In the 2nd and 3rd centuries B.C.E., the Han and Roman empires were hit with out-breaks of smallpox, measles, and possibly bubonic plague. The people didn't have resistance, immunities  or medicine to fight the diseases so the population of both empires decreased rapidly.

The human population in this time frame isn't complete and scientists have to estimate the population. Even though the populations weren't very precise there is enough information to create general estimates. Before the outbreaks, Rome had 60 million people and after the outbreaks, Rome had 40 million people. Before the outbreaks, Han had 60 million people and after the outbreaks, Han had 45 million people.

The decline of the population decreased trade in both empires, causing both empires to become more self-sufficient and only focusing on trade within localized areas. The decline in population was also one of the many factors that caused the Han and Roman empires to collapse.

The people of Persia suffered a similar fate in that its population dramatically decreased like the Han and Roman empires but India seemed to have escaped the worst of the epidemics and their population didn't appear to have sharply declined.