The organism replicates intracellularly after it has been taken up by the macrophages.  A granuloma or tubercle forms as the body tries to wall off the infected macrophages with fibrous tissue.  The granuloma is usually 1-3 cm in diameter, yellow or gray, round and firm.  On cut section, the core of the granuloma consists of dry yellow, caseous, or necrotic cellular debris.  The infection can spread hematogenously to lymph nodes and other areas of the body and cause smaller, 2-3 mm in diameter, tubercles.  The formation of these smaller tubercles is known as “miliary tuberculosis”.   The histological lesions consist of necrotic cells in the center of the tubercle surrounded by epitheloid cells and multinucleated giant cells all encapsulated by collagenous connective tissue.  The necrotic core of cells can often become calcified as the tubercle matures.

Diagnosis of bovine tuberculosis can be accomplished through gross examination, histology, acid-fast staining, culturing the bacteria, and PCR.  In the live animal, interferon gamma testing, enzyme linked immunosorbent assay (ELISA) testing, and tuberculin testing can be performed.  The interferon gamma test is a whole blood immunoassay that detects the presence of the cytokine produced by natural killer cells in response to mycobacterial protein.  However, the most common in vitro test used in the United States is the tuberculin skin test.

  Tuberculin skin testing is based on T-cell response to mycobacterial proteins.  The caudal-fold tuberculin test is performed using 0.10 cc of a purified protein derivative.  This is injected intradermally in the skin of the tail.  The injection site should be examined for a reaction 72 hours post inoculation.  If there is a reaction, such as a discolored raised area, the animal is classified as a responder and undergoes a comparative cervical tuberculin test.  The test is more sensitive and helps to determine whether the animal is infected with M. bovis as opposed to M. avium or M. paratuberculosis.  This test is performed by injecting 0.10 cc of a more potent purified protein derivative intradermally into the cervical skin.  If the animal responds to this injection, it is classified as a reactor; the animal will be euthanized and a necropsy should be performed to determine the extent of the infection.

  Currently, treatment of bovine tuberculosis is not recommended due to its infectious nature.  If an animal is found to be infected, it should be culled from the herd.   However, there are some preventative measures available.  One way to ensure that cattle do not become infected is to eliminate any possible interaction with deer.  A population of white-tailed deer was found to harbor Mycobacterium bovis  in lower Michigan in 1995.  White-tailed deer can be infected with tuberculosis infection and spread it to uninfected cattle through nose to nose contact, aerosol droplets, or indirect contact.  The indirect contact is usually a result of cattle ingesting feed that has been contaminated by deer saliva.  It is recommended that any feed for cattle be protected and stored away from deer.  Other programs to control the deer population, such as hunting and banning feeding, have been implemented to decrease the density of deer and the population of affected deer.

  Vaccination for the prevention of bovine tuberculosis is another option that is being investigated.  A vaccine was created for M. bovis  in the 1920s by Calmette and Guerin.  The BCG vaccine has undergone some scrutiny due to variable efficacy.  The vaccine reduces the severity of the disease, usually allowing the bacteria to infect only a few lymph nodes, but does not prevent infection.  The vaccine can also cause false-positive caudal fold skin tests, which can cause confusion when testing is performed.  There are studies researching the efficacy of combining the BCG vaccine with mycobacterium protein and DNA.  The goal is to develop an enhanced vaccine that can provide protection against the disease.  The vaccine would be given to wildlife in an effort to prevent the spread of the disease to cattle.

  Bovine tuberculosis poses a significant risk to human and herd health.  The only way to be protected from the disease is through prevention.  It is important to limit the exposure of the herd to other infected cattle or wildlife.  Testing and eradication of infected animals is the current method of control, though additional research is currently being explored in the areas of vaccinations and other possible preventative measures.

-by Rose Paylor, Michigan State University Veterinary Student

-edited by Dr. Pam Mouser, ADDL Graduate  Student

References:

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7. O"Brien DJ, Schmitt SM, Fitzgerald SD, et al: 2006.  Managing the wildlife reservoir of Mycobacterium bovis: The Michigan, USA, experience.  Vet Microbiol 112(2-4): 313-323.

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12. The role of experimental models of infection.  Vet Microbiol 112(2-4): 141-150.

13. www.michigan.gov/emergingdiseases