Determinants of Dengue Serotype Shifts: A Narrative Multifactorial Perspective

Dengue Virus (DENV) circulates as four antigenically distinct serotypes whose dominance fluctuates over time in many endemic regions, a phenomenon known as serotype shift that is frequently associated with large outbreaks and increased disease severity. This review, through a synthesis of epidemiological, virological, immunological, entomological, and environmental evidence, observes that serotype shift likely arises from the interaction of multiple determinants rather than solely from viral evolution, with population immunity playing a central role. The accumulation of serotype-specific herd immunity, together with short-lived cross-protection and Antibody-Dependent Enhancement (ADE), reshapes population susceptibility and creates ecological space for heterologous serotypes with higher transmission potential. The synthesis of global dengue studies indicates that these immune dynamics interact with viral genetic diversity, vector competence, climate variability, and human factors such as demography, socioeconomic status, population density and mobility to drive cyclical and sometimes abrupt changes in serotype dominance. Notably, the review indicates that serotype changes often precede or coincide with more clinical severity and patterns of outbreaks, with direct implications for the process of forecasting outbreaks, vaccine performance, and preparedness to respond with appropriate health measures. On the whole, this review confirms the opinion that the change of dengue serotype occurrence becomes a consequence of interconnected biological and ecological processes involved in the transmission of dengue serotype shifts in hyperendemic areas.