OBJECTIVE. The latent tuberculosis infection (LTBI) is a state of persistent immune response to stimulation by Mycobacterium Tuberculosis antigens without clinical manifestation: the healthcare workers (HCWs) have a higher exposure risk so prevention is an important challenge for occupational medicine. The aim of our study is to evaluate the prevalence of LTBI among HCWs of the Foundation Policlinic “Tor Vergata”.
METHODS. This is a retrospective study conducted by analyzing the clinical records of 825 HCWs of the PTV, from January 1st to December 31th 2016. To evaluate the TB infection we used the Quantiferon TB Gold interferon-gamma release assay.
RESULTS. Our study underline the low prevalence of LTBI in the Italian healthcare workers.
CONCLUSION. Although the LTBI status is not contagious, the diagnosis and the safety strategies require specific clinical and preventive considerations

Balbi Ottavia

Baldi Savino

Coppeta Luca

De Zordo Ludovico Maria

Doddato Maria Teresa

Ferraro Mariacarmela

Grande Stefania

Lieto, Piergiorgio

Magrini Andrea

Mattone Pier Francesco

Pietroiusti Antonio

English

Journal of Preventive Medicine and Hygiene (JPMH)

J PREV MED HYG 2021; 62: E759-E762E759https://doi.org/10.15167/2421-4248/jpmh2021.62.3.1471 OPEN ACCESS IntroductionTuberculosis (TB) is one of the top 10 causes of death worldwide: according to the last World Health Organization (WHO) Global report, 10.0 million (range: 8.9-11.0 million) people fell ill with TB in 2019, and 1,6 million died for this infective disease. Despite some progress in the pipeline for the new diagnostic methodic, TB research and development did not improve new drugs and vaccine efficacy [1]. Studies in literature underline that in about 70% of incident cases of TB there is a reactivation of a past infection.The latent tuberculosis infection (LTBI) is a state of persistent immune response to stimulation by Mycobacterium Tuberculosis antigens without evidence of clinically manifested active TB so the fast identification and prophylactic treatment of individuals with LTBI is crucial for the elimination of the disease [2, 3].Approximately two billion people in the world are affected by LTBI: in Italy, the National Health Institute reports that the incidence of TB in 2019 is 6.5 case/100.000 inhabitants [4, 5]. The WHO classified Italy as a low incidence country, even if there are groups of population with increased probability to contract TB infection  [6]. The healthcare workers (HCWs) have a higher exposure risk to tuberculosis, because of their activities in the hospital setting: the prevention of this new-old infective disease is an important challenge for the occupational medicine [2].The HCWs may contract the Mycobacterium Tuberculosis in nosocomial environment by the infected patient or get infected in the community setting and being itself a source of infection for colleagues and patients. According to Italian Legislation is mandatory for Occupational Doctor to evaluate all work risks, including the exposure to biological agents, like viral hepatitis or tuberculosis, and to improve the safety strategies in order to prevent the spread to operators or to limit the severity of its consequences  [7]. For the evaluation of TB work risks, in 2013 the Italian Ministry of Health has classified healthcare settings into 5 increasing levels of risk related to a growing risk of infection [8]. Health surveillance flow chart is established according to the level of risk of the structure to which the HCWs are employed [9, 10].Although the importance of the early identification and treatment of the LTBI among hospital workers is known, only few studies have evaluated the correlation between the infection exposure risk classification and the increased incidence of active disease [11-13]. The aim of our study is to evaluate the prevalence of LTBI in the HCWs of the Foundation PTV Policlinic “Tor Vergata” (PTV) of Rome related to the main demographical and occupational risk factor. MethodsThis is a retrospective study conducted by analyzing all the clinical records of HCWs of the PTV, who Objective. The latent tuberculosis infection (LTBI) is