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R S Clifton-Hadley

Publications and source records attributed to R S Clifton-Hadley.

At least 19 recordsLinked to original sources

Ante mortem diagnosis of tuberculosis in cattle: a review of the tuberculin tests, gamma-interferon assay and other ancillary diagnostic techniques.

The early, preclinical stages of bovine TB can be detected in live animals by the use of tests of cellular immunity (the skin, gamma-interferon and lymphocyte transformation tests). Tests of humoral (antibody) immunity, Mycobacterium bovis PCR probes on early tissue cultures or live cattle specimens, and tests based on "electronic nose" technology have been developed more recently. The key measure of diagnostic test accuracy is the relationship between sensitivity and specificity, which determines the false-positive and false-negative proportions. None of the tests currently available for the diagnosis of bovine TB allow a perfectly accurate determination of the M. bovis infection status of cattle. Although various factors can reduce the sensitivity and specificity of the skin tests, these remain the primary ante mortem diagnostic tools for TB in cattle, providing a cost-effective and reliable means of screening entire cattle populations. Despite the inescapable limitations of existing diagnostic tests, bovine TB has been effectively eradicated from many developed countries and regions with the implementation of sound programmes of regular tuberculin skin testing and removal of reactors, coupled with slaughterhouse surveillance for undetected infections, repeat testing and culling of infected herds, cattle movement restrictions to prevent introduction of infected animals and occasional slaughter of entire herds with intractable breakdowns. This is likely to remain the mainstay of bovine TB control programmes for the foreseeable future. Additionally, newer ancillary in vitro diagnostic assays are now available to TB control programme managers to supplement the skin tests in defined circumstances according to the specific disease situation in each country or region. The strategic deployment of ancillary in vitro tests alongside the primary skin tests has enhanced the detection of M. bovis-infected cattle and reduced the number of animals slaughtered as false positives.

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Bovine tuberculosis infection in wild mammals in the South-West region of England: a survey of prevalence and a semi-quantitative assessment of the relative risks to cattle.

In the United Kingdom, badgers are implicated in the transmission of Mycobacterium bovis to cattle, but little information is available on the potential role of other wild mammals. This paper presents the results of the largest systematic UK survey of M. bovis infection in other wild mammals. Mammal carcasses (4715) from throughout the South-West region of England were subjected to a systematic post mortem examination, microbiological culture of tissues and spoligotyping of isolates. Infection was confirmed in fox, stoat, polecat, common shrew, yellow-necked mouse, wood mouse, field vole, grey squirrel, roe deer, red deer, fallow deer and muntjac. Prevalence in deer may have been underestimated because the majority were incomplete carcasses, which reduced the likelihood of detecting infection. Infected cases were found in Wiltshire, Somerset, Devon and Cornwall, Gloucestershire and Herefordshire. Lesions were found in a high proportion of spoligotype-positive fallow, red and roe deer, and a single fox, stoat and muntjac. M. bovis spoligotypes occurred in a similar frequency of occurrence to that in cattle and badgers. Data on prevalence, pathology, abundance and ecology of wild mammals was integrated in a semi-quantitative risk assessment of the likelihood of transmission to cattle relative to badgers. Although most species presented a relatively low risk, higher values and uncertainty associated with muntjac, roe, red and in particular fallow deer, suggest they require further investigation. The results suggest that deer should be considered as potential, although probably localised, sources of infection for cattle.

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Value of existing serological tests for identifying badgers that shed Mycobacterium bovis.

In the UK there has been a sharp rise in the incidence of bovine tuberculosis since the early 1990s and the badger has been identified as an important wildlife reservoir for this infection. Infected badgers can excrete Mycobacterium bovis, putting other badgers and cattle at risk of becoming infected. Vaccination has been proposed as an approach to reducing the excretion of M. bovis by tuberculous badgers. In order to evaluate the efficacy of a badger vaccine it will be necessary to accurately determine the number of badgers excreting M. bovis without removing them for post-mortem evaluation. The existing live tests for tuberculosis in the badger (culture, indirect ELISA, Western blot) have not been assessed for their ability to detect badgers excreting M. bovis. Over the past 18 years, badgers from 31 social groups have been trapped and sampled in a study area of the Cotswold escarpment. We have examined the serological responses of 128 badgers trapped between 1985 and 1998 from social groups where M. bovis infection was endemic. These responses were compared with culture from faeces, urine, tracheal aspirates and bite wound swabs taken from these animals while alive. ELISA was found to be more sensitive than Western blot in detecting badgers excreting M. bovis. The majority of culture-positive badgers excreted M. bovis intermittently over the period of study. As a result, there was only a 27.5% chance of sampling a badger for culture when it was excreting M. bovis. In contrast, a positive ELISA result correctly predicted 68.2% of badgers with a history of excreting M. bovis. In the absence of alternative live tests for the badger, the Brock Test indirect ELISA appears to be more valuable than culture for measuring the effect of vaccination on reducing the number of badgers at risk of transmitting tuberculosis.

