title: Molecular epidemiology of Plasmodium vivax in Latin America: polymorphism and evolutionary relationships of the circumsporozoite gene.
abstract: BACKGROUND
  The 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.
  
  
  METHODS
  Plasmodium 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.
  
  
  RESULTS
  Four 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.
  
  
  CONCLUSIONS
  The 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.
authors.affiliation: Centro Regional de Investigación en Salud Pública, Instituto Nacional de Salud Pública, Tapachula, Chiapas, Mexico. lgonzal@insp.mx
authors.forename: Lilia
authors.initials: L
authors.lastname: González-Cerón
authors.forename: Jesus
authors.initials: J
authors.lastname: Martinez-Barnetche
authors.forename: Ciro
authors.initials: C
authors.lastname: Montero-Solís
authors.forename: Frida
authors.initials: F
authors.lastname: Santillán
authors.forename: Aida M
authors.initials: AM
authors.lastname: Soto
authors.forename: Mario H
authors.initials: MH
authors.lastname: Rodríguez
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Espinosa
authors.forename: Octavio A
authors.initials: OA
authors.lastname: Chávez
mesh_terms: D016000:Cluster Analysis; D016054:DNA, Protozoan / Q000737:chemistry / Q000235:genetics; D005838:Genotype; D006801:Humans; D016780:Malaria, Vivax / Q000453:epidemiology* / Q000469:parasitology*; D008800:Mexico / Q000453:epidemiology; D017720:Molecular Epidemiology; D008969:Molecular Sequence Data; D009527:Nicaragua / Q000453:epidemiology; D010568:Peru / Q000453:epidemiology; D010966:Plasmodium vivax / Q000145:classification* / Q000235:genetics* / Q000302:isolation & purification; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D015800:Protozoan Proteins / Q000235:genetics*; D017422:Sequence Analysis, DNA; D017385:Sequence Homology
chemical_list: D016054:DNA, Protozoan; D015800:Protozoan Proteins; C041595:circumsporozoite protein, Protozoan