a state of persistent immune response to stimulation by Mycobacterium Tuberculosis antigens without clinical manifestation: the health-care workers (HCWs) have a higher exposure risk so prevention is an important challenge for occupational medicine. The aim of our study is to evaluate the prevalence of LTBI among HCWs of the Foundation Policlinic “Tor Vergata”.Methods. This is a retrospective study conducted by analyzing the clinical records of 825 HCWs of the PTV, from January 1st to December 31th 2016. To evaluate the TB infection we used the Quantiferon TB Gold interferon-gamma release assay.Results. Our study underlines the low prevalence of LTBI in the Italian healthcare workers.Conclusion. Although the LTBI status is not contagious, the diag-nosis and the safety strategies require specific clinical and pre-ventive considerations.ReseaRch aRticleRisk of latent tuberculosis infection  among healthcare workers in Italy:  a retrospective study with Quantiferon TestLUCA COPPETA1, CRISTIANA FERRARI2, MARIACARMELA FERRARO3, SAVINO BALDI2, STEFANIA GRANDE4, LUDOVICO MARIA DE ZORDO2, PIER FRANCESCO MATTONE2, MARIA TERESA DODDATO2, OTTAVIA BALBI2, ANDREA MAGRINI1, ANTONIO PIETROIUSTI1, PIERGIORGIO LIETO21 Department of Biomedicine and Prevention, University of Rome “Tor Vergata”, Rome, Italy; 2 Department of Occupational Medicine, University of Rome “Tor Vergata”, Rome, Italy; 3 Department of Hygiene and Preventive Medicine, University of Rome “Tor Vergata”, Rome, Italy; 4 Department of Anaesthesia, Intensive Care and Pain Management, University of Rome “Campus Bio-Medico”, Rome, ItalyKeywordsLatent tuberculosis • Contact screening • Quantiferon • Occupational healthSummaryL. COPPETA ET AL.E760underwent the annual occupational medical visit from January 1st to December 31th 2016. The analyzed sample included medical doctors, nurses, laboratory and radiology technicians. To evaluate the TB infection we extracted from the clinical records the results of the Quantiferon  -  TB Gold (QFT-G, Qiagen) interferon-gamma (IFN-γ) release assay, highly specific and sensitive. The limit of this test is that it cannot distinguish between active tuberculosis disease and latent tuberculosis infection [14].Analytical data were extracted from ModuLab, software that was adopted by Chemical Analytical Laboratory of PTV during the investigation period. For each study subject Quantiferon plus results were collected as well as the following data: age, gender, job category, seniority of work. According with the manufacturer published criteria, the test was classified as positive when the antigen specific IFN gamma serum values was equal or higher than the cut-off level of 0,35  IU/ml, compared to a negative control  [15]. All HCWs having positive Quantiferon test were studied by specific clinical examination and traditional radiology and retested during the following year. Analyses were performed using IBM Stata 11 statistical package software. Results were considered statistically significant a P value threshold of < 0.05.Results We collected the clinical records of 825 HCWs: 284 men and 541 women. Positive Quantiferon result was found in the 4.2% of the sample (35 from 825 subjects). All those subjects were classified as LTBI after the radiological and clinical evaluation; among those HCWs, 17 were male and 18 female. Regarding job task, 22 of LTBI operators were employed as nurses, 11 were doctors, 2 technicians.Main demographic and occupational charateristics of the study population are shown in Table I. Among operators who resulted positive at Quantiferon test, 7/35 (%) had a negative determination during the previous 12 months, being classified as new TB conversion, whereas 28/35 LTBI cases had a previous positive Quantiferon result. No case of active TB has been documented between those subjects in the year following the study. We evaluated the association between LTBI and main demographic and occupational factors (gender, age class, seniority, risk level of employment setting, and job task). After tested in a multivariate regression model the only variable statistically associated with a higher frequency of LTBI was