The very beginning - Mary is in India, and everyone is getting sick around her, and she gets locked in her room and forgotten, and when she wakes up the house is empty. Everyone she knows in India is dead - that's why she ends up at Misslethwaite.

When I read it at Mary's age, that whole section just freaked me out; I didn't understand what was going on any more than Mary did, but re-reading it as an adult, it's stated outright by some of the grown-ups talking over her head that it was a cholera epidemic. I think maybe the most fascinating thing about it is the child's POV: both the way Mary's is drawn, and the fact that most of us probably read it at that age, too.