While the severity and length of illness varies, most people diagnosed with mononucleosis are able to return to their normal daily routines within two to three weeks, particularly if they rest during this time period. It may take two to three months before a person's usual energy levels return. One of the most common problems in treating mononucleosis, particularly in teenagers, is that people return to their usual activities too quickly and then experience a relapse of symptoms. Once the disease has completely run its course, the person cannot be reinfected.
Infectious mononucleosis diagnosis is confirmed by a peripheral blood picture showing the atypical (monocyte-like) lymphocytes. A heterophil antibody (Paul-Bunnell) infectious mononucleosis test and, if necessary, demonstration of a raised titre of Epstein-Barr virus antibodies are confirmatory. Heterophile antibodies are IgM antibodies that clump together sheep and horse red blood cells. The Paul-Bunnell test for infectious mononucleosis employs sheep red blood cells but more rapid methods are available to detect heterophile antibodies to horse red blood cells by detecting clumping on a glass slide ( Monospot test ). If these tests are negative in an otherwise typical case, cytomegalovirus infection or toxoplasmosis should be considered. Attainment of HIV infection frequently also gives rise to an illness resembling infectious mononucleosis.