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Tuberculosis (TB) is an infectious, granulomatous disease caused by acid-fast bacilli of the genus Mycobacterium. Although commonly defined as a chronic, debilitating disease, TB occasionally assumes an acute, rapidly progressive course. The disease affects practically all species of vertebrates and, before control measures were adopted, was a major disease of humans and domestic animals. Bovine TB is still a significant zoonosis in many parts of the world. Signs and lesions are generally similar in the various species.
Etiology
The main types of M tuberculosis complex (mammalian tubercle bacilli) recognized are M tuberculosis, M bovis, M caprae, M pinnipedii, M microti, and M africanum. The M avium complex includes M avium avium (avian bacilli), M avium hominisuis (isolated from humans and other mammals), and M intracellulare. The types differ in cultural characteristics and pathogenicity. The mammalian types are more closely related to each other than to the avian type. Several serovars of M avium avium are recognized; however, only serovars 1, 2, and 3 are pathogenic for birds. M bovis may survive on pasture for 2 mo or more and M avium may survive in soil for ≥4 yr.
All types may produce infection in host species other than their own. M tuberculosis is most specific; it rarely produces progressive disease in animals other than people and nonhuman primates, occasionally in dogs and pigs, and rarely birds. M bovis can cause progressive disease in most warm-blooded vertebrates, including humans. M caprae has been isolated from cattle and several other species in Europe. M avium avium is the only species of consequence in birds, but it has a wide host range and is also pathogenic for pigs, cattle, sheep, deer, mink, dogs, cats, and some cold-blooded animals. M intracellulare causes disease in cold-blooded animals. Mycobacteria other than tubercle bacilli (see Tuberculosis and other Mycobacterial Infections: Mycobacterial Infections Other than Tuberculosis) are infrequently isolated from exotic and domestic animals.
Pathogenesis
Inhalation of infected droplets expelled from the lungs is the usual route of infection, although ingestion, particularly via contaminated milk, also occurs. Intrauterine and coital methods of infection are recognized less commonly. Inhaled bacilli are phagocytosed by alveolar macrophages that may either clear the infection or allow the mycobacteria to proliferate. In the latter instance, a primary focus may form, mediated by cytokines associated with a hypersensitivity reaction that consists of dead and degenerate macrophages surrounded by epithelioid cells, granulocytes, lymphocytes, and later, multinucleated giant cells. The purulent to caseous, necrotic center may calcify, and the lesion may become surrounded by granulation tissue and a fibrous capsule to form the classic “tubercle.” The primary focus plus similar lesions formed in the regional lymph node is known as the “primary complex.” In alimentary forms of disease, the primary focus may be found in the pharynx or mesenteric lymph nodes or, less commonly, in the tonsils or intestines. The cellular composition of and presence of acid-fast bacilli in tuberculous lesions differ between and within host species.
The primary complex seldom heals in animals and may progress slowly or rapidly. Dissemination through vascular and lymphatic channels may be generalized and rapidly fatal, as in acute miliary TB. Nodular lesions may form in many organs, including the pleura, peritoneum, liver, kidney, skeleton, mammary glands, reproductive tract, and CNS. A prolonged, chronic course may also ensue, with lesions usually having a more localized pattern of distribution.
Clinical Findings
The clinical signs reflect the extent and location of lesions. Generalized signs include progressive emaciation, lethargy, weakness, anorexia, and a low-grade, fluctuating fever. The bronchopneumonia of the respiratory form of the disease causes a chronic, intermittent, moist cough with later signs of dyspnea and tachypnea. The destructive lesions of the granulomatous bronchopneumonia may be detected on auscultation and percussion. Superficial lymph node enlargement may be a useful diagnostic sign when present. Affected deeper lymph nodes cannot always be palpated, but they may cause obstruction of the airways, pharynx, and gut, leading to dyspnea and ruminal tympany.
In pigs, lesions caused by M avium avium are most often seen in lymph nodes associated with the GI tract, although generalized disease does occur.
