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

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.

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!

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

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.

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

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)

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%

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

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

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

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

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

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

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

Conclusion

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!

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