Skin test screening for among healthcareAnn Ig 2013; students 25: 311-315 doi:10.7416/ai.2013.1933311 Skin test screening for tuberculosis among healthcare students: a retrospective cohort study G.B. Orsi*, T. Antoniozzi**, M. Ortis**, V. Pippia*, S. Sernia*,**

Key words: Tuberculosis, skin test, screening, surveillance Parole chiave: Tubercolosi, test cutanei, screening, sorveglianza

Abstract Background: Aim of the study was to document the baseline prevalence of healthcare students positive to tuberculosis skin tests screening. Methods: Between 2008-2010, students admitted to healthcare courses (medicine, nursing, physiotherapy…) at “Sapienza” university in Rome were requested to carry out personal tuberculosis skin test screening in their local district or town healthcare centers according to the italian guidelines. At the time interferon- gamma release assays (IGRA) testing was not adopted for large screening. Demographic characteristics, tuberculosis screening results, healthcare course, tuberculosis vaccination status were recorded. Results: A cohort of 2,500 university healthcare students were screened by several Italian Hygiene Offices using skin test and Tine test. Overall 131 (5.2%) healthcare students resulted positive to some tuberculosis skin test screening. Tuberculin skin test was carried out on 2,029 students (81.2%) and conversion was observed in 107 (5.3%), whereas Tine test was carried out on 498 students (19.9%) and positive result was observed in 24 (4.8%). The Tine test use and non optimal (<72h) recording of the forearm induration in tuberculin skin tests was related mostly to some healthcare centers in Lazio and Campania regions. Previous BCG vaccination was reported by 27 healthcare students (1.1%), and only two of them showed tuberculin skin test conversion, whereas the large majority 105 (98.1%) of Mantoux positives had not been vaccinated. In univariate analysis positive tuberculin skin test was associated to growing students age (29.2 ± 10.3 vs. 23.1 ± 6.0; p<0.01). Positive tuberculin skin test was recorded in 25 (20.3%) foreign and 82 (4.3%) italian students showing a higher risk for International students (RR 4.72; 95%CI 3.14 – 7.11; p<0.01). There was no significant correlation between the different Italian regions, the various healthcare courses or gender. Conclusion: The study evaluated the baseline positive skin test rate for tuberculosis among healthcare students in their first university year, showing a higher risk for the international group and revealed some problematic screening practices which need to be improved in the future screening programs.

Introduction As the risk of tuberculosis transmission in healthcare workers is well known, it Identification and treatment of represents an important target population individuals with for latent tuberculosis infection screening infection is an important component of programs (3). Healthcare workers tuberculosis elimination strategies in low experience greater vulnerability to incidence countries and may contribute to tuberculosis because of close contact and the global tuberculosis control (1, 2). frequent exposure to tubercolotic patients,

