Background: Dengue is one of the most important mosquito-borne viral diseases in Mexico, where transmission is shaped by complex interactions among environmental, demographic, urban, land-use, and climatic conditions. However, long-term national ecological analyses integrating these factors remain limited. This study evaluated ecological associations between environmental, demographic, urban, land-use, and climatic indicators and dengue incidence trends in Mexico from 1990 to 2021. Methods: A national ecological time-series study was conducted using annual aggregated data obtained from official public databases. Dengue fever and severe dengue incidence rates were analyzed in relation to environmental, land-use, urban, demographic, and climatic indicators. Exploratory simple and multiple linear regression analyses were performed, and autoregressive integrated moving average models with exogenous variables (ARIMAX) were used to evaluate temporal associations while accounting for autocorrelation. Results: In simple regression analyses, urban population, population density, renewable internal freshwater resources, forest area, and average annual temperature were significantly associated with dengue incidence. For severe dengue, renewable internal freshwater resources showed the highest explanatory capacity in simple regression analyses (R² = 0.33). In multivariable models, forest area remained positively associated with severe dengue incidence (β = 64.29; p = 0.006), whereas renewable internal freshwater resources showed an inverse association (β = −0.087; p = 0.002). After accounting for temporal autocorrelation, none of the environmental or demographic indicators remained statistically significant in ARIMAX models; however, renewable internal freshwater resources showed the strongest association with severe dengue incidence (p = 0.062). The severe dengue model included a significant first-order moving-average component (MA(1), p < 0.001), indicating short-term temporal dependence in annual incidence rates. Conclusions: Environmental, demographic, urban, land-use, and climatic indicators were associated with long-term national dengue incidence trends in Mexico. Renewable internal freshwater resources emerged as one of the most consistent ecological indicators across analyses, highlighting the relevance of water availability and management within integrated dengue prevention strategies. The temporal dependence observed for severe dengue suggests that ecological time-series analyses may contribute to improving epidemiological surveillance and generating hypotheses for future regional studies.

Dengue is a major public health problem in Mexico, where large epidemics have occurred during recent years. Although demographic and clinical predictors of severe dengue have been widely studied, the impact of epidemic transmission periods on hospitalization and mortality remains poorly understood. This study evaluated the association between epidemic years and hospitalization and mortality among laboratory-confirmed dengue cases in Mexico. A nationwide retrospective analytical study was conducted using laboratory-confirmed dengue cases reported through the Mexican National Epidemiological Surveillance System between 2020 and 2025. Years were classified as epidemic (2023–2024) or non-epidemic (2020–2022 and 2025) according to official endemic channel analyses. Hospitalization and mortality were evaluated as primary outcomes. Multivariable logistic regression models were developed to identify factors independently associated with hospitalization and mortality. A total of 235,226 laboratory-confirmed dengue cases were included, of whom 90,661 (38.5%) were hospitalized and 1604 (0.68%) died. Overall, 170,819 cases (72.6%) occurred during epidemic years. Hospitalization was more frequent during epidemic years than during non-epidemic years (40.2% vs. 34.1%; crude OR 1.30, 95% CI 1.27–1.32; p < 0.001), whereas mortality did not differ significantly (0.68% vs. 0.69%; crude OR 0.99, 95% CI 0.89–1.11; p = 0.919). In multivariable analysis, epidemic-year status remained independently associated with hospitalization (aOR 1.26, 95% CI 1.24–1.29; p < 0.001) but not with mortality (aOR 1.00, 95% CI 0.90–1.12; p = 0.946). Chronic kidney disease showed the strongest independent association with both hospitalization (aOR 5.36, 95% CI 4.33–6.65) and mortality (aOR 6.98, 95% CI 5.23–9.32). Advanced age and other underlying comorbidities were also independently associated with adverse outcomes. Epidemic years were associated with increased hospitalization among laboratory-confirmed dengue cases in Mexico but were not associated with increased mortality. Mortality was more strongly associated with age and underlying comorbidities, particularly chronic kidney disease. These findings highlight the importance of strengthening hospital preparedness during epidemic periods while prioritizing clinical monitoring of high-risk patients.