Considerable debate has arisen regarding the appropriateness of the test and treat malaria policy broadly recommended by the World Health Organization. While presumptive treatment has important drawbacks, the effectiveness of the test and treat policy can vary considerably across regions, depending on several factors such as baseline malaria prevalence and rapid diagnostic test (RDT) performance.To compare presumptive treatment with test and treat, generalized linear mixed effects models were fitted to data from 6510 children under five years of age from Burkina Faso's 2010 Demographic and Health Survey. The statistical model results revealed substantial regional variation in baseline malaria prevalence (i.e., pre-test prevalence) and RDT performance. As a result, a child with a positive RDT result in one region can have the same malaria infection probability as a demographically similar child with a negative RDT result in another region. These findings indicate that a test and treat policy might be reasonable in some settings, but may be undermined in others due to the high proportion of false negatives. High spatial variability can substantially reduce the effectiveness of a national level test and treat malaria policy. In these cases, region-specific guidelines for malaria diagnosis and treatment may need to be formulated. Based on the statistical model results, proof-of-concept, web-based tools were created that can aid in the development of these region-specific guidelines and may improve current malaria-related policy in Burkina Faso.