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Given the high degrees of individual and local heterogeneity within geographic regions or administrative units, effective policy design requires a detailed knowledge of the spatial distribution of relevant population attributes of interest, including size, age, gender, income, nutritional status, vaccination rates, or child mortality. Finally, a strategy for building an open-access database of spatial demographic data that is tailored to epidemiological applications is put forward. Moreover, the importance of acknowledging, measuring, and accounting for uncertainty in spatial demographic datasets is outlined. We review sources of detailed, contemporary, freely available and relevant spatial demographic data focusing on low income regions where such data are often sparse and highlight the value of incorporating these through a set of examples of their application in disease studies. In this paper we discuss the deficiencies of existing spatial population datasets and their limitations on epidemiological analyses. Together, these freely available datasets form a rich resource for quantifying and understanding the spatial variations in the sizes and distributions of those most at risk of disease in low income regions, yet at present, they remain unconnected data scattered across national statistical offices and websites. Moreover, demographic and health surveys continue to collect representative and contemporary samples from clusters of communities in low-income countries where census data may be less detailed and not collected regularly. Subnational breakdowns of population counts by age and sex are routinely collected during national censuses and maintained in finer detail within microcensus data. The disease impact in terms of morbidity, mortality, and speed of spread varies substantially with demographic profiles, so that identifying the most exposed or affected populations becomes a key aspect of planning and targeting interventions. Where risks are heterogeneous across population groups or space or dependent on transmission between individuals, spatial data on human population distributions and demographic structures are required to estimate infectious disease risks, burdens, and dynamics. This expansion has, however, not been matched by advancements in the development of spatial datasets of human population distribution that accompany disease maps or spatial models. In turn, the greater availability of spatially referenced epidemiological data is driving the rapid expansion of disease mapping and spatial modeling methods, which are becoming increasingly detailed and sophisticated, with rigorous handling of uncertainties. The use of Global Positioning Systems (GPS) and Geographical Information Systems (GIS) in disease surveys and reporting is becoming increasingly routine, enabling a better understanding of spatial epidemiology and the improvement of surveillance and control strategies.