Tuberculosis is an infectious zoonotic disease caused by Mycobacterium tuberculosis and Mycobacterium avium complex. It is usually a chronic, debilitating disease; however, symptoms vary across species. Diagnosis is based on the cellular immune response and identification of the organism by culture or molecular tests. Treatment relies on a prolonged course of a cocktail of antimicrobials and is often not attempted in animals, because of public health concerns.
Tuberculosis (TB) is an infectious granulomatous disease of animals and humans that is due to acid-fast bacilli of the genus Mycobacterium, particularly Mycobacterium tuberculosis complex (human and mammalian TB) and Mycobacterium avium complex (avian TB).
Although commonly defined as a chronic, debilitating disease, TB occasionally assumes an acute, rapidly progressive course. The disease affects many species of vertebrates. The widespread occurrence of multidrug-resistant (MDR) strains and extensively drug-resistant (XDR) strains of M tuberculosis is of concern to clinicians and public health and regulatory officials involved in the control of disease.
Bovine TB has been eradicated in some countries but is reemerging in others, often as a result of the establishment of multihost communities involving wildlife and production animals other than cattle. Bovine TB is still an important zoonotic disease in countries without control programs in cattle and without extensive milk pasteurization. Clinical signs and lesions are generally similar in the various species.
Etiology of Tuberculosis in Animals
The genus Mycobacterium comprises more than 170 species, most of which are environmental organisms.
The main recognized types of the Mycobacterium tuberculosis complex (mammalian tubercle bacilli) are M tuberculosis, M canettii, M bovis, M caprae, M pinnipedii, M microti, M mungi, M suricattae, M africanum, and the yet-unnamed dassie bacillus and chimpanzee bacillus.
The Mycobacterium avium complex includes M avium avium (avian tubercle bacilli), M avium hominissuis (isolated from humans, swine, and other mammals), and M intracellulare, among other species.
The types differ in characteristics during culture and in pathogenicity.
All Mycobacterium types may produce infection in host species other than their own.
M tuberculosis is the most host-specific; it produces progressive disease only rarely in animals other than humans and nonhuman primates (mainly dogs, pigs, cattle, and elephants).
M bovis can cause progressive disease in many mammalian species, including humans.
M caprae, an organism closely related to M bovis, has been isolated from humans, goats, cattle, and several wildlife species in Europe.
M avium avium is the species of most importance in birds; however, it has a wide host range and is also pathogenic for pigs, cattle, sheep, deer, mink, dogs, cats, certain exotic hoofed animals, and some cold-blooded animals.
M avium hominissuis is the cause of TB in immunocompromised humans, swine, and other animals.
M intracellulare causes disease in cold-blooded animals and has been isolated from many other species.
Pathogenesis of Tuberculosis in Animals
Inhalation of infected droplets expelled from the lungs is the usual route of TB infection; however, the bacteria can also be ingested, particularly via contaminated milk, water, or food. Transmission via infective bites is common in badgers. Intrauterine and coital methods of infection are less common.
Inhaled bacilli are phagocytosed by alveolar macrophages that may either clear the infection or allow the mycobacteria to proliferate. In the latter instance, a granuloma may form, consisting of dead and degenerate macrophages surrounded by epithelioid cells, granulocytes, lymphocytes, and eventually, multinucleated giant cells. The purulent to caseous necrotic center may calcify, and the lesion may become surrounded by granulation tissue and a fibrous capsule (forming a “tubercle”).
The initial granulomatous lesions in the organ and regional lymph node are known as the “primary complex.” Infection by the oral route can lead to a primary complex in the pharynx or mesenteric lymph nodes or, less commonly, in the tonsils or intestines. The cellular composition and presence of acid-fast bacilli in tuberculous lesions differ between and within host species. Latent infections, where mycobacteria survive in a nonreplicative state within granulomas, are common in human TB and might occur in animal TB, particularly in badgers.
The primary complex can remain stable for long periods or 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 sites, including the pleura, peritoneum, liver, kidney, spleen, skeleton, mammary glands, reproductive tract, and CNS. A prolonged, chronic course may also ensue, with lesions usually having a more localized pattern of distribution.
In pigs, lesions due to M avium hominissuis or M avium avium occur most often in lymph nodes associated with the GI tract. However, generalized disease involving the liver, lung, and spleen does occur.
Clinical Findings of Tuberculosis in Animals
Courtesy of Dr. Charles Thoen.
Courtesy of Dr. Charles Thoen.
Courtesy of Dr. Nuno Santos.
The expression of disease in TB-infected animals can range from latent and subclinical to severe, reflecting the extent and location of lesions. Generalized clinical signs include progressive emaciation, lethargy, weakness, anorexia, diarrhea, 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 and draining abscesses may be present. Affected deeper lymph nodes cannot always be palpated; however, they may cause obstruction of the airways, pharynx, and gut, leading to dyspnea and ruminal tympany.
Diagnosis of Tuberculosis in Animals
Cellular immune response
Identification of the pathogen via culture or molecular tests
The single most important diagnostic test for TB is the intradermal tuberculin test. Purified protein derivatives (PPDs) prepared from the culture filtrate of M bovis or M avium. The delayed-type hypersensitivity response of the host, responsible for much of the pathology of TB, is fundamental to the tuberculin skin test widely used for diagnosis in large animals. For the single intradermal tuberculin test (SITT), the animal is inoculated with bovine PPD. In a reactor (ie, an animal who reacts to the test), 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 hours for maximum sensitivity and at 96 hours for maximum specificity.
