Abstracts

Background

Several studies have shown that health care workers (HCW) are at increased risk of latent tuberculosis infection (LTBI) from occupational exposure to Mycobacterium tuberculosis¹1. Menzies D, Fanning A, Yuan L, Fitzgerald M. Tuberculosis among health care workers. N Engl J Med 1995; 332:92-8.^,22. Cook S, Maw KL, Munsiff SS, Fujiwara PI, Frieden TR. Prevalence of tuberculin skin test positivity and conversions among healthcare workers in New York City during 1994 to 2001. Infect Control Hosp Epidemiol 2003; 24:807-13.^,33. Florence CS, Atherly A, Thorpe KE. Will choice-based reform work for medicare? Evidence from the Federal Employees Health Benefits Program. Health Serv Res 2006; 41:1741-61.^,44. Baussano I, Nunn P, Williams B, Pivetta E, Bugiani M, Scano F. Tuberculosis among health care workers. Emerg Infect Dis 2011; 17:488-94.^,55. Nasreen S, Shokoohi M, Malvankar-Mehta MS. Prevalence of latent tuberculosis among health care workers in high burden countries: a systematic review and meta-analysis. PLoS One 2016; 11:e0164034.. This observation has also been made in Brazil, where the prevalence of LTBI among HCW is higher than in the general population ⁶6. Silva VM, Cunha AJ, Kritski AL. Tuberculin skin test conversion among medical students at a teaching hospital in Rio de Janeiro, Brazil. Infect Control Hosp Epidemiol 2002; 23:591-4.^,77. Silva VMC, Cunha AJLA, Kritski AL. Risco de infecção pelo Mycobacterium tuberculosis entre alunos da Faculdade de Medicina da Universidade Federal do Rio de Janeiro. J Bras Pneumol 2004; 30:459-66.^,88. Roth VR, Garrett DO, Laserson KF, Starling CE, Kritski AL, Medeiros EA, et al. A multicenter evaluation of tuberculin skin test positivity and conversion among health care workers in Brazilian hospitals. Int J Tuberc Lung Dis 2005; 9:1335-42.^,99. Oliveira SMVL, Honner MR, Paniago AMM, Aguiar ESA, Cunha RV. Prevalência da infecção tuberculosa entre profissionais de um hospital universitário. Rev Latinoam Enferm 2007; 15:1120-4.^,1010. Lopes LKO, Teles AS, Souza ACS, Rabahi MF, Tipple AFV. Tuberculosis risk among nursing professionals from Central Brazil. Am J Infect Control 2008; 36:148-51.^,1111. Severo KG, Oliveira JS, Carneiro M, Valim AR, Krummenauer EC, Possuelo LG. Latent tuberculosis in nursing professionals of a Brazilian hospital. J Occup Med Toxicol 2011; 6:15.^,1212. Rogerio WP, Baraona CM, Prado TN, Lacerda TC, Carlesso GF, Maciel EL. Prevalence of latent infection of Mycobacterium tuberculosis among healthcare students in a public university in Vitória, state of Espírito Santo, Brazil. Ciênc Saúde Coletiva 2013; 18:1331-9.. LTBI risk can be significantly reduced with the implementation of effective tuberculosis (TB) infection control measures ⁶6. Silva VM, Cunha AJ, Kritski AL. Tuberculin skin test conversion among medical students at a teaching hospital in Rio de Janeiro, Brazil. Infect Control Hosp Epidemiol 2002; 23:591-4.^,77. Silva VMC, Cunha AJLA, Kritski AL. Risco de infecção pelo Mycobacterium tuberculosis entre alunos da Faculdade de Medicina da Universidade Federal do Rio de Janeiro. J Bras Pneumol 2004; 30:459-66.^,88. Roth VR, Garrett DO, Laserson KF, Starling CE, Kritski AL, Medeiros EA, et al. A multicenter evaluation of tuberculin skin test positivity and conversion among health care workers in Brazilian hospitals. Int J Tuberc Lung Dis 2005; 9:1335-42.^,99. Oliveira SMVL, Honner MR, Paniago AMM, Aguiar ESA, Cunha RV. Prevalência da infecção tuberculosa entre profissionais de um hospital universitário. Rev Latinoam Enferm 2007; 15:1120-4.^,1010. Lopes LKO, Teles AS, Souza ACS, Rabahi MF, Tipple AFV. Tuberculosis risk among nursing professionals from Central Brazil. Am J Infect Control 2008; 36:148-51.^,1111. Severo KG, Oliveira JS, Carneiro M, Valim AR, Krummenauer EC, Possuelo LG. Latent tuberculosis in nursing professionals of a Brazilian hospital. J Occup Med Toxicol 2011; 6:15.^,1212. Rogerio WP, Baraona CM, Prado TN, Lacerda TC, Carlesso GF, Maciel EL. Prevalence of latent infection of Mycobacterium tuberculosis among healthcare students in a public university in Vitória, state of Espírito Santo, Brazil. Ciênc Saúde Coletiva 2013; 18:1331-9.^,1313. World Health Organization. Guidelines on the management of latent tuberculosis infection. http://apps.who.int/iris/bitstream/10665/136471/1/9789241548908_eng.pdf?ua=1&ua=1 (accessed on Oct/2016).
http://apps.who.int/iris/bitstream/10665... . According to World Health Organization (WHO) and Brazilian guidelines, HCW should be screened for TB infection, and preventive anti-TB chemotherapy should be provided only in case of conversion ¹³13. World Health Organization. Guidelines on the management of latent tuberculosis infection. http://apps.who.int/iris/bitstream/10665/136471/1/9789241548908_eng.pdf?ua=1&ua=1 (accessed on Oct/2016).
http://apps.who.int/iris/bitstream/10665... ^,1414. Departamento de Vigilância Epidemiológica, Secretária de Vigilância em Saúde, Ministério da Saúde. Manual de recomendações para o controle da tuberculose no Brasil. Brasília: Ministério da Saúde; 2011.^,1515. Sociedade Brasileira de Pneumologia e Tisiologia. III diretrizes brasileiras para tuberculose. J Bras Pneumol 2009; 35:1018-48.. Routine surveillance for LTBI among HCW and other occupational infection control measures are not a reality in the country yet because of the programs’ focus on case detection and treatment of TB ¹⁶16. Maciel ELN. Post-2015 agenda strategies for tuberculosis control in Brazil: challenges and opportunities. Epidemiol Serv Saúde 2016; 25:423-6..

