Mammalian tuberculosis

What is mammalian tuberculosis?

Mammalian tuberculosis (TB) is a major infectious disease among cattle and affects other domesticated animals, certain wildlife populations and occasionally humans, causing a general state of illness, pneumonia, weight loss, and eventual death. It can have a considerable impact on the welfare of livestock, as well as farmers, vets and butchers, and disrupt the balance of ecosystems. 
 
The name ‘tuberculosis’ comes from the nodules called ‘tubercles’, which form in the lymph nodes and other tissues of affected animals and humans. Despite its impact, vaccination is limited due to its interference with tuberculosis surveillance and diagnostics. Consequently, control relies heavily on testing, culling, and biosecurity measures. Infection in cattle herds has been controlled in high-income countries, however, complete elimination of the disease is complicated by persistent infection of wild animals, such as European badgers in the United Kingdom, white tailed deer in parts of the United States of America and brushtail possums in New Zealand.

Cattle are considered to be the major reservoir M. bovis, and are the main source of infection for humans. Nevertheless, the disease has been reported in many other domesticated and non-domesticated animals.

Mycobacterium bovis has been isolated from numerous wildlife species, including African buffalo, domestic Asian buffalo, bison, sheep, goats, equines, camels, pigs, wild boars, deer, antelopes, dogs, cats, foxes, mink, badgers, ferrets, rats, primates, llamas, kudus, elands, tapirs, elks, elephants, sitatungas, oryxes, addaxes, rhinoceroses, possums, ground squirrels, otters, seals, hares, moles, raccoons, coyotes and several predatory felines including lions, tigers, leopards and lynx.

Mammalian TB is a WOAH-listed disease and must be reported to the WOAH as indicated in its Terrestrial Animal Health Code.

‘‘Most cases of human TB are caused by the bacterial species, Mycobacterium tuberculosis. Zoonotic TB is a form of TB in people predominantly caused by a closely related species, M. bovis, which belongs to the M. tuberculosis complex.’ 

Human exposure to any member of the MTBC (apart from BCG vaccine strain) may result in zoonotic infection.

The WOAH Terrestrial Animal Health Code and WOAH Manual of Diagnostic Tests and Vaccines for Terrestrial Animals provide technical standards and recommendations that are intended to manage the human and animal health risks associated with infection of animals with a member of the Mycobacterium tuberculosis complex, including M. bovis. 

Geographical distribution

Mammalian TB is found throughout the world, but some countries have never detected TB, and many high-income countries have reduced or eliminated mammalian TB from their cattle population and kept the disease limited to one or more zones. However, significant pockets of infection remain in wildlife. Africa and parts of Asia bear the highest burden of mammalian TB, but the disease is also present in Europe and the Americas. 

Transmission and spread

The disease is contagious and can be transmitted directly by contact with infected domestic and wild animals or indirectly by ingestion of contaminated material.

The usual route of infection within cattle herds is by inhalation of aerosols and respiratory droplets from infected animals, which are expelled from the lungs (by coughing). Infection by ingestion of contaminated material also occurs as calves can be infected by ingesting colostrum or milk from infected cows. Less commonly, infection can occur through direct contact with infected urine, faeces, vaginal secretions and semen. 

Humans can become infected by the same routes as animals, including inhalation, ingestion and direct contact with mucous membranes or breaks in the skin. Ingesting raw milk and dairy products from infected cows as well as eating contaminated meat that is raw or undercooked poses a large risk of infection, particularly in rural communities with limited access to pasteurisation. Infection can also occur through direct contact with infected tissues on farms or at abattoirs or butcheries. 

The course of disease is slow and takes months or years to reach the fatal stage. Consequently, an infected animal can shed the bacteria within the herd before the appearance of clinical signs. Therefore, movement of undetected infected domestic animals is a major way of spreading the disease. 

Clinical signs

Mammalian TB may be subacute or chronic, with a variable rate of progression in animals.  A small number of animals may become severely affected within a few months of infection, while others may take several years to develop clinical signs. The bacteria can also lie dormant in the host without causing disease for a long period. 

The usual clinical signs include weakness, loss of appetite and weight, fluctuating fever, dyspnoea and intermittent hacking cough, signs of low-grade pneumonia, diarrhoea enlarged and prominent lymph nodes. 

Diagnosis

Mammalian TB’s clinical signs are not specifically distinctive and, therefore, do not enable veterinarians to make a definitive diagnosis based on clinical signs alone. 

The tuberculin skin test is the standard method of TB diagnosis in live domestic animals. It consists of injecting mammalian tuberculin (a purified protein extract derived from M. bovis) intradermally and then measuring skin thickness at the site of injection 72 hours later to detect any subsequent swelling at the injection site (sign of delayed hypersensitivity associated with infection). 

Blood-based in vitro tests that detect bacteria, antibodies, or cell-mediated immunity are also currently available, or under development. The most widely used blood-based test is a gamma interferon release assay which detects a cell-mediated immune response to infection with M. bovis. This test is based on the principle that bovine blood cells that have previously been exposed to M. bovis through an infection are known to produce elevated levels of gamma interferon following in vitro incubation with M. bovis antigens. 
Meanwhile, the definitive diagnosis is confirmed by bacterial culture and identification in the laboratory, a process that can take eight weeks or more.

Currently, the definitive diagnosis is confirmed by bacterial culture and identification in the laboratory, a process that can take eight weeks or more. 

