Emergence of a Novel Dengue Virus Serotype-2 Genotype IV Lineage III Strain and Displacement of Dengue Virus Serotype-1 in Central India (2019-2023).

Dengue fever remains a significant public health concern in tropical regions, including Central India, where outbreaks are frequent and associated with high morbidity and mortality. This study investigated the dynamics of dengue virus transmission and evolution in Central India from 2019 to 2023, focusing on the emergence of new strains and their impact on outbreak patterns. For this, 40 mosquito pools and 300 patient samples were recruited for the study. Phylogenetic and Bayesian evolutionary analyses performed on CPrM region and whole genome sequences generated by Sanger and Illumina sequencing, respectively, revealed the emergence and predominance of a novel DENV-2 genotype IV lineage III strain in the 2019 and 2023 outbreaks, which displaced the previously circulating DENV-1 genotype responsible for the 2016-2017 outbreak. Despite pre-existing DENV-1 neutralizing antibodies in the community (67 healthy volunteers), the novel DENV-2 strain exhibited higher viral loads and a greater reproduction number (R0), contributing to rapid disease spread. Molecular clock and Shannon entropy analyses suggest that DENV evolution occurred within the mosquito vector, driven by natural selection. Our findings highlight the importance of continuous DENV surveillance, including genetic characterization in both vectors and hosts, to understand viral evolution and predict future outbreaks. Rapid urbanization and inadequate sanitation in densely populated regions like India create ideal breeding grounds for mosquitoes, facilitating the introduction and establishment of novel DENV strains. Interrupting the vector-DENV-host cycle through targeted interventions is crucial for effective dengue control.