* Department of Public Health and Infectious Diseases, Sapienza University of Rome, Italy ** Centre of Occupational Medicine, Sapienza University of Rome, Italy 312 G.B. Orsi et al. eventual inappropriate environmental Data analysis conditions in hospitals and limited or Statistical analyses were performed insufficient preventive measures (4). using Epi-Info (version 2005; CDC, Therefore tuberculosis infection control Atlanta, GA). The chi-square was used programs in healthcare settings are to examine differences between groups. strongly recommended worldwide and Statistical significance was defined as also in Italy (5, 6). a P value of less than 0.05. Univariate Similarly, healthcare students often relationship was tested using relative risk experience patient contact during the and its 95% confidence interval (CI95). training and are exposed to tuberculosis. However few studies worldwide have evaluated the risk of tuberculosis infection Results among this specific population category (7), showing a wide range of incidence Between 2008-2010 a cohort of 2,500 rates in various countries (8-12). university healthcare students (35.9% Aim of this study was to document the males and 64.1% females) underwent baseline prevalence of healthcare students tuberculosis skin test screening for positive to tuberculin skin tests screening tuberculosis and were included in the in a large Italian university (5, 6). study. The students mean age was 23.3 ± 6.3 years (median 21, range 18-66) and the age distribution was as follows: Methods 18-20 (44.8%), 21-25 (34.4%), 26-30 (9.6%), 31-40 (8.2%), >40 (3.0%). This is a retrospective cohort study Most healthcare students were Italian carried out on healthcare students (94.8%), and the principal area of origin admitted between 2008-2010 to the was represented by Rome and Lazio “Sapienza” university in Rome, Italy. region (65.1%) followed by southern This is the largest Italian university and (28.6%), central (4.6%) and northern the students population is not only from regions (1.7%). Most students belonged Rome area but comes also from all over to Nursing (54.1%), Medicine (16.0%), Italy and abroad. Students admitted to all Laboratory technology (5.5%) and healthcare courses (medicine, nursing, Radiology technology (4.7%) courses. laboratory technology, physiotherapy The 2,500 healthcare students were …) were requested by the university screened in several Hygiene Offices by to carry out personal tuberculosis skin tuberculin skin test and Tine test. Overall test screening in their local district or 131 healthcare students (5.2%) out of 2,500 town healthcare centers. All Hygiene resulted positive to some tuberculosis offices carried out Tuberculin skin test skin test screening. Tuberculin skin according to the Italian guidelines (5), test was carried out on 2,029 students although in some centers also Tine test (81.2%) and conversion was observed was used for tuberculosis screening. At in 107 (5.3%). Following the Mantoux the time interferon-gamma release assays technique, the different healthcare centers (IGRA) testing was not adopted for large recorded the forearm transverse diameter screening. Demographic characteristics, induration after 48h (28%) or 72 h (72%). tuberculosis screening results, healthcare We noticed that a non optimal (<72h) course, tuberculosis vaccination status recording of the forearm induration were recorded in a data-base. was related mostly to some healthcare Skin test screening for tuberculosis among healthcare students 313 centers in Lazio and Campania regions. Discussion Tine test was carried out on 498 students (19.9%) and positive result was observed To our knowledge this is the first in 24 (4.8%). Tine test was adopted more study to evaluate the baseline prevalence frequently in some healthcare centers of healthcare students positive to in Lazio and Campania region. All tuberculosis skin tests screenings in students who resulted positive to any skin an Italian university, and analyzing test underwent following controls and the Hygiene Offices compliance to none presented clinical or radiological tuberculosis surveillance and prevention evidence of active tuberculosis. Previous guidelines (5, 6). BCG vaccination was reported by 27 Problematic screening practices were healthcare students (1.1%). Among them identified among some Hygiene Offices only two showed tuberculin skin test and should be highlighted for the future conversion, whereas the large majority screening programs. Despite published 105 (98.1%) of Mantoux positives had Italian guidelines for tuberculosis not been vaccinated. prevention recommended the use of In univariate analysis, we considered Mantoux method for skin testing (5), only students positive to tuberculin skin 1/5 of students were screened using the test, and results showed an association Tine tests. Multiple puncture devices with growing students age (29.2 ± 10.3 vs. are less specific than , 23.1 ± 6.0; p<0.01), see Table 1. Positive with a possible inconsistent delivery of tuberculin skin test was recorded in 25 tuberculin and Tine induration is semi- (20.3%) foreign and 82 (4.3%) italians, quantitative, whereas Mantoux allows showing a significant association with the more precise measurement. The adoption international students group (RR 4.72; of Tine test instead of tuberculin skin 95%CI 3.14 – 7.11; p<0.01), particularly test was concentrated in some Hygiene those coming from eastern Europe Offices of Lazio and Campania regions. (12/52), South America (6/24) and Tuberculin skin test conversion should Africa (4/10). There was no significant be controlled up to 72h after intradermal correlation between the different Italian injection, but results showed that in regions, the various healthcare courses almost 1/3 of patients the reading was or gender. stopped at 48h. Optimal screening should

Table 1 - Dstribution of skin test screening prevalence for tuberculosis among healthcare students

Tuberculin skin test Tine Test All skin test Screening Age (years) + - + - + - 18-20 3.4% 96,6% 3.7% 96,3% 3.5% 96,5% 21-25 3.2% 96,8% 4.4% 95,6% 3.5% 96,5% 26-30 6.1% 93,9% 2.0% 98,0% 5.4% 94,6% 31-40 17.3% 82,3% 15.8% 84,2% 17.2% 82,8% >40 20.0% 80,0% 4.2% 95.8% 18.9% 81,1%

Total 5.3% 94,7% 4.8% 95,2% 5.2% 94,8% 314 G.B. Orsi et al. be carried out at 72h because readings at non erano adottati per ampi screening. Le caratteristiche 48h may underestimate the skin reaction demografiche, i risultati dello screening per la tuberco- size (13). Once again the 48h reading losi, il corso di appartenenza e lo stato vaccinale sono stati registrati. was associated mostly to some Hygiene Risultati: Una coorte di 2.500 studenti è stata sottopo- Offices of Lazio and Campania regions. sta a screening in numerose ASL utilizzando il tuberculin As the vaccinated students were very skin test ed il Tine test. In generale 131 (5,2%) studenti few, and at the time the interferon-gamma delle lauree sanitarie sono risultati positivi ad un qualche released assays were not adopted for large screening per la tubercolosi con test cutanei. Il tuberculin screening, the results referred only to the skin test è stato eseguito su 2.029 studenti (81,2%) ed una conversione è stata osservata in 107 (5,3%), mentre tuberculin skin test (5.3%) were considered il Tine test è stato eseguito su 498 studenti (19,9%) e le indicative for probable latent tuberculosis positività osservate sono state 24 (4,8%). L’impiego del (6). But in the following controls none Tine test ed una lettura non ottimale (<72h) del tuberculin presented any clinical or radiological skin test sono stati associati soprattutto ad alcune ASL evidence of active tuberculosis. del Lazio e della Campania. Una precedente vaccinazione Univariate analysis showed association con BCG è stata riferita da 27 studenti (1,1%), e solo due di loro hanno evidenziato conversione al tuberculin skin of positive tuberculin skin test to age and test, mentre la larga maggioranza 105 (98,1%) dei posi- students nationality specially from eastern tivi alla Mantoux non erano stati vaccinati. Nell’analisi Europe, South America and Africa. univariata la positività al tuberculin skin test era associata We are aware of some limitations to ad una maggiore età (29,2 ± 10,3 vs. 23,1 ± 6.0; p<0,01). our study. Principally, as vaccination La positività al tuberculin skin test è stata registrata in 25 status was reported to the Hygiene offices (20,3%) stranieri ed in 82 (4,3%) italiani, evidenziando by the students, may be the vaccination un rischio più elevato negli studenti internazionali (RR 4,72; 95%CI 3,14-7,11; p<0,01). Non vi era correlazio- rate was underestimated affecting some of ne significativa con le differenti regioni, i vari corsi di the tuberculin skin test interpretations. laurea ed il sesso. In conclusion the study evaluated Conclusioni: Lo studio ha valutato la prevalenza the baseline positive skin test rate for basale degli studenti delle lauree sanitarie positivi ai test tuberculosis among healthcare students in cutanei per la tubercolosi nel primo anno di università, their first university year, showing a higher evidenziando un rischio più elevato per quelli stranieri e rivelando alcuni problemi nelle modalità di esecuzio- risk for the international group and revealed ne dei test che devono essere corrette in previsione di some problematic screening practices screening futuri. which need to be improved in the future screening programs. References

