321 Challenges of T cell Assay Conversions in Serial Testing of Health Care Workers (HCW) in a Tuberculosis (TB) Control Program

Saturday, April 2, 2011: 3:45 PM
Coronado BCD (Hilton Anatole)
Kimberlee S. Fong, DO , Cleveland Clinic Foundation, Cleveland, OH
Lucileia T. Johnson, MD , Cleveland Clinic Foundation, Cleveland, OH
David VanDuin, MD, PhD , Cleveland Clinic Foundation, Cleveland, OH
Thomas G. Fraser, MD , Cleveland Clinic Foundation, Cleveland, OH
J. Walton Tomford, MD , Cleveland Clinic Foundation, Cleveland, OH
Steven M. Gordon, MD , Cleveland Clinic Foundation, Cleveland, OH
Cyndee Miranda, MD , Cleveland Clinic Foundation, Cleveland, OH

Background: In 2007, the Cleveland Clinic replaced the tuberculin skin test (TST) with the T cell-based assay or interferon gamma release assay (IGRA) using the QuantiFERON Gold-In Tube test for pre-employment TB screening in all HCW.  The protocol for all those with a positive IGRA (≥ 0.35 IU/mL) include chest radiograph (CXR) and referral to infectious disease (ID) for evaluation for treatment of latent TB infection (LTBI).  Subsequent annual testing for LTBI was done by IGRA for all HCW with a baseline pre-employment test. 

Objective: We report a review of our process of screening newly hired HCW using the T cell assay and describe the incidence of converters in HCW.

Methods: A computerized list of all HCW who underwent pre-employment IGRA testing from July 2007 to September 2010 was obtained from Occupational Health.  The number of positive, negative, or indeterminate IGRA tests were reported. For HCW with positive tests, the number of CXRs, ID referrals, HCW who accepted treatment for LTBI, and the number of T cell assay converters were determined. A T cell assay converter was defined as negative test at baseline with positive result on subsequent testing.

Results: A total of 16,285 IGRA tests were performed at the Cleveland Clinic during the study period of which 7374 (45.3%) were performed on newly hired HCW.  From this pool, 538 (7.3%) were positive, 305 (4.1%) were indeterminate, and 6531 (88.6%) were negative. A total of 534 (99.3%) HCW with positive tests had CXR performed; 22 (4.1%) were abnormal, but no cases of active pulmonary tuberculosis were identified. Their mean age was 37.4 years and ranged from 16-70 years.  There were 335 (62.3%) HCW with positive tests who were evaluated and counseled by ID physicians, of whom 203 (60.6%) accepted isoniazid (INH) therapy for LTBI. There were 102 (19%) HCW who did not show up for their ID appointment and 88 (16.4%) with positive IGRA tests who had been previously treated for LTBI.  From 2007-2010, a total of 52 (2.8%) of 1861 HCW with serial IGRA tests were identified as converters, with a median value of 0.63 IU/ml (75% were < 1 IU/ml) [Figure 1]. None of the converters had active TB or were part of an outbreak investigation. Forty-four converters were seen by ID physicians and 26 (59.1%) were advised to take INH therapy.  Of the 26 who were recommended INH, 22 (84.6%) accepted therapy, and 4 (15.4%) declined treatment.  There were 6 who repeated the test, 4 of whom reverted from a positive to a negative test.

Conclusions: IGRA testing was successfully implemented in our TB control program as a part of pre-employment screening of HCW and there was acceptance of LTBI treatment for the majority after counseling with an ID physician. Interpretation of IGRA conversion in serial testing is challenging given high number of low positive results (<1 IU/ml), and further data is needed on establishing clinically significant cut-offs for conversions.