Nucleic Acid Amplification Test for Tuberculosis

1. Nucleic Acid Amplification Test for Tuberculosis Heidi Behm, RN, MPH Acting TB Controller HIV/STD/TB Program Oregon, Department of Health Services

2. What is this test? • Nucleic Acid Amplification Test (NAAT) identifies genetic material unique to MTB • Several NAA test have been FDA approved • 1995-Amplified Mycobacterium tuberculosis Direct Test (MTD, Gen-Probe, San Diego, California) was FDA approved in for AFB smear-positive respiratory specimens • 1999-An enhanced test (MTD-2) was approved for AFB smear-negative respiratory specimens. • Oregon State Public Health Lab (OSPHL) will utilize Gen Probe MTD-2 • NAAT is also referred to as Polymerase Chain Reaction (PCR) test.

3. Why is NAAT so great? • TB genetic material can be detected using NAAT within 3-5 hours while cultures take weeks! • Find out faster if smear+ is TB vs. NTM (save time and money on drugs, contact investigation, etc) • Earlier diagnosis for smear- (less delayed diagnosis and TB transmission, decrease the inappropriate use of fluoroquinolones) • It’s easy (no extra sputum needed)! • It’s free for LHDs!

4. How will this work for LHDs? • Collect sputum to rule out TB and send to lab as usual • OSPHL will test the first sputum with NAAT • If the first sputum is smear-/NAAT -, but a subsequent sputum is smear+ that specimen should also get tested. • Others tested by special request only • If you do not want sputum tested, indicate on lab slip

5. How do private providers order NAAT? • Processed sediments may be sent to OSPHL directly from the lab or hospital • There will be a charge of $40.00 for testing • The provider should contact OSPHL at 503-693-4100 or see OSPHL web site for further instruction.

6. When should NAAT not be used? • Do not use if patient has taken TB medications in the past 12 months (not a test of cure, not for previously treated B waivers) • Can detect nucleic acids from dead and live organisms, so may remain positive long after treatment is completed and the culture is negative • Do not use if patient has taken TB medications for more than 7 days • Do not use if low suspicion of TB (example, B waiver). Positive predictive value of the NAA test is <50%

7. What is NAAT MTD-2 FDA approved for? • Smear+ sputum specimens • Smear- sputum specimens • Patients who haven’t received TB treatment • Patients who are highly suspected to have TB • Isn’t approved for non-respiratory specimens, but there may be clinical utility in using test • Further research needed on using for children who cannot produce sputum (gastric aspirates)

8. How good is this test? • Respiratory smear+ specimens from untreated patients with high suspicion for TB. Sensitivity=95%, Specificity=98% • Respiratory smear- specimens from untreated patients with high suspicion for TB. Sensitivity=66%, Specificity=98%

9. How good is NAAT continued… • Good test for smear+ • Sensitivity for smear- is low (66%) • A test with high sensitivity catches all people with a disease. • If test has low sensitivity, may believe patient does not have disease when they do (a false negative) • MTD-2 detects only 50%--80% of AFB smear-negative, culture-positive pulmonary TB cases

10. Interpretation of Results • Not a perfect test. • Does not replace culture results which are the “gold standard”. • Interpret within the context of the patient’s symptoms, chest x-ray, smear and culture

11. Smear+, NAAT+ • Presume active TB disease • Start contact investigation • Start TB medication • Keep in isolation until cleared • Confirm by culture result

12. Smear+, NAAT- • Suspect nontuberculous mycobacterium (NTM). • Does not rule out TB • Consider delaying treatment, contact investigation and removing from isolation. • But…if highly suspected of TB or lives in congregate setting or with high risk individuals request a second NAAT. • Confirm findings with culture result

13. Smear-, NAAT+ • Likely has active TB disease • Consider submitting another specimen for NAAT to verify • Presumed to have TB if two or more specimens are NAAT positive • Use clinical judgment to determine whether to start treatment, start contact investigation and place on isolation. • Confirm by culture result

14. Smear-, NAAT- • For smear- specimens, sensitivity is low • Diagnosis of TB cannot be excluded • Rely on clinical judgment • Requesting a second NAAT may be helpful • Contact investigation may be delayed and patient considered non-infectious if sputum smear- x 2 and all NAAT results are negative. • Confirm by culture result

15. Inhibited NAAT • Amplification was inhibited due to a naturally occurring inhibitor in the specimen or processing reagent (example: blood). • Can result in a false negative • Test for inhibitors will be automatically run by lab on all smear+, NAAT- specimens • If present, lab will contact you for additional specimen to test

16. Conclusion

17. Conclusion • NAAT will provide LHDs with additional information to base decisions upon • LHDs will not need to do anything different when collecting sputum to rule out TB • Do not use NAAT if the patient has been on TB meds. for more than 7 days or was treated within last year • The TB Program is available to assist with interpretation of results!

18. Resources • State summary: http://www.oregon.gov/DHS/ph/tb/tools/NAATguide.pdf • OSPHL: http://oregon.gov/DHS/ph/phl/docs/guide.pdf • CDC: http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5801a3.htm?s_cid=mm5801a3_e