Modifiedmedical mutual - ohioPolicy AHS - G2063

Testing for Diagnosis of Active or Latent Tuberculosis

Defines coverage criteria for laboratory tests used to diagnose active tuberculosis (microbiologic tests) and to screen or diagnose latent TB infection (IGRAs and TST), and lists tests that do or do not meet coverage criteria for members of Medical Mutual - Ohio.

Policy Summary

Payermedical mutual - ohio

PolicyTesting for Diagnosis of Active or Latent Tuberculosis

Policy CodePolicy AHS - G2063

Change TypeMaterial updates to coverage criteria and coding

Effective DateFeb 1, 2026

Next Review DateSep 4, 2025

Key ActionUse updated qualitative NAAT nomenclature and verify coverage/PA for listed CPT/HCPCS codes when submitting claims.

SourceLink

POLICY UPDATE CHANGES

Direct probe testing is no longer available; qualitative NAAT testing becomes CC2.c for Mycobacteria spp., M. tuberculosis, and M. avium complex.

Removed CPT codes 87149, 87550, 87555, 87560 from the policy.

Removed CC9 because with removal of direct probes there is no situation allowing two types of NAAT.

Updated organism naming from 'M. avium intracellulare' to 'M. avium complex' in former CC10 (now CC8).

Added CPT code 0574U (effective date 7/1/2025) in an off-cycle coding modification.

Added CPT code 87564 (effective date 1/1/2025) in a prior off-cycle coding modification.

IGRA >95%reported IGRA specificity for LTBI

TST ~71-82%reported tuberculin skin test sensitivity

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Coverage Criteria for Tuberculosis Testing

Covered Tests and Criteria

Covered when the following conditions are met:

IGRA for LTBI: Interferon gamma release assay (IGRA) meets coverage criteria for (a) individuals who are at risk for infection with Mycobacterium tuberculosis, or (b) individuals who are unlikely to be infected when screening is obliged by law.

IGRA is not covered for diagnosing active tuberculosis (see exclusions).

Tests for suspected TB infection: For all suspected TB infections, AFB smear/stain, culture and culture-based drug susceptibility testing, and qualitative NAAT for Mycobacteria spp., M. tuberculosis, and M. avium complex meet coverage criteria.

Molecular-based DST coverage: Molecular-based drug susceptibility testing meets coverage criteria when one or more of: prior TB treatment; born in or lived ≥1 year in country with TB incidence ≥20/100,000 or high primary MDR-TB prevalence ≥2%; contact of MDR-TB case; or HIV infection.

Repeat DST coverage: Repeat drug susceptibility testing meets coverage criteria when sputum cultures remain positive after 3 months of treatment or when there is bacteriological reversion from negative to positive.

Fluid analysis coverage: For individuals with pleural, pericardial effusion, or ascites and suspected TB infection, cell counts, protein, glucose, and LDH concentrations of relevant fluids meet coverage criteria.

LF-LAM coverage in advanced HIV: In HIV-infected individuals with CD4 ≤100 cells/μL who have signs and symptoms of tuberculosis, urine-based detection of LAM meets coverage criteria.CD4 ≤100 cells/μL

CDC-recommended TB disease evaluation

Covered diagnostic evaluation for suspected TB disease should include all of the following components:

Complete medical evaluation for TB disease: Medical history; Physical examination; Test for TB infection (IGRA or TST); Chest radiograph; Bacteriologic examination (sputum smear microscopy, NAAT, culture, and drug susceptibility testing)

CDC-recommended five components for TB evaluation

LTBI testing and preventive treatment guidance

LTBI testing recommendations (WHO):

LTBI testing methods: Either tuberculin skin test (TST) or interferon-gamma release assay (IGRA) may be used to test for latent TB infection.

WHO: either TST or IGRA acceptable in many settings

Populations for preventive treatment without testing: In people living with HIV and child household contacts <5 years, preventive treatment can be initiated without requiring LTBI testing.

WHO strong recommendation

Molecular diagnostics and resistance testing

WHO recommendations on molecular testing as initial diagnostic tests:

Xpert/Ultra as initial test: Xpert MTB/RIF or Xpert Ultra should be used as initial diagnostic tests for pulmonary TB (adults and children) and for rifampicin-resistance detection in many scenarios, often preferred over smear microscopy/culture for initial testing.

Multiple WHO recommendations for adults, children, and extrapulmonary specimens

Truenat assays: Truenat MTB or MTB Plus may be used as initial diagnostic tests for pulmonary TB; Truenat MTB-RIF Dx may be used for rifampicin resistance when positive.

WHO conditional recommendations

Genotypic assays for resistance: Commercial molecular LPAs and sequence-based assays can be used for detection of resistance to rifampicin and isoniazid and for informing regimens; WGS can rule-in resistance but phenotypic DST remains needed for some drugs.

WHO and consensus statements on genotypic vs phenotypic testing

WHO: Xpert/Xpert Ultra as initial tests

WHO recommendations for molecular testing in adults with signs/symptoms or radiographic abnormalities

WHO Xpert/Ultra initial testing: In adults with signs/symptoms of TB or chest radiograph abnormalities, Xpert MTB/RIF or Xpert Ultra may replace culture as the initial test for pulmonary TB (conditional, low certainty).

