Brazilian guidelines for the management of tuberculosis infection in immune-mediated inflammatory diseases: is retesting in latent tuberculosis screening appropriate and Safe?

Brito, Carlos; Brito, Rita Moraes de

doi:10.1186/s42358-025-00462-7

Abstract

The article "Brazilian Recommendations for the Management of Tuberculosis Infection in Immune-Mediated Inflammatory Diseases" by Viviane de Souza et al. presents important discussions on the subject; however, the recommendation for annual repetition of the TST/IGRA test for three years and after medication changes raises considerable concerns. This approach may lead to overdiagnosis and overtreatment of latent tuberculosis infection (LTBI). Frequent false-positive results in retests can result in unnecessary antibiotic use, contributing to bacterial resistance, a problem of global significance. The recommendation, considered to have a moderate level of evidence, is subject to criticism. Arguments used to support retesting, such as high conversion rates of tests after one year, reports of tuberculosis cases despite negative screenings being attributed to false negatives, and reliance on other sources with lower levels of evidence, do not constitute sufficient evidence to confirm tuberculosis infection or justify the recommendation. On the other hand, there is evidence that has not been considered in the discussion against the recommendation for retesting, indicating that this practice may increase the risk of diagnosing false-positive infections, leading to overtreatment without clinically proven benefits. Potentially harmful interventions should not be implemented without solid evidence to support them. In this letter to the editor, we briefly discuss this recommendation and the arguments against its implementation, highlighting its associated risks.

Keywords
Immunomediated inflammatory diseases; Tuberculosis; Latent tuberculosis

Dear Editor,

The article presents an important discussion, but the recommendation for repeated diagnostic testing in immunomediated inflammatory diseases (IMIDs) raises considerable concerns.

Recommendations 7 and 8 suggest annual repetition of the TST/IGRA test for an initial negative result and after medication changes. These recommendations require critical re-evaluation due to their potential undesirable consequences.

The authors acknowledge that indiscriminate retesting increases costs to the healthcare system but overlook a more significant risk: the overdiagnosis and overtreatment of latent tuberculosis infection (LTBI). Frequent false-positive results in retests may lead to unnecessary antibiotic use, contributing to bacterial resistance, a pressing global health problem [ ¹ – ⁵ ].

The analysis of the 33 studies cited as the basis for these recommendations, of which only five have clear identification, reveals important weaknesses. The conversion rate of 12.8% following retesting, used as the primary justification, does not provide sufficient evidence to confirm TB infection. Studies by Zwerling (2013), Tagmouti (2014) and Moses (2016) demonstrate significant variability in serial testing, with conversions and reversions often attributable not to actual infections but to technical variations or delayed booster effects. A Markov simulation model suggested approximately thirty false-positive results for each true infection [ ³ ].

The research by Jauregui-Amezaga, cited in support of retesting, presents insufficient evidence. The cases of tuberculosis identified in six negative screenings could result from new exposures rather than diagnostic failures. Shimabuco et al. (an article cited in the guideline) support this hypothesis by highlighting re-exposure as a critical factor for incident cases.

Comparison studies also question the relevance of retesting. Thomas et al. observed that among 50 patients with IMID, 10 (20%) had a positive retest after one year, with five receiving treatment for LTBI and five not; however, none developed tuberculosis during follow-up [ ⁴ ]. Magalhães et al. found no statistical difference in the incidence of tuberculosis between groups with IMID, subjected to (136) and not subjected to (81) annual retests [ ⁵ ].

Contrary to what has been described, EULAR 2022 recommendations do not specifically endorse retesting, considering the insufficient data and suggesting a research agenda. A technical note from Brazil was cited, but the document lacks scientific evidence to justify the recommendation. WHO guidelines for endemic countries also do not include this recommendation.

In summary, there is a lack of robust evidence to justify the recommendation for retesting, while there is data that suggest this practice may increase the risk of over-treatment and contribute to the development of bacterial resistance in Mycobacterium tuberculosis, without clinically proven benefit. Potentially harmful interventions should not be implemented without solid evidence to support them.

Funding
Not applicable.
Declarations
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Consent for publication
The final manuscript has been revised critically and approved by all the authors and they have given the necessary attention to ensure the integrity of the work.
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TST Tuberculin skin test
IGRA Interferon-gamma release assay
IMID Immunomediated inflammatory diseases
LTBI Latent tuberculosis infection
WHO World Health Organization
TB Tuberculosis

Acknowledgements

Not applicable.

