Prevalence of latent tuberculosis infection among coal workers’ pneumoconiosis patients in China: a cross-sectional study

China currently has one of the highest rates of pneumoconiosis in the world, with this disease accounting for over 85% of all reported occupational diseases in the country [1, 2]. Coal workers’ pneumoconiosis (CWP) is believed to be the predominant type, accounting for about 60% of the total number of new cases of pneumoconiosis [1, 2]. Tuberculosis (TB) is the most common complication associated with CWP [3]. However, little is known about the prevalence of latent TB infections (LTBI) among CWP patients. A LTBI is defined as the presence of immune responses to Mycobacterium tuberculosis antigens without any clinical evidence of active TB. Patients with LTBI are at risk of developing active TB disease and becoming infectious [4]. The risk of LTBI reactivation can be reduced by preventive treatment. Identification and treatment of LTBI in individuals at high risk of developing active disease has been practiced as an effective strategy for TB control in the US [5].

The World Health Organization has issued guidelines on the management of LTBI for a wide range of risk groups, including patients with HIV or silicosis [6]. There is no diagnostic gold standard test for LTBI, but M. tuberculosis-specific interferon (IFN)-γ-based diagnostic tests offer increased specificity (93%–99%) and at least equivalent sensitivity (75%–90%) as the tuberculin skin test (TST) and are unaffected by previous BCG vaccination [7]. In Norway, a limited number of studies on the results of IFN-γ release assays (IGRAs) in various populations have been published [8‐10], but no study has focused on CWP. Only one study has reported the prevalence of LTBI among aged underground hard coal miners using IGRAs in Germany [11]. The aim of the current study was to estimate the prevalence of LTBI using a T-cell-based IGRA in CWP patients and to determine the risk factors associated with a positive test result.

In total, 376 patients admitted to the Hospital of Occupational Diseases and screened for pneumoconiosis from October to December 2016, were selected for this survey. Of these, 112 (29.8%) were excluded owing to a previous history of TB. Of the remaining 264, 20 (5.3%) did not volunteer to provide blood samples. Therefore, 244 (64.9%) participants actually participated in the investigation and received the QFT test (Fig. 1). The participants were all male and ranged from 42 to 92 years, with a median age of 67 years. The BMI distribution showed that more than half of the participants (59.3%) were overweight. About half of the participants (50.4%) were of primary school or lower education level. Personal income per month showed that more than 70% of the participants earned between 3000 and 4000 RMB, and family income per head per month showed that 67.2% of the participants earned below 6000 RMB. About 90% of the participants were born in the countryside (Table 1).

The prevalence of LTBI in the 244 CWP patients, based on QFT positivity, was 66.4% (95% CI: 61.0%–72.9%) (Additional file 1). The QFT response was negative in 32.8% of cases and was indeterminate in 0.8% (Fig. 1). Excluding two cases for which the QFT results were indeterminate, the remaining 242 CWP cases were analyzed for risk factors. As shown in Table 2, there were no significant difference in the prevalence of LTBI in terms of socio-demographic characteristics and occupational factors. The environmental risk factor for QFT was workplace ventilation. Using the subgroup workplace ventilation as the reference group, the prevalence ratio [PR] was elevated for poor workplace ventilation (PR: 1.25; 95% confidence interval [CI]: 1.04–1.51). The behavioral protective factor for QFT was intake of fruits regularly. Using the subgroup < 1 day of every week of intake of fruit as the reference group, the risk of LTBI was reduced by 21% both for those eating fruit 1 to 3 days of every week (PR: 0.79; 95% CI: 0.63–0.99) and those eating fruit ≥4 days of every week (PR: 0.79; 95% CI: 0.64–0.97).

Job category was included in multivariate log-binomial regression analyses because it was related to LTBI borderline significantly. Table 3 showed the results from the multivariate log-binomial regression model. The poor workplace ventilation (APR: 1.26; 95% CI: 1.03–1.52) was found to be independent risk factor and ≥ 4 days of every week of intake of fruit (APR: 0.81; 95% CI: 0.65–0.99) was found to be independent protective factor associated with a positive QFT result. Job category was not associated with a positive QFT result.

