ENSO-driven climate variability reconfigures the altitudinal frontier of dengue risk in the Andes

Despite the high burden of dengue in Latin America, high elevations have historically protected megacities such as Mexico City, Quito, and Bogota. Climate change is expected to shift these elevational suitability frontiers, yet most long-term projections rely solely on mean-state trends and overlook the role of climate variability, potentially underestimating risk. Using spatiotemporal decomposition techniques, we identified a mechanistic cascade linking (1) the El Nino-Southern Oscillation (ENSO) to local Colombian climate, accounting for [~]85% and [~]40% of interannual temperature and rainfall variability, and (2) local climate to dengue dynamics, explaining [~]63-76% of incidence and [~]42-55% of its altitudinal range. This cascade was further validated by model selection across formulations that incorporated both local and global climate variables. Non-linear effects indicate that dengue incidence and transmission altitude expand exponentially during warm ENSO phases, producing an upward stretch of the transmission distribution that exposes immunologically naive populations in highland areas previously considered unsuitable. If ENSO extremes intensify as projected, such fluctuations may trigger large outbreaks in high-elevation urban centers, fundamentally altering the global landscape of dengue. Our findings demonstrate that climate variability, acting through local temperature and rainfall, can reconfigure the geography of risk on timescales far shorter than decadal trends. This highlights critical limitations in current projections and detection-and-attribution frameworks, underscoring the need to incorporate anthropogenically modified modes of climate variability to accurately quantify the human fingerprint on global epidemic risk. Significance statementWhile rising average temperatures are a known threat to the changing landscape of infectious disease, this study reveals that interannual climate variability is a more immediate driver of disease burden and expansion. We show that the El Nino phenomenon produces local climate anomalies in Colombia that exponentially increase cases and stretch the reach of dengue into high-altitude areas, potentially exposing millions of immunologically naive people. This finding is highly relevant for elevated dengue-free Latin American megacities like Mexico City, Quito, and Bogota. By shifting the focus from decadal trends to climate variability, this paper provides a methodological blueprint for better predicting how infectious diseases will behave as our climate becomes increasingly unstable.