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So lets begin at the start, before the first game, Hugo (a.k.a. the Carrier) was born with a misterious curse called by Alchemists "The Macula" (it is not stated as of yet exactlly what The Macula is, or exactlly how it works or where it came from), all we know about it, is that it wants to take over the carrier through a proccess called Treshold, if a carrier survives the treshold, He gains more power over The Macula, and can controll rats, on the other hand, if He fails, well, lets just say that a great apocalyptic event will fall upon the Earth, Driven by endless sea of Plague rats.
This is pretty much in a nutshell what the Macula is.
Now you are right, the story, being a dirrect sequel to the first game, assumes that you are familliar with the first game, a lot of answers to your confusion will be answered there, so I stronglly suggest that you re-visit the first game.
I will try to summarise it though, if you don't want to find answers yourself.
First things first, don't take any story facts, and try to apply real-life logic to it, it doesn't make sense, so just ignore RL facts, this is a historical setting in a Sci-fi world thing, and Sci-fi doesn't always follow RL facts, regardless of setting.
I have describe the Macula in a nutshell, the rats and the plague (The Bite, as it's called in game) are connected dirrectlly, bassically rats spread the Plague, that's all there is to it.
The Macula influences the rats, that is correct, going back to my description earlier, Macula is what is controlling them, Hugo can (if He is strong enough to resist the Macula) controll rats Through the Macula. But that doesn't come without consequence though, as you will learn latter in the storry.
The Rats also operate on their own, without Hugo's any action, or The Macula is controlling them, but without Hugo's ability to do anything about that, either way, the Plague in the Red City was present long before Hugo arrives there (The rats were bitting people etc.), his arrival, only awakens the rats to the extend that they eat everyone alive instead.
When Lucas said that, He means generally that wherever they go, the rats, and so the plague as well, follows, thus making them somewhat responsible, However I need to state this clearlly, The Plague is not their fault, they may have caused it's progress to accelerate, but they didn't cause the plague to happen, again, the rats were there before they arrive, The Macula, not Hugo is controlling the rats, so where Macula's carrier is, that is where the rat activity will be the strongest, still, even if they didn't arrive, the plague would have progressed, although far slower.
I hope that answers your question about Hugo's connection to what is happenning in the world.
You don't seem to remember the first game's story, so again, I recommend go re-visit it before continuing (a lot of questions will be answered there), else the 2nd game's story may be a bit wierd, after that, continue with the 2nd game, to get the full picture.
I think I mostly remember what happened in the first game, it's just that I really didn't understand some parts of it. The world seems to be a pretty realistic medieval setting to me, apart from the presence and the effects of the macula, so I went in with the assumption that real life logic could be applied to most of the events, but just the Macula brings in that little bit of fantasy that makes me unable to decide what should be taken with real life logic, what should be taken with fantasy logic, what is actually a mystery yet and what I should already understand. So all of this made it really difficult to understand the first game's story as it explained what Hugo's affliction and powers are and how they connect to the rats and the plague. The underrepresentation of the disease in the first game also makes the whole premise somewhat unexpected, since the rats are an immediate and deadly threat all the way through, while the plague itself is barely mentioned and the characters appear to be completely immune to it, so it's just not even a part of the story at all apart from some background context.
As I said, RL should not be applied here, it is historical, but that is as far as it goes when it comes to RL.
The Plague in game, is just a sickness that happens to people that were bitten, but not eaten alive (survived the encounter with rats), and not many people are so lucky, as in, most people are eaten alive, and dead after the encounter with rats.
So there isn't much to talk about in the story in regards to plague itself appart from saying that is a disease that rats bring.
That said, the Plague in game doesn't spread the same way it did in RL, so it doesn't affect everyone as it did in RL.
The rats are much more a threat since the only way to contract plague is to get bitten. Hence why it's called The Bite.