gender, whereas all the other risk factors tested negative at the regression analysis (Tab. II). Finally we calculated the conversion rate for TB (negative to positive result during the 1 year period) both in high and low risk setting; we found no statistical difference in the conversion rate between the different risk levels (P = 0.56 at χ2 test).Discussion The healthcare workers have an increased exposure risk to tuberculosis, because of their activities in the hospital setting: in Italy for tuberculosis, the healthcare setting Tab.I. Main characteristics of the study population.Variables N %Subjects 825 100SexMale 284 34.4Female 541 65.6Mean (SD) age, year 42.9 Age≤ 40 years old 283 34.3> 40 years old 542 65.7Seniority≤ 10 years 348 34.3> 10 years 477 65.7JobNurse 546 66.2Medical doctor 181 21.9Laboratory staff 8 1.0Technical staff 74 9.0Others 16 1.9Working area§Low-average risk (groups A, B, C) 687 83.3High risk (groups D, E) 138 16.7IGRA test outcomesNegative 790 95.8Positive 35 4.2§ Tuberculosis prevention in healthcare workers and similar. Italian Ministry of Public Health 2013.Tab. II. IGRA test outcomes by the main characteristic of the study population.VariablesPositive IGRA%P value univariate P value multivariateSexMale 19/284 6.7 0.017 0.015Female 16/541 3.0Age≤ 40 years old 5/283 1.8 0.006 0.068> 40 years old 30/542 5.5Seniority≤ 10 years 9/348 2.6 0.031 0.142> 10 years 26/447 5.5JobNurse 21/546 3.8 0.46Medical doctor 12/181 6.6Laboratory technician0/8 0.0Technical staff 2/74 2.7Others 0/16 0.0Working area§Low-average risk (groups A, B, C)5/138 3.6 0.82High risk (groups D, E)30/687 4.4§ Tuberculosis prevention in healthcare workers and similar. Italian Ministry of Public Health. 2013.RISK OF LATENT TUBERCULOSIS INFECTION AMONG HEALTHCARE WORKERS IN ITALYE761is classified in 5 levels according to growing exposure risk, from A to E [8]. LTBI condition has been defined by the positivity to Quantiferon test and the negativity to the clinical-radiological assessment, conducted for the purpose of excluding an active infection  [16,  17]. Our study confirms the low prevalence of LTBI among healthcare operators in Italian hospital: we found 35  subjects with LTBI off a sample of 825. This data compared with other similar studies conducted among different sanitary population of various countries, shows a lower prevalence of LTBI condition, 4.2% vs mean LTBI percentages of 9.2% of other groups  [11,  12,  18,  19]. According to this data in our study the prevalence of LTBI assessed by Quantiferon test is statistically related with gender. Furthermore, the low LTBI prevalence in our sample can be associated to the effectiveness of the safety strategies planned by the Amministration and the Occupational Medicine of PTV since 2005, that allows early detecting and reporting of suspected or confirmed case of TB. In previous studies conducted in our hospital during the period 2007/2013, the mean prevalence of positive tests was 5.5% [20]. Lamberti et al retrospective study in 2016 in Naples, based on a sample of students of dentistry showed a prevalence of 2.84% for LTBI [13]. Male Sex, in our study, seems to be statistically associated with LTBI: this data confirms that male gender is a greater tuberculosis risk, as already reported in literature [18]. The work seniority and the higher age class (> 40 years old) showed also an increased risk of latent tuberculosis even if this association was found to be not statistically significant. Moreover, in order to evaluate Italian Health Ministry TB classification for hospital setting to predict the risk of contagion for HCWs, we evaluated the correlation between the areas of employment and the rate of conversion TB test: surprisingly in our study working in high risk setting was not related to a greater prevalence of LTBI and we found no conversion rate differences among high and low work risk groups. In a previous evaluation relative to the year 2014 we found a 16% reversion rate [20], while in the present study no positive QFT test reverted, probably due to the improved standardization of the specific collection, storage and transport procedures. It is also reported