6. Pathogenesis

5. Epidemiology of bovine tuberculosis

African buffalo in Africa and white-tailed deer in the USA [9].

5.2 Geographical distribution and prevalence

5.3 Transmission and risk factors

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Mycobacteria have one of the widest host range and affects mammal, birds, fish, reptiles, and amphibians. Cattle and related ruminants such as buffalo and bison are regarded as the main hosts of M. bovis subspecies. Other mammalian hosts include sheep, goats, camels, horses, llamas, pigs, dogs, cats, humans, and nonhuman primates [40]. Many wild animals, including elephants, rhinoceroses, coyotes, mink, otters, seals, sea lions, hares, bears, warthogs, large cats ferrets, and rodents are affected. Known maintenance hosts include possums and ferrets in New Zealand; badgers, raccoons, and foxes in Europe; bison and elk in Canada; and kudu and

Zoonotic tuberculosis caused by M. bovis has a worldwide distribution. It was reported by 78 of the 181 OIE reporting countries in 2017, distributed in every region of the world [41]. This figure is likely to be much lower due to underreporting, occasioned by inadequate surveillance. Globally, the prevalence has been estimated at 0.8% [42]. Using reports of zoonotic tuberculosis in humans as indication, the highest prevalence is found in African region followed by South East Asia, Western pacific, Eastern Mediterranean, Europe, and lastly Americas [43]. The disease has been largely controlled in developed world through systematic test and slaughter of infected animals, meat inspection surveillance in abattoirs, and milk pasteurization but complete eradication has been hindered by the existence of reservoirs of the agent in wildlife species [44]. In many developing countries, the disease remains largely neglected [45]. MOTTs have mainly been isolated coincidentally from animal lesions while searching for M. bovis. Isolation of MOOTs from cattle carcasses range approximately between 7 and 70% of total isolates [4, 5].

Infected animals shed Mycobacterium via respiratory aerosols, milk, saliva, feces,

Other rare routes of infection include cutaneous, genital during coitus, congen-

ital through placental or umbilical infection, and transmission through udder infections [47]. Contact between domestic and wild animals through pasture contamination is a risk factor. Domestic species reported to be reservoirs and spill-over

urine, and discharging lesions. The main route of infection in cattle is mainly through the inhalation of infective aerosols. This is supported by high frequency of tuberculous lesions found in the respiratory tract and associated lymph nodes [46]. Transmission is facilitated by close contact between animals and therefore the production system plays an important role. Intensive livestock farming, referred to as zero-grazing, promotes close contact between animals. In extensive production, such as practiced by nomadic pastoralists in arid and semiarid regions of Africa, close contact between animals occur in, night shelters, watering points, vaccination centers, marketing yards, and at dipping tanks while in intensive production close contact occurs during milking and in watering and feeding troughs [36]. Ingestion of contaminated feed and water is generally considered to be a secondary, less important route of transmission but in countries where untreated manure is commonly used as a fertilizer in farms, such manure can become a source of infection to animals through pasture and vegetation contamination [36, 37]. The oral route is

also particularly important in calves nursing from infected cows.

5.1 Host range

Bacterial Cattle Diseases

Animals exposed by ingestion of contaminated feed or water often develop primary foci in lymph nodes associated with the intestinal tract, while aerosol exposure leads to the involvement of the lungs and associated lymph nodes. In case of respiratory infection, the mucociliary clearance in the upper respiratory passages may prevent infection in some exposed animals [52]. In the bronchi, the organism penetrates the mucosa and are trapped and phagocytosed in the bronchial and mediastinal lymph nodes. In the lungs, the bacterial are phagocytosed by alveolar macrophages. In case of oral infection, the organism presumably penetrates the bucal or intestinal mucosa and, via the lymphatics, reaches the phagocytes in the draining lymph node. The phagocytosis causes a localized inflammatory reaction and recruitment of mononuclear cells from neighboring blood vessels. The cellular response results in the accumulation of large number of phagocytes leading to the formation of the granuloma or the tubercle that characterizes the disease [36, 47]. The granuloma consists of infected macrophages surrounded by epithelioid cells, granulocytes, lymphocytes, and later, multinucleated giant cells [53].

Mycobacteria are facultative intracellular pathogens, and survive and multiply within the hosts' phagocyte. The ability of the organism to survive intracellular within macrophages involves interfering with the development of the phagosome into a degradative vesicle. It is thought that the organism prevents the phagosome from maturing and fusing with lysosomes to form the phagolysosome. The mycolic acids of the organism are thought to play a role in blocking this phagosome maturation [54, 55]. Some components of the lipid layer, such trehalose dimycolate, may cause death of macrophages by direct cytotoxicity [52]. The Mycobacterium survival and multiplication within the phagosomes eventually destroys the macrophage. When entering into the death phase, infected macrophages release mycobacterial antigens, which are engulfed by uninfected dendritic cells, processed and subsequently presented, via major histocompatibility complex class I, to CD8+ T cells. The cellular hypersensitivity that develops, contributes to cell death and tissue destruction resulting in caseous necrosis. In some instances, liquefaction and cavity formation occur as a result of enzymatic action on proteins and lipids, and the organism multiplies uncontrolled in these cavities. Rapture of the cavities into the bronchi allows aerosol spread of the bacilli. Dissemination by bacteria-containing macrophage may occur through vascular and lymphatic channels to form lesions

in many organs, as in acute miliary TB, which is rapidly fatal [47, 53]. Innate nonspecific and specific cell-mediated immunities are the main host defense mechanisms. The innate resistance may clear the initial infection and prevent mycobacteria to proliferate. Specific resistance is mediated by T-lymphocytes. They destroy infected macrophages or activate them to destroy extracellular bacilli through soluble mediators such as gamma interferon [56]. Where the host has been able to contain spread of infection, lesions consistency progress from caseous, fibro-caseous, fibro-calcified to calcified and are surrounded by a fibrous capsule. Calcified granulomas generally indicate a successful suppression of the infection by the immune response and the lesions may regress completely [53]. During pathological processes, mycobacteria are present in tuberculous tissue and in various body fluids, secretions and excretions such as milk, blood, sputum, bronchoalveolar lavages, cerebrospinal fluid, and semen [36].
