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Dean et al. (1) infer that human ectoparasites were the dominant mode of transmission of plague ( Yersinia pestis ) during the Second Pandemic by comparing models representing distinct transmission routes. The authors are to be commended for providing detailed information on their computational approach (2). However, due to inconsistent modeling choices and reliance on strong assumptions, their analysis does not support their main conclusion.Comparing discrete mechanistic models to infer biological processes is a powerful approach (3), but only for mutually exclusive competing hypotheses. Given that bubonic plague infection can cause secondary pneumonic infection, the possibility of … [↵][1]1To whom correspondence should be addressed. Email: parksw3{at}mcmaster.ca. [1]: #xref-corresp-1-1

Human ectoparasite transmission of the plague during the Second Pandemic is only weakly supported by proposed mathematical models