- Email: [email protected]
A forensic investigation of Mycobacterium bovis infection in badgers
The Veterinary Journal 194 (2012) 135–136
Contents lists available at SciVerse ScienceDirect
The Veterinary Journal journal homepage: www.elsevier.com/locate/tvjl
Guest Editorial
A forensic investigation of Mycobacterium bovis infection in badgers It seems that with many things in life, the harder you look, the more you find, and the search for pathological signs of Mycobacterium bovis infection in badgers is no exception. In this issue of The Veterinary Journal Dr Leigh Corner of the Veterinary Sciences Centre at University College Dublin, and his colleagues, describe the results of what must be the most intensive attempt to estimate the true prevalence of M. bovis infection in a sample of naturally infected badgers (Corner et al., 2012). The authors used an intensive approach to post-mortem investigation that might best be described as a forensic examination. A better understanding of the pathogenesis of tuberculosis in badgers is one important outcome, and the technique itself is currently the most sensitive method for identification of M. bovis infection in badgers. The pathology of M. bovis infection in badgers was first described in detail by Gallagher et al. (1976) who observed characteristic, grossly visible lesions in animals exhibiting clinical signs. In later work he described how the systematic thin slicing of tissues from badgers with no visible lesions yielded further signs of infection in the form of minute, often solitary lesions (Gallagher et al., 1998). Similarly, detailed examination of a sub-sample of badgers culled during the Randomised Badger Culling Trial (RBCT)1 showed that the sensitivity of detection of infection by standard post-mortem protocols was only 55%, relative to a more comprehensive approach (Crawshaw et al., 2008). The study described by Corner et al. (2012) has taken this a stage further and shown that the culture of individual tissue samples from a range of anatomical sites was more sensitive and specific than the identification of histological or grossly visible lesions, suggesting that less intensive protocols substantially underestimated the true prevalence of infection. Similar to previous studies, Corner et al. (2012) identified a range of levels of disease severity in infected badgers consistent with a degree of resilience to the development and progression of disease. This innate resistance to disease may explain why badgers are such a successful host and reservoir of infection for cattle: if infection was followed by rapid deterioration and early demise then they would not be able to survive, breed and excrete bacteria into the environment for so many years. The more sensitive post-mortem approach described by Corner et al. (2012) is clearly a valuable tool for benchmarking the performance of other diagnostic procedures for M. bovis infection in badgers. However, no matter how useful, the costs of such a detailed protocol are likely to render it uneconomic for extensive application as either a research or a surveillance tool. But putting costs aside for a moment, their forensic post-mortem protocol may have value in research into variation in the characteristics of infection amongst
1 See: http://archive.defra.gov.uk/foodfarm/farmanimal/diseases/atoz/tb/isg/ report/final_report.pdf.
1090-0233/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.tvjl.2012.08.006
different demographic groups or populations of badgers. Such a study would be useful should we wish to explore relationships between pathology and M. bovis strain types. Another application of this more sensitive approach to quantifying pathology is in the investigation of Bacillus Calmette-Guérin (BCG) vaccination in badger populations. If the vaccine acts by reducing the severity and progression of disease rather than by preventing infection (Chambers et al., 2010), then the availability of a method which can detect subtle variations in pathology may be particularly useful. So what is the significance of the widespread use in other studies of less sensitive approaches to the detection of M. bovis infection in badgers? Does it matter that they may underestimate the true level of infection in badger populations? The answer to this depends on what you are trying to establish. For example, studies of the spatio-temporal dynamics of infection in live badgers rely on diagnostic tests which are known to be far less sensitive than even relatively basic post-mortem examination and bacteriology procedures, and so inevitably they underestimate the true prevalence of infection in a population. But I would argue that despite their limitations, such imperfect tests remain useful tools for gaining insight into epidemiological patterns in field studies. As relative indices of infection, we can (for example) use them to identify long-term trends in space and time in naturally infected populations, without the disruptive intervention of removing animals for diagnostic purposes. This approach has been employed at the UK’s Food and Environment Research Agency at Woodchester Park where the consistent application of insensitive diagnostic assays for 15 years demonstrated the spatial persistence of aggregations of test positive cases (Delahay et al., 2000). This strong, non-random pattern emerged despite the inherent limitations of the diagnostic approach, and similar spatial clustering of infection was subsequently identified in badgers during the RBCT using postmortem protocols that were substantially more sensitive (Woodroffe et al., 2005). More recently, differences in the incidence of positive responses to an imperfect serological test were observed in vaccinated and unvaccinated animals in an experimental field study of the impact of BCG vaccination on M. bovis infection in free-living badgers (Chambers et al., 2010). Furthermore, by combining the results of several different diagnostic assays of varying sensitivity and specificity, we can enhance our powers of detection through the application of Bayesian statistical approaches (see, for example, Drewe et al., 2010). So the insensitivity of current approaches to the diagnosis of M. bovis infection in live badgers is not an impenetrable barrier to the study of epidemiological trends in undisturbed wild populations, albeit a significant inconvenience! Of course the more we know about the performance of these tests the better, so the more sensitive post-mortem approach described by Corner et al. (2012) represents a useful gold standard for that purpose.
