Zoonotic Mycobacterium bovis–induced Tuberculosis in Humans

Borna Müller

, Salome Dürr, Silvia Alonso, Jan Hattendorf, Cláudio J.M. Laisse, Sven D.C. Parsons, Paul D. van Helden, and Jakob Zinsstag

Author affiliations: Stellenbosch University, Cape Town, South Africa (B. Müller, S.D.C. Parsons, P.D. van Helden); Swiss Tropical and Public Health Institute, Basel, Switzerland (B. Müller, J. Hattendorf, J. Zinsstag); University of Basel, Basel (B. Müller, J. Hattendorf, J. Zinsstag); University of Berne, Berne, Switzerland (S. Dürr); Royal Veterinary College, Hertfordshire, UK (S. Alonso); Veterinary Faculty, Eduardo Mondlane University, Maputo, Mozambique (C. J. M. Laisse)

Abstract

We aimed to estimate the global occurrence of zoonotic tuberculosis (TB) caused by Mycobacterium bovis or M. caprae infections in humans by performing a multilingual, systematic review and analysis of relevant scientific literature of the last 2 decades. Although information from many parts of the world was not available, data from 61 countries suggested a low global disease incidence. In regions outside Africa included in this study, overall median proportions of zoonotic TB of ≤1.4% in connection with overall TB incidence rates ≤71/100,000 population/year suggested low incidence rates. For countries of Africa included in the study, we multiplied the observed median proportion of zoonotic TB cases of 2.8% with the continental average overall TB incidence rate of 264/100,000 population/year, which resulted in a crude estimate of 7 zoonotic TB cases/100,000 population/year. These generally low incidence rates notwithstanding, available data indicated substantial consequences of this disease for some population groups and settings.

Tuberculosis (TB) is among the most devastating human infectious diseases worldwide. An estimated 8.8 million new cases, a global average incidence rate of 128/100,000 population/year, and 1.5 million deaths were attributed to TB in 2010 (1). Human TB is caused principally by M. tuberculosis. The main causative agents of bovine \TB are M. bovis and, to a lesser extent, M. caprae; however, zoonotic transmission of these pathogens is well described and occurs primarily through close contact with infected cattle or consumption of contaminated animal products such as unpasteurized milk (2,3). TB cases caused by transmission of other mycobacteria from other animal reservoirs (e.g., wildlife) have been anecdotally reported (4,5). Globally, most cases of zoonotic TB are caused by M. bovis, and cattle are the major reservoir (2,3). Therefore, for the purpose of this study and the remainder of this report, we refer to zoonotic TB as TB in humans caused by M. bovis or M. caprae.
There is evidence to suggest that zoonotic TB accounted for a significant proportion of the TB cases in the Western world before the introduction of regular milk pasteurization programs (6,7). Currently, in high-income countries, bovine TB is well controlled or eliminated in most areas, and cases of zoonotic TB are rarely seen (6,7). However, reservoirs of TB in wildlife populations have been linked to the persistence or increase of the incidence of bovine TB in some countries, most notably the United Kingdom (UK) (6). The absence of zoonotic TB despite an upsurge in the incidence of bovine TB in the United Kingdom sparked a controversy over the large financial expenditures for disease control in cattle (6).
The situation may be fundamentally different in other regions. For example, in most countries in Africa, bovine TB is prevalent, but effective disease control, including regular milk pasteurization and slaughterhouse meat inspection, is largely absent (2,3). This situation is exacerbated by the presence of multiple additional risk factors such as human behavior and the high prevalence of HIV infections (2,3,7). Although HIV/AIDS is thought to facilitate transmission and progression to active disease of any form of TB, some studies showed a significantly increased proportion of M. bovis infections among HIV–co-infected TB patients compared with HIV-negative TB patients (8–12).
No assessment of the global consequences of zoonotic TB has yet been done. This may have been partially caused by the difficulty of differentiating TB caused by M. tuberculosis or M. bovis, which requires mycobacterial culture and the subsequent use of biochemical or molecular (e.g., genotyping) diagnostic methods. Therefore, in low-income countries, facilities to identify the causative agent of TB are largely absent (2,3,7). A previous comprehensive review on zoonotic TB was published 15 years ago with inferences based primarily on the presence of risk factors rather than the occurrence of actual cases (2). Since then, several studies of zoonotic TB in different parts of the world have been published, enabling a more detailed evaluation of the current importance of the disease. The current study was mandated by the World Health Organization (WHO) Foodborne Disease Burden Epidemiology Reference Group with the aim to determine, on the basis of previously published literature, the global occurrence of zoonotic TB and its contribution to the overall TB prevalence in affected settings.