If you use per domain aliasing then all the users must be in the parent domain
for example you have domain2.com as an alias of domain1.com
mail comes in for firstname.lastname@example.org
ESS will ask your mail server if email@example.com exists. If they do the mail will be accepted and processed.
Per user aliasing uses the data in database and the primary user will of course already exist so there are no issues.
Per user aliasing is usually configured using LDAP or AZURE to build the userlist. It can also be configured manually on a per user basis.
You should NEVER user per domain and per user aliasing at the same time.