So, there are these fantastic creatures (dragons, unicorns and whatnot) they have the advantage in individual strength, but they're massively outclassed in terms of numbers, plus humans can achieve much more together.
God doesn't like the humans' plans to exterminate his fantastic creatures, so he decides to preemptively annihilate humanity, not just the men but the women and the children too.
There is a rule, however: God can only create, and only 1 kg of something, that adheres to the rules of physics and can only create once every thousand years. He can create that thing anywhere, though.
What would be the most surefire way for God to kill off humanity, and only humanity, before they could kill of the fantastic creatures? Note: Despite their impressive death toll, many plagues failed to completely eradicate humans. Tech level is late medieval.