Evidence of the Bovine TB risk posed by resolved Inconclusive Reactor animals

This paper summarises and references the studies undertaken to examine the risks posed by resolved IR animals which were presented to the Technical Advisory Group (TAG), and references currently published on TB hub and in the Godfray bTB Evidence Review Update 2025 Report.

The policy to restrict resolved standard interpretation Inconclusive Reactors (IRs) to the holding for the rest of their life is being introduced in Wales. 

All Standard interpretation IRs in Wales that have a negative result under standard interpretation at the re-test read on or after 1^st January 2026, remain restricted for the rest of their life to the holding in which they were found. The only permitted off movements for such animals are to a slaughterhouse or Approved Finishing Unit (AFU). The cattle can move directly or via an approved slaughter gathering or TB dedicated sale (orange market).

For simplicity and ease of understanding the policy will apply to any test for the whole of Wales irrespective of TB risk area.

• the TAG advises that IR policies in Wales are now too complex for some keepers and their private vets to understand, and that the IR policy should be simplified as part of a revised, holistic TB Eradication Plan for Wales
• modelling outputs indicate, even in a Low-risk area, there is an increased risk of having a bTB breakdown in herds with a history of resolved standard IRs
• IRs being disclosed at surveillance tests have historically been the first indication of emerging TB into previously low incidence areas

The TAG strongly advised against the use of the gamma interferon test to lift restrictions on a resolved IR animal (As is allowed in England). The gamma interferon test was not designed for use in this way. The test is used to maximise detection of infected animals but is not designed to be used to negate a positive skin test. Whilst using the gamma interferon test to negate a resolved IR result mitigates against some of the risk associated with resolved standard IRs, it will not remove the risk altogether as the gamma interferon does not detect 100% of infected animals. Unfortunately, there is insufficient data from England to inform this issue as there has been low uptake of this option.

The evidence prepared for TAG by WG on standard IRs and severe IR animals provided data to suggest that severe resolved IRs are 2.9 times more likely than a clear testing animal to be subsequently identified and culled as a reactor, or IR, or as a confirmed SLH case than a clear testing animal (compared with a figure of 2.8x for standard IRs). 

The data provided also suggest that of the cattle population still alive or within Wales after 5 years (between 2013-2018), 30.3% of resolved standard IRs, 30.5% of resolved severe IRs and 10.7% of clear testing animals were identified and culled as reactors or IRs or confirmed SLH cases (although the authors suggest that this is likely to be an over representation of the true risk of these animals). 

The TAG’s analysis of these data and their advice is that these IR animals - both standard and severe IRs - show a greater likelihood of being infected with Mycobacterium bovis, and therefore pose a higher risk of spreading TB to other animals and herds than clear testing animals.

May et al¹ (2019) used separate mixed-effects logistic regression models to examine the relationship between IR status and subsequent reactor status for each risk area of England and for Wales, adjusting for other explanatory variables. They found that the odds of an animal becoming a subsequent reactor during the study period were greater for IR animals than for negative animals in the high-risk area (odds ratio (OR): 6.85 (5.98–7.86)) and edge area (OR: 8.79 (5.92–13.04)) of England and in Wales (OR: 6.87 (5.75–8.22)). In the low-risk area of England, the odds were 23 times greater, although the confidence interval around this estimate was larger due to the smaller sample size (11–48, p < 0.001).

In a paper by Clegg et al² (2011a), a study population included all standard IRs identified in Ireland between 2005 and 2009 (inclusive) in a herd otherwise Officially TB free (OTF). The paper concluded that all resolved (transient) standard IRs that moved out of the disclosing herd within 6 months of the IRR (Inconclusive Reactor Retest) were 12 times more likely to be bovine tuberculosis (bTB) positive at the next test/slaughter compared to all animals in the national herd. The same increased risk did not apply to the SICTT negative cohort animals that moved out of the same herds at the same time.

A separate paper by Clegg et al³, (2011b) had a study objective to critically evaluate the future bTB status of resolved (transient) IR animals, by examining the future risk of bTB diagnosis over the 4 years following initial standard IR diagnosis and clearance at the subsequent retest. They found that animals that were deemed SICTT IRs in 2005 and passed a subsequent retest were significantly more likely to be diagnosed, at a later date, with bTB (during subsequent testing; either field or abattoir surveillance) than control animals. The proportion of resolved IRs (termed TIRs) diagnosed with bTB during the study was almost four times higher compared with non-TIRs (9.34% versus 2.58%). Indeed, during the study period the time to bTB detection was 78% shorter among TIRs compared to non-TIR animals. Although the risk of a TIR being diagnosed with bTB decreased after around 500 days the hazard was always greater, than that of non-TIR animals, throughout the study period.

In unpublished data from the APHA Wales Field Epidemiology Team, based on Poisson regression modelling outputs for the West Pembrokeshire study area, using seven known bovine tuberculosis (bTB) risk factors in herds not currently under bTB restriction (with a new incident 2022 as the outcome), four factors were retained as significant in the model offering the best fit (Annex 12). The herd having a history of resolved standard IRs was shown to increase the risk of a bTB incident by almost two times compared to herds with no history of resolved standard IRs (Incidence Rate Ratio (IRR): 1.80 (1.33-2.42)). On Anglesey, the outcome of the analysis was similar, with the history of resolved standard IRs increasing a risk of having a bTB breakdown by almost 8-fold. (IRR: 7.49 (3.86-14.54)).

