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An interesting hypothesis about the epidemiology—the appearance, spread, and especially disappearance—of plague from Europe is that the flea-bearing rodent reservoir of disease was eventually succeeded by another species. The Black Rat (Rattus rattus) was originally introduced from Asia to Europe by trade, but was subsequently displaced and succeeded throughout Europe by the bigger Brown Rat (Rattus norvegicus). The brown rat was not as prone to transmit the germ-bearing fleas to humans in large die-offs due to a different rat ecology.[4][5] The dynamic complexities of rat ecology, herd immunity in that reservoir, interaction with human ecology, secondary transmission routes between humans with or without fleas, human herd immunity, and changes in each might explain the eruption, dissemination, and re-eruptions of plague that continued for centuries until its unexplained disappearance.

It has also been noted that the disease was reduced by far, but never totally eradicatd. It did pop up again in other areas of the world.