- Research
- Open access
- Published:
Spotlight on latent tuberculosis infection screening for juvenile idiopathic arthritis in two countries, comparing high and low risk patients
Advances in Rheumatology volume 62, Article number: 20 (2022)
Abstract
Background
Rheumatic diseases are associated with an increase in overall risks of tuberculosis (TB). The aim of this study was to evaluate the frequency of TB and the frequency of latent TB infection (LTBI), in clinical practice, for juvenile idiopathic arthritis (JIA) patients from high and low risk of TB incidence endemic countries.
Methods
This is an international, multicenter, cross-sectional, observational study of data collection from Brazil and Registry of Portugal at REUMA.PT. The inclusion criteria were patients with Juvenile Idiopathic Arthritis (JIA) with age ≤ 18 years who underwent screening for Mycobacterium tuberculosis infection [tuberculin skin test (TST) and/or interferon gamma release assay (IGRA)]. Chest X-rays and history of exposure to TB were also assessed.
Results
292 JIA patients were included; mean age 14.3 years, mean disease duration 7.5 years, 194 patients (66.4%) performed only TST, 14 (4.8%) only IGRA and 84 (28.8%) both. The frequency of LTBI (10.6%) and TB was similar between the two countries. The reasons for TB screening were different; in Brazil it was performed more often at JIA onset while in Portugal it was performed when starting Disease Modified Anti-Rheumatic Drugs (DMARD) treatment (p < 0.001). Isoniazid therapy was prescribed in 40 (13.7%) patients (31 with LTBI and 9 with epidemiologic risks and/or due to contact with sick people). Only three patients (1%) developed active TB.
Conclusion
We found nearly 10% of patients with LTBI, a small percentage of patients with treatment due to epidemiologic risks and only 1% with active TB. Distinct reasons and screening methods for LTBI were observed between the two countries.
Introduction
Tuberculosis (TB), caused by Mycobacterium tuberculosis (MT), is a major cause of morbidity and mortality among children and adolescents globally, with a mortality rate of around 1.6 million people every year [1]. In 2018, Brazil registered 37.4 new cases of TB per 100,000 habitants according to the Ministry of Health, remaining a highly endemic country, whereas Portugal registered 16.6 cases per 100,000 habitants, thus being considered a low TB risk country [2, 3].
Juvenile idiopathic arthritis (JIA) is the most common pediatric autoimmune rheumatic disease. Despite JIA outcome improvement, infections, particularly TB, remain a major concern for pediatric rheumatologists [4]. Indeed, rheumatic diseases are associated with a 2- to 4-fold increased TB risk, due to immune dysregulation and immunosuppressive treatments [5,6,7]. The frequency of latent tuberculosis infection (LTBI) has been described as twice as high in JIA patients after one year of methotrexate (MTX) treatment, compared to the healthy pediatric population [8, 9]. After starting biologic agents, the risk of LTBI reactivation and new TB infections in adults increased from 2 to 30 times, depending on the clinical setting and the type of tumor necrosis factor (TNF) inhibitor used, being particularly higher for monoclonal antibodies [10,11,12,13,14,15].
Therefore, it is recommended that all candidates for biologic Disease Modified Anti-Rheumatic Drugs (bDMARDs) treatment should be screened for MT infection before starting the treatment [16]. Long-term evaluation revealed that LTBI screening and primary prophylaxis before anti-TNF treatment is effective in preventing TB in a highrisk JIA population. Tuberculin skin test (TST) is the most used test to assess previous TB exposure [17]. Cellular response to MT-specific antigens such as interferon gamma release assay (IGRA) and enzyme linked immune absorbent spot (Elispot), could also be used, with the advantage of lower occurrence of false negative results, due to the use of immunosuppressors, but with the disadvantage of a higher cost [18]. To our knowledge, there is no previous study assessing the frequency of TB and LTBI screening in JIA patients, comparing high and low risk TB incidence endemic countries.
The aim of this study was to evaluate the frequency of TB and the frequency of latent TB infection (LTBI) in clinical practice for juvenile idiopathic arthritis (JIA) patients from high and low risk of TB incidence endemic countries.
