Temporal genomic diversity of Dengue virus in South India from 2019 to 2024

Dengue is an endemic disease in over 100 countries, causing an estimated 500,000 hospitalizations each year. The global mortality rate for severe dengue infections is around 2.5 %. India is a major dengue hotspot, accounting for almost a third of all global cases. Despite this significant burden, there are limited studies on the circulating serotypes and genetic lineages of the dengue virus (DENV) within the country. This retrospective study investigates the distribution and genetic diversity of circulating dengue virus (DENV) variants based on clinical samples collected from healthcare centres between 2019 and 2024 in South India. A total of 1015 samples from dengue patients tested positive for at least one of the dengue NS1, IgM, or IgG markers. Among these, 210 NS1-positive samples underwent DENV serotyping via RT-PCR, and 84 of those were further characterized through Sanger sequencing of the C-prM gene to determine genotype and lineage associations. The analysis revealed a decline in dengue infection rates with increasing age, supported by a corresponding rise in IgG seropositivity. Notably, individuals under 20 years of age exhibited a significantly higher frequency of severe disease compared to older age groups. All four DENV serotypes, DENV-1 through DENV-4, were detected across the study period, with a shift in dominant serotype approximately every 2-3 years. DENV-2 and DENV-3 emerged as the most prevalent serotypes. Phylogenetic analysis identified the following genotype-lineage associations: DENV-1 as Genotype III (Lineage: 1III_A), DENV-2 as Genotype II (Cosmopolitan) (Lineages: 2II_A and 2II_F), DENV-3 as Genotype III (Lineage: 3III_B), and DENV-4 as Genotype I (Lineage: 4I_B). These findings underscore the dynamic nature of dengue virus transmission and genetic evolution in the region, emphasizing the importance of age-specific surveillance and targeted prevention strategies. This study contributes valuable insights into local DENV circulation patterns, which are critical for informing diagnostic, therapeutic, and vaccine development efforts.