Dengue fever remains as a public health challenge in Colombia, standing as the most prevalent infectious disease in the country. The cyclic nature of dengue epidemics, occurring approximately every three years, is intricately linked to meteorological events like El Niño Southern Oscillation (ENSO). Therefore, the Colombian system faces challenges in genomic surveillance. This study aimed to evaluate local dengue virus (DENV) transmission and genetic diversity in four Colombian departments with heterogeneous incidence patterns. For this study, we processed 266 serum samples to identify DENV. Subsequently, we obtained 118 genome sequences by sequencing DENV genomes from serum samples of 134 patients infected with DENV-1 and DENV-2 serotypes. The predominant serotype was DENV-2 (108/143), being the Asian-American (AA) genotype (91/118) the most prevalent one. Phylogenetic analysis revealed concurrent circulation of two lineages of both DENV-2 AA and DENV-1 V, suggesting ongoing genetic exchange with sequences from Venezuela and Cuba. The continuous migration of Venezuelan citizens into Colombia can contribute to this exchange, emphasizing the need for strengthened prevention measures in border areas. Notably, the Time to Most Recent Common Ancestor analysis identified cryptic transmission of DENV-2 AA since approximately 2015, leading to the recent epidemic. This challenges the notion that major outbreaks are solely triggered by recent virus introductions, emphasizing the importance of active genomic surveillance. The study also highlighted the contrasting selection pressures on DENV-1 V and DENV-2 AA, with the latter experiencing positive selection, possibly influencing its transmissibility. The presence of a cosmopolitan genotype in Colombia, linked to Brazil, raises concerns about transmission routes, emphasizing the necessity for thorough DENV evolution studies. Despite limitations, the study underscores genomic epidemiology's crucial role in early detection and comprehension of DENV genotypes, advocating for advanced sequencing techniques as an early warning system to aid in preventing and controlling dengue outbreaks in Colombia and globally.
