The cornerstone of diagnosis is examination of the peripheral blood smear. Repeat smear examinations is often required and should include 300 or more microscopic fields.
Problems in examiniation of the peripheral blood smear:
(1) low level of parasitemia
(2) failure to perform an adequate evaluation
(3) misidentification of the parasites
Serology may be helpful but can also pose problems.
(1) Immunoconversion may be limited if the patient is immunosuppressed.
(2) It may take 2 weeks after infection for IgM to appear.
(3) IgG can persist after recovery.
(4) IgM without IgG can occur as a false positive result (with autoimmune disease, HAMA, etc)
PCR or other molecular amplification method can be performed but often is delayed since the specimen needs to be sent to a reference laboratory.
If the diagnosis is still suspected but all testing is negative, then a sample of blood can be injected into a small rodent in the laboratory (xenodiagnosis).