For many years, the tuberculin skin test (TST) was the only diagnostic test for LTBI. More recently, T-cell based interferon-γ release assays (IGRA) became available. The U.S. Food and Drug Administration (FDA) have approved two commercial brands of IGRAs for use: the QuantiFERON-TB Gold in-tube (QFT-GIT) assay (Cellestis, QIAGEN Co., Ltd., Carnegie, Australia) and the T-SPOT.TB assay (Oxford Immunotec, Abingdon, U.K.). IGRA has several advantages over TST, including: requiring only one visit (one sample to be sent for processing), lower cross-reactivity with non-tuberculosis mycobacteria, not being affected by Bacillus Calmette-Guérin (BCG) vaccination and lack of subjectivity in measuring results and reduction in costs due to follow-up and treatment of false positives ¹⁷17. Diel R, Loddenkemper R, Meywald-Walter K, Gottschalk R, Nienhaus A. Comparative performance of tuberculin skin test, QuantiFERON-TB-Gold In Tube assay, and T-Spot.TB test in contact investigations for tuberculosis. Chest 2009; 135:1010-8.^,1818. Ringshausen FC, Schablon A, Nienhaus A. Interferon-gamma release assays for the tuberculosis serial testing of health care workers: a systematic review. J Occup Med Toxicol 2012; 7:6..

