TUBERCULOSIS IN ZOO ANIMALS 183 Int. Zoo Yb. (2011) 45: 183–202 DOI:10.1111/j.1748-1090.2011.00141.x Mycobacterial infections in zoo animals: relevance, diagnosis and management* A. LE´CU1 & R. BALL2 1Parc Zoologique de Paris, M.N.H.N., 53 avenue de St Maurice, 75012 Paris, France, and 2Lowry Park Zoo, 1101 W Sligh Avenue, Tampa, Florida 33604, USA E-mail: [email protected] While the world prevalence of tuberculosis (TB) is (Table 1). One-third of the human population increasing in the human population, TB infection remains is currently infected by TB (World Health a real concern in some animal populations all around the globe. Most mycobacteria of the TB complex are able to Organization, 2010) and in 2008 1 Á 8 million infect zoo and wildlife species, in which the pathogen- people died from the disease (United Nations, esis, receptivity and immune responses vary widely. The 2010). Recent increases of Multi Drug Resis- diagnostic tools usually applied in domestic animals tance (MDR-TB) or even Extreme Drug Re- show limited performance in zoo species, especially sistance (XDR-TB) strains, and co-infection when prevalence is low. Conversely, investigations of cell-mediated immunity through in vitro assay of g- with human immunodeficiency virus (HIV), interferon may have numerous advantages, as long as make the battle against TB more difficult the technical limits are known and can be improved upon. (Hanekom et al., 2010). TB is now placed on Furthermore, recent tools based on the investigation of the ‘most relevant diseases’ list in the health- humoral immunity seem very promising for the detection of antibodies directed against certain immunogenic my- related Millennium Development Goal 6 by cobacterial antigens in a wide range of species. All these the World Health Organization (WHO) and methods are currently evaluated in field studies, despite the United Nations (UN), together with ac- the difficulties to ensure rigorous validation. The devel- quired immune deficiency syndrome (AIDS) opment of these diagnostic tools is also impaired by the and malaria (United Nations, 2001, 2005; prevalence of mycobacteria other than TB also able to infect and create relevant disease in their host. Thus, World Health Organization, 2010). Vigorous decisions on positive and suspicious-animals issues action plans are applied to fight the disease in should be taken based on the evaluation of the risk of developing countries, although these coun- transmission to the rest of the zoological collection, the tries are also facing notable incidences of TB possible treatment options, animal welfare, conservation considerations and, of course, the zoonotic potential of within the animal population. this pathogen. The majority of the mycobacteria from the MTC have the ability to infect wild animals Key-words: interferon-g; mycobacteria; non-tuberculo- (Table 1), whereas the susceptibility, patho- sis mycobacteria; serology; tuberculosis; zoo. geny and immune responses towards myco- bacterial infection vary widely between INTRODUCTION mycobacteria (Mostowy et al., 2005) and Tuberculosis (TB) is the common name of the host-animal species. Although some mam- disease that could be caused by different mals species seem to show a lower incidence species of bacteria belonging to the Myco- rate (e.g. equids, New World monkeys), the bacterium tuberculosis Complex (MTC) predictability of infection outcome is still *An earlier and partial version of this article was published as: EAZWV Tuberculosis Working Group (2010): Tuberculosis in zoo species: diagnostic update and management issues. In Transmissible diseases handbook (4th edn): 1–20. Kaandorp, J. (Ed.). Switzerland: European Association of Zoo and Wildlife Veterinarians Tuberculosis Working Group. This current manuscript is published with kind permission of the European Association of Zoo and Wildlife Veterinarians. Int. Zoo Yb. (2011) 45: 183–202 c 2011 The Authors. International Zoo Yearbook c 2011 The Zoological Society of London 184 RESEARCH IN ZOOS: EPIDEMIOLOGY & CONSERVATION MEDICINE MYCOBACTERIA OF THE MAJOR HISTORICAL KNOWN TUBERCULOSIS COMPLEX HOST OR BURDEN REPORTED WILD AND ZOO HOST M. tuberculosis human, non-human elephant, non-human primates, beisa oryx, addax, goats, primates birds, lowland tapir, giraffes, springboks, mongoose, rhinoceros, addra gazelle M. bovis cattle (1buffalo, bison) all ruminants, badgers, possums, meerkats, big cats, canids, rodents, non-human primates, wild boars elephants, camelids, rhinoceros, onager, horse, birds M. africanum human cattle, swine, non-human primates M. microti vole, camelids New World monkeys, big cats M. pinnipedii pinnipeds camel, tapir, big cats M. caprae goat, sheep, swine swine, cattle wild boars, red deer, white-tailed deer, camel, bison