of P. vivax csp suggests this parasite introduction to the region and likely LA by different independent events.

Genetic Characterization of Plasmodium vivax Isolates from Pakistan Using Circumsporozoite Protein (PvCSP) and Merozoite Surface Protein-1 (PvMSP-1) Genes as Genetic Markers

“…The results of PvCSP uphold the ndings of the previously published results showing that VK210 strain is predominant type with the prevalence rate ranging between 81-100% [9,12,14,36]. There are few malaria endemic areas where VK247 isolates are commonly present [37,38]. In the present study, the translated nucleotide sequences suggested that there were peptide repetitive motifs in which GDRADGQPA (PRM1) and GDRAAGQPA (PRM2) which found to be the two major PRMs.…”

Frequency of Plasmodium vivax circumsporozoite protein genotypes in humans and anopheline mosquitoes in an endemic area of southeastern Pará State, Brazil

“…This could lead to higher parasitemia as well as more severe clinical conditions. Although the VK247 variant is ancestral and its CSP repeat region is more stable than that of VK210 42 , the distribution of this genotype can be quite heterogeneous in other regions of Brazilian Amazon, most likely due to the absence or presence of VK247 polymorphisms in different locations and this fact may be related to changes in the geographical distribution profile of this variant 37,43 .…”

“…This profile change may be related to the evolution of P. vivax. González-Cerón et al 37 observed in samples of P. vivax from Mexico, Nicaragua, and Peru that the genetic diversity of the CSP gene is restricted mainly to the central repeat domain and 3'-terminal portion. These authors also stressed that this variation occurs due to changes in the type of nucleotides and number of repeats of the repeat region.…”

Genetic structure of Plasmodium vivax using the merozoite surface protein 1 icb5-6 fragment reveals new hybrid haplotypes in southern Mexico

“…Accordingly, pvs25 and pvs28 [9], and the csp [56] genes of P. vivax from southern Mexico were found close related to parasites from Iran and Eastern Asia and probably much of the gene pool of Mexico has been provided by genotypes of these countries that have suffered continuously migration, which needs further investigation.…”