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Microscopic demonstration of typical intracytoplasmic E. canis morulas in monocytes is seen during the acute stage of the disease in about 4% of cases and is diagnostic of the disease. Therefore, blood and buffy-coat smears should be carefully evaluated. Other methods used mainly for research purposes are culturing the parasite, PCR and Western immunobloting.

A study comparing PCR, culturing the parasite, IFA and Western blot in the early detection of the parasite has shown that cell culture reisolation methods proved to be the most sensitive and definitive for early diagnosis of ehrlichiosis. However, it is not a convenient method as it requires 14-34 days to obtain positive results.