Bovine Tuberculosis (BTB) in cattle and African buffaloes in southern Africa affects communal and commercial livestock production and wildlife conservation programs. The zoonotic nature of the causative agent Mycobacterium bovis poses a risk to human health, in addition to the soaring incidence of M.tuberculosis (TB)infection present in humans in South Africa. Many non-tuberculous mycobacteria (NTM) species identified in humans have also been isolated from animals and their environment in the Kruger National Park, where the prevalence of M.bovis, especially in buffaloes and lions, is high. Currently, besides BCG with limited effectivity, no effective vaccines are available for tuberculosis in man and animals, most likely partly due to exposure to NTM. It is hypothesized that exposure to, and immune responses against NTM together with host genetic factors play a decisive role in immune responsiveness to (B)TB vaccine candidates and M.bovis or M.tuberculosis, and thus in the development of tuberculosis in natural hosts. The proposed research aims at defining prevalence and characteristics of dominant NTM species and the immune responses they induce. Partly the study is a model approach employing NTM, M.bovis and BCG genetically modified to express model antigens. It is envisaged that this approach will enable analysis of differential immune responsiveness induced due to subsequent or concurrent exposure to the mycobacteria as compared to single contacts. Identification of host genetic factors that influence M.bovis, BCG and NTM specific immune responsiveness in cattle and buffaloes will help to understand the pathogenesis of BTB and may enable marker assisted breeding. Development of vaccines for humans, domestic and wild animals and diagnostics in the field of tuberculosis, can benefit from results of this unique opportunity where experimental NTM exposure, BCG vaccination and M.bovis challenge will be performed in natural hosts. Furthermore results may contribute to ensuring a sustainable environment by controlling BTB in a multitude of species in infected conservation areas. As a consequence, stakeholders active in the medical, wildlife, livestock, pharmaceutical, and (non-)governmental (inter)national sectors including policymakers will be able to utilise the results of the research program. The proposed research will contribute to research capacity building, also beyond the field of mycobacterial diseases in southern African institutions, immediately as well as through (regional) international collaboration and interaction between veterinary and medical research groups. It offers an opportunity for South-South collaboration seen the important position of the Onderstepoort Veterinary complex in education and research into infectious diseases in the region.

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