I ran a 1 person Dr Who game last weekend at Concord gaming convention, though by accident rather than by design: only 1 player turned up. It went well. He ran 2 characters - Sarah Jane Smith and Sir Humphrey Appleby - and had fun with them providing distractions for each other during the investigation phase. They sent UNIT off to do the fighty bits on their behalf, which works fine in Dr Who.
I had to prod a couple of times (“Do you want to go and look at the crime scene now?”) but to be fair I have to do that in some games with 5 players!
On the topic of diseases… I think it makes a hell of a difference if the player has chosen to take a disease (as a GURPS disadvantage, for instance) than if the GM inflicts it on them. Especially if the GM hasn’t thought through the consequences of said disease!
Thus in Stargate one GM gave us Telepathic Vegan Disease. Any animal could contract it, from caterpillars to people. If you harmed another creature, you got headaches and took damage. So cows collapse in agony if they try to eat grass. The PCs response was “If we go back to Earth, whole ecosystems will collapse and billions will die”, which I’m not sure was the response the GM was expecting.
Another Stargate game (different GM) we caught Blue Crystal Disease, which slowly turned you into a statue. We doggedly trudged about trying to find a cure and getting very frustrated that none of our dice rolls, not matter how good, was pointing us in the right direction. Because that’s how the TV show works - catch disease at the start and find the cure before the end credits. Eventually the GM had to tell us she intended us to have this disease for several sessions, and do non-disease related adventures in the meantime.
And in my current Vampire campaign - the one I’m playing not running - I ended up with a Tzimiche wibbly-wobbly, fleshy-weshy disease/curse which was passed on to everyone I fed from. It nerfed my character, because I wasn’t willing to radically alter his morality and infect everyone I bit. Lots of conversations like this:
GM: Why aren’t you using Celerity?
Me: Because it costs blood. And if I spend blood I have to feed. So I’m not doing it.