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DELAWARE HEALTH & SOCIAL SERVICES
Division of Public Health
Laboratory


LPAC - November 14, 2008

Implementation of QuantiFERON testing

Debbie Rutledge & Diane Hindman
Clinical Microbiology Laboratory
Delaware Public Health Laboratory

New FDA Approved Test

* QuantiFERON (QFT) - blood test for the detection of tuberculosis (TB) 
  infection.
* Modern alternative to the 100 year old tuberculin skin test (TST).
* Offers simpler and more accurate, reliable, and convenient TB diagnostic tool.

QFT-TB Gold In-Tube 

* Highly specific & accurate.
* Positive test - strongly predictive of true infection with Mycobacterium 
  tuberculosis (M. tb). 
* Aid for diagnosing both active TB disease and latent TB infection (LTBI)-
  does not differentiate the two.

Benefits of QFT vs TST

Specific Antigen Targets for TB

* Detects responses to two proteins (early secretory antigenic target-6 
  [ESAT-6] & culture filtrate protein-10 [CFP-10]).
* Made by M. tb. and are absent from all BCG vaccine preps & environmental 
  nontuberculous mycobacteria (NTM), with the exception of M. kansasii, 
  M. marinum, and M. szulgai. 

Cost Savings

* Medical staff time - elimination of a 2nd patient visit for test 
  interpretation .
* Elimination of false-positive -unnecessary follow-up testing and treatment 
  for LTBI. 
* Eliminate repeat (2 step) testing - used for screening health care workers. 
* Lower cost of maintaining testing compliance in health care facilities, 
  offset the slightly higher reagent cost compared to the TST.

High-risk populations to screen

* Immunocompromised (e.g. HIV-infected or immunosuppressive meds, including 
  TNF-alpha antagonists, pre-organ transplant patients).
* Contacts to cases of active TB.
* Medical risk factors for TB reactivation (e.g. diabetes, chronic renal 
  failure, silicosis, malnutrition, certain cancers).
* Recent immigrants- from TB endemic areas, regardless of age.

High-risk populations to screen

* Homeless individuals.
* Injection drug users.
* Patients with an abnormal CXR consistent with old or active TB.
* Residents and employees of high-risk congregate settings (e.g. shelters, 
  nursing homes, jails, substance abuse treatment facilities).

Screen Health Care Workers

* Routine monitoring practices, including screening following an exposure to 
  M. tb. 
* 2005 CDC guidelines introduced QFT as an alternative to the TST for initial 
  and serial screening of health care workers for TB infection.


Test Interpretation

* Like the TST, the QFT is a useful but imperfect diagnostic aide. It should 
  not replace clinical judgment. 

Negative:

* Same interpretation as negative TST.
*  No further TB evaluation is needed unless indicated by clinical judgment.

Positive:

* Same interpretation as positive TST.
* Medical evaluation and chest x-ray are needed to determine whether TB disease 
  or latent TB infection.

* Note:  TB disease still requires culture for identification & susceptibility 
  testing. 


Indeterminate:

* Test inconclusive. Repeat QFT or administer TST
* May be due to laboratory problems or patient anergy (immune compromised) 
* If two different specimens from a patient yield indeterminate results, do 
  not repeat for that person.

Importance of Collection

* Correct collection of blood specimens is absolutely critical in the QFT 
  In-tube test. 
* Differs from other lab tests drawn off-site - testing process begins 
  IMMEDIATELY upon the correct volume of blood entering the tube. 

QFT Collection 

* Collect tubes in order (Nil, Antigen, Mitogen) (Green/Red/Purple=GRP=“Grape”).
* Tubes are calibrated to accept 1 mL of whole blood.
* Shake tubes vigorously for 5 seconds, must see “FOAMING”.  


Incubation & Transport

* Incubate in 37ºC incubator for 16-24 hours
	(within 16 hours of collection).
* Following incubation, specimens should be stored and transported at 2-27ºC 
  (Frig or RT) within 3 days. Collection Mon-Thurs for DPHL.
* After centrifugation, samples stable for 28 days at 4ºC.


References

* Guidelines for Using QuantiFERON-TB Gold Test for Detecting Mycobacterium 
  tuberculosis Infection, United States. MMWR 2005;54 -RR-15:49-55.
* Guidelines for Preventing the Transmission of Mycobacterium tuberculosis 
  in Health Care Settings, 2005. MMWR 2005;54 RR-17:1-141.
* Richeldi L. An update on the diagnosis of tuberculosis infection. Am J 
  Respir Crit Care Med. 2006;174:736-42.
* Cellestis, Ltd., Carnegie, Australia.  www.cellestis.com
* NYC, Bureau of TB Control, QFT-G Provider Fact Sheet February 2007