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Temperature and rainfall predicted for the twenty-first century by global coupled models as reported by IPCC, (2014a, and b)were obtained regionally for Burkina Faso and through the Paluclim project, 2011-2014. One of the goals of this project was to assess the upcoming evolution of malaria transmission dynamics. From an impact model on malaria risk linked to climate variability, temperature and rainfall indices were derived. Malaria transmission dynamics were then predicted using the derived temperature and rainfall for the twenty-first century. Similar to the historical evidence of rainfall being an important factor for regulating the seasonal density of malaria vectors, this study also reports a definitive link between low-frequency rainfall variability and malaria in the region under the influence of the Atlantic Multidecadal Oscillation (AMO). This finding can be used by local stakeholders involved with the geography-based population health planning. Moreover, the predicted increase in temperature during the twenty-first century suggests a reduction of larvae survival in Burkina Faso and thus the malaria risk. More generally, the temperature increase could become a new limiting factor for malaria transmission dynamics in the Sahel Region (as reported by Mordecai et al. (2013).