In the current study, the genetic diversity of the
P. vivax merozoite surface protein 1 gene was investigated in field isolates from vivax malaria patients in a high transmission area of the Republic of Korea (ROK) as a continuation of two previous reports [
27,
28]. In order to compare the genetic structure of the ROK isolates, sequences from Block 5 were analysed, a variable region of PvMSP-1. After the PvMSP-1 Sal-1 type and Belem type were first reported in 2000 and 2003, respectively, all three strains of
P. vivax (Sal-1, Belem, and recombinant types) were found in 2011–2013. Interestingly, a PvMSP-1 S-b like type, containing p.G725E, which changes glycine to glutamic acid, was found in an isolate collected in 2013. It seems likely that genetic recombination resulting in a single nucleotide polymorphism (SNP) occurred in the PvMSP-1 gene, because PvMSP-1 is a highly polymorphic antigen [
29]. Moreover, the
P. vivax recombinant type increased in the later years (2012 and 2013) compared with 2011, which is likely a result of genetic recombination or a crossing of
P. vivax Sal-1 and Belem types. However, co-infection of PvMSP-1 Sal-1 and Belem types in a single sample was not observed, which could have indicated the possibility of crossing of the
P. vivax types. That might be due to the fact this genotyping that used simple PCR methods and followed sequencing analysis tends to amplify only the dominant type. Therefore, further polyclonal infection studies should be done using microsatellite or pyrosequencing analysis, which are known to be capable of identifying mixed infections. In addition, only the original PvMSP-1 recombinant type (10×Q) appeared during the three-year period (2011–2013), whereas high levels of polymorphism in the number of Q repeats were observed in 2010 (12×Q, 14×Q, and 27×Q). Although the regions of sample collection were the same, the new subtypes with different numbers of Q residue repeats were not observed during the recent sample collection period. This indicates that the 12×Q, 14×Q, and 27×Q subtypes did not become established and subsequently disappeared from the
P. vivax population of the ROK, like the S-c and B-2 subtypes only in 2003 and 2006, respectively. This also suggests that transmission might not be dynamic in the ROK. This finding was supported by a microsatellite study of ROK isolates suggesting continuous introduction of
P. vivax variants into the ROK from other parasite population sources, especially from DPRK [
30,
31].
Vivax malaria in the ROK is characterized by a long latent infection. The incubation period of a primary infection of vivax malaria is 7–30 days; however, in the ROK, the disease sometimes does not show an onset of symptoms until several months after the initial infection by mosquito bites [
32]. Therefore, in the present study, samples were divided into short (July–August) and long (January–May) latent periods using an arbitrary definition. And then,
P. vivax isolates were analysed in order to determine the dominant strains involved in both the short and long latent periods of vivax malaria. To date, the major
P. vivax strains inducing the short or long latent periods of vivax malaria have not been investigated. This study, using field isolates of the short and long latent periods, showed that
P. vivax of the PvMSP-1 recombinant type was dominant in the long latent period isolates. This finding was consistent over three successive years (2011–2013). Based on this result, it is likely that this specific
P. vivax strain easily induces long latency and the development of the hypnozoite. However, further broad surveillance studies would be necessary in order to verify this finding.
The merozoite surface protein 1 is one of the most studied vaccine candidates of vivax malaria. High genetic polymorphism within PvMSP-1 has been reported in other countries. In addition, the genetic diversity has increased over the past decade from two genotypes to six found in the ROK. This allelic polymorphism is one of the greatest hurdles to inducing a protective immune response against the genetically diverse P. vivax because amino acid variations can affect the immunogenic properties of antigens. Therefore, continuous research will be necessary to determine the impact of antigenic diversification on the immunogenicity of the PvMSP-1 antigen in natural populations.