Bovine TB: Research project summary
Project SE3024: Low dose infection in cattle: disease dynamics and diagnostic strategies
Project duration: 4 years
The minimum infective dose of Mycobacterium bovis in cattle was determined by challenging four groups of animals by the intra-tracheal route with 103, 102, 10 and 1 Colony Forming Units (CFU) of M. bovis. In the group infected with the lowest dose, 3 of the 6 animals were skin test positive and presented with visible pathology typical of bTB which suggests that the minimum infective dose is 1 CFU. All animals that developed pathology were skin test positive and there were no difference in the size of the skin test reaction, the time taken to achieve a positive interferon-gamma (IFN- result, or in the levels of IFN- and interleukin-4 (IL-4) between animals infected with different doses of M. bovis. This indicates that current diagnostic tests can detect cattle soon after M. bovis infection.
Experiments were undertaken to treat animals with the antituberculous medication Isoniazid (INH), to determine if protection from re-infection could be achieved and to monitor immune parameters to try to identify those associated with protection. A total of 24 calves were recruited and were divided into 3 groups: Group A was challenged with spoligotype 9 (sp9) M. bovis and treated with INH; Group B was sp9 M. bovis challenged, INH treated and spoligotype 35 (sp35) re-challenged; and the control Group C was challenged with sp35 M. bovis only. All animals were skin test positive and the results indicated that Group A and B displayed significantly less pathology than C. Therefore, INH-treatment of infected animals resulted in the development of protective immunity.
Immunological responses were monitored throughout the INH study and an important additional finding was that of a potential surrogate marker for protection.
An aerosol challenge model was developed to mimic the natural infection process. Therefore animals were dosed with 104, 102 and 10 CFU using a modified Madison aerosol chamber, and a reduction in pathology was observed with decreasing infective doses.
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January 28, 2008