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Screening badgers (Meles meles) for Mycobacterium bovis infection by using multiple applications of an ELISA.

The current indirect ELISA used to evaluate whether live badgers are infected with Mycobacterium bovis has a low sensitivity (40.7 per cent), but a relatively high specificity (94.3 per cent). The low sensitivity of the test makes the diagnosis unreliable, but its sensitivity can be increased by using multiple tests. Two multiple testing procedures (involving up to three sequential tests) were investigated. A procedure in which two positive results were required from three tests before an animal was declared positive resulted in a lower sensitivity, but a higher specificity than the single test (38 and 98 per cent respectively). A more rigorous procedure, in which only one positive result was required from three tests, resulted in a marked increase in sensitivity but a slight reduction in specificity (79.5 and 83.1 per cent respectively) when compared to the single test.

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Cattle-to-cattle transmission of Mycobacterium bovis.

This review, illustrated with data on the characteristics of herds infected with Mycobacterium bovis (TB) in Great Britain (GB), attempts to identify the role of cattle-to-cattle transmission (CCT) of TB. CCT plays a part in the entry of infection into herds, through purchased infected animals or contiguous spread, although CCT can have a relatively small role in comparison with an established wildlife source. Experimental studies have shown that it is possible for CCT to occur within herds. In 1999, more than one reactor was found in over two-thirds of confirmed TB incidents in Great Britain. The details of transmission from an infectious animal to a susceptible animal are described: proximate, which depends on factors such as closeness of contact and ventilation, or indirect, which also depends on survival outside the host. Herd size is a risk factor for the incidence of TB, both in herds and in individual cattle. Control of TB is considered in relation to the skin test: failure of the test to remove all infected animals from incidents is possible, but probably of less significance than failure to prevent reinfection from sources external to the herd. It is concluded that CCT may have significance in determining the total number of reactors. Safeguarding herds from other sources of TB is likely to reduce CCT as a side effect.

Animal Husbandry↗

Wildlife disease reservoirs: the epidemiology of Mycobacterium bovis infection in the European badger (Meles meles) and other British mammals.

Mycobacterium bovis infection has been confirmed in a wide range of mammals hosts throughout the world. The European badger (Meles meles) and the brushtail possum (Trichosurus vulpecula) are implicated as significant sources of infection for domestic cattle in the UK and New Zealand respectively. The risk of transmission of infection between a wildlife population and domestic animals will be determined by both the epidemiology of the disease and the ecology of the host. In the UK, surveys by the UK Ministry of Agriculture, Fisheries and Food (MAFF) have identified M. bovis infection in deer (Cervus sp., Capreolus sp., Dama sp.), red fox (Vulpes vulpes), mink (Mustela vison), feral ferret (Mustela furo), mole (Talpa europaea), brown rat (Rattus norvegicus) and feral cat (Felis catus). However, the potential contribution to cattle herd breakdowns, of reservoirs of M. bovis infection in mammals other than the badger is poorly understood and is the subject of current research. In contrast, M. bovis infection in the badger has been the subject of a long term ecological and epidemiological study at Woodchester Park in South-West England, where the prevalence and distribution of infection in a wild population has been intensively monitored. The pattern of infection in the population and potential risks to cattle, are profoundly influenced by badger social organization and behaviour. The pattern of land use and cattle farming practices in the UK brings badgers into close contact with domestic animals and provides conditions that may enhance the likelihood of disease transfer.

Animal Husbandry↗

Tuberculosis in badgers; a review of the disease and its significance for other animals.

This review examines the current state of knowledge of aspects of tuberculosis in the badger. The gross pathology and pathogenesis are elaborated as well as the immune mechanism, diagnosis of infection and excretion and viability of infected products. The epidemiology in badgers is considered, as is the significance of infection in this species for other wildlife species as well as domestic animals sharing the same habitat. Trials of the effects of the removal of badgers on the occurrence of tuberculosis in cattle are summarised. It is concluded that badgers are well adapted as the primary host of bovine tuberculosis in parts of Britain and much of Ireland.

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Molecular epidemiology of bovine tuberculosis. II. Applications of genotyping.

The applications of genotyping of Mycobacterium bovis are reviewed. Published research to date has been conducted predominantly within the context of validating typing methods, and few studies have been specifically epidemiological. This is contrasted with the situation in human tuberculosis, where the application of restriction fragment length polymorphism typing using insertion sequence IS6110 has successfully led to insights into the epidemiology and molecular evolution of the pathogen. Based upon the medical experience, the adoption of an integrated approach which combines epidemiology and molecular biology is recommended for future studies. Accordingly, clear identification and explanation of type clustering should be possible, which should facilitate decisions related to disease control.

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Molecular epidemiology of bovine tuberculosis. I. Mycobacterium bovis genotyping.

