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Background: Infectious diseases are often studied by characterising the population structure of the pathogen using genetic markers. An unresolved problem is the effective quantification of the extent of transmission using genetic variation data from such pathogen isolates. Methods: It is important that transmission indices reflect the growth of the infectious population as well as account for the mutation rate of the marker and the effects of sampling. That is, while responding to this growth rate, indices should be unresponsive to the sample size and the mutation rate. We use simulation methods taking into account both the mutation and sampling processes to evaluate indices designed to quantify transmission of tuberculosis. Results: Previously proposed indices generally perform inadequately according to the above criteria, with the partial exception of the recently proposed Transmission-Mutation Index. Conclusion: Any transmission index needs to take into account mutation of the marker and the effects of sampling. Simple indices are unlikely to capture the full complexity of the underlying processes.