BOVINE TUBERCULOSIS

You're doing a rotation with Heifer International in a village in Kenya, assisting the HI veterinarians help the locals with their livestock. You provide vaccinations and antibiotics perform physical examinations. A Masai herdsman from the village complains that his cattle are showing a variety of bad symptoms. They're failing to thrive, are weak and off feed. Many are lethargic and somewhat emaciated. A few have rough haircoats. Many of his cows remain open throughout the breeding season and those who conceive often abort their calves. Furthermore, lactating cows often come down with mastitis. You examine the cattle the cattle and find they are meager and thin. A number of the cattle are dyspneic and have a frequent cough. The lungs of these animals sound wet upon auscultation.

You ask the herdsman how long the condition has persisted and he indicates that it has been this way for some time. He also remarks that a former neighbor's swine had a similar problem. He turns away for a moment and coughs violently for about a minute. Your HI supervisor advises you to put on a surgical mask and gloves, and do a tuberculin test on the cattle. It comes up positive.


DIAGNOSIS

This is a case of chronic bovine tuberculosis affecting an entire herd. Bovine tuberculosis is caused by Mycobacterium bovis, a nasty organism that's the target of vigorous eradication programs throughout the world. It can infect and cause disease in most mammals and is also a zoonosis, hence the organized efforts to combat it. Control efforts in the United States have been largely successful, but occasional outbreaks may still occur (typically in Western states or in herds that have had contact with foreign animals) but it's still a fairly common problem in the developing world.

Diagnosis of bovine tuberculosis can be quite difficult, especially in areas where it has been assumed to be eliminated. Typical signs in cattle involve the respiratory system, as would be expected. Low grade coughing and dyspnea are common signs as is a general unthriftyness. Long term systemic infection can be very difficult to diagnose since symptoms may be noted in many different organ systems. In this case, some cows had abortions, indicating uterine involvement, and others had mastitis, indicating mammary involvement.

Definitive diagnosis relies on tuberculin testing: this involves intradermal injection of tuberculin and observation of the injection site for 96 hours. The test is eliciting an immune response to the tuberculin, and a negative result—no swelling—indicates that the animal hasn't been infected or exposed. A positive result, however, indicates the animal has circulating antibodies and has been exposed. This is the reason why we don't vaccinate against bovine tuberculosis in the U.S.: antibodies against the vaccine would negate the tuberculin test's ability to find diseased cattle. A vaccine is no good for monitoring prevention if you can't differentiate a response to disease from a response to vaccination.

In the United States there is a national policy for the control and elimination of bovine tuberculosis. It is a "reportable" disease, meaning that if you find it, you had better let the state veterinarian know right away. The farm and all the people who work on it, possibly including you, will be quarantined. In the U.S., we don't treat bovine tuberculosis. The policy is to "test and slaughter": any animal that tests positive will be culled, and in fact it's likely that the entire herd would be condemned out of hand simply to avoid the risk of missing a reactor and allowing the infection to persist.

Mycobacterium bovis is particularly difficult to combat because it is a facultative intracellular parasite and is thus shielded from the humoral immune system. The bacterium does evoke a strong cell mediated immune response but that response is generally ineffective: the result is a chronic infection predominately composed of macrophages. These macrophages surround the infected cells but they are unable to engulf the bacteria. The bacteria continue to multiply, evoking a continuous call for more macrophages, and the macrophages respond by forming a granuloma at the site of infection.

Mycobacterium infections are acquired principally through inhalation or ingestion, so the site of these primary granulomas is either in the lungs or in the intestines. In M. bovis infections, the lungs are typically affected: an example is shown at left from a gross specimen. The infection spreads via the lymphatic system as new bacteria drain into the local lymph nodes around the granuloma. This, of course, stimulates macrophages to accumulate in the lymph nodes where yet more granulomas form. In chronic cases, it's possible for the infection to move throughout the host's body, causing granulomas and loss of function in multiple systems.

Remember that this is a zoonotic; if you suspect you are dealing with a mycobacterium infection, wear gloves and masks, and take precautions when handling samples.


HISTOPATHOLOGY

This is a lymph node that has been infected with M. tuberculosis. The normal architecture has been obliterated. The cortex and medulla are indistinct, the outer edge of the tissue is irregular, and there are no distinct germinal centers.

Normal lymph nodes have a distinct separation between cotex and medulla with dense, ordered cords of lymphocytes aligned along fibrous scaffolds. This node contains a mixture of inflammatory cells but they reacting to infection within the lymph node itself.

The lungs of this animal show granulomas both grossly (left) and in low-power microscopic view. These appear grossly as varying knot-like condensations of material among the few remaining alveoli: the extent of obliteration of alveoli can be better appreciate in the microscopic image. No wonder these cattle have difficulty breathing!


In the center of this image is a round focus of granulomatous inflammation surrounded by an irregular zone of necrosis and inflammatory cells. The necrotic area around it is collateral damage from the inflammation that resulted in dealing with some of the bacterial colonization. There are other areas of caseous necrosis visible in the periphery of this field, and the congestion of blood vessels is obvious. As the granulomas grow and increase in numbers pulmonary circulation is impaired, exacerbating the problem. At right below is a close view of a zone of caseous necrosis. The principal visible difference between this form of necrosis and coagulative necrosis is that the dead cells are indistinct. They have lose all resemblance to their original form; in coagulative necrosis "ghosts" persist. Here they've been reduced to a semi-solid mass sprinkled with cell debris. On the periphery in addition to the cellular debris, there are some neutrophils and macrophages present, cleaning up the mess. Mixed inflammatory cells are being drawn toward the pink necrotic zones as part of an ongoing stimulus caused by the infection.

 

This field is a medium magnification view, in which numerous giant cells are visible. The giant cells are the hallmark of a granuloma: they form in response to a persistent stimulus, so their presence is an indication that what's happening isn't an overnight phenomenon, but one that has been there for days, weeks, or months.

 

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