Temporal Changes in the Genetic Diversity of Plasmodium vivax Merozoite Surface Protein-1 in Myanmar

Despite a significant decline in the incidence of malaria in Myanmar recently, malaria is still an important public health concern in the country. Although Plasmodium falciparum is associated with the highest incidence of malaria in Myanmar, the proportion of P. vivax cases has shown a gradual increase in recent years. The genetic diversity of P. vivax merozoite surface protein-1 block 5-6 (pvmsp-1 ICB 5-6) in the P. vivax population of Myanmar was analyzed to obtain a comprehensive insight into its genetic heterogeneity and evolutionary history. High levels of genetic diversity of pvmsp-1 ICB 5-6 were identified in the P. vivax isolates collected from Myanmar between 2013 and 2015. Thirty-nine distinct haplotypes of pvmsp-1 ICB 5-6 (13 for Sal I type, 20 for recombinant type, and 6 for Belem type) were found at the amino acid level. Comparative analyses of the genetic diversity of pvmsp-1 ICB 5-6 sequences in the recent (2013–2015) and the past (2004) P. vivax populations in Myanmar revealed genetic expansion of the pvmsp-1 ICB 5-6 in recent years, albeit with a declined incidence. The recent increase in the genetic heterogeneity of Myanmar pvmsp-1 ICB 5-6 is attributed to a combination of factors, including accumulated mutations and recombination. These results suggest that the size of the P. vivax population in Myanmar is sufficient to enable the generation and maintenance of genetic diversity, warranting continuous molecular surveillance of genetic variation in Myanmar P. vivax.

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

Background: Circumsporozoite surface protein (CSP) of malaria parasites has been recognized as one of the leading vaccine candidates. Clinical trials of vaccines for vivax malaria incorporating Plasmodium vivax CSP (PvCSP) have demonstrated their effectiveness in preventing malaria, at least in part. However, genetic diversity of PvCSP in the natural population is still a major concern. Methods: A total of 171 blood samples collected from patients infected with Plasmodium vivax in Myanmar analysed in this study. The gene for PvCSP was amplified by polymerase chain reaction, followed by T&A cloning and sequencing. Polymorphic characteristics and natural selection of Myanmar PvCSP population in Myanmar were analysed using DNASTAR, MEGA6 and DnaSP programs. The polymorphic pattern and natural selection of publicly accessible global PvCSP sequences were also comparatively analysed. Results: Myanmar PvCSP sequences were divided into two subtypes VK210 and VK247 comprising 143 and 28 sequences, respectively. The VK210 subtypes showed higher levels of genetic diversity and polymorphism than the VK247 subtypes. The N-terminal non-repeat region of PvCSP displayed limited genetic variations in the global population. Different patterns of octapeptide insertion (ANKKAEDA in VK210 and ANKKAGDA in VK247) and tetrapeptide repeat motif (GGNA) were identified in the C-terminal region of global PvCSP population. Meanwhile, the central repeat region (CRR) of Myanmar and global PvCSP, both in VK210 and VK247 variants, was highly polymorphic. The high level of genetic diversity in the CRR has been attributed to the different numbers, types and combinations of peptide repeat motifs (PRMs). Interestingly, 27 and 5 novel PRMs were found in Myanmar VK210 and VK247 variants, respectively. Conclusion: Comparative analysis of the global PvCSP population suggests a complex genetic profile of PvCSP in the global population. These results widen understanding of the genetic make-up of PvCSP in the global P. vivax population and provide valuable information for the development of a vaccine based on PvCSP.

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

Background: Circumsporozoite surface protein (CSP) of malaria parasites has been recognized as one of the leading vaccine candidates. Clinical trials of vaccines for vivax malaria incorporating Plasmodium vivax CSP (PvCSP) have demonstrated their effectiveness in preventing malaria, at least in part. However, genetic diversity of PvCSP in the natural population is still a major concern.Methods: A total of 171 blood samples collected from patients infected with Plasmodium vivax in Myanmar analysed in this study. The gene for PvCSP was amplified by polymerase chain reaction, followed by T&A cloning and sequencing. Polymorphic characteristics and natural selection of Myanmar PvCSP population in Myanmar were analysed using DNASTAR, MEGA6 and DnaSP programs. The polymorphic pattern and natural selection of publicly accessible global PvCSP sequences were also comparatively analysed.Results: Myanmar PvCSP sequences were divided into two subtypes VK210 and VK247 comprising 143 and 28 sequences, respectively. The VK210 subtypes showed higher levels of genetic diversity and polymorphism than the VK247 subtypes. The N-terminal non-repeat region of PvCSP displayed limited genetic variations in the global population. Different patterns of octapeptide insertion (ANKKAEDA in VK210 and ANKKAGDA in VK247) and tetrapeptide repeat motif (GGNA) were identified in the C-terminal region of global PvCSP population. Meanwhile, the central repeat region (CRR) of Myanmar and global PvCSP, both in VK210 and VK247 variants, was highly polymorphic. The high level of genetic diversity in the CRR has been attributed to the different numbers, types and combinations of peptide repeat motifs (PRMs). Interestingly, 27 and 5 novel PRMs were found in Myanmar VK210 and VK247 variants, respectively.Conclusion: Comparative analysis of the global PvCSP population suggests a complex genetic profile of PvCSP in the global population. These results widen understanding of the genetic make-up of PvCSP in the global P. vivax population and provide valuable information for the development of a vaccine based on PvCSP.