The Mexican population was decimated during the 1600s by cocoliztli, a disease supposedly indigenous to Mexico. But why did these epidemics occur not long after Mexico was colonized? Did the Spanish have anything to do with it, or was it coincidence that the epidemics happened to happen at this time? Also, are there any known cases of diseases destroying large populations in the Americas prior to 1492?
Not to discourage further answers, but /u/400-Rabbits and I discussed some of the influence of colonization on cocoliztli in this thread. You might also be interested in a previous answer I wrote on diseases and epidemics in the New World before contact.