The other recommended diagnostic methods and the procedures for manufacturing and administering mammalian tuberculin, are described in the WOAH Manual of Diagnostic Tests and Vaccines for Terrestrial Animals. 

Public health risk

The most common form of TB in people is caused by M. tuberculosis. However, it is not possible to clinically differentiate infections caused by M. tuberculosis from those caused by M. bovis, which is estimated to account for up to 10% of human tuberculosis cases in some countries.

Diagnosis may be further complicated by the tendency of M. bovis infections to be located in tissues other than the lungs (i.e. extrapulmonary infection) and the fact that M. bovis is naturally resistant to one of the antimicrobials that is commonly used to treat human tuberculosis, pyrazinamide, one of the antimicrobials that is commonly used to treat human tuberculosis.

The WOAH Terrestrial Animal Health Code and WOAH Manual of Diagnostic Tests and Vaccines for Terrestrial Animals provide technical standards and recommendations  that are intended to manage the human and animal health risks associated with infection of animals with a member of the Mycobacterium tuberculosis complex, including M. bovis.

Roadmap for zoonotic tuberculosis

Human TB is a major cause of illness and mortality worldwide. It is primarily caused by M. tuberculosis and is usually transmitted by close contact and inhalation of infected aerosols.  Zoonotic TB is a less common form of human TB that is caused by a related member of the Mycobacterium tuberculosis complex (M. bovis). The zoonotic form is primarily transmitted indirectly, through the consumption of contaminated milk, dairy products, or meat containing infected material. In regions where food hygiene is consistently applied, the risk to the general public has been reduced, however zoonotic tuberculosis infection remains an occupational hazard for farmers, abattoir workers and butchers, which can impact their health and disrupt meat supply chains.

WOAH, the World Health Organization (WHO), the Food and Agriculture Organization of the UN (FAO) and the International Union Against Tuberculosis and Lung Disease (The Union) jointly launched the first-ever roadmap to tackle zoonotic TB in October 2017. It is based on a One Health approach recognising the interdependence of human and animal health sectors for addressing the major health and economic impacts of this disease.

This roadmap calls for concerted action from government agencies, donors, academia, non-governmental organisations and private stakeholders across political, financial and technical levels. It defines ten priorities for tackling zoonotic TB in people and bovine TB in animals. These fall under three core themes:

• Improve the scientific evidence base
• Reduce transmission at the animal-human interface
• Strengthen intersectoral and collaborative approaches

Prevention and control

National control and eradication programs based on test and slaughter of infected animals have been successfully implemented in many countries, as the preferred approach to managing mammalian TB. However, this approach remains impractical in many heavily infected countries because it could necessitate slaughtering large numbers of cattle, which may not be feasible due to human resource or financial limitations within the animal health program, or for cultural reasons. Therefore, countries use varying forms of test and segregation in early stages and then switch to test-and-slaughter methods in the final stage. 

In regions with high prevalence of human tuberculosis and close interface with livestock, humans may also represent as maintenance host for livestock infections. Spillovers from humans to animals reported for M. tuberculosis, M. bovis and M. orygis.

Several disease eradication programmes have been very successful in reducing or eliminating the disease in cattle, by employing a multi-faceted approach that includes:

• post mortem meat inspection (looking for tubercles in the lungs, lymph nodes, intestines, liver, spleen, pleura, and peritoneum), for detection of infected animals and herds
• intensive surveillance including on-farm visits
• systematic individual testing of cattle
• removal of infected and in-contact animals
• adequate local legislation
• effective movement controls
• individual animal identification
• effective traceability.

Detecting infected animals prevents unsafe meat from entering the food chain and allows Veterinary Services to trace-back to the herd of origin of the infected animal which can then be tested and eliminated if needed. Pasteurisation or heat treatment of milk from potentially infected animals to a temperature sufficient to kill the bacteria has proven effective for preventing the spread of disease to humans. 

Prevention also includes educating farmers and the public about the risks of consuming raw animal products, promoting pasteurisation, and implementing rigorous testing of dairy products and meat. As well as educating abattoir workers and butchers about TB risks and safe practices including hygiene and safety protocols.  

Antimicrobial treatment of infected animals is rarely attempted because of the doses and duration of treatment that would be required, high cost of medications, and interference with the primary goal of eliminating the disease, and potential risk of developing resistance.

Vaccination is practiced in human medicine, but it is, so far, not used as a preventive measure in animals, due to the lack of availability of safe and effective vaccines, and potential interference with mammalian tuberculosis surveillance and diagnostic tests, due to false positive reactions in vaccinated animals. Researchers are actively investigating potential new or improved mammalian tuberculosis vaccines and alternate routes of vaccine delivery for use in domestic animals and wildlife reservoirs, as well as new diagnostic tests to reliably differentiate vaccinated animals from infected animals.

For more information on AMR, contact: Antimicrobial Resistance and Veterinary Products Department

Guidelines for the control of Mycobacterium tuberculosis complex in livestock 

Guidelines are available for Members and stakeholders of the livestock industry in advancing the control of mammalian TB, using strategies other than or to complement, testing and slaughtering (T&S) of animals. These strategies complement the framework of standards provided by the WOAH Terrestrial Animal Health Code (Terrestrial Code) and the Manual of Diagnostic Tests and Vaccines for Terrestrial Animals (Terrestrial Manual). 

To understand how the guidelines could be used, watch the webinar replay: Beyond test and slaughter – control of Mycobacterium tuberculosis complex in livestock.

For more information on guidelines, contact Science department.