Tuberculosis among correctional facility workers: A systematic review and meta-analysis

Introduction Prison inmates can transmit tuberculosis, including drug-resistant strains, to correctional facility workers and the community. In this systematic literature review, we investigated the magnitude of active and latent tuberculosis infection (LTBI) and associated risk factors among correctional facility workers. Methods We searched MEDLINE, EMBASE, LILACS, Cochrane CENTRAL, ISI Web of Science, CINAHL, and SCOPUS databases (January 1, 1989–December 31, 2017) for studies with the MeSH terms “prison” (and similar) AND “tuberculosis”, without language restriction. We searched for gray literature in Google Scholar and conference proceedings. Stratified analyses according to tuberculosis burden were performed. Results Of the 974 titles identified, 15 (nine good, six fair quality) fulfilled the inclusion criteria (110,393 correctional facility workers; six countries; 82,668 active tuberculosis; 110,192 LTBI). Pooled LTBI prevalence and incidence rates were 26% (12–42, I2 = 99.0%) and 2% (1–3, I2 = 98.6%), respectively. LTBI prevalence reached 44% (12–79, I2 = 99.0%) in high-burden countries. Active tuberculosis was reported only in low-burden countries (incidence range, 0.61–450/10,000 correctional facility workers/year). LTBI-associated risk factors included job duration, older age, country of birth, current tobacco smoking, reported contact with prisoners, and BCG vaccination. Conclusion Despite the risk of bias and high heterogeneity, LTBI was found to be prevalent in correctional facility workers, mainly in high-burden countries. LTBI risk factors suggest both occupational and community exposure. Active tuberculosis occurrence in low-burden countries suggests higher vulnerability from recent infection among correctional facility workers in these countries. Systematic surveillance and infection control measures are necessary to protect these highly vulnerable workers.

Introduction Tuberculosis (TB) is one of the leading causes of morbidity and mortality from infectious diseases worldwide, with 10.4 million new cases and 1.3 million deaths in 2016 [1]. In particular, TB management has become increasingly challenging in inmates of correctional facilities, wherein TB prevalence can be as high as 1,913/100,000 population, with incidence of up to 70/ 100,000 population/year [2]. The prevalence of latent TB infection (LTBI) among inmates can increase by approximately 5% every year [3], suggesting that there is a high risk of transmission in prisons. Occupational exposure was responsible for recently acquired LTBI in onethird of New York State prison employees [4]. In a TB outbreak in Madrid, Spain, 23% of all cases, including 38 inmates and five employees, were caused by the same strain, according to molecular epidemiological analyses [5].
TB in inmates may also be responsible for transmission to the community. Up to 54% of Mycobacterium tuberculosis strains in the community are similar to those found in prisons [6]. Similarly, TB transmission to correctional facility workers (CFW) has also been documented [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21]. The magnitude of the epidemics in this population, however, varies significantly. While data on burden of TB among inmates is available, data on burden among CFW are only available from individual studies. Moreover, since longitudinal studies are time consuming, labor intensive and expensive, prevalence studies are more likely to be conducted in resourceconstrained settings and provide information on LTBI burden. A systematic review on the current burden of LTBI among CFW in high-and low-burden countries would provide evidence of existing occupational risk of infection in prison facilities settings, raise awareness among CFW to adopt and practice necessary infection control measures, and guide policy makers to explore and implement necessary prevention and control measures to reduce disease burden. Because TB is a preventable disease, and prevention is one of the cornerstones of the END TB Strategy [22], it is important to identify populations at high risk for recent LTBI and active TB. Therefore, we conducted a systematic review and meta-analysis to estimate the pooled prevalence and incidence of LTBI and active TB among CFW, as well as their associated risk factors.

Materials and methods
The study protocol was registered at the International Prospective Register of Systematic Reviews-CRD42016048858. Ethical approval was not necessary, since all data are publicly available. The current report follows the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) [23].

Search strategy
We searched the MEDLINE (through PubMed), EMBASE (through Elsevier), LILACS (through BVS), Cochrane Central Register of Controlled Trials (CENTRAL), ISI Web of Science, CINAHL (through EBSCO), and SCOPUS databases for studies published between January 1, 1989 and December 31, 2017, without language restriction. We searched for gray literature in Google Scholar and congress abstract books. We also searched for relevant studies in the reference lists of articles included in the review. MeSH terms were used for the searches were "tuberculosis" and "prison" (and its synonyms). The search strategy was adapted for each database and is detailed in the supplement material (S1 Table).

Study selection, inclusion criteria, and data extraction
Identified titles were imported to EndNote online, and duplicated studies were removed. The remaining titles were independently reviewed by two authors (MLG and SMVLO), who selected abstracts from articles, with no language restriction. The same authors independently selected full texts from the abstract list. Divergence was resolved by consensus. Observational (including cross-sectional, retrospective, and longitudinal) or experimental studies were eligible, regardless of the population size, if they tested CFW in any sector (security, administration, or healthcare workers). Studies that considered bacteriologically confirmed or clinicalradiological diagnoses of active TB were included. For LTBI diagnosis, we included studies that used either the tuberculin skin test (TST) or interferon-gamma release assays (IGRA). Cut-off values for prevalence and TST conversion were those considered by authors. We excluded studies in which more than one population was described and in which it was not possible to extract or calculate the indicators of interest. We included studies that reported prevalence/incidence rates or allowed the calculation of these variables by providing the necessary data.

