Genomic Epidemiology of CHIKV During the Largest Outbreak in Mainland China-Implication for CHIKV intervention

Chikungunya virus (CHIKV) has caused recurrent epidemics across tropical and subtropical regions globally. In 2025, Guangdong, China, experienced the largest documented CHIKV outbreak in mainland China, with 23,464 reported cases across all 21 prefecture-level cities. We conducted integrated epidemiological, genomic, and phylodynamic analyses to investigate the outbreak’s origins, transmission dynamics, and viral adaptive evolution. The Guangdong strain belongs to the ECSA-MAL lineage, with a long internal branch indicating substantial surveillance gaps in endemic regions. Phylodynamic analysis using a local molecular clock model estimated the viral introduction to have occurred within a narrow window in early April 2025 (95% HPD: March 26 – April 12). This suggests a 2.5-month period of sustained cryptic transmission prior to detection. The prolonged silent phase aligns with vector dynamics: low mosquito densities in April (12/trap/night) suppressed widespread transmission, while the subsequent abundance peak in July (120/trap/night) directly triggered the first epidemic outbreak. Human migration from two epicenters (Foshan and Jiangmen) explained ∼50% of case distribution variance, while mosquito ecology constrained spatial spread. Adaptation analysis on global circulating strains identified 33 lineage-defining adaptive mutations across 9 proteins and 14 epidemic lineages, including experimentally validated mutations and 15 novel adaptive mutations. Notably, 12 novel mutations were identified in the Asian lineage (AUL), with NSP3 harboring the most mutations (18.2%). This study demonstrates the critical need for enhanced genomic surveillance during pre-peak months and underscores the importance of monitoring adaptive mutations across diverse ecological regions.