136
Guest Editorial / The Veterinary Journal 194 (2012) 135–136
Finally, it is worth asking what is the epidemiological significance of an estimate of infection prevalence when all infected hosts may not be equal? In terms of transmission (and hence disease control) some infected hosts are likely to be more important than others. Variations in pathology mediated by the characteristics of both host and pathogen help to drive this heterogeneity by determining the infectious state of the host at any point in time. This phenomenon is not captured in a simple metric describing the total number or proportion of infected individuals in a population at a given timepoint. So the measure will not help us to identify those groups with the highest potential for transmission, which we may wish to target for optimal disease control, although a detailed forensic approach to describing the range of pathological states of infection might provide valuable insights. In this respect the study by Corner et al. (2012) makes a significant contribution to our diagnostic armoury for studying M. bovis infection in badgers. Of course there’s a whole lot more to transmission dynamics than pathology; host behaviour for instance, but that’s another story. . . Dr. Richard J. Delahay Wildlife Biologist, Food and Environment Research Agency, Woodchester Park, Gloucestershire, UK E-mail address: [email protected]
References Chambers, M.A., Rogers, F., Delahay, R.J., Lesellier, S., Ashford, R., Dalley, D., Gowtage, S., Davé, D., Palmer, S., Brewer, J., Crawshaw, T., Clifton-Hadley, R., Carter, S., Cheeseman, C., Hanks, C., Murray, A., Palphramand, K., Pietravalle, S., Smith, G.C., Tomlinson, A., Walker, N.J., Wilson, G.J., Corner, L.A.L., Rushton, S.P., Shirley, M.D.F., Gettinby, G., McDonald, R.A., Hewinson, R.G., 2010. Bacillus Calmette-Guérin vaccination reduces the severity and progression of tuberculosis in badgers. Proceedings of the Royal Society B 278, 1913–1920. Corner, L.A.L., O’Meara, D., Costello, E., Lesellier, S., Gormley, E., 2012. The distribution of Mycobacterium bovis infection in naturally infected badgers. The Veterinary Journal 194, 166–172. Crawshaw, T.R., Griffiths, I.B., Clifton-Hadley, R.S., 2008. Comparison of a standard and a detailed post-mortem protocol for detecting Mycobacterium bovis in badgers. Veterinary Record 163, 473–477. Delahay, R.J., Langton, S., Smith, G.C., Clifton-Hadley, R.S., Cheeseman, C.L., 2000. The spatio-temporal distribution of Mycobacterium bovis (Bovine Tuberculosis) infection in a high density badger (Meles meles) population. Journal of Animal Ecology 69, 1–15. Drewe, J.A., Tomlinson, A., Walker, N.J., Delahay, R.J., 2010. Diagnostic accuracy and optimal use of three tests for tuberculosis in live badgers. PLoS ONE 5, e11196. http://dx.doi.org/10.1371/journal.pone.0011196. Gallagher, J., Muirhead, R.H., Burn, K.J., 1976. Tuberculosis in wild badgers (Meles meles) in Gloucestershire: Pathology. Veterinary Record 98, 9–14. Gallagher, J., Monies, R., Gavier-Widen, D., Rule, B., 1998. Role of infected, nondiseased badgers in the pathogenesis of tuberculosis in the badger. Veterinary Record 142, 710–714. Woodroffe, R., Donnelly, C.A., Johnston, W.T., Bourne, F.J., Cheeseman, C.L., CliftonHadley, R.S., Cox, D.R., Gettinby, G., Hewinson, R.G., Le Fevre, A.M., McInerney, J.P., Morrison, W.I., 2005. Spatial association of Mycobacterium bovis infection in cattle and badgers Meles meles. Journal of Applied Ecology 42, 852–862.