Data pooling and statistical analyses
Pooled prevalence and incidence of active TB and LTBI, and their 95% confidence intervals (CI) were calculated with STATA software (STATA/SE 12.1, StataCorp, College Station, TX, USA) using random effects models. I 2 values of 25-49%, 50-74%, and �75% were considered to represent low, moderate, and high levels of heterogeneity [24], respectively.
Sources of heterogeneity were explored using sensitivity analyses. Analyses were performed by removing studies with less than 100 participants, and subgroup analyses were conducted according to diagnostic criteria and the country's TB burden [1].

Quality of study methods
For quality evaluation, we used the Quality Assessment Tool for Observational Cohort and Cross-sectional Studies of the National Heart, Lung and Blood Institute [25], which evaluates the internal validity of studies. Each study was assessed for 14 criteria: the research question or objective, the study population, the participation rate of eligible persons, individuals selected or recruited from the same or similar populations, sample size justification, exposure(s) of interest measured before outcome, sufficient deadline, different levels of exposure to outcome, exposure measurement (independent variables) clearly defined, blinded as to the exposure status of participants, follow-up, main potential confounders measured and statistically adjusted. Studies were classified as good, fair, or poor if they fulfilled �12, 5-11, and < 5 criteria, respectively.

Results
We identified 3028 titles: 3019 from the databases and nine through additional searches. After removing duplicates, 974 titles remained, of which 948 abstracts were excluded because they did not analyze TB or LTBI among CFW. Of the 26 abstracts retained for full text reading, 11 studies were further excluded: three could not be found even after contacting the author(s) [26][27][28] and eight did not allow calculation of prevalence or incidence in the population of interest [29][30][31][32][33][34][35][36]. Thus, 15 studies were included in this review and 14 in the meta-analysis (S1 Fig).

Active TB
Overall, 82,668 CFW were evaluated for active TB in three countries [7,12,14,18] between 1999 and 2016. Incidence of active TB ranged from 0.61 to 450/10,000 CFW/year. We did not perform meta-analyses, since the time of follow up was 1, 3, and 10 years.

Risk factors
We heterogeneously analyzed risk factors for prevalence and incidence of LTBI in seven studies that controlled for confounding by using multivariate regression models (Table 3). Older age, BCG vaccination after infancy, history of contact with prisoners, work in correctional facilities for more than one year, permanence in endemic countries for more than three months, place of birth, and current smoking status were found to be associated with LTBI. Risk factors for active TB were not reported in any of the four studies.

Publication bias
The funnel plot for the included studies was not symmetrical (S6 Fig). Most studies are outside the 99.8% limit. Six studies [8,10,14,17,18,21] contribute to the asymmetry, with smaller standard error and greater effect size, suggesting a risk of publication bias.

Discussion
TB transmission among inmates in correctional facilities is well reported, and represents a challenge for TB control [37]. Prisons and jails are frequently overcrowded, and the environmental conditions facilitate transmission [38]. The current study shows that the high risk of TB transmission is not restricted to inmates. The occurrence of LTBI is frequent among CFW, regardless of whether they worked in administrative, security, or healthcare services. Prevalence and incidence of LTBI are especially high in countries with high TB burden, despite the high heterogeneity among studies. Heterogeneity may be partially explained by the settings (TB burden, BCG vaccination policies), but methodological differences in sample selection and outcome definition (different cut-off values for TST) may also have played an important role.
Previous evidence suggests that TB should be considered an occupational disease in CFW [4,5,20]. Our study supports this point of view, although it is difficult to prove that transmission occurred within the correctional facilities. There are more studies on LTBI than on active TB and, unlike active TB, epidemiologic molecular evidence cannot be obtained to establish the source of LTBI transmission. However, indirect evidence suggests occupational transmission. Firstly, the magnitude of LTBI is similar to that reported in healthcare workers, a population known to have high work-related exposure [39]. Moreover, many of the reported LTBI risk factors for CFW are the same as those for healthcare workers [40,41]. In addition, molecular studies have shown that inmates are a source of TB transmission in both the correctional facilities and the community [6]. Finally, in our review, the duration of work in correctional facilities was strongly and significantly associated with higher risk for LTBI in low-burden countries [9,11,20], whereas duration of contact with inmates was the main factor associated with LTBI in high-burden countries. These findings corroborate the plausibility of the occupational nature of the transmission. Nevertheless, a significant correlation was also found between TB risk and non-occupational variables, such as older age, place of birth, trips longer than three months and BCG after infancy in low-burden countries, and smoking [9,11,16,19,20] and region of the country in high-burden countries [21], suggesting that community exposure-as well as the BCG effect on TST results-has an effect in this setting.
The included studies had some limitations, although the methodological quality was considered good in nine studies. Most studies were cross-sectional, and therefore, evaluated the prevalence of LTBI; however, data on the incidence of LTBI would provide better evidence for occupational exposure, or at least, for recent infection. TST (and interferon-γ release assays) cannot distinguish between recent and remote infection [42]; thus, it is not possible to infer that infection occurred in the correctional facilities. Data stratified by occupation and exposure were not provided, precluding meta-regression and stratified analyses by level of exposure. Finally, most studies were conducted more than 17 years ago, and may not reflect the current situation.
Our review also presents limitations. The funnel plot suggests that we might have overestimated the prevalence of LTBI, since a larger effect size is suggested. However, the study has many strengths. We searched nine comprehensive databases and the gray literature, with no language restriction, and we had access to most of the literature.
In summary, employees of correctional facilities are at risk for TB. These findings emphasize the need for infection control measures in such high-risk settings. Close surveillance and timely treatment when necessary are recommended. More studies are required to elucidate the risk factors for TB in this setting.
Supporting information S1 Checklist. This is checklist PRISMA. (DOC) S1 Table. This is the S1