Diagnostic testing History: Heifer #11

Heifer #11 was experimentally infected with M. paratuberculosis by feeding it a low dose (one million bacterial cells) in its evening bottle of milk on each of three nights when one month old. Every 4 weeks it was tested for Johne's disease using BACTEC fecal culture, the ELISA for serum antibodies, and the gamma interferon test.

Blue arrows under the time axis show when the cow was fecal culture-positive. This cow was sporadically shedding M. paratuberculosis bacteria in her feces. Fecal culture was the first test to detect that the animal was infected. This is not always the case. For unknown reasons, possibly bad luck or possibly genetics of the cow, the infection progressed very rapidly.

The red line indicates the gamma interferon response. The interferon response was biphasic (two peaks) and started before serum antibodies were produced. Shortly before heifer #11 died, the interferon response declined to zero. Lack of a cellular immune response in the terminal stages of M. paratuberculosis infection has been observed by others.

The yellow line shows the rapid rise of antibodies in serum that occurred about 6 months before the cow died. Generally, tests for serum antibodies become positive late in the course of paratuberculosis and a rapid rise or high levels of serum antibodies indicates a bad prognosis: the animal will soon have clinical signs of Johne's disease.

The pattern of diagnostic tests seen in heifer #11 illustrates an important principle about diagnostic testing for paratuberculosis: even though an animal is infected, at any given point in time any single diagnostic test can easily miss detection of the infection in the animal. Only by use of multiple tests over time can confidence in negative test results be obtained. These results also show that for different tests there are different "windows" of time during progression of the infection when each is best used. Chose the test that works the best for age of animals being tested.