Methods
An international, multicenter, cross-sectional, observational, study was carried out on JIA patients from Portugal and Brazil according to the revised International League of Associations for Rheumatology (ILAR) criteria [19], and ruling out other causes of chronic arthritis, registered at REUMA.PT. REUMA.PT is a prospective longitudinal real-world registry developed by the Portuguese Society of Rheumatology to record data from patients with several rheumatic diseases, including JIA. Partnerships have been formed with other countries, specifically with Brazil, that uses the same Portuguese version of the database, kindly provided for their own use [20]. All patients aged ≤ 18 years who had available data from TST and/or IGRA were included. From Sao Paulo state, the centers included were two in Sao Paulo city, one in Ribeirao Preto city, one in Botucatu city (with an incidence rate of tuberculosis of 31–50/100,000 habitants, considered as high risk), and from Rio de Janeiro state, one in Rio de Janeiro city was included (with an incidence of 51–65/100,000 habitants, considered as high risk). On the other hand, Portugal presented a rate of 16.6 cases per 100,000 habitants (considered as low risk) [2, 3].
The electronic registry data collection was performed up to May 2019, with a total of 1549 JIA patients included, of those, 292 patients with JIA diagnoses met the inclusion criteria, including sociodemographic, clinical description and treatment during follow up in tertiary centers clinics, being from twelve centers in Portugal and five in Brazil.
The TB screening, the use of conventional Disease Modified Anti-Rheumatic Drugs (cDMARDs) and biologic DMARDs (bDMARDs), and the TB events were systematically assessed. TST and/or IGRA were performed at JIA onset or before starting cDMARDs use, and always prior to the introduction of bDMARDs therapy to screen for LTBI, in accordance with Brazilian and Portuguese guidelines for biological therapies for children and adolescents with JIA [21, 22]. In both countries, 2TU units were used to perform TST. We only considered the information from the first performance of the TST and IGRA.
Screening tests included TST, IGRA, chest X-ray and history of exposure to TB. A positive TST was defined as the papule diameter as being equal to or greater than 5 mm. The chest X-ray findings looking for previous signs of TB were also considered. IGRA test values were also recorded. TB exposure was defined as current or past family history of close contact, professional contact, or school contact with an individual with known TB at any time. LTBI is defined clinically by a reactive TST and/or positive IGRA, in the absence of clinical and radiological findings, and LTBI treatment was recommended [23]. In the case of active TB (by clinical and/or radiological findings), treatment referral and follow up was offered.
Anti-bacillar treatment was indicated if a diagnosis of LTBI was established, in case of close contact with TB diagnosed individuals, or if TB was diagnosed. LTBI treatment was administered with isoniazid (INH) at 5 mg/kg (up to 300 mg/day) for six consecutive months or longer according to local guidelines [20, 21]. Anti-TNF therapy could be prescribed after one month of starting INH.
Sociodemographic data (current age, sex, educational level,) were also collected. Variables related to the disease such as its duration and treatment received, were obtained by direct interview with patients and from medical records. The types and doses of cDMARDs and bDMARDs treatment were registered. Patients receiving biological therapy with TNF inhibitors (TNFi) (etanercept, adalimumab, infliximab, certolizumab or golimumab), interleukin 6 (IL6) inhibitor (tocilizumab), or inhibitor of the T-lymphocyte co-stimulatory signal by CTLA4 (abatacept) were included.
Local Ethics Committee approval was obtained, and Reuma.PT was approved by the Portuguese data protection authority (Comissão Nacional de Proteção de Dados). Parents provided a written informed consent and children signed an assent form provided by Reuma.PT.
Statistical analysis
Descriptive statistics were used to calculate the mean (standard deviations) or median (range) for continuous variables, and frequencies (percentages) for categorical variables. Normal distribution was assessed using Kolmogorov–Smirnov test. Comparisons between countries were performed using Student’s t-tests, chi-square, or Fisher’s exact tests, as deemed appropriate. In order to detect differences between groups, comparisons in JIA patients performing TB screening tests for different reasons, Fisher’s exact test, chi-square test or one-way analysis of variance (ANOVA) were used. A p-value of less than 0.05 was considered statistically significant.
Results
A total of 292 JIA patients (188 Portuguese and 104 Brazilian), 61.3% female, with a mean age of 14.3 ± 6.7 years and mean disease duration of 7.5 ± 6.2 years, were included in the study. Table 1 shows demographic data and clinical descriptors. The Portuguese population was older and presented a longer disease duration.
