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
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%
positive predictive valueis the proportion of patients with positive test results who are correctly diagnosed. It is the most important measure of a diagnostic method as it reflects the probability that a positive test reflects the underlying condition being tested for

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:
OSPHL:
CDC: