Background The largest health employer in XXXXXX requires the majority of its over 20,000 workers to submit to a interferon-gamma release assay (IGRA) blood test yearly as a condition of employment.^{1 2}

Testing For this predominately low risk population annual screening with the IGRA over time can be expected to produce an initial false positive rate of approximately 15% and subsequent cumulative rate of a positive result of 27% over 7 years of screening.³ After testing positive an employee is assumed to have Latent Tuberculosis (LTB) per CDC guidelines and must submit to antimicrobial therapy or more invasive radiologic testing as a condition of continued employment. In 2011 the employer ceases to permit new employees or those who have ever had an IGRA test to use tuberculin skin testing for annual screening, effectively phasing out this more convenient option which costs less than 1/3^rd the price of the IGRA with fewer false positives in those not vaccinated with BCG.

Treatment Treatment of presumed LTB based on serologic testing alone lacks prospective evidence of improved patient outcomes in absence of pulmonary findings.⁴ Yet for the majority of this system’s health care workers who test positive but do not actually have LTB (false positive tests) the CDC recommended pharmacotherapy confers risks without any potential benefit.

Employee Estimates If a conservative estimate of 10,000 employees submit to annual blood testing as required, over 1,500 would test positive and per CDC definition have LTB. If all 1,500 accepted the recommended antimicrobial therapy they would be subjected to a 3 to 9 month course of isoniazid and repeated blood testing for hepatic function monitoring, yet 98% the employees would not truly have LTB (false positive test).

Harms The recommended CDC guidelines for treatment of LTB involves 3 or 9 months of isoniazid (INH) therapy +/- other medications. Though small INH carries the potential for fatal immune mediated hepatic toxicity in addition to the well know direct dose dependent toxicity. Over a recent nine year period the Drug-Induced Liver Injury Network reported 69 cases of severe hepatic toxicity due to INH with 97% of those affected taking INH for presumed LTB. (5) 20% of the affected patients either died or required liver transplantation. INH carries a reported rate of 1% for acute hepatitis and 0.01% for acute hepatic failure.(6) For the medical center’s 1500 positive testing employees a course of treatment could be expected to lead to 15 cases of acute hepatitis yearly. Yearly treatment in this pattern would lead to 1 case of acute hepatic failure over 7 years with a 20% mortality or need for liver transplant.

Conclusion One large North American Health Employer’s mandatory TB testing strategy leads to significant overdiagnosis of LTB with subsequent mandated employee overtesting and potent overtreatment that carries risk without a proven benefit for the employees or increased protection for their patients.