Establishing a dengue genomic monitoring in Cuba: uncovering virus dynamics to enhance local response

Background: A major dengue outbreak was reported by the Cuban Ministry of Health in 2022, highlighting the need for strong surveillance, with high pediatric cases showing warning signs. Using phylogenetic and epidemiologic approaches, we provide evidence toward a better understanding of dengue's recent transmission history. Methods: This study details the implementation of the genomic surveillance system for Dengue virus. Pre-screened DENV-3 positive samples (reverse transcription–polymerase chain reaction [RT-PCR] cycle threshold [Ct] <30) with epidemiologic metadata—including symptom onset, sample collection date, sex, age, residence, symptoms, and disease classification—underwent whole genome sequencing using Nanopore technology. Results: Genome sequences from 2022 to 2023 confirmed DENV-3 genotype III circulation in western, central, and eastern Cuba, covering 15 provinces and one special municipality. All cases were autochthonous, with 93% classified as dengue without warning signs and 7% as severe dengue. Long-term analysis identified a seasonal window of heightened suitability from May to November. Phylogenetic analyses revealed that DENV-3 genotype III has been introduced into Cuba multiple times, primarily from Asia and the Americas. These independent introduction events, likely driven by international travel and trade, underscore the importance of continued viral importation monitoring. The newly sequenced Cuban DENV-3 genotype III genomes were assigned to two distinct sub-lineages within genotype III: 3III_C, corresponding to the older American lineage I (2001-2014), and 3III_B.3, representing a novel introduction into Cuba associated with the more recent American lineage II (2022-2023). Evidence suggests that 3III_C, previously circulating in the country, may have been replaced by 3III_B.3 around 2020. Conclusions: This study outlines the development of a dengue genomic monitoring system in the country. The system will contribute to Cuba's public health response, facilitating timely interventions and potentially reducing the disease's impact on the local population.