Riassunto 1. Broekmans JF, Migliori GB, Rieder HL, et al. European framework for tuberculosis control and Screening per la tubercolosi mediante test cutanei in elimination in countries with a low incidence. studenti delle lauree sanitarie: uno studio a coorte Recommendations of the World Health Orga- retrospettivo nization (WHO), International Union Against Tuberculosis and Lung Disease (IUATLD) and Introduzione: Gli A.A. hanno condotto uno studio per documentare la prevalenza basale degli studenti delle lau- Royal Netherlands Tuberculosis Association ree sanitarie positivi ai test cutanei per la tubercolosi. (KNCV) Working Group. Eur Respir J 2002; Metodi: Agli studenti delle lauree sanitarie (medicina, 19 (4): 765-75. infermieristica, fisioterapia…) di “Sapienza” università 2. Dye C, Watt CJ, Bleed DM, Hosseini SM, di Roma è stato richiesto di condurre uno screening Raviglione MC. Evolution of tuberculosis per la tubercolosi mediante test cutanei presso le ASL control and prospects for reducing tuberculosis di appartenenza secondo le line guida italiane. In quel incidence, prevalence, and deaths globally. periodo i test ad interferon-gamma release assays (IGRA) JAMA 2005; 293 (22): 2767-75. Skin test screening for tuberculosis among healthcare students 315

3. Joshi R, Reingold AL, Menzies D, Pai M. Tuber- 9. Holmuth BA, Yamanija JC, Dayal AS, Nardell culosis among health-care workers in low- and E, Salazar JJ, Smith Fawzi MC. Latent tubercu- middle-income countries: a systematic review. losis infection: risks to health care students at a PLoS Medicine 2006; 3: e494. hospital in Lima, Peru. Int J Tuberc Lung Dis 4. Baussano I, Nunn P, Williams B, Pivetta E, Bugiani 2006; 10 (10): 1146-51. M, Scano F. Tuberculosis among health care work- 10. Jung da H, Jo KW, Shim TS. Prevalence of latent ers. Emerg Infect Dis 2011; 17 (3): 488-94. tuberculosis infection among medical students 5. Ministero del Lavoro, della Salute e delle in South Korea. Tuberc Respir Dis 2012; 73 (4): Politiche Sociali. Gestione dei contatti e della 219-23. tubercolosi in ambito assistenziale, 2009. 11. Pérez-Lu JE, Cárcamo CP, Garcia PJ, Bussal- 6. Conferenza Stato Regioni. Prevenzione della leu A, Bernabé-Ortiz A. tuberculin skin test tubercolosi negli operatori sanitari e soggetti ad conversion among health sciences students: a essi equiparati. G.U. n° 63 del 15 marzo 2013. retrospective cohort study. Tuberculosis 2013; 7. Seidler A, Nienhaus A, Diel R. Review of epi- 93 (2): 257-62. demiological studies on the occupational risk of 12. Texeira EG, Kritski A, Ruffino-Netto A, et al. tuberculosis in low-incidence areas. Respiration Medical students at risk of nosocomial tubercu- 2005; 72: 431-46. losis. J Hosp Infect 2011; 77 (1): 80-1. 8. Chistopher DJ, James P, Daley P, et al. High an- 13. Singh D, Sutton C, Woodcock A. Tuberculin nual risk of tuberculosis infection among nursing test measurement: variability due to the time of students in South India: a cohort study. Plos One reading. Chest 2002; 122: 1299-301. 2011; 6 (10): e26199.

Corresponding Author: Prof. Giovanni Battista Orsi, Department of Public Health and Infectious Diseases, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy e-mail: [email protected] 316 G.B. Orsi et al.