In my reality when I play Sid Meier's Colonization the fact that illnesses aren't simulated in the game don't help them much. Every time I cannot resist to disrupt their culture by sending missionaries, bribing and making allies with weak to get rid of the strong and eventually taking out weak one by one. They help fight other Europeans as well (few times I managed to get Spanish into war with three tribes at the same time, too bad Spanish always win, because they're good in fighting locals). When I'm done, it's Natives-clean territory.
I'm not sure if co-exisitng with Natives is even possible in Colonization, they're overprotective of their territory and quite fast become a problem for expansion. When you're on the peak of your power it's hard to resist not to wipe them out.
