High genetic diversity of circumsporozoite surface protein in Vietnamese Plasmodium malariae isolates

Abstract Background: Plasmodium malariae is an apicomplexan parasite that causes quartan malaria in humans but remains understudied despite its global distribution. Furthermore, growing evidence suggests that P. malariae infections are more prevalent than previously recognized. In this study, the genetic diversity of P. malariae circumsporozoite surface protein gene ( pmcsp ) in recently emerged Vietnamese P. malariae isolates was investigated. Methods: DNA samples of 116 P. malariae -infected patients in Khanh Hoa Province, Vietnam, collected during 2023–2024 were used. Full-length pmcsp was amplified and sequenced, and the genetic diversity and natural selection profiles of Vietnamese and global pmcsp were analyzed. Results: The two non-repeat terminal regions of Vietnamese pmcsp exhibited low genetic diversity, whereas the central repeat region (CRR) showed high genetic diversity due to variation in the number, composition, and arrangement of peptide repeat motif (PRM) species. Global pmcsp CRR also displayed extensive polymorphism in repeat length and PRM composition, though Vietnamese pmcsp CRR exhibited the greatest diversity. Although modest genetic differences were observed among pmcsp populations from Asia and Africa, no strong geographical bias was observed. Conclusion: Vietnamese pmcsp exhibits substantial genetic diversity despite the limited spatial and temporal range of isolates. Global pmcsp diversity is greater than previously recognized. Given the limited genetic information currently available for the global P. malariae population, studies with larger numbers of global P. malariae isolates from different origins are required to better understand the genetic nature and evolutionary aspects of the gene.