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A variation of Years of Rice and Salt
Some event (it does not have to be a pandemic, although I suspect that makes the best means) empties Africa of 95% of it's Sub-saharan population circa 1405.
1) Is such an event remotely plausable or simply ASB?
2) What non-pandemic mechanisms might have this effect?
3) How does this effect history?
No African slave trade. The slaves for the Americas come from native populations. Possible development of indentured servitued into an even more overt slavery.