Abstract
Plasmodium vivax apical membrane antigen-1 (PvAMA-1) is an important vaccine candidate for vivax malaria. However, antigenic variation within PvAMA-1 is a major obstacle to the design of a global protective malaria vaccine. In this study, we analyzed the genetic polymorphism and selection of the PvAMA-1 gene from 152 P. vivax isolates from imported cases to China, collected in the China–Myanmar border (CMB) area in Yunnan Province (YP) during 2009–2011 (n = 71) and 2014–2016 (n = 81), in comparison with PvAMA-1 gene information from Myanmar (n = 73), collected from public data. The overall nucleotide diversity of the PvAMA-1 gene from the 152 YP isolates was 0.007 with 76 haplotypes identified (Hd = 0.958). Results from the population structure suggested three groups among the YP and Myanmar isolates with optimized clusters value of K = 7. In addition, YP (2014–2016) isolates generally lacked some K components that were commonly found in YP (2009–2011) and Myanmar. Meanwhile, PvAMA-1 domain I is found to be the dominant target of positive diversifying selection and most mutation loci were found in this domain. The mutation frequencies of D107N/A, R112K/T, K120R, E145A, E277K, and R438H in PvAMA-1 were more than 70% in the YP isolates. In conclusion, high genetic diversity and positive selection were found in the PvAMA-1 gene from YP isolates, which are significant findings for the design and development of PvAMA-1-based malaria vaccine.
Highlights
Malaria is still a serious infectious disease that threatens human health and affects social and economic development in the world
Among the 180 blood samples infected with P. vivax from the China–Myanmar border (CMB) area during 2009–2011 (n = 77) and 2014–2016 (n = 103), 152 (71 and 81, respectively) samples were successfully sequenced for the Plasmodium vivax apical membrane antigen-1 (PvAMA-1)
The Ka/Ks values of PvAMA-1 were positive and statistically significant in all cases of the Yunnan Province (YP) samples, which indicated that the PvAMA-1 of P. vivax populations in the CMB area was under significant positive selection during these times
Summary
Malaria is still a serious infectious disease that threatens human health and affects social and economic development in the world. According to the World Health Organization (WHO), by 2019, there were 229 million malaria cases, an increase of one million over 2018 and 409,000 malaria deaths worldwide (WHO, 2020). Plasmodium vivax is widely prevalent in parts of Asia (Flannery et al, 2019), especially, in some countries bordering China, such as Myanmar, Laos, and Vietnam (von Seidlein et al, 2019; Brashear et al, 2020). In the China–Myanmar border (CMB) area, with the development of the Belt and Road Initiative, the risk of imported malaria cases to China is increasing (Lai et al, 2019). Studies to dissect the genetic backgrounds of P. vivax in the CMB area are of great significance to provide information for the control and elimination of vivax malaria in Myanmar and other related countries
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