A diagnosis of Colorado tick fever can be established through the direct detection of viral antigens, virus isolation, or serologic tests. The best, most rapid method is detection of viral antigen on the surfaces of erythrocytes in a blood smear through the use of immunofluorescence. Laboratory tests may be available through state public health departments or the Centers for Disease Control and Prevention.
The titers of antibody in acute and convalescent specimens must be compared for a serologically based diagnosis to be rendered because subclinical infections can occur and antibody may persist for a lifetime. Specific IgM is present for approximately 45 days after the onset of illness, and its detection is also presumptive evidence of an acute or very recent infection. Immunofluorescence is the best technique, but complement fixation, neutralization, and enzyme immunoassay are also used to detect Colorado tick fever antibody.