On the other hand, the use of IGRA for serial testing is complicated by the lack of clear data on optimal cut-offs for such procedure and unclear interpretation and prognosis of conversions and reversions, reproducibility or time interval to conversion of IGRA after exposure to TB ¹⁹19. 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.^,2020. Trajman A, Steffen RE, Menzies D. Interferon-gamma release assays versus tuberculin skin testing for the diagnosis of latent tuberculosis infection: an overview of the evidence. Pulm Med 2013: 2013:601737.. Therefore, a borderline zone may be helpful to distinguish true conversion and reversion from variations caused by chance, i.e., inherent within subject and/or test variability. Schablon et. al. ²¹21. Schablon A, Nienhaus A, Ringshausen FC, Preisser AM, Peters C. Occupational screening for tuberculosis and the use of a borderline zone for interpretation of the IGRA in German healthcare workers. PLoS One 2014; 9:e115322. found a QFT conversion rate of 2.8% and a reversion rate of 37.3% among HCWs repeatedly tested using the dichotomous definition of a positive test result. On application of a borderline zone from 0.2 to 0.7IU/mL, conversions decreased to 1.1% and reversions decreased to 18.8%, which seems to be more realistic than the results of the dichotomous approach ²¹21. Schablon A, Nienhaus A, Ringshausen FC, Preisser AM, Peters C. Occupational screening for tuberculosis and the use of a borderline zone for interpretation of the IGRA in German healthcare workers. PLoS One 2014; 9:e115322..

In Brazil, LTBI diagnosis is still based on medical history, TST result, chest X-ray and physical examination ¹⁴14. Departamento de Vigilância Epidemiológica, Secretária de Vigilância em Saúde, Ministério da Saúde. Manual de recomendações para o controle da tuberculose no Brasil. Brasília: Ministério da Saúde; 2011.. A recent study, however, found that the LTBI prevalence estimated by TST was higher than that estimated by QFT-GIT. This discrepancy was thought in part to be due to prior BCG vaccination, suggesting that the QFT-GIT may provide a more accurate estimate of LTBI prevalence in countries with high coverage of BCG vaccination. Besides BCG vaccination, exposure to environmental mycobacteria in places such as Brazil may also play a role in explaining these findings ²²22. Reichman LB, Bhavaruju R. Guidelines for the diagnosis of latent tuberculosis infection in the 21st century. 2nd Ed. Newark: New Jersey Medical School Global Tuberculosis Institute; 2008.^,2323. Souza FM, Prado TN, Pinheiro JS, Peres RL, Lacerda TC, Loureiro RB, et al. Comparison of interferon-? release assay to two cut-off points of tuberculin skin test to detect latent Mycobacterium tuberculosis infection in primary health care workers. PLoS One 2014; 9:e102773..

In 2004, after the Brazilian Tuberculosis Control Program redirected TB control efforts from the inpatient setting to primary health care facilities, strengthening decentralization of care ¹⁴14. Departamento de Vigilância Epidemiológica, Secretária de Vigilância em Saúde, Ministério da Saúde. Manual de recomendações para o controle da tuberculose no Brasil. Brasília: Ministério da Saúde; 2011., a discussion about the safety and risk of TB in HCW who work at primary health care facilities ensued. While few studies have examined LTBI associated factors among community health workers (CHW) in Brazil, there were none with large sample sizes ²⁴24. Oliveira JS, Possuelo LG, Severo K, Carneiro M, Krummenauer E, Machado C, et al. Avaliação da reatividade ao teste tuberculínico em trabalhadores da rede básica de saúde. Rev HCPA 2011; 31:13-7.^,2525. Moreira TR, Zandonade E, Maciel ELN. Risco de infecção tuberculosa em agentes comunitários de saúde. Rev Saúde Pública 2010; 44:332-8.. No studies in Brazil have evaluated the risk of LTBI among all classes of HCW at primary health care facilities. Here we provide a comprehensive assessment of LTBI risk among all classes of HCW from a multi-center study using the QFT-GIT to estimate the prevalence of LTBI and to identify associated factors among primary HCW in five Brazilian cities.

