Nucleic Acid Amplification Test for Tuberculosis

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Nucleic Acid Amplification Test for Tuberculosis

• Heidi Behm, RN, MPH
• Acting TB Controller
• HIV/STD/TB Program
• Oregon, Department of Health Services

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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.

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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)
• Its easy (no extra sputum needed)!
• Its free for LHDs!

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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

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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.

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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 lt50

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What is NAAT MTD-2 FDA approved for?

• Smear sputum specimens
• Smear- sputum specimens
• Patients who havent received TB treatment
• Patients who are highly suspected to have TB
• Isnt 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)

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How good is this test?

• Respiratory smear specimens from untreated
  patients with high suspicion for TB.
  Sensitivity95, Specificity98
• Respiratory smear- specimens from untreated
  patients with high suspicion for TB.
• Sensitivity66, Specificity98

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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

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Interpretation of Results

• Not a perfect test.
• Does not replace culture results which are the
  gold standard.
• Interpret within the context of the patients
  symptoms, chest x-ray, smear and culture

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Smear, NAAT

• Presume active TB disease
• Start contact investigation
• Start TB medication
• Keep in isolation until cleared
• Confirm by culture result

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Smear, NAAT-

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

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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

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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

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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

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Conclusion
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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!

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Resources

• State summary http//www.oregon.gov/DHS/ph/tb/to
  ols/NAATguide.pdf
• OSPHL http//oregon.gov/DHS/ph/phl/docs/guide.pdf
  
• CDC http//www.cdc.gov/mmwr/preview/mmwrhtml/mm58
  01a3.htm?s_cidmm5801a3_e