Table 2 shows TB screening tests, treatment, and risk factors for TB in Portuguese and Brazilian populations. The reasons for TB screening were different for the two countries; it was performed more often at JIA onset in Brazil, whereas in Portugal it was performed when starting DMARD treatment, especially before starting biological treatment (p < 0.001). The use of chest X-ray and IGRA as screening tools were significantly more frequent in Portugal than in Brazil (77.1% and 55.8%, p < 0.001; and 51.1% and 1.92%, p < 0.001, respectively). Forty patients (13.7%) were treated with INH as a prophylactic therapy. From these, 31 had criteria for LTBI and 9 received the medication due to being considered at high risk of TB and/or due to contact with active TB cases. Patients with criteria for LTBI treatment were similar in Portuguese and Brazilian JIA patients (10.6% in both countries). Only three patients (1%) were identified as having active TB (1 in Portugal and 2 in Brazil, corresponding in both cases to 1% of the patients screened).
Table 3 shows the demographic data, clinical characteristics, TB screening tests and treatment for TB in patients performing the test at JIA onset or prior to the use of DMARDs.
Twelve out of 76 patients (15.8%) that performed TST and/or IGRA before initiating cDMARD presented a positive TB screening test; and 5 out of 87 patients (5.7%) that performed TST and/or IGRA before initiating bDMARD presented a positive TB screening test.
At the time the patients underwent LTBI test, 212 patients were off immunomodulators/immunosuppressants and the others were on immunomodulators/immunosuppressants (65 on methotrexate, 3 on sulfasalazine, one on leflunomide). The medications of the eleven patients who had performed the TB screening for other reasons were: 6 on treatment with methotrexate (the others were off medication).
Discussion
We found 10.6% JIA patients with criteria for LTBI and 1% classified as having active TB. Distinct reasons and methods to perform LTBI screening occurred in both countries.
TB is still a public health problem in developing or developed countries. The disease is even more worrisome in patients with systemic rheumatic diseases, such as JIA, especially in those under anti-TNF agents [4]. In our study, the reason for TB screening in Brazil was most often at JIA onset, whereas in Portugal the screening was mostly due to DMARD treatment onset, especially biological treatment. Screening using chest radiography and IGRA was more frequently performed in Portugal. Anti-bacillar therapy was indicated in cases classified as LTBI and/or history of contact with active TB patients, and/or in the case of the existence of high epidemiological risk factors for TB. LTBI treatment was performed more frequently in patients who underwent TST prior to the beginning of cDMARDs than prior to the use of bDMARDs or at disease onset. The frequency of indication for LTBI treatment was similar in Portuguese and Brazilian JIA patients. Only 3 patients had criteria for active TB.
The incidence of TB in Brazil is markedly higher than in Portugal. Non-mandatory BCG vaccination has occurred in Portugal since 2017, consistent with a TB low-risk country, whereas in Brazil it is included in the vaccination calendar during the first months of life [24, 25]. Recent studies have shown that the influence of BCG vaccination on TST depends more on the age at which the vaccine is administered than on the interval between BCG vaccination and TST performance [26]. This effect decreases over time, especially if the vaccine is administered before the age of two, the period during which it is administered in the Brazilian population [26]. Therefore, we imagine that the TST was not influenced by the BCG vaccination in our study population.
TST was performed either in the context of JIA diagnosis or post- diagnostic. TB is a major concern in the differential of diagnosis of chronic arthritis, especially in a highrisk setting. This justifies the higher frequency of TST performance at JIA onset in Brazil. In contrast, Portuguese patients had a TST performed mainly post-diagnostic, before the beginning of bDMARDs. A previously reported small JIA case series showed a high frequency of LTBI performed prior to MTX therapy, in Brazil. This study may suggest the recommendation of LTBI screening not only before the use of biological agents but also prior to the use of cDMARDs [9].
In a retrospective cohort of sixty-nine JIA patients on anti-TNF treatment, LTBI screening was positive in three patients (4.3%) and no active TB was diagnosed during a median follow up time of 3.8 years [17]. We also observed a low incidence of TST positivity (5.7%) in patients submitted to LTBI screening prior to bDMARDS therapy.
Importantly, although TB risk is much higher in Brazil than in Portugal, the rate of TST positivity was roughly the same (8.7% in Portugal vs 10.8% in Brazil). The prevention of active TB through the treatment of LTBI is one of the main strategies for reducing the incidence of this disease [27].
The introduction of biological agents during the 2000s for the treatment of JIA has dramatically changed the prognosis of children and adolescents with this chronic disease, but it has also raised concerns about possible risk of infections and other events in these patients. In a recent report of the Pharmachild registry, in 32 countries, a significant number of opportunistic infections was found, including 27.4% of TB and 4.1% of LTBI in JIA patients under immunosuppressive therapy, across different geographic areas [28].
