HC Deb 20 May 2004 vol 421 cc1103-7W
Andrew George

To ask the Secretary of State for Environment, Food and Rural Affairs what assessment she has made of the effect of repeated intradermal skin tests on the ability of the test to detect bovine TB infection in individual cattle. [172530]

Mr. Bradshaw

There is often a trade-off between test sensitivity and specificity. The skin test used in GB has been fine tuned to optimise specificity (i.e. keep false positives to a minimum) while retaining a good sensitivity (i.e. probability of identifying infected herds). However, because of the dynamics ofMycobacterium bovis (M. bovis—the causative organism for bovine tuberculosis) transmission and the time it takes to mount a detectable immune response to the intradermal injection of tuberculin, the skin test cannot be relied upon to detect every animal infected with M. bovis at the time of the disclosing test. This phenomenon is not unique to the tuberculin test and, in fact, this is quite normal for any immunological test.

For these reasons, it is well accepted that the tuberculin tests are more suited to the detection of infected herds rather than the detection of infected individual cattle, i.e. a small proportion of infected animals in reactor herds may escape detection when the herd is first tested (false negatives). In order to increase the sensitivity of the skin test and detect any animals in the early stages of infection, reactor herds are re-tested at 60 day intervals until no further reactor animals are found and restrictions can be lifted. Reactor herds are then re-tested 6 and 18 months after the lifting of restrictions. Additionally, if infection has been confirmed in the herd by post mortem examination or culture, a more severe interpretation of test readings is applied. This further enhances the ability of the test to detect any residual infection after the initial screening. In other words, the imperfect sensitivity of the skin test is compensated for by the application of short-interval testing and severe interpretation.

Defra has also sponsored experimental work at the Institute of Animal Health (Compton), to look into the effects of repeat skin testing. The main finding of this experiment was that repeat testing at 56-day intervals before experimental infection of calves with M. bovis had no effect on the animals' ability to respond to an intradermal test carried out seven weeks post-infection. Therefore, no matter how often an animal is skin tested before it contracts TB, the sensitivity of the skin test after infection will not be compromised.

Andrew George

To ask the Secretary of State for Environment, Food and Rural Affairs what research she has evaluated on the specificity and sensitivity of the Bovigam gamma in interferon test; and what conclusions she has drawn. [172550]

Mr. Bradshaw

The Veterinary Laboratories Agency (VLA) has reviewed 13 papers reporting gamma-interferon (γ-IFN) field trials in Australia, New Zealand, Northern Ireland, Republic of Ireland, Brazil, Italy, Spain and USA. Eight papers gave 20 estimates of sensitivity (80 per cent. were in the range 71–94 per cent.) and 8 papers gave 22 estimates of specificity (80 per cent. were in the range 89–99 per cent.). These estimates for sensitivity are similar to those for the skin test as practiced in the UK, but the estimates for specificity are lower. If the γ-IFN test were used at the same time or shortly after the skin test and animals positive to either test were removed, the combined tests would have a greater sensitivity than the skin test alone. If used with the defined, more specific, antigens developed by VLA, the gamma interferon test can in certain circumstances identify uninfected animals that are positive to the skin test.

The γ-IFN assay is widely considered to be at least as sensitive as the skin tests and, in addition, will detect a proportion of infected cattle that fail to react to the skin tests. This is thought to be because the γ-IFN test detects infection at an earlier stage than the skin test does, although there is also evidence that the two tests detect slightly different populations of tuberculouses cattle. However, the γ-IFN test is hardly ever used for mass TB screening on its own. This is because the test is relatively expensive, it does not detect all skin test-positive infected animals, it tends to be less specific than the SICCT (the single intradermal comparative cervical test, which is the version of the skin test used in the UK and Ireland) and, the SICCT, it is unlikely to detect infected animals that are negative to the tuberculin test due to a depressed immune response to tuberculin (this can occur in cattle with advanced TB). The need to process samples within 24–30 hours of collection also poses some logistical problems for mass screening.

