Introduction
Current recommended guidelines from the Centers for Disease Control and Prevention (CDC) and the National Tuberculosis Controllers Association recommend screening for all healthcare workers (HCW) at initiation of employment for TB (tuberculosis). Reference Sosa, Njie and Lobato1 A risk assessment and symptom evaluation should be performed. Those who have not had previous active or latent tuberculosis (LTBI) should have an interferon-gamma release assay (IGRA) or tuberculin skin test (TST) performed. A person is deemed at low risk for TB if there is no residence for >1 month in a country with a high TB rate, no current or planned immunosuppression nor previous close contact with someone with infectious TB. As recommended by the American Thoracic Society (ATS), Infectious Disease Society of American (IDSA) and the CDC, those without symptoms who are unlikely to be infected with TB and have a low risk for progression but are required to have testing performed should have an IGRA test performed and if positive have repeat testing performed before being considered infected with TB. Reference Lewinsohn, Leonard and LoBue2 This recommendation by the ATS, IDSA and CDC was deemed a conditional recommendation with very low-quality evidence. In 2020 our hospital adopted the new conditional recommendations. The purpose of this report is to provide the first set of data in support of the new recommendations.
Methods
Between October 1, 2021 and October 31, 2023 we screened all new HCW who had not previously been confirmed to have prior TB infection (latent or active) with the Liaison QuantiFERON®-Gold Plus (QFT-Plus). Those deemed not at high risk based on the CDC criteria (1) who had a positive test had a repeat test with a T-SPOT®.TB (T-spot). A chest radiograph and symptom review were performed on all to exclude evidence of active TB. Only those who then had a positive T-spot were recommended to proceed with therapy for LTBI. We subsequently followed all HCW with a positive QFT-Plus annually for the presence of symptoms of TB through June 30, 2025.
Results
In the 25-month period, we screened 4283 individuals as new hires with a QT-Plus test. 173 had positive results. Among the 173, we identified 56 individuals at low risk for TB. The mean age among the 56 individuals was 34 and 40 were females. Nine of the fifty–six had a positive T-spot, four had a borderline result and forty-three were negative. The positivity rate was 16% with 95% confidence interval of 8.5–28.4%. There was a correlation between the TB1-nil and TB2-nil values on the QFT-Plus and the likelihood of a positive T spot. Those with a positive T-spot had TB1-nil mean values and TB2-nil mean values on QFT-Plus testing of 3.38 IU/ml and 2.82 IU/ml, compared to 0.69 IU/ml and 0.78 IU/ml for those with a negative T-spot. However, of the 13 individuals with a TB1-nil or TB2-nil of >1 IU/ml, only 6 had positive T-spots. In follow-up symptom reviews on all HCW with a positive QFT-plus, none had symptoms suggestive of active TB through June 30, 2025.
Discussion
Among low-risk HCW, we found that the positive predictive value of QFT-Plus testing was only 16% (95%CI 8.5–28.4), assuming those with both QFT-Plus and T-spot positive results represented true positives and those with QFT-Plus positive and T-spot negative testing were false positives. A previous large metanalysis noted that among HCW with a baseline positive IGRA 48% were negative upon serial retesting with the same test, Reference Sosa, Njie and Lobato1 however those results included both high-risk and low-risk individuals. We are unaware of studies similar to ours that evaluated retesting among HCW with positive IGRA results in which high-risk subjects were excluded. In testing for LTBI, there is no definitive diagnostic test to utilize as a gold-standard. QFT-Plus testing has a reported specificity of 0.98 (95%CI 0.95–0.99). Reference Jonas, Riley and Lee3 Data on specificity is inferred by testing subjects deemed at low risk in the absence of a gold-standard. The positive predictive value of a test even of high specificity may be low in the setting of low disease prevalence as demonstrated by our findings. Current guidelines recommend treatment for all infected HCW unless medically contraindicated. Reference Sosa, Njie and Lobato1 Our utilization of a QFT-Plus followed by a T-spot in low risk HCW significantly reduced those in whom treatment for LTBI was recommended and provides evidence-based support for the current guidelines.
Data availability statement
We will share the data underlying this article with the corresponding author upon reasonable request.
Acknowledgments
None.
Author contribution
A.S. and D.B designed the study, obtained the data, analyzed and interpreted the data. A.S. drafted and D. B. revised the manuscript. All the authors critically reviewed the text and approved the final version of the manuscript.
Financial support
This study received no financial support.
Competing interests
There were no conflicts of interest relevant to this article.
Ethical standard
The institutional review board of the University of Missouri-Kansas City approved the study.
