Bovine TB: APPENDIX C - Pathogenesis and Diagnosis of Infections with M. bovis in Cattle
The following key points are apparent from a review of the literature on the pathogenesis and diagnosis of bovine tuberculosis:
- The infective dose of M. bovis has a profound influence on the kinetics of infection and severity of disease in cattle.
- Comparison of the pathology in naturally and experimentally infected cattle suggests that most natural infections are initiated by a low infective dose of M. bovis.
- Available information on the kinetics of bacterial excretion, although limited, indicates that there is an early period of sustained bacterial excretion in the first few weeks of infection followed by more intermittent excretion. However, there is a lack of quantitative date on this aspect of the disease.
- Observations on the numbers of reactor cattle per herd indicate that many reactor cattle do not transmit infection to in-contact animals: The basis of the variability in infectivity is unclear as is the route by which animals become infected.
- The currently used tuberculin test is highly specific (>99%) but its sensitivity at standard interpretation appears to be only about 90%. This implies that up to 10% of herds containing a single infected animal remain undetected and that the test is unlikely to detect all infected animals in multiple reactor herds.
- Because a positive skin test result is often based on measuring small differences in skin thickness, the test is likely to be subject to error on the part of the operator. The interpretation of the test is also complicated by non-specific responses induced by other species of mycobacteria, which although controlled for by the use of M. avium antigen in the test, probably limit its sensitivity.
- There is also a lack of reliable experimental data on the kinetics of skin test responses and the period of non-reactivity to a second skin test in infected cattle. The possible influence of multiple skin tests, as occurs in protracted breakdown incidents, on the sensitivity and specificity of subsequent tests also needs to be examined.
- While these limitations have not prevented the eradication of TB in many parts of the UK, they may be a significant constraint to control of the disease in areas of the country where TB has persisted.
- An alternative in vitro diagnostic test, based on measurement of interferon-gamma
(IFN-
)
production in cultured blood, gives similar sensitivity to the skin
test but has inferior specificity. However, the two tests detect slightly
different populations of diseased cattle.
Experimental studies using recombinant M. bovis-specific antigens
in an IFN-
test have produced promising results, suggesting that development of a
more specific IFN-
test may be possible.
Four areas of high priority for research, which could potentially lead to improved herd testing protocols and also provide a stronger scientific basis for conveying advice to farmers on management of TB incidents, are identified:
- The analysis of risk factors in herds that suffer recurrent breakdowns.
- The development of improved diagnostic tests.
- Pathogenesis of M. bovis infections in cattle, focusing particularly on aspects relating to transmission of infection and diagnosis.
- Mathematical modelling of M. bovis transmission in cattle.
Introduction
1. Current control measures for bovine tuberculosis (TB) aim to detect and remove infected cattle and to prevent spread of infection both within and between farm premises. While these measures have been effective in eradicating TB in a large part of the UK and in other countries, the disease has persisted in certain regions of the country and recently has shown an alarming increase in incidence, despite an intensive programme of testing. This has been interpreted as evidence for the existence of a wildlife reservoir of infection in these regions. Irrespective of the source of infection, the increased risk of infection places greater demands on the testing programme. There is, therefore, a need to consider whether or not control of the disease is constrained by limitations in current testing procedures and whether there are areas of research that could lead to improved efficacy of the control measures.
2. This document assesses available data on the efficacy and scientific basis of current cattle testing procedures, and reviews those aspects of the pathogenesis of TB in cattle that relate to diagnosis and transmission of infection between cattle. Because of possible differences in the epidemiology of the disease and the performance of TB testing in different parts of the world, discussion of the natural disease is focused on data obtained in the British Isles. Several areas of research considered relevant to development of improved disease control measures are identified.
On to Pathogenesis
Page last modified:
12 August 2003
Page published: 5 February 2003