In contrast, it has been postulated that the use of the γ-IFN test in tandem with the skin test could allow the removal of more (but not necessarily all) infected cattle from particular breakdown herds than the skin test alone. If this is correct, use of the two tests in quick succession should speed up the elimination of infection from infected herds. Under this premise, the European Commission approved the γ-IFN test in 2002 for use as an ancillary test in animals that fail to respond to the skin test and it now complements the skin tests in cattle herds with intractable, confirmed infection in many EU member states. It is worth noting that most of these member states use a version of the skin test different to that used in the UK and Ireland.

Andrew George

To ask the Secretary of State for Environment, Food and Rural Affairs what level of specificity and sensitivity she has concluded might be applied to control bovine TB in cattle herds which (a) are subject to repeated and persistent bovine TB breakdowns, (b) are subject to a first TB breakdown and which are also in a TB hotspot, (c) are subject to a first TB breakdown and which are not in a TB hotspot, (d) have not been subject to TB breakdowns and which are in a TB hotspot and (e) have not been subject to TB breakdowns and which are not in a TB hotspot. [172551]

Mr. Bradshaw

Sensitivity and specificity of tests for bovine TB in cattle have relative rather than absolute meanings as it is not possible to conclusively demonstrate that an animal with no sign of TB is not in the early stages of infection. In addition, it is possible to increase the sensitivity and decrease the specificity by lowering the reading above which the test is declared positive (as occurs with standard and severe interpretations of the skin test).

The Divisional Veterinary Managers (DVMs) have the discretion to remove cattle from herds that are not skin test positive—they are generally termed Dangerous Contacts. The DVMs use their epidemiological judgment to vary the criteria used to remove animals in cases (a) to (e) in the question.

Andrew George

To ask the Secretary of State for Environment, Food and Rural Affairs what assessment her Department has made of the predictive models used in other countries to assess the feasibility of controlling bovine TB using the Bovigam gamma interferon test. [172552]

Mr. Bradshaw

Other countries with a bovine TB problem comparable to Great Britain's—New Zealand, Republic of Ireland, Northern Ireland—have used the interferon test, but there are no published predictive models for its use.

Andrew George

To ask the Secretary of State for Environment, Food and Rural Affairs what the maximum(a) specificity and (b) sensitivity achieved by the Bovigam gammas interferon test in experiments conducted in the UK is; and under what conditions these results were achieved. [172553]

Mr. Bradshaw

Specificity and sensitivity must be quoted together as they are inversely related, and they suffer from the lack of an absolute measure of whether an animal is infected. In the UK, the gamma interferon (γ-IFN) test has been used without the skin test only in laboratory studies.

No large-scale validation of the γ-IFN test has been carried out in GB. The ongoing field trial sponsored by Defra and the Welsh Assembly Government in Wales and the Midlands aims to measure the cost effectiveness of using the γ-IFN in infected herds in conjunction with the single intradermal comparative cervical test (SICCT) and provide some data on the γ-IFN test sensitivity under GB conditions. There are also plans in train to assess the specificity of the γ-IFN test in areas of GB with little or no incidence of TB.

Andrew George

To ask the Secretary of State for Environment, Food and Rural Affairs what the(a) maximum and (b) minimum (i) sensitivity and (ii) specificity is of the comparative intradermal tuberculin test in the UK. [172554]

Mr. Bradshaw

There is often a trade-off between sensitivity and specificity of a diagnostic test and no test is 100 per cent. sensitive and 100 per cent. specific. When used as a routine screening test in GB, the single intradermal comparative cervical test (SICCT) is designed to maximise specificity while retaining a good sensitivity.

Statistical analysis of TB testing data suggests that the maximum sensitivity of disclosing tests is 90 per cent. and the maximum sensitivity of subsequent (short-interval) tests is 70 per cent. The average specificity of the disclosing test in low-incidence districts of Great Britain is between 99.98 per cent. and 99.99 per cent.