Methods

We conducted a cross-sectional study between 2011 and 2013 in five Brazilian cities: Cuiabá, Mato Grosso State (TB incidence of 78.21/100,000); Manaus, Amazonas State (TB incidence of 72.03/100,000); Salvador, Bahia State (TB incidence of 61.14/100,000); Porto Alegre, Rio Grande do Sul State (TB incidence of 105.00/100,000); and Vitória, Espírito Santo State (TB incidence of 42.10/100,000) (Brazilian Ministry of Health. http://tabnet.datasus.gov.br/cgi/tabcgi.exe?idb2010/d0202.def, accessed on Jan/2016).

HCWs were informed about the study at their workplace and were enrolled if they agreed to participate and provided informed consent. Study’s exclusion criteria included: (1) known HIV-positive status, (2) rapid test positive for HIV, (3) prior TB, or (4) pregnancy. Trained nurses carried out interviews using a standardized questionnaire with variables distributed in three groups: demographic ENT#091;gender, age group (18-29, 30-39, 40-49 and ≥ 50 years) and cityENT#093;; clinical and behavioral ENT#091;presence of a BCG scar, household TB contact, smoking status, comorbidities (diabetes and hypertension)ENT#093;; and occupational and biosafety ENT#091;professional category (CHW, nurse technician, nurses and physicians), working in a higher TB burden city, working in health care facilities with a TB control program in place, working only at a primary health care unit, years served in a primary health care unit (< 10 and ≥ 10), involvement in TB patient care, involvement in TB training, DOTS (directly observed treatment, short course), type health care facilities and use of N95 mask during work (Figure 1). BCG vaccination status was assessed by visual inspection for a BCG scar by a trained nurse. These variables were included according to the theoretical model presented in Figure 1, which includes potential explanatory and confounding variables, both distal and intermediate, which were evaluated in the multivariate model.

After the standardized questionnaire was completed, 3mL of blood were collected for the QFT-GIT (1mL in each tube). The test was performed according to the manufacturer’s instructions. The samples were transported to a reference laboratory in each capital city (Municipal Laboratory of Cuiabá; Municipal Laboratory of Salvador; Center of Immunology and Infectious Diseases of the Federal University of Espírito Santo, Vitória; Laboratory of Microbiology of the Tropical Medicine Foundation Dr. Heitor Vieira Dourado, Manaus; and the Municipal Laboratory, Porto Alegre) within 4-6 hours of collection and incubated for 16-24 hours at 37ºC. The samples were centrifuged at 3000x RCF (relative centrifugal force) for 15 minutes, and the collected plasma was stored at -70ºC until the interferon-γ (IFN-γ) assay was performed. Plasma samples collected in Cuiabá, Manaus, Porto Alegre and Salvador were transported inside a cooler with ice packs to the Center of Immunology and Infectious Diseases of the Federal University of Espírito Santo in less than 6 hours, and stored at -70ºC. The optical density (OD) of each test was read with a 450nm filter and a 620nm reference filter, with an ELISA plate reader.

Results were interpreted according to the manufacturer’s instructions. The cut-off value for a positive test was 0.35IU/mL of IFN-γ in the plasma after stimulation, regardless of the result of the mitogen control. The result of the test was considered indeterminate if an antigen-stimulated sample tested negative and if the value of the positive control was less than 0.5IU/mL after subtraction of the value of the negative control. The rapid HIV test was performed on the same blood sample (Rapid Check HIV 1 & 2/NDI-UFES, Vitória, Brazil).