The overall incidence rate of active mycobacterial infection in our previous Brazilian study including children, adolescents, and adults with chronic inflammatory arthritis, after using TNFi, was 86.9/100.000 person-years for patients and 35.8/100.000 person-years for the control group, with significant differences between both groups [29]. This data reinforces the indication of LTBI screening in this population.
In this study, chest X-rays showed non-specific pulmonary infiltrates and interstitial pulmonary infiltrates in very few JIA patients. These imaging findings were unrelated to TB disease, as confirmed by a pediatric pulmonologist.
We presume that the better economic situation facilitates access to exams such as chest X-rays and IGRA. Recently, WHO recommended that IGRA should not be used in low and middle-income countries (generally those with a higher TB burden), as there is insufficient data and evidence about the performance of IGRA in these populations [30]. IGRA has similar performance to TST but is more expensive and more complex to perform, therefore TST should be preferential in these countries. Studies on infection detection supported the use of TST [31]. IGRA may have an advantage over TST in patients under corticosteroids therapy and during a short period of time immediately after BCG vaccination. However, data from pediatric population and immunosuppressed individuals who could benefit from IGRA is limited and more studies with a large sample size would be desirable [32].
The indications for treatment of LTBI according to the recommendations in Brazil and Portugal are quite similar and include TST positivity (≥ 5 mm) and/or IGRA positivity in cases without previous LTBI treatment, or chest X-ray showing disease sequels of previous untreated TB, or presence of epidemiological data suggestive of TB contact (history of TB exposure in the last two years, previous TB illness, immigrants and residents from high prevalence/incidence areas of TB, comorbidities associated with increased risk of TB, and travel to endemic areas) after exclusion of active TB [21, 22].
LTBI treatment includes INH with different treatment protocols for the two countries (in Brazil for six months, in Portugal for nine months) [21, 22]. We observed in our study that LTBI therapy was indicated more frequently in patients due to positive TST before using cDMARDs than before bDMARDs.
The main limitations of the present study are the retrospective design (registry based) and a small number of JIA patients submitted for IGRA test. Another limitation was the use of glucocorticoids or DMARDs that may have affected the accuracy of the TST [33]. Furthermore, we do not think that the sample is representative, as it only included five Brazilian cities from one region, and two Portuguese cities.
Conclusion
This international multicenter study evaluated the frequency of TB and the value of LTBI screening in clinical practice of JIA patients at high and low risk of TB incidence in two endemic countries. We observed no differences in the occurrence of patients with criteria for LTBI and TB treatment in both countries.
Availability of data and materials
Not applicable.
References
Jenkins HE, Yuen CM, Rodriguez CA, Nathavitharana RR, McLaughlin MM, Donald P, et al. Mortality in children diagnosed with tuberculosis: a systematic review and meta-analysis. Lancet Infect Dis. 2017;17:285–95.
Ministério da Saúde (BR), Secretaria de Vigilância em Saúde. Boletim Epidemiológico Especial. Tuberculose 2021. (Ministry of Health (BR), Health Surveillance Secretariat. Special Epidemiological Bulletin. Tuberculosis 2021). Vol 50|Mar. 2019.
Tuberculose em Portugal – Desafios e Estratégias – 2018. Ministério da Saúde. Direção-Geral da Saúde (DGS). (Tuberculosis in Portugal - Challenges and Strategies - 2018. Ministry of Health. Directorate-General for Health). https://www.dgs.pt/paginas-de-sistema/saude-de-a-a-z/tuberculose1/relatorios.aspx.
Brunelli JB, Schmidt AR, Sallum AME, Goldenstein-Schainberg C, Bonfá E, Silva CA, et al. High rate of serious infection in juvenile idiopathic arthritis patients under biologic therapy in a real-life setting. Mod Rheumatol. 2018;28(2):264–70.
Bouza E, Moya JG, Munoz P. Infections in systemic lupus erythematosus and rheumatoid arthritis. Infect Dis Clin North Am. 2001;15:335–61.
Aydin V, Akici A, Isli F, Aksoy M, Aydin M, Gursoz H. Relative risk of tuberculosis in patients with rheumatic diseases managed with anti-tumor necrosis factor-alpha therapy: a nationwide cohort study. J Clin Pharm Ther. 2019;44(4):553–60.
