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My talk presents recent results on the population dynamics of vector-borne infectious diseases and the role played by climate variability, climate change, and spatial heterogeneity. I rely on the study of malaria in cities of India and in highlands of Africa, to illustrate application of a statistical inference method and process-based mathematical models to interrogate time series data on underlying drivers of transmission. I then transition to the dynamics of dengue as it emerged in Brazil, to address limitations of “well-mixed” SIR (Susceptible-Infected-Recovered) models to predict re-emergence of outbreaks in heterogeneous urban landscapes.