Pearson’s chi-square test was used to compare proportions of baseline covariates between LTBI positive and LTBI negative study participants. Covariates associated with the LTBI in bivariate analyses (p ≤ 0.20) were selected to be included in the logistic regression. For the multivariable logistic regression analysis, three models were performed, in which the variables were inserted in blocks, according to the methodology proposed by authors of similar studies ²⁶26. Petarli GB, Salaroli LB, Bissoli NS, Zandonade E. Autoavaliação do estado de saúde e fatores associados: um estudo em trabalhadores bancários. Cad Saúde Pública 2015; 31:787-99.. Model 1 was composed only of the demographic variables; model 2, of demographic, clinical and behavioral variables, and model 3 was composed of demographic, clinical, behavioral, occupational and biosafety variables. Final multivariable logistic regression models include all predictors with p-values < 0.05. All statistical significance tests were two sided. All data analyses wwere performed using Stata 13 (StataCorp LP, College Station, USA).

The Institutional Review Board of the Federal University of Espírito Santo (UFES) approved the study under registration number 007/10. Primary HCW who had a positive rapid HIV test were referred to a health-care provider. As the QFT result is not the standard of care for LTBI diagnosis in Brazil, participants who were QFT-GIT positive were evaluated for the need to receive LTBI treatment or to rule out active TB by a physician, by an evaluation that included chest X-ray, symptom screening and TST testing. According to the Brazilian guidelines, preventive anti-TB chemotherapy should be provided only in case of conversion of TST ¹⁴14. Departamento de Vigilância Epidemiológica, Secretária de Vigilância em Saúde, Ministério da Saúde. Manual de recomendações para o controle da tuberculose no Brasil. Brasília: Ministério da Saúde; 2011.^,1515. Sociedade Brasileira de Pneumologia e Tisiologia. III diretrizes brasileiras para tuberculose. J Bras Pneumol 2009; 35:1018-48.. In our study, no HCW was treated for latent TB infection because none had previous TST results to assess conversion. In addition, because of the physician’s evaluations, no HCW was diagnosed and treated for active tuberculosis disease.

Results

We enrolled 718 HCW (Figure 2). Two (0.3%) participants were excluded because they refused to take a blood test, 7 (0.9%) because they had active TB or were under TB treatment, and 1 (0.1%) because of a positive-HIV test. Of the 708 primary HCW included in this study, 326 (46%) were CHW, 94 (13.3%) were nurses, 241 (34%) were nurse technicians and 47 (6.7%) were physicians. The median participant age was 41 years (range 20-70) and 633 (89.4%) were female. Prior BCG vaccination was common, with 620 (87.6%) participants having a BCG vaccine scar. The median time of work as a primary HCW was 9 years (range 1-39). LTBI prevalence in the study population was 27% (n = 196; 95%CI: 24%-31%). We did not observe an indeterminate result of QFT-GIT test among the health professionals included in our study.

Table 1 shows the results of the bivariate analyses. Age ≥ 50 years (p < 0.0001), having a household member with TB (p = 0.014), male gender (p = 0.048), comorbidities (diabetes or high blood pressure, p = 0.042), positive smoking status (p = 0.034) and city (p = 0.002) were all associated with LTBI in HCW. A BCG scar was present in 80% of HCW who tested positive for LTBI versus 90% among those who tested negative (p < 0.001).

Table 2 shows the associations between occupational and biosafety characteristics and LTBI in primary HCW. The proportions of the different categories of HCW varied significantly between people who were LTBI positive and LTBI negative (p = 0.05). QFT-GIT was positive in 71% of HCW working in health care facilities with a TB control program, compared with 29% among those not working in health care facilities with this program (p = 0.05). Serving as a health care professional at a primary health care unit for ≥ 10 years was associated with positive QFT-GIT results (p = 0.05). The use of the N95 mask varied significantly among the HCWs that were LTBI positive when compared with those that were LTBI negative (p = 0.016).

