The risk of nosocomial infection with M. tuberculosis due to significant exposure to patients with active tuberculosis and their specimens, together with the insufficient use of protective equipment and inadequate ventilation of working areas, remains an important problem in healthcare settings.
The authors of the present study prospectively assessed the prevalence of LTBI in healthy HCW by means of QTF GIT and TST, in Poland. As far as we know, there was no other multicentre evaluation of LTBI prevalence and its related risk factors among HCWs in Eastern Europe. All participants were BCG vaccinated at least twice in their life: in the neonate period, and above the sixth year of age. Therefore, according to published recommendations, the method of choice to assess LTBI among BCG vaccinated HCW should be an IGRA test . Nevertheless TST results were analysed as well, as some investigators indicate that TST is more sensitive than IGRA, although less specific, in the vaccinated population . According to Polish National Anti-Tuberculosis Program , the TST induration ≥10 mm is considered positive, while other studies  and guidelines developed by Centres for Disease Control (CDC) and the American Thoracic Society (ATS) assume that for individuals who are not in high risk groups, LTBI can be diagnosed if TST induration is ≥15 mm [18, 19].
In our study positive results of TST (≥10 mm and ≥ 15 mm) were found in 58 and 33% participants of the study respectively, positive QTF GIT results (≥0.35 IU/ml) in 27%. The overall prevalence of LTBI in medical staff was found to be consistent with LTBI prevalence in 700 healthy Polish adults from randomly selected family practice, investigated in the same period of time . In this study Kuś et al. found that 50% participants had TST ≥ 10 mm, 26% had TST ≥ 15 mm and QFT GIT ≥0.35 IU/ml was detected in 23% of enrolled subjects . The comparison of these results revealed that the overall prevalence of LTBI in Polish HCW was only slightly higher than in general Polish population.
The analysis of TST results in selected age groups, performed by Kuś et al., revealed that the test was more often positive in younger participants comparing to older ones: 55% of those in the age group of 25–44 years, 52% of those aged 45–59 years, and 35% of those above 60 years of age . On the contrary, positive QTF GIT results were found more often in the older participants, comparing to younger ones: 14% of those 25–44 years of age, 33% of those aged 45–59 years and 49% of those above 60 years of age . Results of LTBI assessment with QFT GIT, were in agreement with epidemiological data of tuberculosis in Poland. In the same period, tuberculosis incidence rate in general population was 19.7 per 100,000, significantly lower incidence rate was found in young comparing to older age groups: 14.3 per 100,000 among those 22–44 years of age, 35 per 100,000 in those aged 45–64 years, and 38 per 100,000 in those above 65 years of age .
In the presently investigated group of Polish HCW, opposite to the general population of Polish citizens, the percentage of participants with TST ≥10 mm and TST ≥ 15 mm have been increasing with age, moreover the differences between age groups were much more pronounced if TST ≥ 15 mm was regarded as a cut-off. This original observation suggests that the impact of occupational contact with M. tuberculosis in HCW prevails the effect of prior BCG vaccination on TST results.
The percentage of positive QFT GIT results in the groups of medical staff aged 45–59 and 60–70 years, were very similar to those with TST ≥ 15 mm. Large discrepancy was found between TST ≥ 15 mm and QFT GIT in healthcare workers aged 23–44 years. Based on IGRA test, LTBI would be diagnosed in 14%, based on TST ≥ 15 mm – in 25% of them. We assume, that this difference was mainly due to vanishing reaction to past BCG vaccinations in older HCW, comparing to younger ones. This is consistent with the guidelines of ECDC, stating that TST reactivity caused by BCG usually wanes with time . We can also conclude that TST ≥ 15 can be used as LTBI marker comparable with IGRA in individuals over 45 years, vaccinated with BCG in childhood. QTF GIT is preferred for LTBI diagnosis in adults younger than 44 years as the results of TST in this group are confounded by BCG vaccination .
It is worth to notice, that the prevalence of positive IGRA results in medical caregivers was 49% in those aged 45–59 years and even 80% - in those aged 60–70 years, compared to 33 and 49%, respectively - in general Polish population . Therefore we conclude that despite the similar overall prevalence of LTBI assessed by QFT GIT in both populations, the prevalence of LTBI in medical staff aged 45 years or more, was higher than in age-adjusted general population.
An effort was made to compare the LTBI prevalence measured with QFT GIT in Polish HCW with the results obtained with the same method and in comparable period of time, in medical staff of other countries [24,25,26,27,28,29,30].
The results of those studies, indicate that LTBI prevalence in the population of HCW is influenced by epidemiological situation in the country, but also, to the great extent, by the participants’ age, place of birth, the work place, and family history. Thus, these populations shouldn’t be directly compared.
In our study, LTBI risk, as evidenced by QFT GIT results, in the entire group of HCW was age-dependen but also differed with respect to factors such as the length of employment, as well as the intensity and duration of the exposure to TB patients or their specimens. The risk of obtaining positive IGRA in medical workers was increased by 3 times - in those above 44 years of age, by 5 times - in those employed for more than 10 years, and by 8–12 times in those declaring continuous contact with TB patients and their specimens. Recently published data from South Korea revealed that LTBI risk in medical staff of tertiary hospital was independently connected with age of participant, but not with length of occupation .