that reversion may be indicative of recent exposure to a patient with active and infective Tuberculosis  [21,  22]. According to the progression and reactivation rate reported in literature  [1,  3], for our sample we may estimate that about 2 to 4 HCWs affected by LTBI could develop the active tuberculosis throughout working life, so as reported by the main scientific statements  [1,  2,  7], prophylactic therapy should be offered to those who don’t have contraindications. Conclusions The control of work exposure to TB infection in the hospital setting represents a major health issue for the Occupational medicine specialists. Results of our study underline the low prevalence of LTBI in the Italian healthcare workers; although LTBI status is not contagious, given the risk of reactivation of active tuberculosis following immunosuppressive treatment or other medical conditions, a specific TB control program should be improved in order to prevent the nosocomial spread of the infection. Based on the results of our study, serial screening for latent TB infection should include all HCWs, regardless to risk classification of the employment setting. Ethical statementEthics approval and consent to participate: all procedures performed in this study were approved by the ethical committee of Policlinic Tor Vergata.AcknowledgementsFunding sources: this research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.Conflict of interest statementThe authors declare no conflict of interest.Authors’ contributionsLC: conception and design of the study; acquisition of data, final approval of the version to be submitted.CF: revising the article critically for important intellectual contentMF: acquisition of data.SB: acquisition of data.SG: drafting the article or revising it critically for important intellectual content.LMD: analysis and interpretation of data.Mattone Pier Francesco: analysis and interpretation of data.MTD: drafting the article or revising it critically for important intellectual content.OB: acquisition of data.AM: drafting the article or revising it critically for important intellectual content.AP: conception and design of the study.PL: conception and design of the study, drafting the article or revising it critically for important intellectual content, final approval of the version to be submitted.References[1] World Health Organization. Global Tuberculosis Report - 2018.[2] Jensen PA, Lambert LA, Iademarco MF, Ridzon R; CDC. Guidelines for preventing the transmission of Mycobacterium tuberculosis in health-care settings, 2005. MMWR Recomm Rep 2005;54:1-141.L. COPPETA ET AL.E762[3] World Health Organization. WHO policy on TB infection control in health-care facilities, congregate settings and households - 2009. http://whqlibdoc.who.int/publications/2009/9789241598323_eng.pdf[4] Centers for Disease Control and Prevention. Guidelines for the investigation of contacts of persons with infectious tuberculo-sis.  Recommendations from the National Tuberculosis Control-lers Association and CDC. MMWR Morb Mortal Wkly Rep 2005;54:1-47.[5] Istituto Superiore di Sanità. Tubercolosi. Aspetti epidemiolo-gici: dati generali. Antonietta Filia. http://www.epicentro.iss.it/problemi/Tubercolosi/epid.asp[6] https://www.who.int/tb/publications/global_report/gtbr2018_main_text_28Feb2019.pdf?ua=1[7] Decreto legislativo 9 aprile 2008, n. 81 “Attuazione dell’articolo 1 della legge 3 agosto 2007, n. 123, in materia di tutela della salute e della sicurezza nei luoghi di lavoro”.[8] Conferenza permanente per i rapporti tra lo Stato, le Regioni e le Province Autonome di Trento e Bolzano - Provvedimento 17 dicembre 1998 - Linee Guida per il controllo della malattia tu-bercolare, su proposta del Ministro della Sanità, ai sensi dell’art. 115, comma 1, lettera b), del decreto legislativo 31 marzo 1998, n. 112.[9] Ministero del Lavoro della Salute e delle Politiche Sociali. Ag-giornamento delle raccomandazioni per le attività di controllo della tubercolosi in Italia. Anno 2013. http://www.salute.gov.it/imgs/C_17_pubblicazioni_1221_allegato.pdf[10] Ministero del Lavoro della Salute e delle Politiche Sociali. Pre-venzione della tubercolosi negli operatori sanitari e soggetti ad essi equiparati. Approvato come Accordo nella Conferenza Stato-Regioni-Province Autonome del 7 febbraio 2013.