Table 3 shows the models with progressive adjustments for variables with a value of p less than 0.2 in the bivariate analyses. After adjusting for the variables of all domains, we found that HCWs aged > 50 years (OR = 2.94; 95%CI: 1.44-5.99) were more likely to have LTBI than people aged 18-29 years, HCWs without BCG scar (OR = 2.10; 95%CI: 1.28-3.43) were more likely to have LTBI than HCW who has BCG scar, HCWs who had self-reported ex-smoker status (OR = 1.80; 95%CI: 1.04-3.11) were more likely to have LTBI than HCW who had never smoked. Being a nurse (OR = 2.97; 95%CI: 1.13-7.83), being a nurse technician (OR = 3.10; 95%CI: 1.26-7.60), being a CHW (OR = 2.60; 95%CI: 1.06-6.40) increased the odds of LTBI compared with being a physician. In addition, HCWs who did not work in health care facilities with a TB control program were less likely to have LTBI (OR = 0.66; 95%CI: 0.45-0.97) than HCWs who worked in this type of service. HCWs who reported use of N95 masks irregularly (OR = 2.51; 95%CI: 1.11-5.98) were more likely to have LTBI than HCW who reported regular use of N95 masks.

Discussion

Brazilian primary HCW are a group at high risk of occupational TB exposure, but no prior studies have systematically quantified the prevalence of LTBI nor examined risk factors for LTBI in this population. Using a multi-center, cross-sectional study design comprising five cities in Brazil, we showed here that the prevalence of LTBI among primary HCW in these cities was 27%. The following factors were positively associated with LTBI in primary HCW: age > 50 years, absence of a BCG scar, self-reported ex-smoker status, being a nurse, being a nurse technician, being a CHW, irregular use of N95 masks. In contrast, HCWs who do not working in health care facilities with a TB control program were less likely to have LTBI.

