It would appear that, in the 16th century, Europe was still experiencing repeated infestations by the plague. When the Spaniards of that period set out to loot the treasures of the Aztecs and the Incas, about 90% of the people with whom they had contact were said to have died from introduced diseases (against which they had no protection), and from a campaign of killing by the invaders.
A great disrespect for human life, juxtaposed with a policy of religious conversion, seems odd. Death and debility of ‘native’ peoples through dangerous diseases was allegedly commonplace throughout the world in the colonial era. The great despoliation of indigenous cultures everywhere has, however, been adequately documented. Thankfully for mankind, a few sensitive and/or learned men among the European occupiers and their descendants have enabled part of the legacy of hitherto durable local cultures and civilisations to endure. The surviving remainder of the indigenous populations may, naturally, have been colonised as cheap labour or enslaved.
Since Earth has been subject to terrible prolonged droughts here and there, over time, turning fertile land such as the Sahara into a desert, it is almost likely that the people so affected would have moved on. When the bed of one of the arms of the River Indus allegedly re-located itself (a not unusual occurrence for rivers), the settlements affected would have been vacated in favour of other locations.
The vast movements of people across Central Asia in history is testament to what would be normal practice for settled peoples to re-settle elsewhere, or to return to nomadism, when either Nature or human marauders turn against them.