The lack of a typing system for Mycobacterium bovis has, until recently, been an impediment to undertaking sophisticated epidemiological studies to assist in the control and eradication of tuberculosis in domestic animals. Molecular biology techniques for mycobacteria have been in development since the mid-1980s, leading to the availability of a number of genetic typing systems for M. bovis. The authors summarise the available techniques, identify those which are most useful at present and those which might prove useful in the future. The present recommendation is to use spoligotyping analysis for rapid, large scale screening of M. bovis isolates, and to use restriction fragment length polymorphism analysis using the polymorphic guanine and cytosine-rich repeat sequences probe where greater differentiation of isolates is required. In the future, systematic analysis of the genome sequence of M. bovis will allow the development of improved techniques that combine good discrimination with ease of use.

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Movement of badgers (Meles meles) in a high-density population: individual, population and disease effects.

The movement of 1763 badgers trapped between 36 social groups in Woodchester Park, Gloucestershire, over 18 years was analysed to determine the frequency and duration of moves, the factors associated with a predisposition to move and the spatial pattern of movements. Of those badgers whose capture history could be categorized, nearly half had moved. Of these, 73.1% were classified as 'occasional movers', 22.1% as 'permanent movers' and 4.8% as 'frequent movers'. Most adult badgers that moved made occasional moves (78.8%, n = 67). Cubs made all types of move including permanent moves (29%, n = 10). Seventy per cent of females were non-movers compared with 37% of males. Badgers were significantly more likely to move to smaller groups, whereas male badgers were significantly more likely to move to groups with a greater proportion of females. The spatial pattern of movement differed from the distribution of groups with bovine tuberculosis in the study area. However, temporal changes in movement were significantly related to the incidence of Mycobacterium bovis infection in the following year, indicating that as the movement of badgers between groups varies so does the incidence of bovine tuberculosis in the population. This finding is of central importance in the formulation of badger control policy.

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The kinetics of serum antibody responses to natural infections with Mycobacterium bovis in one badger social group.

Bovine tuberculosis remains a significant problem in some parts of Great Britain and Ireland largely because of a reservoir of infection in badgers. Little is currently known about the immunopathology of Mycobacterium bovis infection in the badger. Badgers, from 31 social groups, in a study area of the Cotswold escarpment, have been trapped and sampled from 1981 to 1995. Serum antibody responses directed against the 25 kDa antigen (MPB83) of M. bovis have been studied in detail in a selected social group (JM) which has endemic infection. Sequential sera from 44 badgers were studied and results compared with culture from faeces, urine, tracheal aspirates, bite wound swabs and at post mortem. The results indicate that some badgers (about 10%) remain uninfected despite exposure to endemic M. bovis infection within the social group. In culture-positive animals active excretion of organisms is not necessarily concomitant with seropositivity. Conversely, seropositivity is not an indicator that culture positivity is present or imminent. This is particularly true in cubs when a transient seropositivity can occur within the first 6-8 months of life but these animals can remain culture-negative for up to 5 years. Western blotting confirms that at least some of these antibodies, detectable by ELISA in the culture-negative cubs, are directed against the 25 kDa M. bovis antigen. In contrast antibodies detectable in the culture-positive animals do not Western blot prior to a positive culture. Thus, differential reactivity in Western blotting may distinguish between serum antibodies indicative of potentially culture-positive animals and animals which will remain culture-negative.

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Evaluation of an ELISA for Mycobacterium bovis infection in badgers (Meles meles).

The performance of an indirect ELISA for diagnosing Mycobacterium bovis infection in live badgers was evaluated by examining blood samples collected from 1982 badgers captured during statutory badger removal operations in south west England. The Validity of the test and the factors affecting the prevalence of infection are described. The sensitivity of the ELISA was 40.7 percent, its specificity was 94.3 percent, the predictive value of a positive test was 67.5% percent and the predictive value of a negative test was 84.6 percent. Its sensitivity was significantly higher in males and animals with gross lesions typical of tuberculosis. The sensitivity and positive predictive values were enhanced when the results were grouped by control operation. Variables of significance for prevalence were the county, the time of year, the age and sex of animal, and the time after the start of a control operation. The possible use of the ELISA as a screening test is discussed.

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The occurrence of Mycobacterium bovis infection in cattle in and around an area subject to extensive badger (Meles meles) control.

The occurrence of Mycobacterium bovis infection in cattle herds during the period 1966-92 in two geographically related areas in South-West England is compared. In one area comprising 104 km2 all badgers were systematically destroyed from 1975-81, after which recolonization was allowed; in the other, comprising 116 km2, small scale, statutory badger removal operations were undertaken from 1975 onwards where specific herds were detected with M. bovis infection. In the area with total clearance, no further incidents with M. bovis isolation occurred from 1982-92. Survival analysis and proportional hazards regression indicated that the risk of herds being identified with infection was less once badgers had been cleared from their neighbourhood, whereas it was greater in herds with 50 or more animals, and once cattle in a herd had responded positively to the tuberculin skin test, even though infection with M. bovis was not confirmed subsequently. The study provides further evidence that badgers represent an important reservoir of M. bovis infection for cattle and that badger control is effective in reducing incidents of cattle infection with M. bovis if action is thorough and recolonization is prevented.

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