Diagnosis
The single most important diagnostic test for TB is the intradermal tuberculin test; purified protein derivatives (PPD) prepared from the culture filtrate of M bovis or M avium can be used. Diagnosis based on clinical signs alone is very difficult, even in advanced cases. Radiography is useful in nonhuman primates and small animals. Microscopic examination of sputum and other discharges is sometimes used. Necropsy findings of the classic “tuberculous” granulomas are often very suggestive of the disease. Confirmation of diagnosis is by isolation and identification of the organism, with culture usually taking 4–8 wk, or by PCR, which requires only a few days. Molecular techniques, such as restriction fragment length polymorphism and spoligotyping provide useful information in conducting epidemiologic investigations.
The delayed-type hypersensitivity response of the host, responsible for much of the pathology of TB, is fundamental to the tuberculin skin test that is widely used for diagnosis in large animals. The single intradermal (SID) test involves inoculation of PPD. In a reactor, the antigen stimulates a local infiltrate of inflammatory cells and causes skin swelling that can be detected by palpation and measured by calipers. The reaction is read at 48–72 hr for maximum sensitivity and at 96 hr for maximum specificity. Test sites vary in sensitivity and between countries and include the neck region, caudal fold at the tail base, and vulval lip. One disadvantage of the M bovis SID test is that cross-reactions occur in animals infected with M avium avium, M tuberculosis, or M avium paratuberculosis.
In areas with a high incidence of either avian TB, atypical mycobacteriosis, or paratuberculosis, the comparative tuberculin skin test can be used, with biologically balanced M bovis and M avium PPD tuberculins inoculated simultaneously but at separate sites in the neck. The agent causing sensitization provokes the greater skin reaction. Other diagnostic tests used for TB include the thermal test, which may detect a pyrexic peak (104°F [>40°C]) at 6–8 hr after SC inoculation with tuberculin. The Stormont test uses an intradermal inoculation of PPD followed by a second inoculum at the same site 7 days later. The test is read for swelling 24 hr later.
False-negative results may occur in animals with poor immunity such as those in the early stages of infection, anergic cases in advanced disease, or old animals. Cattle that have recently calved also may have false negative results. Current research is focused on the identification of antigens such as secretory proteins and genetically engineered proteins of M bovis for use in improved diagnostic tests. Serologic tests such as ELISA appear to be of limited diagnostic use, consistent with the lesser role of antibody compared with the cellular immune response in TB. In vitro cellular assays (ie, interferon-γ assay) developed using WBC stimulated with M bovis antigen show promise as a supplemental test to the widely used SID test; however, they have not come into widespread use.
Control
The main reservoirs of infection are humans and cattle. However, other animals have been found to be reservoirs in some countries, including badgers and red deer (England, Ireland); red deer, brushtail possums and ferrets (New Zealand); mule deer, white-tailed deer, elk, and bison (North America); buffalo (South Africa); and water buffalo (Australia). The prevalence of disease in such reservoirs influences the incidence of disease in other species. Carnivores and scavengers can acquire M bovis by consumption of infected carcasses. These species include lion, coyote, wolf, hyena, cheetah, bobcat, and leopard. Warthogs, ferrets, raccoons, opossums, and feral pigs have also been found to be infected with M bovis.
The 3 principal approaches to the control of TB are test and slaughter, test and segregation, and chemotherapy. The test and slaughter policy is the only one assured of eradicating TB and relies on the slaughter of reactors to the tuberculin test. In an affected herd, testing every 3 mo is recommended to rid the herd of individuals that can disseminate infection. Routine hygienic measures aimed at cleaning and disinfecting contaminated food, water troughs, etc, are also useful. Test and slaughter has been used widely in the UK, USA, Canada, Germany, New Zealand, and Australia. In most European countries, where test and slaughter would have been impractical, varying forms of test and segregation have been used, with test and slaughter used only in the final stages of eradication.
Treatment of TB infections in elephants and nonhuman primates has been attempted using drugs that have had success in humans, eg, isoniazid, ethambutol, and rifampin. Efficacy is limited, and there are overriding arguments against therapy, based on the removal of infected animals, zoonotic risks, and the danger of encouraging drug resistance. Treatment is illegal in some countries. The BCG (bacille Calmette-Guérin) vaccine, sometimes used to control TB in humans, has proved to provide little protection in most animal species, and inoculation often provokes a severe local granulomatous reaction.
Last full review/revision March 2012 by Charles O. Thoen, DVM, PhD
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