A Concise Review on Zoonotic Tuberculosis
B.S. Bharath Kumar1* and Vyankat Gangadhar Jadhav2
1 Veterinary Officer, Veterinary Dispensary, Katgal, Kumta, Uttara Kannada, Department of Animal Husbandry and Veterinary Services, Government of Karnataka-581362
2 Livesstock Development Officer, Taluka Mini Veterinary Polyclinic, Degloor, Nanded, Maharashtra-431717
Introduction:
A zoonosis is an infection directly transmissible from animals to humans naturally (WHO, 2020b) and for this to happen regularly, there needs to be a reservoir in an animal population. The majority of zoonoses occur where there is close contact between humans and relatively abundant animal species (Johnson et al., 2020). The 2020 World Health Organization (WHO) Global Tuberculosis Report (WHO, 2020a) estimates that in 2019, 10 million people (range, 8.9–11.0 million) developed TB disease of which approximately 1.2 million people died, with a further 208,000 deaths attributed to the TB-HIV syndemic (WHO, 2020a). Zoonotic tuberculosis (TB) is a form of TB in people predominantly caused by the bacterial species, Mycobacterium bovis, which belongs to the M. tuberculosis complex. The implications of zoonotic TB go beyond human health. Although, cattle is a common host for M. tuberculosis complex, it also causes TB in other animal species including wildlife. Bovine TB has an important economic impact and threatens livelihoods. The Strategy calls for diagnosis and treatment of every person with TB, and this must include zoonotic TB.
Transmission:
The main route of transmission of M. bovis to people is indirect. It is most commonly transmitted through the consumption of contaminated milk and other dairy products that have not been heat-treated. Less commonly, it can be transmitted through the consumption of raw or improperly cooked contaminated meat. Direct airborne transmission of M. bovis has also been reported from infected animals or animal products to people, as well as between people.
Clinical signs:
In animals
Bovine TB is a chronic debilitating disease usually characterized by formation of nodular granulomas known as tubercles. In many animals the course of the infection is chronic and signs may be absent, even in advanced cases when many organs may be involved. Subclinical signs include weakness, dyspnea, anorexia, emaciation, enlargement of lymph nodes, and cough, particularly with advanced tuberculosis. Lesions are commonly observed in the lymph nodes mainly of the head and thorax, lungs, intestines, liver, spleen, pleura, and peritoneum. Head and neck lymph nodes may become visibly affected, sometimes rupture, drain, and in advanced cases may be greatly enlarged and may obstruct air passages, alimentary tract, or blood vessels. Clinical signs vary with the involvement of the lung manifested through cough, dyspnea, and other signs of low-grade pneumonia which can be induced by changes in temperature or manual pressure on the trachea. Digestive tract involvement is manifested by intermittent diarrhea or constipation, extreme emaciation, and acute respiratory distress may occur during the terminal stages of tuberculosis [WHO, 2009].
In humans
Bovis infection in humans has similar clinical forms as those caused by M. tuberculosis [HPA, 2010]. Most of the studies have suggested that the common clinical manifestation of M. bovis infection in man is associated with the extra-pulmonary form of the disease; however, about half of the post-primary cases involve the lung which is responsible for human-to-human transmission of tuberculosis due to M. bovis [Cosivi et al., 1998]. The primary infection of the organism in the intestine may heal or it may progress in the intestines or disseminate to other organs. Cervical lymphadenopathy, intestinal lesions, chronic skin tuberculosis, and other non-pulmonary forms are particularly common. Infection due to M bovis in humans usually has a prolonged course and symptoms generally takes months or years to appear. Sometimes, the bacteria remain dormant in the host without causing diseases. The common clinical signs of zoonotic TB include loss of appetite, diarrhea, weight loss, intermittent fever, intermittent hacking cough, large prominent lymph nodes, weakness, and so on.
Young children infected with M. bovis typically have abdominal infections and older patients suffer from swollen and sometimes ulcerated lymph glands in the neck. Pulmonary disease is more common in people with reactivated infections and this would occur only when some of the animals had active tuberculosis. The symptoms may include fever, cough, chest pain, cavitation, and hemoptysis. The pulmonary form of tuberculosis occurs less frequently and is usually occupationally related [Teppawar et al., 2018].
