“… of young and old not one in fifty of those Tribes are now living.”
The first smallpox epidemic on Canadian Plains was brutal. The quote above indicates that, for a few native tribes, it was estimated that at least 49 (at least 98%) out of 50 indigenous people died of smallpox. According to the following, it started to spread after the Snake tribe defeated some smallpox-infected Spaniards and took their scalps:
The evidence indicates that, when your baseline immunity to a communicable pathogen is low, then epidemics can happen.
Reference
Houston CS, Houston S. The first smallpox epidemic on the Canadian Plains: In the fur-traders' words. Can J Infect Dis. 2000 Mar;11(2):112-5. doi: 10.1155/2000/782978. PMID: 18159275; PMCID: PMC2094753. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2094753/