The first person I asked was the author of APSW (Roger Binns). He told me:

"The ultimate cause of that is some interaction with the compilation
environment.  Some sort of CFLAGS is ultimately ending up in some
Python code like above when it should be [ ('_FORTIFY_SOURCE', '2') ].
 Note this is not part of the APSW source - it is something external."

"I have seen it before when using the Ubuntu PPA build service.  When
building locally everything was fine, but the build service injected
_FORTIFY_SOURCE like above and got it wrong.  I presume your version
of Debian is doing something similar.  Sadly I have no idea how to fix it."

So clearly he believes it is not a problem with his setup.py file.

Also, it strikes me as a bit unpythonic that a function should demand a specific type (i.e., tuple) especially when this is just for the convenience of being able to use % formatting.

I'm not asking or expecting you to add my change to distutils; but at least now if someone encounters the same problem, they will have a potential fix.