Occupational Screening for Tuberculosis and the Use of a Borderline Zone for Interpretation of the IGRA in German Healthcare Workers

Abstract

IntroductionHealthcare workers (HCWs) in low incidence countries with contact to patients with tuberculosis (TB) are considered a high-risk group for latent TB infection (LTBI) and therefore are routinely screened for LTBI. The German Occupational TB Network data is analyzed in order to estimate the prevalence and incidence of LTBI and to evaluate putative risk factors for a positive IGRA and the performance of IGRA in serial testing.Methods3,823 HCWs were screened with the Quantiferon Gold in Tube (QFT) at least once; a second QFT was performed on 817 HCWs either in the course of contact tracing or serial examination. Risk factors for a positive QFT were assessed by a questionnaire.ResultsWe observed a prevalence of LTBI of 8.3%. Putative risk factors for a positive QFT result were age >55 years (OR 6.89), foreign country of birth (OR 2.39), personal history of TB (OR 6.23) and workplace, e.g. internal medicine (OR 1.40), infection ward (OR 1.8) or geriatric care (OR 1.8). Of those repeatedly tested, 88.2% (721/817) tested consistently QFT-negative and 47 were consistently QFT-positive (5.8%). A conversion was observed in 2.8% (n = 21 of 742 with a negative first QFT) and a reversion occurred in 37.3% (n = 28 of 75 with a positive first QFT). Defining a conversion as an increase of the specific interferon concentration from <0.2 to >0.7 IU/ml, the conversion rate decreased to 1.2% (n = 8). Analogous to this, the reversion rate decreased to 18.8% (n = 9).DiscussionIn countries with a low incidence of TB and high hygiene standards, the LTBI infection risk for HCWs seems low. Introducing a borderline zone from 0.2 to ≤0.7 IU/ml may help to avoid unnecessary X-rays and preventive chemotherapy. No case of active TB was detected. Therefore, it might be reasonable to further restrict TB screening to HCWs who had unprotected contact with infectious patients or materials.

Early diagnosis and effective treatment regimens are the keys to tackle antimicrobial resistance in tuberculosis (TB): A report from Euroscicon's international TB Summit 2016

“…However, screening guidelines issued by the public health systems of different countries suggest a varied combination of X-ray, tuberculin skin test (TST) and interferon-g release assays (IGRA) with no consensus on the best strategy. 24,25 He suggested that in circumstances when IGRA is positive and X-ray negative, LTBI can be confirmed and followed by prophylactic measures if the risk of avoiding treatment is deemed higher than the risk posed by administering it. Encouragingly the detection of LTBI in HCW has been increasing over the years as diagnostic technologies improve and it is expected that investigations into the risk-reward dynamics of treatment will allow for the development of a uniform global solution.…”

Numbers needed to treat to prevent tuberculosis

“…WHO recommends that individuals with a positive TST or IGRA should be treated for LTBI if they have the following risks: HIV infection, are contacts of pulmonary TB cases, initiate anti-tumour necrosis factor treatment, receive dialysis, prepare for transplantation, or have silicosis. The WHO guidelines groupcomposed of leading world experts using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach [6] -made a strong recommendation for LTBI treatment in these groups, on the premise of both direct and surrogate evidence for an increased risk of progression from infection to disease when compared with the general population, and much less upon a positive LTBI test. Martina Sester and colleagues argue that the number of individuals who need to take prophylactic medication in order to prevent one active case (number needed to treat (NNT)) would have been a better outcome measure to select at-risk populations.…”

“…Although not selected by a systematic approach, we made use of the fact that several studies with large sample sizes from low-incidence countries of tuberculosis were recently published from three major groups classically considered at risk for progression. In these studies, tuberculosis contacts [2,4,5], immunocompromised hosts [3] and healthcare workers [6][7][8] were evaluated for LTBI and subsequent progression. We have calculated the number needed to treat to prevent one case of tuberculosis (table 1), and found that the number needed to treat was very similar across three studies evaluating 1579, 5020 and 4774 tuberculosis contacts, respectively, with a positive TST or IGRA, ranging from 30 to 37 [2,4,5] (table 1).…”

“…It should be emphasised that incident tuberculosis cases also occurred in individuals with negative test results [2,3,5], especially among patients with HIV infection. In patients with chronic renal failure (n=270) or rheumatoid arthritis (n=199), stem cell (n=103) or solid organ transplant recipients (n=197) [3], and healthcare workers (n>15 000) [6][7][8], the number of individuals with LTBI needed to treat to prevent one case could not be calculated because no tuberculosis cases occurred during 2 years of follow up in these cohorts…”

“…Finally, some groups formerly considered at risk of tuberculosis (e.g. healthcare workers) are no longer risk groups in low-incidence countries [6][7][8], unless having had substantial contact to a patient with tuberculosis. It should be stated that given the inadequate test characteristics of the current diagnostics, not all tuberculosis will be prevented by these strategies, since active disease will continue to occur in those tested negative.…”