Temporal genetic changes in Plasmodium vivax apical membrane antigen 1 over 19 years of transmission in southern Mexico.

Background: Mexico advanced to the pre-elimination phase in 2009 due to a significant reduction in malaria cases, and since 2000, Plasmodium vivax is the only species transmitted. During the last two decades, malaria transmission has been mostly local and isolated to a few regions. Hence, the aim of the current study was to determine detailed changes in P. vivax genetic diversity and population structure based on analyzing the gene that encodes the apical membrane antigen 1 (pvama1). This analysis covered from control to pre-elimination (1993-2011) in a hypo-endemic region in southern Mexico. Materials and Methods: From 213 P. vivax infected bloods, a nucleotide fragment containing theama1 gen domains I-II (pvama1I-II) was used to estimate parameters of diversity, recombination and natural selection. To make comparison through time, parasite isolates were arbitrarily grouped into periods of three years. Temporal haplotype networks and population structure were carried out.Results: The pvama1I-IIsequences showed low genetic diversity, with 15 haplotypes resolved. Among the DNA sequences, there was a gradual decrease in genetic diversity, the number of mixed genotype infections and the intensity of positive selection, in agreement with the parallel decline inmalaria cases. At the same time, linkage disequilibriumincreased. The three-dimensionalhaplotype network revealed that pvama1I-IIhaplotypes were separated by 1-11 mutationalsteps, and between one another by 0-3 unsampled haplotypes. In the temporal network, seven haplotypes were detected in at least two of the six time layers, and only four distinct haplotypes were evidenced in the pre-elimination phase. Structure analysis indicated thatthree subpopulations fluctuated over time. Only 8.5% of the samples had mixed ancestry. In the pre-elimination phase, subpopulation P1 was drastically reduced and admixture wasabsent. Conclusions: The results suggest that P. vivax in southern Mexico evolved based on local adaptation into three “pseudoclonal” subpopulations that diversified at the regional level and persisted over time, although with varying frequency. Control measures and climactic events influenced the number of malaria cases and the genetic structure. The sharp decrease in parasite diversity and other related genetic parameters during the pre-elimination phase suggests that malaria elimination is possible in the near future.