Gardam MA, Keystone EC, Menzies R, Manners S, Skamene E, Long R, et al. Anti-tumor necrosis factor agents and tuberculosis risk: mechanisms of action and clinical management. Lancet Infect Dis. 2003;3(3):148–55.
Hsin YC, Zhuang L, Yeh K, Chang C, Horng J, Huang JL. Risk of tuberculosis in children with juvenile idiopathic arthritis: a nationwide population-based study in Taiwan. PLoS One. 2018;10(6). eCollection
Sztajnbok F, Boechat NLF, Ribeiro SB, Oliveira SJK, Sztajnbok DCN, Sant’Anna CC. Tuberculin skin test and ELISPOT/T. SPOT.TB in children and adolescents with juvenile idiopathic arthritis. Pediatr Rheumatol Online J. 2014;12:17.
Baronnet L, Barnetche T, Kahn V, Lacoin C, Richez C, Schaeverbeke T. Incidence of tuberculosis in patients with rheumatoid arthritis. A systematic literature reviews. Joint Bone Spine. 2011;78:279–84.
Arkema EV, Jonsson J, Baecklund E, Bruchfeld J, Feltelius N, Askling J, et al. Are patients with rheumatoid arthritis still at an increased risk of tuberculosis and what is the role of biological treatments? Ann Rheum Dis. 2015;74(6):1212–7.
Yonekura CL, Oliveira RDR, Titton DC, Ranza R, Ranzolin A, Hayata AL, et al. Incidence of tuberculosis among patients with rheumatoid arthritis using TNF blockers in Brazil: data from the Brazilian registry of biological therapies in rheumatic diseases. Rev Bras Reumatol Engl Ed. 2017;57(Suppl 2):477–83.
Scrivo R, Armignacco O. Tuberculosis risk and anti-tumor necrosis factor agents in rheumatoid arthritis: a critical appraisal of national registry data. Int J Rheum Dis. 2014;17(7):716–24.
Askling J, Fored CM, Brandt L, Baecklund E, Bertilsson L, Cöster L, et al. Risk and case characteristics of tuberculosis in rheumatoid arthritis associated with tumor necrosis factor antagonists in Sweden. Arthritis Rheum. 2005;52:1986–92.
Dixon WG, Hyrich KL, Watson KD, Lunt M, Galloway J, Ustianowski A, et al. Drug-specific risk of tuberculosis in patients with rheumatoid arthritis treated with anti -TNF therapy: results from the British Society for Rheumatology Biologics Register (BSRBR). Ann Rheum Dis. 2010;69:522–8.
Ledingham J, Wilkinson C, Deighton C. British Thoracic Society (BTS) recommendations for assessing risk and managing tuberculosis in patients due to start anti-TNF-{alpha} treatments. Rheumatology (Oxford). 2005;44:1205–6.
Brunelli J, Bonfiglioli K, Silva CA, Kozu K, Goldenstein-Schainberg C, Bonfa E, et al. Rastreamento da infecção latente por tuberculose em pacientes com artrite idiopática juvenil previamente à terapia anti-TNF em um país de alto risco para tuberculose. (Screening for latent tuberculosis infection in patients with juvenile idiopathic arthritis prior to anti-TNF therapy in a country at high risk for tuberculosis). Rev Bras Reumatol. 2017;57(5):392–6.
Mazurek GH, Jereb J, Vernon A, LoBue P, Goldberg S, Castro K, IGRA Expert Committee; Centers for Disease Control and Prevention (CDC). Updated guidelines for using Interferon Gamma Release Assays to detect Mycobacterium tuberculosis infection—United States, 2010. MMWR Recomm Rep. 2010;59:1–25.
Petty RE, Southwood T, Manners P, Baum J, Glass DN, Goldenberg J, et al. International League of Associations for Rheumatology Classification of Juvenile Idiopathic Arthritis: second revision, Edmonton, 2001. J Rheumatol. 2004;31:390–2.
Canhão H, Faustino A, Martins F, Fonseca JE. Reuma.pt—the rheumatic diseases Portuguese register. Acta Reumatol Port. 2011;36(1):45–56.
Brasil. Manual de Recomendações para o Controle da Tuberculose no Brasil / Ministério da Saúde, Secretaria de Vigilância em Saúde, Departamento de Vigilância das Doenças Transmissíveis. – Brasília: Ministério da Saúde, 2019. (Manual of Recommendations for the Control of Tuberculosis in Brazil / Ministry of Health, Secretariat of Health Surveillance, Department of Surveillance of Communicable Diseases. - Brasília: Ministry of Health, 2019).
