@metalinvader665, actually you've got a point there. Drought and epidemics did finish them off although you do see Cahokia being abandoned and mound building drastically reduced at a time that unusual amounts of fortifications appear across the region. Seems like there was some fighting which broke up the Middle Mississippian states. That would make them much weaker when the drought and diseases come along.
I was thinking of the Europeans being restricted to such a small amount of land that the states originally controlling the area aren't completely gone, they've just lost some land and can continue on. Perhaps small enough that when decolonization happens the area can be flooded by Amerindians who will become the majority again.
The immune population refers to the fact that first contact is non European and occurs in the late 1300's to 1400. Variolation is invented in the alternate 1450's. OTL it was invented in the 1500s but in this timeline there's more people with a higher standard of living and education. The fact that the industrial revolution happened in the 1410's speeds up tech development too. The diseases begin to cause mass death some time in the 1410s to the 1420's during which they are not invaded by their current trading partners.
There were still fluorishing communities after Cahokia (a bit smaller and less monumental), including in nearby places (East St. Louis/modern St. Louis, demolished many decades ago), but around the time of the de Soto expedition, you see widespread depopulation and chaos, and after de Soto, it gets even worse. So probably a lot of migrations and abandoning of settlements, made worse with the start of the European fur trade which caused huge amounts of conflicts between Indian groups and provoked even more migration.
So this is clearly something which will take an early medieval POD to prevent this depopulation and mass migrations. Some of it is geological, since lengthy droughts were once common in North America, as for some reason (based on climate data), no major drought (even the Dust Bowl) has been as bad and long-lasting as those of the 17th century and earlier, even in the Southwest. But I notice you clearly have an early POD for early industrial revolution. This isn't good for anyone north of Mesoamerica, even surviving/more successful Mississippian cultures, since they'll be easy bait for European conquerers armed with far greater tech than what they have. European medicine will also have advanced, along with agriculture, creating a population surplus meaning there will be a widespread desire for land which neither Eastern Europe nor Africa can provide.
I wonder how variolation would work in Amerindian populations? Historically, some people died from variolation, either from contact with the virus or from improper variolation. And the Amerindian immune system is more susceptible to such diseases, so the death rate would be slightly higher than in Old World populations. It would have to be an independent development, or maybe one spurred by contact with Asians or Africans and then widely spread throughout the Americas within a few centuries.
The other easy solution which is almost cheating is to have
Variola minor (or a strain with similar characteristics) emerge and become widespread far earlier than OTL. It was more recent to evolve, and became widespread since it doesn't cripple the victim nearly as much (allowing easier transmission) and has a fatality rate of no more than 1%. And once you survive smallpox, it's basically impossible to ever get smallpox again.
Variola minor helped burn the disease out since even though it was highly infectious, it innoculated many populations from the more deadly
variola major without the need of variolation or vaccination. Now, would it kill slightly more Amerindians than it killed Africans, Europeans, etc.? Probably, but it wouldn't be a particularly bad epidemic, and probably one that would mainly kill children. In a place with high population density, it could help immunity develop in the population so when an epidemic of
Variola major does hit, the majority of people survive, especially adults and elders who are essential for transmitting cultural practices and civilisation to the next generation. You do need a high population density for
Variola minor to become endemic, though.
How long Europe would take to capitalize on this opportunity makes a huge difference to this scenario. In my current draft Europe took 60 years to respond properly (they arrive in 1480). They are however preceded by a wave of piracy which foreshadowed their arrival similar to how the Portugese conducted piracy before large scale seizing of land in Asia or Africa. These fleets were private and small. They were destroyed by aggravated traders still trying to get sugar and other resources from North America or the Native American states when they landed. If you think that a different lag for Europe world be better I would consider updating the figure.
During that time the European states were busy fighting each other. They lagged behind the most advanced nations. Tech wise they're roughly in the OTL 1600's during most of the alternate 1400's and due to imported knowledge suddenly start going through the industrial revolution (Byzantium first) in the year 1490. By that time North America is immune (the large pandemics stopped being so frequent OTL after about 60 years implying that immunity had kicked in), they've got the ability to manufacture guns from Africa (who got them from Asia), organisation on a large scale is happening and coastal forts and patrols guarding valuable coastal zones have appeared. These defenses were intended to stop pirates (who tend to try and grab or raid valuable land).