M. canetti human ? Dassie bacillus variant hyraxes meerkats Table 1. Tuberculosis complex Mycobacteria and their reported hosts. hard to guess and, therefore, the eradication immunopathological mechanisms of lympho- of TB is potentially linked to the capacity of cytes in a way that allows them to stay within early diagnosis in domestic and wild host the macrophage they infect. There are four species. Genetic key factors [e.g. interferon- groups of T-helper lymphocytes (Th). The g (IFN-g) receptor or vitamin D genotypes] Th1 group participates in cell-mediated im- are likely contributing towards these differ- munity (CMI) by producing cytokines such ences (Rhodes et al., 2003; Schluger, 2005). as IFN-g, and then activating other immune The course of the disease and occurrence of cells participating in the fight against the latent infection versus active infection are mycobacteria. The Th2 group provides help variable among species, from extremely sen- to B lymphocytes, which are in charge of sitive Old World monkeys to apparently more producing humoral responses (immunoglo- resistant equids. bulins). During the course of the disease, the Species of mycobacteria out of the MTC Th2 pathway is also activated, although hu- and other than Mycobacterium leprae (caus- moral protection seems to be poorly effective ing leprosy) are known as mycobacteria other against this intracellular pathogen. These im- than tuberculosis (MOTT), non-tuberculous munological mechanisms normally lead to mycobacteria (NTM) or atypical mycobacter- the eradication or the containment of the ia. These are mainly environmental mycobac- mycobacteria, and their systemic local effects teria found in water and soil, but they are also could be tracked to assess previous or current able to contaminate vertebrates, although the presence of mycobacteria. When the Th1 occurrence of disease seems to be more pathway fails, it could lead to active disease related to the immune status of host or to very with active replication of mycobacteria in the close or repeated contact. surrounding cells (macrophage, dendritic Except for M. leprae, all mycobacteria are cells) or, more often, to containment within a facultative intracellular pathogens, often in- granuloma, which is the specific latency vading macrophages as the first host cell. phase of mycobacterial infection that is able Thus, a direct diagnostic will require cellular to last for years. The probability of latency samples and techniques to highlight the pre- depends on the host species, the mycobacteria sence of mycobacteria (stains) or their DNA. species, the infection dose and the route of For their survival, mycobacteria are driving transmission. Int. Zoo Yb. (2011) 45: 183–202 c 2011 The Authors. International Zoo Yearbook c 2011 The Zoological Society of London TUBERCULOSIS IN ZOO ANIMALS 185 TRANSMISSION AND ZOONOTIC mycobacteria already reported within zoolo- RISK FROM ZOO ANIMALS gical collections, whereas ‘dassie bacillus’ was found in Meerkats Suricata suricatta Interspecific transmission can occur between and hyraxes Procavia sp but never reported taxonomically distant species as has been in humans. Atypical mycobacteria found in recorded in the literature (Lewerin et al., zoo species may also infect humans (espe- 2005; Jurcynski et al., 2007; Moser et al., cially if immunosuppressed) but they cannot 2008). Thus, silent extension of TB into a be named as truly ‘zoonotic’ as they are zoological collection owing to an increase of mainly acquired from the environment. latent-form cases should be a real concern for Third, the route of absorption will have a zoo managers. Transmission routes between bearing on the zoonotic risk of any mycobac- animals are directly associated with the loca- terial disease. Respiratory shedding of any lization of granulomas in shedding indivi- mycobacterial pathogens will have greater duals: pulmonary lesions generally lead to zoonotic potential than oral absorption of airborne transmission, whereas mesenteric mycobacteria. lymph-node lesions may lead to intestinal Fourth, exposure is another essential com- excretion of mycobacteria. Horizontal trans- ponent of any zoonotic spread of mycobac- mission is the most significant means of teria. Prolonged exposure and close contact contamination but vertical transmission could will increase the likelihood of zoonotic trans- also occur through placental or umbilical mission. The risk for TB transmission from infection (Kaneene & Pfeiffer, 2006). an animal with a case of active TB is higher The potential for a human to acquire any for daily handlers than for people with only mycobacterial disease from a zoo animal brief contact, such as members of the viewing requires a combination of several events. public. Trained elephants (Furley,