In this study, we found that the prevalence of LTBI among CWP patients in China was 66.4% based on the QFT. This was considerably higher than that reported in a community-based study conducted in rural China (13%–20%) [13]. To date, besides a study that investigated the prevalence of LTBI among aged underground hard coal miners using IGRAs in Germany and reported positive rates of 46.6% (QFT) and 61.0% (T-SPOT) [11], no studies have reported the prevalence of LTBI among CWP patients in the rest of the world. As for occupational studies, a few reports employed the IGRA in healthcare workers and detected positive rates of 9.9% (QFT) in Japan [14], 10.6% (QFT) in Malaysia [15], 25% (QFT) in Italy [16], 40.8% (QFT) in Russia [17], 46% (QFT) in Georgia [18], 76.7% (QFT) and 65.7% (A.TB, a Mycobacterium tuberculosis-specific cell-mediated immune response detection kit) in China [8], and 46.0% (QFT) among village doctors in China [19]. The prevalence of LTBI in healthcare workers therefore varied greatly between countries, with a much higher LTBI rate in China than in any of the other countries.

In our study, 29.8% of CWP patients had a history of previous TB. This finding was in agreement with a previous study among 1107 patients in a coal mine industry group [20], which showed the total rate of pneumoconiosis complicated with tuberculosis was 30.5%.The prevalence (66.4%) of LTBI among CWP patients in our study was higher than among village doctors (46.0%) [19] but lower than that among healthcare workers (76.7%) in China [8]. This suggested that those exposed to TB via their occupation have a higher risk of LTBI in China. In our study, poor ventilation condition was positive associated with QFT positivity. These findings were in agreement with previous active TB studies [21, 22] that demonstrated that poor ventilation condition was vital risk factor for CWP with active TB. It is therefore clear that careful monitoring and dust control measures need to be improved in workplaces to ensure the safety of workers. Furthermore, physical examination and QFT tests should be performed regularly to facilitate the early detection of LTBI with CWP. Active treatment and better management of patients are required to reduce the risk of LTBI with CWP. We also found regular intake of fruit (≥4 days of every week) was associated with LTBI among CWP. Few studies have reported whether intake of fruits is significantly associated with LTBI. A case–control study in a community that investigated relation between specific dietary and susceptibility of tuberculosis, concluded that an inadequate intake of fruits and vegetables was associated with an increased risk of new tuberculosis infection [23]. However, large prospective and interventional studies are needed to confirm the effect of fruits.

To date, most community-based studies of LTBI have shown that a positive QFT result is associated with age. This has been shown in studies in rural China [13] and among healthcare workers [14, 24, 25]. However, in our study, this correlation was not detected among CWP patients. This may be explained by the fact that our study population predominantly comprised older participants who had survived CWP and who were all over 40 years of age (median age: 67 years). Studies have demonstrated a high risk of M. tuberculosis infection among individuals in close contact with TB cases [13, 22, 26]. However, in the present study, the positivity of QFT was not affected by a previous history of close contact with TB patients, and this was in agreement with the previous findings from some studies of healthcare workers [16, 25, 27]. This could be explained by the fact that some of the CWP patients in our study may have been unknowingly exposed to TB either within their working environment or in the community. Our study did not confirm the potential protective effect of BCG vaccination in CWP patients. This finding was consistent with the results of studies carried out in populations involved in other occupations [27, 28]. This finding may be explained by the fact that China has a high TB burden and a high coverage of BCG vaccination. However, BCG vaccination has been included in the national immunization program in China since 1978, so there would be poor vaccination coverage in participants born before that time possibly explaining the lack of impact of BCG vaccination among our study population. There is evidence showing that smoking is significantly associated with silicosis [29, 30] and with TB [22, 31, 32]; however, few studies have verified whether smoking is significantly associated with LTBI among CWP patients. In our study, smoking was not associated with LTBI.

This study showed that the high prevalence of LTBI among CWP patients in China. We found that poor workplace ventilation could be a risk factor and intake of fruits regularly (≥4 days of every week) found to be a protective factor. In response, specific measures need to be implemented including the proactive reduction of workers’ exposure to coal dust by improving ventilation conditions and regular screening of those at high risk of CWP to ensure the early detection of LTBI. Large studied should be studied for the effect intake of fruits regularly on the risk of LTBI.