Cryptic transmission and re-emergence of Cosmopolitan genotype of Dengue Virus Serotype 2 within Ho Chi Minh City and Southern Vietnam

BackgroundDengue virus (DENV) is a major global public health threat and causes substantial morbidity and mortality in hyperendemic countries like Vietnam with its largest city, Ho Chi Minh City (HCMC), recently experiencing its largest DENV outbreak in over a decade. Despite this, there is currently a lack of data on circulating DENV serotypes/genotypes and monitoring of transmission dynamics within HCMC, which presents a challenge for the design and implementation of effective DENV mitigation strategies. MethodsWe generated 45 DENV envelope (E) gene sequences from human plasma samples collected in southern Vietnam between 2017 and 2022. We applied phylogenetic methods to infer the probable route of virus introductions into HCMC and its surrounding areas, as well as their approximate timing, using additional sequences from Southern and South-east Asia. FindingsWe found evidence of the co-circulation of multiple DENV serotypes/genotypes and the re-emergence of the DENV-2 Cosmopolitan genotype in southern Vietnam. Furthermore, we detected at least three independent seeding events of the Cosmopolitan genotype into Vietnam, the earliest of which is estimated to have occurred two years before the earliest sampling date, providing evidence of at least two seasons of cryptic transmission. InterpretationOur findings emphasize the urgent need for comprehensive DENV surveillance in HCMC and Vietnam to guide appropriate and effective public health responses and improve understanding of recent outbreak dynamics in Vietnam and neighbouring countries. Such efforts may also help predict epidemic dynamics of DENV in future seasons. FundingThis work was supported by the Wellcome Trust [106680] and Wellcome Trust [226052/Z/22/Z] Evidence before this studyDengue virus (DENV) is a significant threat to global health causing high levels of morbidity and economic damage. With the limited surveillance infrastructure for DENV, particularly during the COVID-19 pandemic, little is currently known about the transmission dynamics in Ho Chi Minh City (HCMC) and Vietnam presenting a challenge for the design and implementation of DENV mitigation strategies. Added value of this studyGenomic epidemiology is a powerful approach to gain insights into the spatio-temporal dynamics of viruses and to detect new viral variants. Our analyses shows the existence of multiple co-circulating DENV-2 genotypes in southern Vietnam with multiple distinct and continued introductions of the Cosmopolitan genotype into HCMC over multiple years. Implications of all the available evidenceFindings from this study will assist local and regional dengue surveillance and control programs as well as adding to our understanding on DENV genomic epidemiology and transmission dynamics. Critically, current dengue screening and surveillance methodology should be modified to enable detection of these novel lineages. The emergence of these genotypes and their impact on dengue evolution need to be explored on a larger scale. These results will also allow vital missing genomic data to be incorporated into models used for importation dynamics analysis. We plan to integrate these findings into a DENV forecasting tool being developed as part of Wellcome funded multidisciplinary project - DART (Dengue Advanced Readiness Tools), which aims to build an integrated digital system for dengue outbreak prediction and monitoring.