[11] Zwerling A, van den Hof S, Scholten J, Cobelens F, Menzies D, Pai M. Interferon-gamma release assays for tuberculosis screening of healthcare workers: a systematic review. Thorax 2012;67:62-70. https://doi.org/10.1136/thx.2010.143180[12] Uden L, Barber E, Ford N, Cooke GS. Risk of tuberculosis in-fection and disease for health care workers: an updated meta-analysis. Open Forum Infect Dis 2017;4:ofx137. https://doi.org/10.1093/ofid/ofx137[13] Lamberti M, Muoio MR, Westermann C, Nienhaus A, Arnese A, Ribeiro Sobrinho AP, Di Giuseppe G, Garzillo EM, Crispino V, Coppola N, De Rosa A. Prevalence and associated risk fac-tors of latent tuberculosis infection among undergraduate and postgraduate dental students: a retrospective study. Arch Envi-ron Occup Health 2016:1-7.[14] Mazurek GH, Jereb J, Vernon A, LoBue P, Goldberg S, Cas-tro K; IGRA Expert Committee; Centers for Disease Control and Prevention (CDC). Updated guidelines for using Interferon Gamma Release Assays to detect Mycobacterium tubercu-losis infection - United States, 2010. MMWR Recomm Rep 2010;59:1-25. [15] https://www.diasorin.com/sites/default/files/allegati_prodotti/brochure-qft_m0870004375_lr.pdf[16] Muñoz L, Stagg HR, Abubakar I. Diagnosis and management of latent tuberculosis infection. Cold Spring Harb Perspect Med 2015;5:a017830. https://doi.org/10.1101/cshperspect.a017830[17] https://www.ecdc.europa.eu/sites/portal/files/media/en/publica-tions/Publications/1103_GUI_IGRA.pdf[18] Coppeta L, Baldi S, Somma G, Tursi E, Policardo S, Balbi O, Lieto P, Pietroiusti A, Magrini A. QuantiFERON-TB Gold Plus evaluation for latent tuberculosis infection among Italian healthcare workers: a cross-sectional study. Epidemiol Biostat Public Health 2019;16:2. https://doi.org/10.2427/13123[19] Coppeta L, Somma G, Baldi S, Tursi E, D’Alessandro I, Torrente A, Perrone S, Pietroiusti A. Cost-effectiveness of annual screen-ing for tuberculosis among Italian healthcare workers: a retro-spective study. Int J Environ Res Public Health 2020;17:1697. https://doi.org/10.3390/ijerph17051697[20] Magrini A, Coppeta L, Somma G, Neri A, Gentili S, Fiocco G, Pietroiusti A. Risk of tuberculosis in healthcare workers: risk assessment and medical surveillance. Ig Sanità Pubbl 2016;72:137-43.[21] Verrall AJ, Netea MG, Alisjahbana B, Hill PC, van Crevel R. Early clearance of Mycobacterium tuberculosis: a new fron-tier in prevention. Immunology 2014;141:506-13. https://doi.org/10.1111/imm.12223[22] Nardell EA, Wallis RS. Here today gone tomorrow: the case for transient acute tuberculosis infection. Am J Respir Crit Care Med 2006;174:734-5. https://doi.org/10.1164/rccm.200607-923ED.Received on January 10, 2020. Accepted on July 17, 2021.Correspondence: Piergiorgio Lieto, Department of Occupational Medicine, University of Rome “Tor Vergata”, viale Oxford 81, 00133 Rome, Italy - Tel.: +39 3289611446 - E-mail: piergiorgiolieto@gmail.comHow to cite this article: Coppeta L, Ferrari C, Ferraro M, Baldi S, Grande S, De Zordo LM, Mattone PF, Doddato MT, Balbi O, Magrini A, Pietroiusti A, Lieto P. Risk of latent tuberculosis infection among healthcare workers in Italy: a retrospective study with Quantiferon Test. J Prev Med Hyg 2021;62:E759-E762. https://doi.org/10.15167/2421-4248/jpmh2021.62.3.1471© Copyright by Pacini Editore Srl, Pisa, ItalyThis is an open access article distributed in accordance with the CC-BY-NC-ND (Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International) license. The article can be used by giving appropriate credit and mentioning the license, but only for non-commercial purposes and only in the original version. 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Risk of latent tuberculosis infection among healthcare workers in Italy: a retrospective study with Quantiferon Test

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Risk of latent tuberculosis infection among healthcare workers in Italy: a retrospective study with Quantiferon Test

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