Test sites vary in sensitivity and by anatomic location; they include the neck region, caudal fold at the tail base, and vulval lip. One disadvantage of the bovine SITT is that cross-reactions may occur in animals infected with M kansasii, M avium, M tuberculosis, M avium paratuberculosis, or other mycobacteria that share some antigenic determinants with M bovis.
In areas with a high incidence of avian TB or other mycobacterial infections such as paratuberculosis, the single comparative intradermal tuberculin test (SCITT) can be used, with biologically balanced bovine and avian PPD tuberculins inoculated simultaneously at separate sites in the neck. The agent that induces sensitization provokes the greater skin reaction.
False-negative results may occur in animals with poor immune response, such as those in the early stages of infection, nonresponsive cases in advanced disease, or old animals. Cattle that have recently calved may also have false-negative results.
Clinical signs can direct diagnosis but are not pathognomonic, even in advanced cases. Radiography, computed tomography, cytology, and PCR assay of buffy coat or exudates can be useful in nonhuman primates and pets. Microscopic examination of sputum and other discharges can be used to direct diagnostic investigations. Necropsy findings of granulomas are often very suggestive of the disease.
The diagnosis is confirmed by isolation and identification of the organism, with culture usually taking 4–15 weeks, or by PCR assay. Molecular genotyping techniques such as spoligotyping, variable-number-tandem-repeat typing, and whole-genome sequencing are useful in conducting epidemiologic investigations.
In vitro cellular assays (ie, interferon-gamma assay) using WBCs stimulated with M bovis antigen can be used to supplement the widely used intradermal tuberculin test. In many countries, however, they have not come into widespread use, because of cost and the necessity to conduct cellular assays in the laboratory within 24 hours (preferably within 8 hours) after blood specimens are collected.
Despite the lesser role of a humoral immune response in TB, serologic tests such as ELISA perform well in swine, and lateral flow tests have been developed for a cocktail of antigens in several species, including elephants.
Control of Tuberculosis in Animals
Control: test-and-cull and abattoir surveillance
Treatment: rarely attempted in pets and endangered species because of zoonotic risk
The main reservoir of M bovis infection is cattle. However, bovine TB often persists in a multihost community that includes wildlife and other domestic animals: Eurasian badgers, cervids, and wild boars in Europe; red deer, possums, and ferrets in New Zealand; cervids and American bison in North America; African buffalo in South Africa; and water buffalo in Australia. Control is particularly challenging when M bovis or M caprae is present in a multihost community.
Carnivores and scavengers can acquire M bovis by consuming infected carcasses or by interacting with affected animals of other species. These species include Eurasian badger ferret, raccoon, lion, coyote, wolf, hyena, cheetah, black bear, bobcat, and leopard. Wild pigs, warthogs and wild boars are particularly susceptible to environmental contamination with M bovis.
The main approaches to the control of TB in production animals are test-and-cull and abattoir surveillance. Test-and-cull relies on routinely scheduled testing, after which reactors to the intradermal tuberculin test or interferon-gamma assay are slaughtered. Alternatively, test-and-cull may be carried out prior to any animal or herd transport. In an affected herd, testing every 2 months is recommended to rid the herd of individuals that can disseminate infection.
Routine hygienic measures aimed at cleaning and disinfecting contaminated premises, as well as strict biosecurity, are useful. Test-and-slaughter is mandatory in many countries, in some cases leading to eradication. In some countries, where test-and-cull is impractical, test-and-segregate strategies have been used for control.
In pet animals, treatment can control the progression of disease but should be performed with caution because of public health concerns. The causative agent should be identified by culture of lesion biopsies, and excretion of infective mycobacteria should be monitored.
No reliable TB vaccine is available for any species. Live attenuated, heat-inactivated, protein subunit, and DNA vaccines have all been developed; they are not administered, however—in part because they interfere with the diagnostic assays used in eradication programs.
Zoonotic Potential of Tuberculosis in Animals
All members of the M. tuberculosis complex are zoonotic pathogens capable of infecting humans. The burden of zoonotic tuberculosis can be substantial in lower resource settings where eradication programs and milk pasteurization have not been implemented. Herders, abattoir workers, and game meat handlers are most at risk.
The global burden of zoonotic tuberculosis is underrecognized due to the inability of standard laboratory procedures to differentiate human cases of zoonotic TB from overall tuberculosis cases. Zoonotic TB lesions often have an extrapulmonary location which may hinder diagnosis. Treatment failures are more common in zoonotic TB.
Key Points
TB-causing bacteria are typically transmitted by inhalation or ingestion, leading to granulomatous lesions in the lungs and in the cephalic, thoracic, or mesenteric lymph nodes.
Symptoms are nonspecific. Diagnosis is based on the intradermal tuberculin test, interferon-gamma test, or specific identification of the organism by culture or molecular tests.
Control in production animals is based on test-and-cull and abattoir surveillance. Treatment of pets and endangered captive wildlife is often not attempted, because of public health concerns.
For More Information
World Organisation for Animal Health. Manual of Diagnostic Tests and Vaccines for Terrestrial Animals 2022. Accessed March 2, 2023. https://www.woah.org/en/what-we-do/standards/codes-and-manuals/terrestrial-manual-online-access/
World Health Organization. Global Tuberculosis Report 2022. Accessed March 2, 2023. https://www.who.int/teams/global-tuberculosis-programme/tb-reports/global-tuberculosis-report-2022
Roadmap for Zoonotic Tuberculosis (WHO, FAO, and OIE, 2017).
Also see pet health content regarding tuberculosis in cats, dogs, and horses.
