Estimating the Risk of Contracting Zoonotic TB

Many factors make it extremely difficult to determine the extent of zoonotic TB in populations. These include the lack of and the complexity of the required routine diagnostic procedures and the importance of obtaining appropriate samples from which to culture M.

Since there is no routine or even survey testing for M. bovis in the livestock populations of most of the African countries, and given the overwhelming burden of M. tuberculosis, attempts to quantify the burden of zoonotic TB are difficult, and, at best, a very rough estimate. Health care in all African countries is over-burdened and under-funded, and in terms of the priorities for allocating scare human and financial resources, introducing expensive testing for zoonotic TB on a routine basis for the assumed very few possible infections is not justified by policymakers. This approach resulted in the circular argument expressed to the authors by officials at a routine diagnostic laboratory in Africa that we do not test for zoonotic TB, because we do not have any. These problems are not likely to be resolved in the near future.

The risk of contracting bovine TB clearly depends on the level of exposure. The prevalence of the disease in cattle thus plays a critical role in this regard, and the marked variation in prevalence in various countries in Africa, and within countries will thus influence this risk, and the likely prevalence of zoonotic BTB. In Mali, for instance, 24% of cattle are infected (Diallo et al. 2016) while in Ethiopia the prevalence is 3.8% (Duguma et al. 2017). In Nigeria 11% of cattle had TB lesions in one area (Okeke et al. 2016), and in Zambia a herd prevalence of 50%, and up to 28% of individual cattle were reportedly infected (Malama et al. 2013). In Zambia despite these high prevalence rates, M. bovis could either not be recovered from human TB cases (Ayles et al.

Close contact with infected and diseased animals and the consumption of raw milk are the main risk factors for the general population to contract zoonotic TB. For instance, the odds are eight times higher for persons in households where their cattle suffer from BTB to contract the disease, than those living with TB-negative livestock (Mengistu et al. 2015).

The process of pasteurization of food to kill pathogens was adopted for milk by 1886. The initial application of this process was limited, but by the early decades of the twentieth century it was used widely, although without proper quality controls or standards. The supply of pasteurized milk to urban areas in Africa improved during the latter half of the twentieth century, but the situation is far from optimal and varies from country to country. In rural African areas access to pasteurized milk is exceedingly limited, and the populations there consume large volumes of raw milk. Many rural African communities, however, do not consume fresh milk, as they prefer it to be naturally soured before consumption. The souring process limits mycobacterial growth, and even kills the bacilli, especially when souring takes place in hot climates (Macuamule et al. 2016; Michel et al. 2015). Many people of Bantu origin, such as in South Africa and elsewhere, suffer from lactose intolerance, and for this reason also prefer not to drink fresh milk.

The risk of contracting zoonotic TB from meat is extremely difficult to assess, and if meat is thoroughly inspected, rejected for consumption when containing tubercu­lous lesions, and cooked well enough, the risk is likely to be minimal, particularly if the internal organs and lymph nodes are not consumed. These precautionary mea­sures, however, are generally not applied in many African countries. Large amounts of uninspected meat are consumed throughout the continent, and, even when meat inspection is done in abattoirs, the process is often flawed because in many instances the meat inspectors are poorly trained, and do not adequately inspect the carcasses for the presence of tuberculous lesions.

Great care must be taken when interpreting reports on the prevalence of TB in animals and humans. For example, the methodology used may vary, cut-offs for skin testing may not be the same, and there may be false-positive skin tests or INF-γ reactors. For example, in Ethiopia, cattle, goats, and wildlife in an intensive interface area were infected with many NTMs, but not by M. bovis (Tschopp et al. 2010). Sufficient studies were conducted in Tanzania, South Africa, Ethiopia, and Nigeria to know that there are considerable differences in the prevalence of the disease between regions within countries and that the results from a survey in one region do not necessarily represent the prevalence of the disease in the country as a whole.

Better information exists about the risk of transmission of M. bovis when humans were in contact with live, infected animals. Of humans with active TB, 16.4% of persons in contact with livestock had pulmonary BTB, while of those with no known contact with livestock, 1.6% had zoonotic pulmonary BTB (Cutbill and Lynn 1944). In the UK at that time (1944), between 0 and 5.7% of cases of pulmonary TB were infected with M. bovis. The more intensive the contact, the higher thus the risk. For example, in Denmark where in rural areas cattle were housed with their owners during winter, 41% of pulmonary TB cases were due to M. bovis infection (Sigurds- son and Andersen 1945). Similar conditions where livestock and humans live in such close association do not generally exist in Africa, and the risk of transmission is likely to be lower.

In general, the situation in Africa is unclear owing to the lack of published data and the lack of the ability in the past, and even today, to do large-scale, routine laboratory diagnosis of M. bovis. The likelihood of contracting the human form of TB (M. tuberculosis) remains extremely high in many areas, and it poses a far greater risk, and far out-strips the risk of becoming infected with M. bovis (Wood et al. 2011). Overall the zoonotic disease risk from reported cases for Africa appears to be surprisingly low, and many studies conducted in recent years reported either no or very few cases of zoonotic BTB (Ayles et al. 2013; de Garine-Wichatitsky et al. 2013; Durr et al. 2013; Kazwala et al. 2001). A major weakness in these studies, however, is that Lowenstein-Jensen slants without pyruvate were commonly used for culture, and M. bovis does not grow well on this medium. In addition, laboratory- supported current human case diagnosis in South Africa and many other countries is largely smear- and GeneXpert-based, or MGIT culture-based. GeneXpert is an automated PCR test, unable to differentiate between M. tuberculosis and M. bovis. Likewise, smear and MGIT culture alone cannot differentiate M. tuberculosis from M. bovis. Thus, any sample sent for routine testing is likely to be diagnosed as M. tuberculosis unless special circumstances suggest that it must be processed differently or further. In the case of primary TB cases that give no indication of antibiotic resistance to isoniazid or rifampicin, further testing is highly unlikely. Furthermore, bovine TB frequently manifests as ePTB (often alimentary), and obtaining good samples for speciation is extremely difficult in this form of the disease. In addition, studies based on sputum sampling will considerably under­estimate zoonotic BTB (Durr et al. 2013), particularly in cases with HIV co-morbidity (Steingart et al. 2014). It is therefore likely that the diagnostic systems currently used in many African countries, are not geared to detect zoonotic M.

In 1994, the WHO estimated that M. bovis could be the causative organism globally of 3% of human TB cases (WHO 1994). This is a global estimate, and the number of cases may vary widely between countries and within countries. More recently it was estimated that zoonotic TB caused by M. bovis globally constituted < 1.4% of all human TB cases but that in Africa there were seven zoonotic BTB cases/100,000 population per year (Muller et al. 2013). If this were true, for South Africa it would mean that there should be approximately 3850 zoonotic BTB cases, which is health systems are not geared for it, and the logistics and cost implications are probably too daunting for African health authorities to implement it on a wide scale.

In summary, the extent of M. bovis infection in the global human population today is unknown, as is the significance of M. bovis in human tuberculosis in Africa. An integrated and inter-disciplinary One Health approach is therefore needed to investigate this problem in depth to ascertain whether it is a real public health issue or not, and to recommend how to deal with it in a cost-effective manner.

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