Data availability

No datasets were generated or analysed during the current study.

References

¹ Zwerling A, Benedetti A, Cojocariu M, McIntosh F, Pietrangelo F, Behr MA, et al. Repeat IGRA testing in Canadian health workers: conversions or unexplained variability? PLoS ONE. 2013;8(1):e54748. https://doi.org/10.1371/journal.pone.0054748 .
» https://doi.org/10.1371/journal.pone.0054748
² Tagmouti S, Slater M, Benedetti A, Kik SV, Banaei N, Cattamanchi A, et al. Reproducibility of interferon gamma (IFN-γ) release assays. A systematic review. Ann Am Thorac Soc. 2014;11(8):1267–76. https://doi.org/10.1513/AnnalsATS.201405-188OC .
» https://doi.org/10.1513/AnnalsATS.201405-188OC
³ Moses MW, Zwerling A, Cattamanchi A, Denkinger CM, Banaei N, Kik SV, et al. Serial testing for latent tuberculosis using QuantiFERON-TB gold In-Tube: A Markov model. Sci Rep. 2016;6:30781. https://doi.org/10.1038/srep30781 .
» https://doi.org/10.1038/srep30781
⁴ Thomas K, Hadziyannis E, Hatzara C, Makris A, Tsalapaki C, Lazarini A, et al. Conversion and reversion rates of tuberculosis screening assays in patients with rheumatic diseases and negative baseline screening under Long-Term biologic treatment. Pathog Immun. 2020;5(1):34–51. https://doi.org/10.20411/pai.v5i1.349 .
» https://doi.org/10.20411/pai.v5i1.349
⁵ de Oliveira Magalhães V, Bonfiglioli KR, Gomes CMF, Bonfá E, de MedeirosRibeiro AC, Saad CGS, de Medeiros Pinheiro M. Tuberculin skin test repetition after TNF-α inhibitors in patients with chronic inflammatory arthritis: a long-term retrospective cohort in endemic area. Adv Rheumatol. 2024;64(1):70. https://doi.org/10.1186/s42358-024-00406-7 .
» https://doi.org/10.1186/s42358-024-00406-7

Publication Dates

Publication in this collection
09 Mar 2026
Date of issue
2025

History

Received
17 Apr 2025
Accepted
24 June 2025
Published
01 July 2025

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[1] ¹ Zwerling A, Benedetti A, Cojocariu M, McIntosh F, Pietrangelo F, Behr MA, et al. Repeat IGRA testing in Canadian health workers: conversions or unexplained variability? PLoS ONE. 2013;8(1):e54748. https://doi.org/10.1371/journal.pone.0054748 .
» https://doi.org/10.1371/journal.pone.0054748

[2] ² Tagmouti S, Slater M, Benedetti A, Kik SV, Banaei N, Cattamanchi A, et al. Reproducibility of interferon gamma (IFN-γ) release assays. A systematic review. Ann Am Thorac Soc. 2014;11(8):1267–76. https://doi.org/10.1513/AnnalsATS.201405-188OC .
» https://doi.org/10.1513/AnnalsATS.201405-188OC

[3] ³ Moses MW, Zwerling A, Cattamanchi A, Denkinger CM, Banaei N, Kik SV, et al. Serial testing for latent tuberculosis using QuantiFERON-TB gold In-Tube: A Markov model. Sci Rep. 2016;6:30781. https://doi.org/10.1038/srep30781 .
» https://doi.org/10.1038/srep30781

[4] ⁴ Thomas K, Hadziyannis E, Hatzara C, Makris A, Tsalapaki C, Lazarini A, et al. Conversion and reversion rates of tuberculosis screening assays in patients with rheumatic diseases and negative baseline screening under Long-Term biologic treatment. Pathog Immun. 2020;5(1):34–51. https://doi.org/10.20411/pai.v5i1.349 .
» https://doi.org/10.20411/pai.v5i1.349

[5] ⁵ de Oliveira Magalhães V, Bonfiglioli KR, Gomes CMF, Bonfá E, de MedeirosRibeiro AC, Saad CGS, de Medeiros Pinheiro M. Tuberculin skin test repetition after TNF-α inhibitors in patients with chronic inflammatory arthritis: a long-term retrospective cohort in endemic area. Adv Rheumatol. 2024;64(1):70. https://doi.org/10.1186/s42358-024-00406-7 .
» https://doi.org/10.1186/s42358-024-00406-7