The difference between quarantine and isolation can be summed up like this: 1  Isolation applies to persons who are known to be ill with a contagious disease. 2  Quarantine applies to those who have been exposed to a contagious disease but who may or may not become ill.he difference between quarantine and isolation can be summed up like this: 1  Isolation applies to persons who are known to be ill with a contagious disease. 2  Quarantine applies to those who have been exposed to a contagious disease but who may or may not become ill.