Diagnosis:
TB in live animals is mainly diagnosed using the intradermal tuberculin skin test (TST) to detect delayed hypersensitivity response to tuberculin. Culture or molecular techniques (PCR and WGS) are used for microbiological confirmation of the TB‐causing agent. Blood tests based on host immune responses (e.g. IFN-ɣ release assay, ELISA, ELISpot, Differentiating Infected from Vaccinated Animal [DIVA] test) [Vordermeier et al., 2011] are also used for identification of infection with M. bovis, but its accuracy for diagnosing infection with other zTB agents has not been established. For all these tests, the identification of the zTB agent depends on proper collection of quality specimen. However, these tests are not routinely done in high burden countries, due to lack of resources and adequately trained personnel. This is particularly the case for molecular diagnostics, meaning that TB data often lack the resolution required for epidemiological studies.
Vaccine development:
Historically, eradication of bovine TB from cattle herds by test-and-slaughter or test-and-cull of infected animals was preferred over control by vaccination of cattle. Eradication efforts, have, however, proven unsuccessful possibly because a wildlife reservoir is present or where eradication is not affordable or culling is culturally unacceptable. Oral BCG administration has demonstrated significant protection against human and animal TB.
Oral BCG vaccine administered to wildlife reservoirs including European badgers, brushtail possums, wild boar, and deer has shown to induce protection against TB and could prove to be a practical means to vaccinate these species at large scale [Buddle et al., 2018]. This offers a potential solution in settings where “test and cull” is not an option and especially in wildlife species threatened by extinction. A major constraint of using BCG vaccination in cattle is the fact that trading blocs like the European Union prohibit the use of TB vaccines in cattle, since vaccination compromises the interpretation of traditional TB diagnostic tests. However, these concerns have been addressed with the development of more specific tests that differentiate infected from vaccinated animals (DIVA®) [Vordermeier et al., 2011] and of a diagnostic compatible BCG vaccine strain not eliciting an immune response in the compatible skin test. Although BCG should offer some protection against multiple MTBC species, including M. orygis, it should be recognized that protection will not be complete and should be used to complement, rather than replace, more traditional control measures.
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 bovine tuberculosis. However, this approach remains impractical in some heavily infected countries because it could necessitate slaughtering large numbers of cattle, and this 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.
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.
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 bovine tuberculosis surveillance and diagnostic tests, due to false positive reactions in vaccinated animals. Researchers are actively investigating potential new or improved bovine 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.
References:
[1] WHO . 2020b. Health Topics: Zoonoses. Geneva, Switzerland.
[2] WHO . 2020a. Global Tuberculosis report 2020. Geneva, Switzerland.
[3] Johnson C.K., Hitchens P.L., Pandit P.S., Rushmore J., Evans T.S., Young C.C.W., et al. Global shifts in mammalian population trends reveal key predictors of virus spillover risk. Proc R Soc B Biol Sci. 2020;287(April (1924)):20192736.
[4] World Organisation for Animal Health. Manual of Diagnostic Tests and Vaccines for Terrestrial Animals Chapter 2.4.7: Bovine tuberculosis adopted; 2009
[5] Health Protection Agency (HPA). Reducing the risk of human M. Bovis infection: Information for farmers. Bovine TB; 2009. p. 2010
[6] Cosivi O, Grange JM, Daborn CJ, Raviglione MC, Fujikura T, Cousins D. Zoonotic tuberculosis due to Mycobacterium bovis in developing countries. Emerging Infectious Diseases. 1998;4:59-70
[7] Vordermeier M., Jones G.J., Whelan A.O. DIVA reagents for bovine tuberculosis vaccines in cattle. Expert Rev Vaccines. 2011;10(July (7)):1083–1091.
[8] Buddle B.M., Vordermeier H.M., Chambers M.A., de Klerk-Lorist L.-M. Efficacy and Safety of BCG Vaccine for Control of Tuberculosis in Domestic Livestock and Wildlife. Front Vet Sci. 2018;5(October)