Contents lists available at SciVerse ScienceDirect
The Veterinary Journal journal homepage: www.elsevier.com/locate/tvjl
Guest Editorial
A forensic investigation of Mycobacterium bovis infection in badgers It seems that with many things in life, the harder you look, the more you find, and the search for pathological signs of Mycobacterium bovis infection in badgers is no exception. In this issue of The Veterinary Journal Dr Leigh Corner of the Veterinary Sciences Centre at University College Dublin, and his colleagues, describe the results of what must be the most intensive attempt to estimate the true prevalence of M. bovis infection in a sample of naturally infected badgers (Corner et al., 2012). The authors used an intensive approach to post-mortem investigation that might best be described as a forensic examination. A better understanding of the pathogenesis of tuberculosis in badgers is one important outcome, and the technique itself is currently the most sensitive method for identification of M. bovis infection in badgers. The pathology of M. bovis infection in badgers was first described in detail by Gallagher et al. (1976) who observed characteristic, grossly visible lesions in animals exhibiting clinical signs. In later work he described how the systematic thin slicing of tissues from badgers with no visible lesions yielded further signs of infection in the form of minute, often solitary lesions (Gallagher et al., 1998). Similarly, detailed examination of a sub-sample of badgers culled during the Randomised Badger Culling Trial (RBCT)1 showed that the sensitivity of detection of infection by standard post-mortem protocols was only 55%, relative to a more comprehensive approach (Crawshaw et al., 2008). The study described by Corner et al. (2012) has taken this a stage further and shown that the culture of individual tissue samples from a range of anatomical sites was more sensitive and specific than the identification of histological or grossly visible lesions, suggesting that less intensive protocols substantially underestimated the true prevalence of infection. Similar to previous studies, Corner et al. (2012) identified a range of levels of disease severity in infected badgers consistent with a degree of resilience to the development and progression of disease. This innate resistance to disease may explain why badgers are such a successful host and reservoir of infection for cattle: if infection was followed by rapid deterioration and early demise then they would not be able to survive, breed and excrete bacteria into the environment for so many years. The more sensitive post-mortem approach described by Corner et al. (2012) is clearly a valuable tool for benchmarking the performance of other diagnostic procedures for M. bovis infection in badgers. However, no matter how useful, the costs of such a detailed protocol are likely to render it uneconomic for extensive application as either a research or a surveillance tool. But putting costs aside for a moment, their forensic post-mortem protocol may have value in research into variation in the characteristics of infection amongst
1 See: http://archive.defra.gov.uk/foodfarm/farmanimal/diseases/atoz/tb/isg/ report/final_report.pdf.
1090-0233/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.tvjl.2012.08.006
different demographic groups or populations of badgers. Such a study would be useful should we wish to explore relationships between pathology and M. bovis strain types. Another application of this more sensitive approach to quantifying pathology is in the investigation of Bacillus Calmette-Guérin (BCG) vaccination in badger populations. If the vaccine acts by reducing the severity and progression of disease rather than by preventing infection (Chambers et al., 2010), then the availability of a method which can detect subtle variations in pathology may be particularly useful. So what is the significance of the widespread use in other studies of less sensitive approaches to the detection of M. bovis infection in badgers? Does it matter that they may underestimate the true level of infection in badger populations? The answer to this depends on what you are trying to establish. For example, studies of the spatio-temporal dynamics of infection in live badgers rely on diagnostic tests which are known to be far less sensitive than even relatively basic post-mortem examination and bacteriology procedures, and so inevitably they underestimate the true prevalence of infection in a population. But I would argue that despite their limitations, such imperfect tests remain useful tools for gaining insight into epidemiological patterns in field studies. As relative indices of infection, we can (for example) use them to identify long-term trends in space and time in naturally infected populations, without the disruptive intervention of removing animals for diagnostic purposes. This approach has been employed at the UK’s Food and Environment Research Agency at Woodchester Park where the consistent application of insensitive diagnostic assays for 15 years demonstrated the spatial persistence of aggregations of test positive cases (Delahay et al., 2000). This strong, non-random pattern emerged despite the inherent limitations of the diagnostic approach, and similar spatial clustering of infection was subsequently identified in badgers during the RBCT using postmortem protocols that were substantially more sensitive (Woodroffe et al., 2005). More recently, differences in the incidence of positive responses to an imperfect serological test were observed in vaccinated and unvaccinated animals in an experimental field study of the impact of BCG vaccination on M. bovis infection in free-living badgers (Chambers et al., 2010). Furthermore, by combining the results of several different diagnostic assays of varying sensitivity and specificity, we can enhance our powers of detection through the application of Bayesian statistical approaches (see, for example, Drewe et al., 2010). So the insensitivity of current approaches to the diagnosis of M. bovis infection in live badgers is not an impenetrable barrier to the study of epidemiological trends in undisturbed wild populations, albeit a significant inconvenience! Of course the more we know about the performance of these tests the better, so the more sensitive post-mortem approach described by Corner et al. (2012) represents a useful gold standard for that purpose.
