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      Risk of Occupational Latent Tuberculosis Infection among Health Personnel Measured by Interferon-Gamma Release Assays in Low Incidence Countries—A Systematic Review and Meta-Analysis

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          Abstract

          Healthcare workers (HCWs) have increased risk for latent tuberculosis infection (LTBI) and tuberculosis (TB) disease due to their occupational exposure. For some years now, interferon-γ release assays (IGRAs) have replaced the tuberculin skin test for the diagnosis of LTBI in many countries. This review examined the occupational risk of LTBI in HCWs with IGRA testing in low incidence countries. A systematic review and meta-analysis of studies from 2005 onwards provide data regarding the prevalence of LTBI in HCWs. In addition, the pooled effect estimates were calculated for individual regions and occupational groups. 57 studies with 31,431 HCWs from four regions and a total of 25 countries were analysed. The prevalence of LTBI varied from 0.9 to 85.5%. The pooled estimation found the lowest prevalence of LTBI for North American and West Pacific countries (<5%), and the highest prevalence for Eastern Mediterranean countries (19.4%). An increased risk for LTBI was found only for administrative employees. Studies on the occupational risk of LTBI continue to show increased prevalence of HCWs, even in low-incidence countries. Good quality studies will continue to be needed to describe occupational exposure.

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          Systematic review: T-cell-based assays for the diagnosis of latent tuberculosis infection: an update.

          Interferon-gamma-release assays (IGRAs) are alternatives to the tuberculin skin test (TST). A recent meta-analysis showed that IGRAs have high specificity, even among populations that have received bacille Calmette-Guérin (BCG) vaccination. Sensitivity was suboptimal for TST and IGRAs. To incorporate newly reported evidence from 20 studies into an updated meta-analysis on the sensitivity and specificity of IGRAs. PubMed was searched through 31 March 2008, and citations of all original articles, guidelines, and reviews for studies published in English were reviewed. Studies that evaluated QuantiFERON-TB Gold, QuantiFERON-TB Gold In-Tube (both from Cellestis, Victoria, Australia), and T-SPOT.TB (Oxford Immunotec, Oxford, United Kingdom) or its precommercial ELISpot version, when data on the commercial version were lacking. For assessing sensitivity, the study sample had to have microbiologically confirmed active tuberculosis. For assessing specificity, the sample had to comprise healthy, low-risk individuals without known exposure to tuberculosis. Studies with fewer than 10 participants and those that included only immunocompromised participants were excluded. One reviewer abstracted data on participant characteristics, test characteristics, and test performance from 38 studies; these data were double-checked by a second reviewer. The original investigators were contacted for additional information when necessary. A fixed-effects meta-analysis with correction for overdispersion was done to pool data within prespecified subgroups. The pooled sensitivity was 78% (95% CI, 73% to 82%) for QuantiFERON-TB Gold, 70% (CI, 63% to 78%) for QuantiFERON-TB Gold In-Tube, and 90% (CI, 86% to 93%) for T-SPOT.TB. The pooled specificity for both QuantiFERON tests was 99% among non-BCG-vaccinated participants (CI, 98% to 100%) and 96% (CI, 94% to 98%) among BCG-vaccinated participants. The pooled specificity of T-SPOT.TB (including its precommercial ELISpot version) was 93% (CI, 86% to 100%). Tuberculin skin test results were heterogeneous, but specificity in non-BCG-vaccinated participants was consistently high (97% [CI, 95% to 99%]). Most studies were small and had limitations, including no gold standard for diagnosing latent tuberculosis and variable TST methods and cutoff values. Data on the specificity of the commercial T-SPOT.TB assay were limited. The IGRAs, especially QuantiFERON-TB Gold and QuantiFERON-TB Gold In-Tube, have excellent specificity that is unaffected by BCG vaccination. Tuberculin skin test specificity is high in non-BCG-vaccinated populations but low and variable in BCG-vaccinated populations. Sensitivity of IGRAs and TST is not consistent across tests and populations, but T-SPOT.TB appears to be more sensitive than both QuantiFERON tests and TST.
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            Risk of tuberculosis infection and disease associated with work in health care settings.

