Manifestation of the Disease in Humans
Pathways for contracting an M. bovis infection in humans include consumption of raw milk from diseased animals, inhalation of aerosol droplets during contact with infected animals, and consumption of undercooked contaminated meat.
Although it has been possible for many decades to distinguish between M. tuberculosis and M. bovis using laboratory techniques, the process is time-consuming, laborious, and expensive, and therefore not routinely done, and the available data on the prevalence of M. bovis infections in humans are consequently patchy and incomplete. Furthermore, the disease caused by either M. tuberculosis or M. bovis is both clinically and pathologically indistinguishable, and neither the lesions nor their distribution can be used to determine the specific mycobacterial species causing the infection. Any study that focuses only on the pathology of TB to determine the specific cause will thus have some inherent bias.As is the case with tuberculosis (TB) caused by M. tuberculosis in humans, not all M. bovis infections in humans progress from infection to active disease. When interpreting studies providing information about the disease in humans, one must thus distinguish carefully between those that measure infection and those that measure active disease. In human TB, for example, in the absence of immunosuppression, only 10% of infected people are thought to be likely to develop active disease. Studies that measure the rate of infection can thus not be used to extrapolate the prevalence of active disease.
Based on many early studies, it was initially widely accepted that zoonotic TB largely manifested as extra-pulmonary TB (ePTB), and that the occurrence of extra- pulmonary TB could therefore be used as an indicator of the prevalence of zoonotic TB. The death rate from abdominal TB in young children was one such surrogate measure.
Evidence in records from various counties in the UK and elsewhere showed that after the introduction of the pasteurization of milk, the death rate due to abdominal TB declined dramatically. This decline was considered most likely to be due to the reduction in the zoonotic proportion of TB in children, and it was seen as further evidence for this assumption. Until the mid-twentieth century in Europe, 50% of tuberculous lymphadenitis was considered to be of bovine origin. This pattern changed over time: by 1975 only 8% of cases with tuberculous lymphadenitis in the UK were infected with M. bovis (Kleeberg 1975), and it further declined during the 1980s to 1.4% (Yates and Grange 1992). Recent studies confirmed that we cannot use ePTB as a surrogate for estimating bovine TB risk (Berg et al. 2015; Firdessa et al. 2013), and we cannot thus simply extrapolate from decades-old earlier findings and expect that ePTB today will have M. bovis as its major etiological component.What is clear though is that zoonotic tuberculosis caused by M. bovis can be a major problem under certain circumstances, particularly when people consume unpasteurized milk. Studies done in Germany (Lange 1932; O'Reilly and Daborn 1995; Durr et al. 2013) showed that many of the zTB cases were extra-pulmonary, with a strong bias toward alimentary TB that was most likely contracted by consuming M. bovis-infected unpasteurized milk or infected meat. In one study of the abdominal TB cases, 35% were due to M. tuberculosis and 65% due to M. bovis infection (Blacklock 1947). All ePTB are thus not caused by M. bovis, nor will pasteurization prevent all ePTB cases as people may become infected by other routes.
It is assumed that currently, although the number of cases may vary substantially across ethnic groups, a median of 63% of zTB cases globally are ePTB (Durr et al. 2013). For Africa, the data are almost non-existent and totally inadequate, and an assessment of the situation there is largely based on small, local studies, and unreliable anecdotal information.
No M. bovis, for instance, could be detected in humans in some studies (Ayles et al. 2013), but a recent study in Ethiopia found that 2 of 70 cases with tuberculous lymphadenitis (2.9%) were caused by M. bovis (Nuru et al. 2017). It is unknown what the current prevalence of zoonotic BTB is in African countries, or whether its prevalence will change over time, as it did in Europe. Given the high prevalence of HIV-AIDS in Africa, co-morbidity with HIV may alter the situation, but the actual situation is unknown, and the assumption that it may increase the number of zoonotic cases is highly speculative. Some light may be cast on the situation if the current prevalence of zoonotic TB in South Africa is considered. Based on the quoted figures, it can be expected that ePTB will occur in approximately 15-20% of immunocompetent adults and in 20-70% of HIV-infected, immune-incompetent individuals with TB caused by M. tuberculosis (Karstaedt 2014). However, currently most ePTB cases in humans in South Africa appear to be caused by M. tuberculosis or species of mycobacteria other than the TB complex (non-tuberculous mycobacteria, NTMs).3.3