Logistic regression analysis revealed that the odds ratio, i.e. the possibility of having TST induration of ≥10 mm and TST ≥15 did not differ between all selected subgroups of the total population of enrolled subjects. Only in the group of laboratory personnel we confirmed 2.36 times higher risk of having TST ≥ 10 mm and 3 times of TST ≥15 associated with continuous contact with clinical specimen. In the group of HCW carrying for TB patients, the risk of having TST ≥ 15 was 6.338 times higher than in the group of workers from non-TB wards. This observation is consistent with the study by Kuś et al. who claimed that TST is not a reliable test for LTBI detecting in Polish population . Major reason for this could be lower specificity and false positivity associated with TST in BCG vaccinated population, or with occupational or environmental exposure to non-tuberculous mycobacteria (NTM) influencing TST results. Tuberculin is a mixture of antigens common to a variety of mycobacterial species. The hydrophobic NTM can be readily aerosolized causing NTB sensitisation in health-care settings . These results, in comparison to previously discussed TST results, support the usefulness of the QFT GIT as an universal tool for the detection of LTBI in Poland .
In our study the cut-off point for continuous variable “the length of employment” (10 years) was arbitrarily selected. Therefore we considered necessary to determine if an optimal cut-off point to stratify enrolled subjects with higher degree of objectivity, can be found. According to ROC analysis the optimal cut-off point for the parameter “length of employment” to predict the TST result (≥10 and ≥ 15) or QTF GIT (≥0.35 IU/ml) could not be found. The „length of employment” has better discriminating ability as a predictor of QTF result than TST result (as measured by the area under the curve), however the analysis does not support the use of this parameter as an accurate predictor of QTF GIT result.
Interestingly, according to the logistic regression analysis the risk of being latently infected with TB was significantly higher in clinical staff (OR = 17.071) than in laboratory personnel (OR = 8.135). This may point to the better protective measures in TB laboratories in comparison to tuberculosis wards in Poland. On the basis of our results we conclude that there is an urgent need to implement effective procedures and precautions to reduce the risk for exposure to airborne pathogens for managing patients who may have active TB.
Our results showed that TB transmission in healthcare facilities in Poland is high. We may speculate that it can be due to ineffective control measures in dedicated care facilities. The precautions for laboratory safety, such as local exhaust ventilation and laboratory hoods, are more effective but still insufficient in Polish TB laboratories. On the other hand, the analysis of our results showed that the TB transmission in healthcare facilities is steadily decreasing as LTBI prevalence is significantly lower in those employed for less than 10 years as HCW. The modernisation of old buildings from XIX century, hosting most of TB departments in Poland, enables implementation of more effective interventions to improve ventilation in existing infrastructure.
It is also important to notice, that despite great reduction in tuberculosis incidence rate, prevalence of LTBI in HCW has not been reduced proportionally, suggesting the need of further surveillance in this group, especially in those working in high-risk settings and the implementation of evidence-based infection control practices. Therefore LTBI screening should be strongly advised in Polish medical staff, especially in those exceeding 44 years of age, or those employed for a long time with the direct contact with infective materials or patients. QTF can be recommended for serial testing as boosting effect does not occur, contrary to repetitive tuberculin administration.
Both TST and IGRA are based on immune response of activated antigen presenting cells and sensitized lymphocytes to M.tuberculosis antigens. The TST rely on the reaction to intradermal injection of tuberculin, which induces a local inflammatory induration that can be measured, whereas IGRAs are in vitro tests measuring IFN-γ released from CD4+ lymphocytes upon stimulation by ESAT-6 and CFP-10, two antigens encoded in the region of difference 1 locus present in M. tuberculosis genome and also present in tuberculin. Therefore, additionally to the comparison of tests characteristics, we aimed to directly correlate the surrogate markers of the adaptive immune response to tuberculin antigens as measured by TST induration or IFN-γ production. A moderate positive correlation between both results was obtained confirming that, even though both test do not measure the same components of the immunologic reaction, both are a part of the same a complex and multifaceted immune response developed during M. Tuberculosis dormancy. As mentioned before, the data about incidence of LTBI in polish HCW is scarce, the available analyses are limited in scope and the collected data come from single institutions in Warsaw [34, 35]. Our findings advocate for widespread screening of HCW exposed to active TB patients or their specimens. Furthermore, the risks and benefits of LTBI therapy at the individual level need to be carefully balanced, considering an increased risk of progression to overt disease versus drug-related side effects. Polish recommendations for preventive treatment for LTBI apply only to persons with LTBI and: HIV-infected, those who are on immunosuppressive therapy (i.e. TNF-α antagonists). organ transplant recipients, children and adolescents. The isoniazid in dose 5 mg/kg is administered for 6 months to these patients . The LTBI treatment to everyone with a positive QFT or TST is not recommended in Poland. Our results strongly suggest that employers should be encouraged to implement and monitor occupational infection control strategies for preventing TB transmission, such as specific procedures, environmental controls in healthcare facilities and use of personal protection equipment . The prevalence of LTBI and active TB in HCWs compared with the general population should be monitored, to ensure that sufficient protective measures are in place.
According to ECDC report, weak evidence showed no increased risk of LTBI, but an increased risk of active TB in all HCW compared to the general population. Analysis showed that LTBI screening of all HCW is not likely to be cost-effective, except for individuals working with active TB patients or their specimens . These statements are consistent with our findings.