Santos MJ, Conde M, Mourão AF, Ramos FO, Cabral M, Brito I, et al. 2016 update of the Portuguese recommendations for the use of biological therapies in children and adolescents with Juvenile Idiopathic Arthritis. Acta Reumatol Port. 2016;41(3):194–212.
Hasan T, Au E, Chen S, Tong A, Wong G. Screening and prevention for latent tuberculosis in immunosuppressed patients at risk for tuberculosis: a systematic review of clinical practice guidelines. BMJ Open. 2018;8(9): e022445.
Portugal. Ministério da Saúde. Direção-Geral da Saúde Programa Nacional de Vacinação 2017. Lisboa: DGS, 2016. (Ministry of Health. Directorate-General for Health National Vaccination Program 2017. Lisbon: DGS, 2016). https://www.dgs.pt/documentos-e-publicacoes/programa-nacional-de-vacinacao-2017-pdf.aspx.
Guia de imunização SBIm/SBI (Immunization Guide SBIm/SBI) – 2019/2020. https://sbim.org.br/images/calendarios/calend-pg-crianca-adolesc-0-19.pdf.
Mancuso JD, Mody RM, Olsen CH, Harrison LH, Santosham M, Aronson NE. The long-term effect of bacille Calmette-Guérin vaccination on tuberculin skin testing: a 55-Year Follow-Up Study. Chest. 2017;152:282–94.
World Health Organization (WHO). Global Health TB Report. WHO; 2018. p. 277.4.
Giancane G, Swart JF, Castagnola E, Groll AH, Horneff G, Huppertz HI, et al. Opportunistic infections in immunosuppressed patients with juvenile idiopathic arthritis: analysis by the Pharmachild Safety Adjudication Committee. Arthritis Res. 2020;22(1):71.
Gomes CM, Terreri MT, Moraes-Pinto MI, Barbosa C, Machado NP, Melo MR, et al. Incidence of active mycobacterial infections in Brazilian patients with chronic inflammatory arthritis and negative evaluation for latent tuberculosis infection at baseline—a longitudinal analysis after using TNFɑ blockers. Mem Inst Oswaldo Cruz. 2015;110(7):921–8.
World Health Organization. Guidance for national tuberculosis programme on the management of tuberculosis in children. 2nd ed. Geneva: World Health Organization; 2014.
Tahan TT, Gabardo BM, Rossoni AM. Tuberculosis in childhood and adolescence: a view from different perspectives. J Pediatr (Rio J). 2020;96(S1):99–110.
Rangaka MX, Wilkinson KA, Glynn JR, Ling D, Menzies D, Mwansa-Kambafwile J, et al. Predictive value of interferon-gamma release assays for incident active tuberculosis: a systematic review and meta-analysis. Lancet Infect Dis. 2012;12:45–55.
Çanlar SA, Makay B, Appak O, Appak YC, Esen N, Günay T, et al. Performance of tuberculin skin test and interferon gamma assay for the diagnosis of latent tuberculosis infection in juvenile idiopathic arthritis. Clin Rheumatol. 2011;30:1189–93.
Acknowledgements
Our gratitude to all colleagues in Brazil and Portugal for including their patients, the Brazilian Rheumatology Society and the computer technician, Fernando Martins.
Funding
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Author information
Authors and Affiliations
Contributions
All authors read and approved the final manuscript.
Corresponding author
Ethics declarations
Ethical approval and consent to participate
This study was approved by the Local Ethics Committee, and Reuma.PT was approved by the Portuguese data protection authority (Comissão Nacional de Proteção de Dados). Parents provided a written informed consent and children signed an assent form provided by Reuma.PT.
Consent for publication
All coauthors have agreed to have seen and approved the manuscript for submission.
Competing interests
The authors declare that they have no conflict of interest.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
About this article
Cite this article
Piotto, D., Nicacio, A., Neto, A. et al. Spotlight on latent tuberculosis infection screening for juvenile idiopathic arthritis in two countries, comparing high and low risk patients. Adv Rheumatol 62, 20 (2022). https://doi.org/10.1186/s42358-022-00251-6
Received:
Accepted:
Published:
DOI: https://doi.org/10.1186/s42358-022-00251-6