Transcript Nucleic Acid Amplification Test for Tubeculosis

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?
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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!
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How will this work for LHDs?
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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?
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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?
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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%
What is NAAT MTD-2
FDA approved for?
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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?
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Respiratory smear+ specimens from untreated
patients with high suspicion for TB.
Sensitivity=95%, Specificity=98%
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Respiratory smear- specimens from untreated
patients with high suspicion for TB.
Sensitivity=66%, Specificity=98%
How good is NAAT continued…
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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 smearnegative, culture-positive pulmonary TB cases
Interpretation of Results
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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+
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Presume active TB disease
Start contact investigation
Start TB medication
Keep in isolation until cleared
Confirm by culture result
Smear+, NAAT
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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+
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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
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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
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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
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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
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State summary:
http://www.oregon.gov/DHS/ph/tb/tools/N
AATguide.pdf
OSPHL:
http://oregon.gov/DHS/ph/phl/docs/guide.p
df
CDC:
http://www.cdc.gov/mmwr/preview/mmwrht
ml/mm5801a3.htm?s_cid=mm5801a3_e