How does the Prima Macula actually propagate itself across time?

Greetings everyone.

As per title; I'm raising this question on account of APT: Requiem's secret mini-ending (it plays after the Credits, for those who don't know).

Is it a family-genetics thing, and both sexes can carry it, but only boys/men can manifestate it? Are the De Runes descendants / related of the original Carrier?

It's through neither Basilius' nor Hugo's bloodline; they die as children. You can assume / speculate that eventually Amicia can / will have children (with Lucas!), but as far as we know (or I know, correct me if I'm wrong), Aelia died childless. That said there is no indication of this -- maybe in those Scrolls in the Sacred Quarters --, for all we know she was much older and a mother already, or there was a 3rd sibling.

Also, as far as we know, the Prima Macula first appeared in Basilius; was this random, an alchemical experiment by what would become the Order (they were pretty quickly all onto Basilius), or something else?

Have there been any other Carriers in the intervening ~814 years, potentially being missed by the Order, or just unknown to the players? (Between the De Runes' saga and the Secret Ending, only APT3 could tell us.)

If this is a regular thing, the "first" Prima Macula was dated to ~534, though it would have been a couple of years old by then. APT: Innocence starts in 1348, and it is implied Hugo's Prima Macula (Secunda Macula?) has been a problem for some years then. Maintaining the gap, this would mean the Secret Ending occurs in 2163; ask the United Federation of Planets for help? #spaceamicia

Is the Macula manifestating just the Bubonic Plague, or can it cause / strengthen any disease, and there have been indeed more Carriers, who spawned their own epidemics? (Tuberculosis! Spiders!)

For context, I'm assuming that all of the Count's "lore" is made up, and that a great deal of what the Order "knows" is wrong, a lie, or poorly-understood / incomplete. I finished Innocence about 2 weeks ago, and I am currently 2/3 of the way done with Requiem's NG+ run, to mop up missing achienvements (only "Malignant" (opportunist skill tree) and Platinum left). I great deal of the games' lore is still in my head, but I've forgotten a lot as well (only in the NG+ run did I notice that Arnaud is the original commander of the starting mercenaries, who will later chase us in full plate as we try to release the boat.

Thoughts?