Our results are consistent with previous studies of LTBI prevalence in hospital-based HCW but expand on this prior work by evaluating LTBI prevalence and risk factors among all classes of primary HCW ¹1. Menzies D, Fanning A, Yuan L, Fitzgerald M. Tuberculosis among health care workers. N Engl J Med 1995; 332:92-8.^,22. Cook S, Maw KL, Munsiff SS, Fujiwara PI, Frieden TR. Prevalence of tuberculin skin test positivity and conversions among healthcare workers in New York City during 1994 to 2001. Infect Control Hosp Epidemiol 2003; 24:807-13.^,33. Florence CS, Atherly A, Thorpe KE. Will choice-based reform work for medicare? Evidence from the Federal Employees Health Benefits Program. Health Serv Res 2006; 41:1741-61.^,44. Baussano I, Nunn P, Williams B, Pivetta E, Bugiani M, Scano F. Tuberculosis among health care workers. Emerg Infect Dis 2011; 17:488-94.^,66. Silva VM, Cunha AJ, Kritski AL. Tuberculin skin test conversion among medical students at a teaching hospital in Rio de Janeiro, Brazil. Infect Control Hosp Epidemiol 2002; 23:591-4.^,77. Silva VMC, Cunha AJLA, Kritski AL. Risco de infecção pelo Mycobacterium tuberculosis entre alunos da Faculdade de Medicina da Universidade Federal do Rio de Janeiro. J Bras Pneumol 2004; 30:459-66.^,88. Roth VR, Garrett DO, Laserson KF, Starling CE, Kritski AL, Medeiros EA, et al. A multicenter evaluation of tuberculin skin test positivity and conversion among health care workers in Brazilian hospitals. Int J Tuberc Lung Dis 2005; 9:1335-42.^,99. Oliveira SMVL, Honner MR, Paniago AMM, Aguiar ESA, Cunha RV. Prevalência da infecção tuberculosa entre profissionais de um hospital universitário. Rev Latinoam Enferm 2007; 15:1120-4.^,1010. Lopes LKO, Teles AS, Souza ACS, Rabahi MF, Tipple AFV. Tuberculosis risk among nursing professionals from Central Brazil. Am J Infect Control 2008; 36:148-51.^,1111. Severo KG, Oliveira JS, Carneiro M, Valim AR, Krummenauer EC, Possuelo LG. Latent tuberculosis in nursing professionals of a Brazilian hospital. J Occup Med Toxicol 2011; 6:15.^,1212. Rogerio WP, Baraona CM, Prado TN, Lacerda TC, Carlesso GF, Maciel EL. Prevalence of latent infection of Mycobacterium tuberculosis among healthcare students in a public university in Vitória, state of Espírito Santo, Brazil. Ciênc Saúde Coletiva 2013; 18:1331-9.. Our work adds to existing knowledge by showing that the prevalence LTBI in this group is within the range, although closer to the lower limit of prevalence observed in hospital-based HCWs published in other studies using IGRA (range from 24% to 71%) ²⁷27. Pai M, Gokhale K, Joshi R, Dogra S, Kalantri S, Mendiratta DK, et al. Mycobacterium tuberculosis infection in health care workers in rural India: comparison of a whole-blood, interferon-g assay with tuberculin skin testing. JAMA 2005; 293:2746-55.^,2828. Drobniewski F, Balabanova Y, Zakamova E, Nikolayevskyy V, Fedorin I. Rates of latent tuberculosis in health care staff in Russia. PLoS Med 2007; 4:e55.^,2929. Torres Costa J, Silva R, Sá R, Cardoso MJ, Nienhaus A. Serial testing with the interferon-? release assay in Portuguese healthcare workers. Int Arch Occup Environ Health 2011; 84:461-9.^,3030. Lien LT, Hang NT, Kobayashi N, Yanai H, Toyota E, Sakurada S, et al. Prevalence and risk factors for tuberculosis infection among hospital workers in Hanoi, Viet Nam. PLoS One 2009; 4:e6798.. Although we did not find association of type health care facilities and LTBI, we have identified that the HCW who does not work in health care facilities with a TB control program was less likely to have LTBI. We believe that this finding is due to the lower exposure to M. tuberculosis³¹31. Kritski A, Dalcolmo M, Souza R, Holanda T, Melo F, Gontijo P. Tuberculose entre profissionais de saúde. Risco ocupacional? J Bras Pneumol 1993; 19:113-21..

The high LTBI prevalence we observed among nursing professionals is consistent with prior work on LTBI in this group and may be due to increased exposure to TB patients compared with all the other categories of HCW in our study. Consistent with this possibility, we found that the median time worked by HCW was highest for nurse technicians, followed by nurses. Our study also found a high prevalence of LTBI among older HCWs compared with younger HCWs. The explanation for this association could be either a longer time exposed to risks or the decreasing immunity that comes with age ³²32. Christopher DJ, Daley P, Armstrong L, James P, Gupta R, Premkumar B, et al. Tuberculosis infection among young nursing trainees in South India. PLoS One 2010; 5:e10408.^,3333. Keskiner R, Ergönül O, Demiroglu Z, Eren S, Baykam N, Dokuzoguz B. Risk of tuberculous infection among healthcare workers in a tertiary-care hospital in Ankara, Turkey. Infect Control Hosp Epidemiol 2004; 25:1067-71.. CHW in our study had the highest risk of LTBI compared with all the other groups. This finding may be explained by the fact that they usually live in the high-risk TB communities where they work. In addition, TB care has been undergoing a decentralization process to primary care in Brazil. This process needs to be followed by strengthening environmental, individual and administrative controls strategies at the same level of care. Our results highlighted the need to keep this as a priority. Studies showed that CHW providing TB care do not always use appropriate respiratory protection ²⁵25. Moreira TR, Zandonade E, Maciel ELN. Risco de infecção tuberculosa em agentes comunitários de saúde. Rev Saúde Pública 2010; 44:332-8..

