It's also possible that you have reversed part of the flow of the river enough to have sewage flowing towards your inputs. If you have enough water pumps up the river from water treatment plants, you will actually see the flow of the river reverse. I myself had this happen, and accidentally had 5% water pollution before I noticed -- the water was still blue, but the brown had managed to make it close enough that some of it was making it to the pipes by the shore.
Make sure that you have clean drinking water by checking the "pollution" overlay (looks like a barrel) on the side. If the problem is your water intake, a simple solution is to move your sewage farther down the river, onto the ocean, or spread them apart slightly.
A city-wide health emergency can often be linked to that, or to a lack of death care. Do you have sufficient space for bodies? Are your cemeteries and crematoriums overburdened? Are your hearses making it to the bodies or are they being stopped by traffic? All things worth checking. Problems in Cities: Skylines tend to snowball.
Surprisingly, sometimes it's simply that your city grew too fast at some point and everyone is dying at once. I've never had this happen to me, nor have I seen that happen on any of the streams or series I follow, but apparently it is possible that if you had a week or two of massive growth, a bunch of people will die at once and tangle your healthcare system.
(for the title: everybody dies, sorry.)
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