136
Guest Editorial / The Veterinary Journal 194 (2012) 135–136
Finally, it is worth asking what is the epidemiological significance of an estimate of infection prevalence when all infected hosts may not be equal? In terms of transmission (and hence disease control) some infected hosts are likely to be more important than others. Variations in pathology mediated by the characteristics of both host and pathogen help to drive this heterogeneity by determining the infectious state of the host at any point in time. This phenomenon is not captured in a simple metric describing the total number or proportion of infected individuals in a population at a given timepoint. So the measure will not help us to identify those groups with the highest potential for transmission, which we may wish to target for optimal disease control, although a detailed forensic approach to describing the range of pathological states of infection might provide valuable insights. In this respect the study by Corner et al. (2012) makes a significant contribution to our diagnostic armoury for studying M. bovis infection in badgers. Of course there’s a whole lot more to transmission dynamics than pathology; host behaviour for instance, but that’s another story. . . Dr. Richard J. Delahay Wildlife Biologist, Food and Environment Research Agency, Woodchester Park, Gloucestershire, UK E-mail address: [email protected]
References Chambers, M.A., Rogers, F., Delahay, R.J., Lesellier, S., Ashford, R., Dalley, D., Gowtage, S., Davé, D., Palmer, S., Brewer, J., Crawshaw, T., Clifton-Hadley, R., Carter, S., Cheeseman, C., Hanks, C., Murray, A., Palphramand, K., Pietravalle, S., Smith, G.C., Tomlinson, A., Walker, N.J., Wilson, G.J., Corner, L.A.L., Rushton, S.P., Shirley, M.D.F., Gettinby, G., McDonald, R.A., Hewinson, R.G., 2010. Bacillus Calmette-Guérin vaccination reduces the severity and progression of tuberculosis in badgers. Proceedings of the Royal Society B 278, 1913–1920. Corner, L.A.L., O’Meara, D., Costello, E., Lesellier, S., Gormley, E., 2012. The distribution of Mycobacterium bovis infection in naturally infected badgers. The Veterinary Journal 194, 166–172. Crawshaw, T.R., Griffiths, I.B., Clifton-Hadley, R.S., 2008. Comparison of a standard and a detailed post-mortem protocol for detecting Mycobacterium bovis in badgers. Veterinary Record 163, 473–477. Delahay, R.J., Langton, S., Smith, G.C., Clifton-Hadley, R.S., Cheeseman, C.L., 2000. The spatio-temporal distribution of Mycobacterium bovis (Bovine Tuberculosis) infection in a high density badger (Meles meles) population. Journal of Animal Ecology 69, 1–15. Drewe, J.A., Tomlinson, A., Walker, N.J., Delahay, R.J., 2010. Diagnostic accuracy and optimal use of three tests for tuberculosis in live badgers. PLoS ONE 5, e11196. http://dx.doi.org/10.1371/journal.pone.0011196. Gallagher, J., Muirhead, R.H., Burn, K.J., 1976. Tuberculosis in wild badgers (Meles meles) in Gloucestershire: Pathology. Veterinary Record 98, 9–14. Gallagher, J., Monies, R., Gavier-Widen, D., Rule, B., 1998. Role of infected, nondiseased badgers in the pathogenesis of tuberculosis in the badger. Veterinary Record 142, 710–714. Woodroffe, R., Donnelly, C.A., Johnston, W.T., Bourne, F.J., Cheeseman, C.L., CliftonHadley, R.S., Cox, D.R., Gettinby, G., Hewinson, R.G., Le Fevre, A.M., McInerney, J.P., Morrison, W.I., 2005. Spatial association of Mycobacterium bovis infection in cattle and badgers Meles meles. Journal of Applied Ecology 42, 852–862.