Other studies also showed that cigarette smoking has adverse effects in respiratory immune function and is associated with an increased risk of respiratory tract infections, including TB ³⁴34. Garmendia J, Morey P, Bengoechea JA. Impact of cigarette smoke exposure on host-bacterial pathogen interactions. Eur Respir J 2012; 39:467-77.^,3535. den Boon S, van Lill SWP, Borgdorff MW, Verver S, Batemen ED, Lombard CJ, et al. The association between smoking and tuberculosis infection: a population survey in a high tuberculosis incidence area. Thorax 2005; 60:555-7.^,3636. Plant AJ, Watkins RE, Gushulak B, O'Rourke T, Jones W, Streeton J, et al. Predictors of tuberculin reactivity among prospective vietnamese migrants: the effect of smoking. Epidemiol Infect 2002; 128:37-45.. Our study showed an increased probability of LTBI among those who reported themselves as former smokers. A study carried out in a tertiary medical center in Taiwan showed that both previous (OR = 1.64; 95%CI: 1.00-2.68) and current smoking (OR = 1.88; 95%CI: 1.16-3.03) were independent factors associated with LTBI ³⁷37. Feng JY, Huang SF, Ting WY, Lee MC, Chen YC, Lin YY, et al. Impact of cigarette smoking on latent tuberculosis infection: does age matter? Eur Respir J 2014; 43:630-2.. Therefore, TB control programs should offer smoking awareness and smoking cessation strategies in partnership with the primary health care facilities. Finally, HCWs without BCG scar were more likely to have LTBI, pointing to the increased risk of M. tuberculosis infection among those who were not immunized, high specificity of the QFT-GIT, as well as the high capacity of this test to correlate occupational HCW risk with M. tuberculosis exposure ³⁸38. Ringshausen FC, Schablon A, Nienhaus A. Interferon-gamma release assays for the tuberculosis serial testing of health care workers: a systematic review. J Occup Med Toxicol 2012; 7:6..

Our study has some limitations. First, it is a cross-sectional study and therefore temporality between the positive QFT-GIT and infection by M. tuberculosis could not be established nor could changes over time be monitored. Second, there is no gold standard for detecting LTBI and, therefore, LTBI prevalence estimate might be impacted by the QFT-GIT performance. We believe that these limitations, while important to acknowledge, are outweighed by this study’s strengths: its large sample size and the fact that it is the first multicenter study of LTBI prevalence and risk factors among primary HCW in Brazil. Our research adds to the body of evidence on LTBI prevalence among HCW in Brazil and suggests the potential utility of using QFT to screen candidates for TB chemoprophylaxis. Future study is needed to explore the latter possibility in more depth, but the use of IGRAs instead of the TST could result in false positives. False positive tests would reduce the number of people that need to be treated and thus increase the feasibility of broad treatment of LTBI among HCW in Brazil. Nowadays, Brazil is facing shortage of TST and QFT should be considered as a viable alternative by the TB Control Program ³⁹39. Lewinsohn DM, Leonard MK, LoBue PA, Cohn DL, Daley CL, Desmond E, et al. Official American Thoracic Society/Infectious Diseases Society of America/Centers for Disease Control and Prevention clinical practice guidelines: diagnosis of tuberculosis in adults and children. Clin Infect Dis 2017; 64:e1-33..

Finally, this study demonstrated a substantial occupational risk of LTBI among primary HCW in Brazil. The Brazilian TB control program, as well as local programs, need to guide these high-risk HCW with education as well as with better personal protective equipment to prevent acquisition of new TB infection.

Acknowledgments

This study was supported by CNPq (Brazilian National Research Council; MCT/CNPq n. 14/2009 - Universal), FAPES (Espírito Santo State Research Foundation; Universal 012/11), and the Capes (Brazilian Graduate Studies Coordinating Board; with the provision of a sandwich scholarship at the University of California, Berkely, USA). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

References

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