References

1. Exploring the Risk Posed by Animals with an Inconclusive Reaction to the Bovine Tuberculosis Skin Test in England and Wales, May et al (30/11/2019) Open access article, Veterinary Sciences Volume 6 Issue 4 10.3390/vetsci6040097
2. Shorter-term risk of Mycobacterium bovis in Irish cattle following an inconclusive diagnosis to the single intradermal comparative tuberculin test, Clegg et al (15/12/2011a), Preventive Veterinary Medicine, Volume 102, Issue 4, Pages 255-264
3. Longer-term risk of Mycobacterium bovis in Irish cattle following an inconclusive diagnosis to the single intradermal comparative tuberculin test, Clegg et al (01/07/2011b), Preventive Veterinary Medicine Volume 100, Issues 3–4, Pages 147-154

Evidence published in TBhub

The same studies undertaken to examine the risks posed by resolved IR animals have also been summarised and referenced as follows on TB hub:

Scientific studies looking at resolved IRs in the Republic of Ireland^4,5 where bovine TB is widespread, have demonstrated that such animals have significantly higher odds of becoming reactors at a subsequent test in the same or another herd.  The studies concluded that:

• resolved IRs that moved out of the herd within six months of passing their re-test were 12 times more likely to be positive at the next test or slaughter compared to all animals in the national herd⁴
• between 11.8% and 21.4% of IRs slaughtered prior to re-test showed visible lesions suspicious of TB at post mortem meat inspection, compared with less than 0.3% of non-IR animals⁴
• during the study period, the time to detect TB in resolved IRs was 78% shorter, on average, compared to clear-testing cattle⁵

These studies provided evidence for the introduction of a new policy for resolved IRs in the Republic of Ireland in 2012. After reviewing the evidence, Defra introduced a similar policy in England in 2017.

Further research has been carried out exploring the risk posed by resolved IRs in England and Wales^6,7, which adds to the evidence above. This latest research found that the odds of a resolved IR becoming a subsequent reactor during the study period were seven and nine times greater than for negative testing animals in the HRA and Edge Area of England, respectively⁶. The increased risk of becoming a reactor supports the policy to restrict resolved IRs to the herd in which they were found for life.

At herd level, the time interval before a new TB breakdown in IR-only herds (those with IRs only and no reactors) in England and Wales was around half that of herds with a negative whole herd test. The hazard of a subsequent TB breakdown was 2.7 times greater for IR-only herds compared with clear herds in year one, after accounting for the influence of accepted risk factors of TB⁷. Analyses of cattle herds in England in 2019 showed that in the High Risk Area (HRA), 40% of IR-only herds went on to have a TB incident (with lesion and/or culture positive animals) within the following 15 months (33% in the Edge Area)⁸. 

References

4. Clegg, T. A. et al. Shorter-term risk of Mycobacterium bovis in Irish cattle following an inconclusive diagnosis to the single intradermal comparative tuberculin test; Preventive Veterinary Medicine 102(4):255-64
5. Clegg, T. A. et al. Longer-term risk of Mycobacterium bovis in Irish cattle following an inconclusive diagnosis to the single intradermal comparative tuberculin test; Preventive Veterinary Medicine 100 (3-4):147-154
6. May E, Prosser A, Downs S. H, Brunton L. A. Exploring the Risk Posed by Animals with an Inconclusive Reaction to the Bovine Tuberculosis Skin Test in England and Wales (on mdpi.com)
7. Brunton L. A, Prosser A, Pfeiffer D. U, Downs S. A. Exploring the Fate of Cattle Herds With Inconclusive Reactors to the Tuberculin Skin Test (on frontiersin.org)
8. Bovine TB epidemiology and surveillance in Great Britain, 2019, APHA (on gov.uk)

Reference in the Godray bTB Evidence Review Update 2025 Report

It should also be noted that an updated review of the Bovine TB strategy applied in England, chaired by Professor Sir Charles Godfray CBE FRS, also acknowledged the increased risk posed by resolved standard IRs at Chapter 3, paragraph 3.XVI of the published report: Godfray bTB Evidence Review Update 2025.

Recently published research suggests IRs may pose a risk to future herd health. In the HRA and EA, the odds of a resolved IR becoming a subsequent reactor were seven (HRA) and nine (EA) times greater than for animals that tested negative⁹. At herd level, the time interval before a new TB breakdown in IR only herds (those only with IRs and no reactors) in England and Wales was around half that of herds where all animals tested negative. Adjusted for confounding variables, the risk of a subsequent TB breakdown the following year was 2.7 times greater for IR-only herds compared with all-negative herds¹⁰. Data from England in 2019 showed that overall 40% (HRA) or 33% (EA) of IR only herds went on to have a TB incident (with lesion and/or culture positive animals) within the following 15 months. Data from the Republic of Ireland also suggest that IRs (from standard and severe interpretation of the SICCT test) are at greater risk of subsequently testing positive for the disease¹¹.

9. May et al., 2019, Exploring the Risk Posed by Animals with an Inconclusive Reaction to the Bovine Tuberculosis Skin Test in England and Wales (on mdpi.com)
10. Brunton et al., 2018, Exploring the Fate of Cattle Herds With Inconclusive Reactors to the Tuberculin Skin Test (on frontiersin.org)
11. Byrne et al., 2022, Can more information be extracted from bovine TB skin test outcomes to inform animal risk management? A retrospective observational animal-level study (on sciencedirect.com)