Tuberculosis Caused by M. bovis in Humans in Uganda

In humans, TB is mostly caused by Mycobacterium tuberculosis; however, M. bovis remains an important pathogen capable of infecting and causing clinical disease (zoonotic TB) in humans (See Chap.

22.5.1 Diagnosis of Zoonotic Tuberculosis

Direct microscopic examination of sputum specimen is the most widely used method for TB screening in humans in Uganda. This approach presents an important obstacle because direct microscopy does not differentiate between M. tuberculosis and M. bovis. Additionally, zoonotic TB mostly presents as extrapulmonary TB (Cosivi et al. 1998; Durr et al. 2013). As only sputum samples are customarily examined, cases with extrapulmonary lesions are not detected.

The correct identification of M. bovis as a causal agent of TB in humans is important especially in rural communities in which BTB is endemic in the local cattle populations. In such areas, sociocultural practices create close interaction between livestock and humans, thus increasing the probability of direct and indirect transmission of M. bovis from livestock (and their products) to humans.

From a public health perspective, it is critical to identify patients with TB infected with M. bovis, because it differs from that of M. tuberculosis by being naturally resistant to pyrazinamide. Thus, zoonotic TB patients require longer treatment regimens and are inadequately treated if M. bovis is not identified. Additionally, because of the attrition that occurs during protracted treatment periods, antimicrobial resistance is more likely to develop in M. bovis (Durr et al. 2013).

The epidemiology and transmission dynamics of M. bovis to humans differ considerably from M. tuberculosis, which is mostly transmitted by spread of aerosol droplets during coughing and sneezing. These differences ought to be reflected in the diagnostic regimen used, but unfortunately in Uganda, sensitive and specific diag­nostic tests to correctly identify M. bovis as the causal agent of TB in humans are not readily available in rural areas. It is therefore not surprising that most of the reported zoonotic TB cases in Uganda are the results of individual research projects (Oloya et al. 2008; Nasaka 2014) rather than of the national TB surveillance programs. These reports showed that the prevalence of zoonotic TB ranges from 1.4% to 6.9% in various parts of the UCC. There have been efforts to patch these holes (Bretzel et al. 1999), but to acquire accurate and more comprehensive estimates of the true burden of zoonotic TB in Uganda, a holistic One Health approach, involving the Ministries of Health and Agriculture, Animal Industry and Fisheries, the National TB program, National Animal Disease Diagnostics, and the National Epidemiology Centre, is needed to conduct adequate surveillance programs using adequate diag­nostic techniques.

22.5.2 Mycobacterial Culture

Mycobacterial culture is performed in four laboratories, three of which are located in the capital city, Kampala. These include the National TB Program Laboratory (under the Ministry of Health), the laboratory at the Makerere University Teaching Hospital, and the HIV/AIDS Research-Oriented TB Culture Laboratory (Everett et al.

22.5.3 Molecular Typing Tools

Molecular typing is the process by which different types of organisms within a species are identified (Sabat et al. 2013). Spacer Oligonucleotide typing (spoligotyping) and MIRU-VNTR are the two commonly used molecular methods to type mycobacteria in Uganda. The former is reported to be highly reproducible with results that allow inter-laboratory comparison, but it has low discriminatory power, and it can produce homoplasy (Rodriguez-Campos et al. 2011). In Uganda, it is used to differentiate between members of the MTC including M. bovis (Asiimwe et al. 2009) and for predicting TB transmission patterns (Lukoye et al. 2014). MIRU- VNTR analysis was introduced in Uganda in 2010 and is used mainly to detect multiple infection and transmission patterns (Dickman et al. 2010). Although rarely used now, IS6110 restriction fragment length polymorphism (IS6110 RFLP) has been used in Uganda for the last 15 years, and there is a considerable amount of molecular data stored in this format (Joloba et al. 2000; Niemann et al. 2002). The National TB Program Laboratory and the Mycobacteriology Diagnostic Laboratory in Kampala have also recently acquired sequencing machines that are likely to change the landscape of molecular typing and epidemiology because of the access to the high-throughput data generated by this technique.

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