West African States are much more powerful (they're successors of a fallen Malian Empire) and project their power into the surrounding area. The West and East African states are already aligned with Asia through trade so if they feel under pressure from Europe, they'll likely turn to various Asian nations for backup. On the other hand, immune Amerindians are now usable as a slave population which don't have to be shipped in.
Measles and Malaria does seem to be a problem though. How does the scenario sound so far? Any suggestions for revisions?
Who introduced sugar to the New World though? Sugar is also not a crop you'd grow except on the fringes of the Gulf Coast since it's very difficult to grow elsewhere in the South. Of course, Mesoamerica and much of tropical Central/South America and the Caribbean are prime land for it. The Taino in particular, with their seafaring tradition, would be able to become fantastic traders, and could basically be like the Malays of the New World.
I don't see how East Asia and West Africa could have much direct contact (it's a huge distance, and East Africa has much gold, ivory, etc.) since the majority of West Africa's trade was with North Africa since Antiquity, and later Europe more directly traded with them. More just here West Africa has more incentive to develop trade with the New World in addition to trade with North Africa and Europe. Cassava is a fantastic crop which will no doubt be imported sooner or later. Even East Africa is more likely to have links with a strong Indian empire (or just whoever's ruling places like Gujarat) than China or Japan. Speaking of which, the Chinese would probably be settling in large numbers in Mesoamerica and the Andes, as merchants or as miners and other labour. If the West Coast has any decent civilisations, they might settle there too. More traditional settler colonisation would be difficult to do, though. If Japan is stable and united, once they're done with Karafuto and Kamchatka they might want to expand down the West Coast, but a lot of Asian activity there would likely be pretty small scale and not settler colonialism.
Also, in any wanked Mississippian TL, I'd expect yaupon to emerge as a much more valuable crop than OTL, and be selectively bred/semi-domesticated (full domestication of
Ilex species appears tricky, as yerba mate was not effectively domesticated until the late 19th/early 20th century) to increase caffeine levels to be more akin to tea or coffee. So that's another important export you could have which Europeans would no doubt like to seize. It grows in subtropical lowlands near the Gulf Coast, so you could probably naturalise it in parts of Africa, as well as Mesoamerica (a subspecies grows in Chiapas) since the Taino would be selling it to the Maya and other Mesoamericans.
Gun manufacture I'm not so sure about. Amerindians have a lot of reasons to just buy their guns from traders instead. They can pay in slaves, sugar, yaupon, peppers, or just straight up gold and silver (which will leak the precious metals into the world economy). The Mississippians might be a bit different, though, since the core of the region around the inland Mississippi, Ohio, and Tennessee valleys doesn't have much to offer since yaupon and sugar can't grow there. They'll need the cotton gin to be invented to get cotton established, and also they'll need tobacco varieties suited for export. Even then, not all the land is suitable for cotton cultivation (especially the Highland Rim and Cumberland Plateau), and tobacco cultivation has similar constraints--it's also vulnerable to changes in taste in tobacco (like early proliferation of cigarettes via an early Bonsack machine, by far the most successful aspect of the tobacco industry and a key product of the industrial revolution), since Tennessee/Kentucky tobacco is generally not used for cigarettes for various reasons. They might have a lot of reason to make their own industry, especially since the Tennessee/Cumberland valleys have a lot of caves which are rich in saltpeter. Of course, you'd need to find a way to get the prerequisite industries for gunsmithing established, and the disease-ravaged Mississippians of this region are far less capable in that regards than Japan and their
tanegashima rifles or Europe and their handcannons. So once again, you need to get metalsmithing established (copper was smelted widely in the pre-Columbian Great Lakes at once point) and get an "iron age" established. IIRC, that region, especially Missouri (and even moreso the Great Lakes), has readily available iron reserves, although I believe in Tennessee at least they aren't as high quality as in the Great Lakes region, but they'd be good enough for an Iron Age culture to develop. Even though it would be unprecedentedly rapid development compared to other civilisations.
Amerindians would be a much more effective slave population TTL since they'd have much lower mortality rates, although they'd be best on islands where they can't easily escape back to fellow Amerindians. And someone will be needed to farm all that sugar, cotton, yaupon, etc. So probably less of an African slave trade which changes things big time.
Non-smallpox diseases are the real problem, since Amerindians suffered disproportionate casualties from them and they don't have an "easy" solution like variolation outside of modern medicine. This would depopulate many areas, to the point where they'd need to bring in African slaves more resistant to those diseases.