Cross-border importation-initiated limited local transmission of dengue virus serotype 4 genotype I in the China, Myanmar, and Laos border region, 2024

Dengue virus serotype 4 (DENV-4) has rarely been reported in the China-Myanmar-Laos (CML) border region since 2013, where serotypes 1, 2, and 3 have predominated. In 2024, after a nine-year absence of DENV-4 in this region, 17 DENV-4 cases were identified from 2,417 dengue patients through the surveillance network in Jinghong City, China. Over half of the patients presented with dengue fever with warning signs, accompanied by hepatic dysfunction and coagulopathy. Nine complete envelope gene sequences were obtained, and phylogenetic analysis classified the strains into DENV-4 genotype I lineages I_A.3 and I_A.3.2. Integration of epidemiological and phylogenetic data demonstrated that importation of I_A.3.2 from Myanmar initiated limited local transmission in China, whereas I_A.3 importation occurred later and was not associated with local spread. The 2024 I_A.3.2 strains formed a distinct subcluster characterized by the I351 V substitution in envelope protein domain III. Multiple nonsynonymous mutations were identified across the envelope protein, several of which differed from current tetravalent vaccine reference strains, highlighting potential implications for vaccine efficacy. This study documents the importation-initiated limited local transmission of DENV-4 genotype I in the CML border region in 2024 and reveals the accumulation of critical envelope protein mutations. The findings fill important gaps in understanding DENV-4 evolution in this region and underscore the urgency of sustained genomic surveillance in high-risk border areas to inform regional dengue prevention and control strategies.