When used in herds with confirmed TB, the cut off point of the test is shifted to increase sensitivity at the expense of specificity.

Andrew George

To ask the Secretary of State for Environment, Food and Rural Affairs how many studies the Government have funded in the last 15 years into the specificity and sensitivity of the Bovigam gamma interferon test; which research establishments conducted each study; what the conclusions of each study were, with reference to specificity and sensitivity; when the results of each study were drawn to the attention of(a) the chief veterinary officers and (b) Ministers; and where and when the results were published. [172556]

Mr. Bradshaw

The Bovigam test became commercially available around 1991. Since then, field research in a number of countries, including Britain, has confirmed the test to be a valuable ancillary test to the skin test. We have not conducted studies designed to look particularly at the specificity and sensitivity of the Bovigam test in the UK. However, there are nine current research projects which are looking at the development of moreMycobacterium bovis specific gamma interferon antigens or on the validation of the ones already trialled.

Further details of these can be found in Annex 2 of the paper presented to the TB Forum on Gamma Interferon (TBF62) available on line at www.defra.gov.uk/animalh/tb/forum/papers/tbf62.htm.

Work is continuing in the form of the policy pilot field trial. In addition, a number of peer-reviewed papers have been published in academic journals.

Andrew George

To ask the Secretary of State for Environment, Food and Rural Affairs what assessment she has made of combinations of specificity and sensitivity applied in countries which have a bovine TB problem, in their use of the Bovigam gamma interferon test. [172565]

Mr. Bradshaw

The performance of the gamma interferon (γ-IFN) test (Bovigam) has been assessed by many authors in trials carried out in several countries with bovine tuberculosis (TB) problems. This research has been carefully evaluated by Defra and scientists from the Veterinary Laboratories Agency.

In these trials, the sensitivity of the test has ranged between 55.4 and 100 per cent. and the specificity between 70.0 and 99.6 per cent. However, these results are influenced by the characteristics of the cattle populations in which the studies were carried out, the prevalence of cross-reacting organisms, the cut-off point used to interpret the γ-IFN test and the criteria used to establish the M. bovis infection status of the trial animals (often known as the "gold standard"). It is not, therefore, straight forward to extrapolate specificity and sensitivity estimates directly from one country to another. Ideally, the performance of a diagnostic test for TB should be evaluated under the conditions and in the geographical area in which the test will be used.

Andrew George

To ask the Secretary of State for Environment, Food and Rural Affairs whether her Department has undertaken a cost and benefit analysis of the use of the Bovigam gamma interferon test. [172568]

Mr. Bradshaw

No large-scale validation of the gamma interferon (γ-IFN) test has been carried out in GB. Although the γ-IFN test is now used in several countries, experimental data is lacking on the cost-effectiveness of using γ-IFN in infected herds in conjunction with the single intradermal comparative cervical test. Desk studies have estimated that significant savings will need to accrue from the use of the γ-IFN before it becomes cost-effective in GB. The on-going field trial sponsored by Defra and the Welsh Assembly Government in Wales and the Midlands aims to resolve this question.

Andrew George

To ask the Secretary of State for Environment, Food and Rural Affairs what advice the Central Scientific Laboratory has provided to her Department on the(a) specificity and (b) sensitivity of the Bovigam gamma interferon test; and what advice it has provided on the applicability of the test as a bovine TB control measure; [172999]

(2) what recent discussions her Department and its agencies have had with Central Science Laboratory on the practical application of its Bovigam gamma interferon test for bovine TB in cattle. [172555]

Mr. Bradshaw

No discussions have taken place with the Central Science Laboratory on the subject of the Bovigam gamma interferon test. The Bovigam test was developed by Commonwealth Serological Laboratories Veterinary Ltd., Australia.