            Tuberculosis (TB) in health care workers (HCWs) was not considered a serious problem following the advent of effective antibiotic therapy. Interest was re-stimulated by the occurrence of several major nosocomial outbreaks. We have reviewed the available published literature regarding prevalence and incidence of TB infection and disease among HCWs in countries categorised by mean income. We included studies published in English since 1960 from low- and middle-income countries (LMICs) and since 1990 from high-income countries (HICs). We excluded outbreak reports and studies based only on questionnaires. The median prevalence of latent TB infection (LTBI) in HCWs was 63% (range 33-79%) in LMICs and 24% in HICs (4-46%). Among HCWs from LMICs, LTBI was consistently associated with markers of occupational exposure, but in HICs it was more often associated with non-occupational factors. The median annual incidence of TB infection attributable to health care work was 5.8% (range 0-11%) in LMICs and 1.1% (0.2-12%) in HICs. Rates of active TB in HCWs were consistently higher than in the general population in all countries, although findings were variable in HICs. Administrative infection control measures had a modest impact in LMICs, yet seemed the most effective in HICs. TB remains a very important occupational risk for HCWs in LMICs and for workers in some institutions in HICs. Risk appears particularly high when there is increased exposure combined with inadequate infection control measures.
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              Tuberculosis among Health Care Workers

              To assess the annual risk for latent tuberculosis infection (LTBI) among health care workers (HCWs), the incidence rate ratio for tuberculosis (TB) among HCWs worldwide, and the population-attributable fraction of TB to exposure of HCWs in their work settings, we reviewed the literature. Stratified pooled estimates for the LTBI rate for countries with low ( 100/100,000 population) TB incidence were 3.8% (95% confidence interval [CI] 3.0%–4.6%), 6.9% (95% CI 3.4%–10.3%), and 8.4% (95% CI 2.7%–14.0%), respectively. For TB, estimated incident rate ratios were 2.4 (95% CI 1.2–3.6), 2.4 (95% CI 1.0–3.8), and 3.7 (95% CI 2.9–4.5), respectively. Median estimated population-attributable fraction for TB was as high as 0.4%. HCWs are at higher than average risk for TB. Sound TB infection control measures should be implemented in all health care facilities with patients suspected of having infectious TB.
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                Author and article information

                Journal
                Int J Environ Res Public Health
                Int J Environ Res Public Health
                ijerph
                International Journal of Environmental Research and Public Health
                MDPI
                1661-7827
                1660-4601
                16 January 2020
                January 2020
                : 17
                : 2
                : 581
                Affiliations
                [1 ]Competence Center for Epidemiology and Health Services Research for Healthcare Professionals (CVcare), Institute for Health Services Research in Dermatology and Nursing (IVDP), University Medical Centre Hamburg-Eppendorf, 20246 Hamburg, Germany; a.kozak@ 123456uke.de (A.K.); albert.nienhaus@ 123456bgw-online.de (A.N.); a.schablon@ 123456uke.de (A.S.)
                [2 ]Department of Occupational Medicine, Hazardous Substances and Public Health, Institution for Statutory Accident Insurance and Prevention in the Health and Welfare Services (BGW), 22089 Hamburg, Germany
                Author notes
                [* ]Correspondence: c.peters@ 123456uke.de ; Tel.: +49-(0)-40-7410-59702
                Article
                ijerph-17-00581
                10.3390/ijerph17020581
                7027002
                31963207
                1bf95dd4-902b-42b7-95b2-d40bd42ffd8a
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 30 December 2019
                : 12 January 2020
                Categories
                Review

                Public health
                latent tuberculosis infection (ltbi),health personnel,occupational risk,interferon-gamma release assays (igra),low incidence countries

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