Genetic signatures of Plasmodium vivax Circumsporozoite Surface Protein during malaria resurgence in Thailand

Parsakorn Tapaopong; Aurel Holzschuh; Gustavo da Silva; Palakorn Chintanawiwat; Sirasate Bantuchai; Wasinee Rungsarityotin; Liwang Cui; Cristian Koepfli; Jetsumon Sattabongkot; Wang Nguitragool

doi:10.1016/j.ijpara.2025.12.001

Genetic signatures of Plasmodium vivax Circumsporozoite Surface Protein during malaria resurgence in Thailand

Int J Parasitol. 2025 Dec 9:S0020-7519(25)00226-7. doi: 10.1016/j.ijpara.2025.12.001. Online ahead of print.

Affiliations

¹ Mahidol Vivax Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
² Department of Medicine, Swiss Tropical and Public Health Institute, Allschwil, Switzerland; University of Basel, Basel, Switzerland.
³ Department of Biological Sciences, Eck Institute for Global Health, Galvin Life Sciences, University of Notre Dame, Notre Dame, IN, USA.
⁴ Mahidol University Frontier Research Facility, Mahidol University, Salaya, Nakhon Pathom, Thailand.
⁵ Division of Infectious Diseases and International Medicine, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
⁶ Mahidol Vivax Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Department of Molecular Tropical Medicine and Genetics, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. Electronic address: wang.ngu@mahidol.ac.th.

Abstract

The Plasmodium circumsporozoite surface protein (CSP) is the best characterized pre-erythrocytic vaccine target for malaria. It is a multifunctional protein important for sporozoite mobility, mosquito salivary gland invasion, and hepatocyte invasion. We analyzed diversity of Plasmodium vivax CSP gene (pvcsp) during the 2022-2023 malaria resurgence in northwestern Thailand and assessed how pvcsp haplotypes may affect parasite development in the mosquitoes. Amplicon sequencing of 69 P. vivax isolates revealed both canonical pvcsp variants: VK210 (n = 66) and VK247 (n = 3). The VK210 type exhibited high polymorphism within the central repeat region, with 21 haplotypes (H1-H21) composed of 13-20 repeat motifs. Haplotype H2 was the most common, accounting for half of all VK210 sequences, and in membrane feeding assays with Anopheles dirus, appeared to produce more salivary-gland sporozoites per oocyst than other haplotypes, suggesting that repeat-region variation may modulate vector competence. Together, these findings report contemporary pvcsp diversity in Thailand's highest transmission area, provide functional evidence that repeat-region polymorphisms shape vector-parasite interactions, and highlight three globally prevalent motifs (GDRADGQPA, GDRAAGQPA, ANGAGNQPG) as prime targets for future PvCSP vaccines.

Keywords: Circumsporozoite surface protein; Genetic diversity; Malaria; Plasmodium vivax; Thailand.

Grants and funding

U19 AI181583/AI/NIAID NIH HHS/United States