Applies where immediate treatment decision is needed and supplementary tests are unavailable or delayed; one Xpert Ultra may be used rather than two in similar populations (conditional, very low certainty).

WHO: Truenat and LPA recommendations

WHO recommendations on Truenat and LPAs

Truenat initial diagnostic use: Truenat MTB or MTB Plus may be used as an initial diagnostic test for pulmonary TB in adults and children with signs/symptoms rather than smear microscopy/culture (conditional, moderate certainty).

Truenat MTB-RIF Dx may be used as initial rifampin-resistance test when Truenat is positive (conditional, very low certainty).

LPA use and limits: Commercial molecular LPAs may be used as initial test instead of phenotypic DST for rifampicin and isoniazid in sputum smear-positive specimens or cultured isolates; not recommended for direct testing of smear-negative sputum. Conventional culture-based DST remains necessary for other agents and to monitor additional resistance.

Applies to pulmonary and extrapulmonary specimens as extrapolated; LPAs less sensitive in children for sputum.

WHO: LF-LAM guidance

WHO recommendations on LF-LAM in HIV-positive patients

LF-LAM inpatient strong recs: LF-LAM is strongly recommended to assist diagnosis of active TB in HIV-positive inpatients with TB symptoms or who are seriously ill, or with advanced HIV or CD4 <200 cells/mm3 (strong recommendation, moderate certainty).

LF-LAM outpatient conditional recs: LF-LAM is suggested for HIV-positive outpatients with TB symptoms or who are seriously ill, and in those with CD4 <100 cells/mm3 (conditional recommendations).

WHO recommends against its use in HIV-positive persons without TB symptoms or with higher/unknown CD4 counts in most outpatient scenarios.

ATS/IDSA/CDC: LTBI and TB disease testing

ATS/IDSA/CDC recommendations for TB disease and LTBI testing

LTBI testing age-stratified: IGRA is recommended over TST in individuals ≥5 years in many circumstances (especially if prior BCG or inability to return for TST); TST is preferred in healthy children <5 years when testing is warranted. A second diagnostic test is suggested if initial test is positive in those ≥5 years.

Testing should not be performed in persons at low risk; active TB must be excluded before LTBI treatment.

TB disease diagnostics: Perform AFB smear microscopy, both liquid and solid cultures, and NAAT on initial respiratory specimens for suspected pulmonary TB. Rapid molecular DST for rifampin (± isoniazid) is recommended in specified risk groups.

For extrapulmonary TB, perform smear, culture, NAAT, histology and relevant fluid studies (ADA, IFN-γ) as indicated.

NIH: HIV and DST recommendations

NIH guidance for persons with HIV and resistance testing

HIV-specific testing and DST: All persons with HIV should be tested for LTBI at HIV diagnosis. In people with HIV and suspected TB, perform AFB smear, NAAT, and culture even with normal chest radiograph. Consider drug resistance testing in those with exposures, residence in high-resistance areas, persistent positive tests at/after 4 months, or prior TB treatment. Rapid molecular DST for rifampin (and isoniazid if available) should be performed on initial isolates.

Repeat resistance testing if cultures remain positive at/after 4 months or reversion occurs; reserve second-line DST to specimens with evidence of first-line resistance and use experienced reference labs.

Molecular DST interpretation and limitations

Guidance on molecular DST and sequencing

Rapid molecular DST and follow-up: When rifampin resistance is detected, obtain additional rapid DST for first-line drugs, fluoroquinolones, and aminoglycosides; repeat DST if cultures remain positive during treatment. Molecular tests for resistance may miss some mutations and should be confirmed by phenotypic methods when necessary.

WGS offers comprehensive sequence data but clinical interpretation is limited for many mutations; culture-based DST remains gold standard for many drugs.

USPSTF: LTBI screening in adults at increased risk

USPSTF screening recommendations for LTBI

USPSTF LTBI screening: Screen asymptomatic adults 18+ who are at increased risk for LTBI using TST or IGRA; ensure follow-up and treatment for positive screens. This recommendation does not apply to symptomatic adults or to children/adolescents.

Screening frequency should be individualized by risk, ranging from one-time to annual in ongoing exposure scenarios.

AAP: pediatric LTBI/TB guidance

Pediatric testing considerations

AAP pediatric recommendations: For children <2 years, TST is preferred; for children ≥2 years either TST or IGRA may be used, with IGRA preferred in BCG-vaccinated children. Immediate testing indicated for contacts, symptomatic or radiographic findings suggesting TB, recent immigrants/adoptees from endemic countries, significant travel exposure, and annual testing for children with HIV.

Universal testing is discouraged due to low yield and false positives.

Covered diagnostic testing and scenarios

Covered tests and testing scenarios recommended by cited guidelines

Rapid testing for suspected pulmonary TB: For patients suspected of pulmonary TB, obtain at least two sputum specimens for microscopy and one for rapid molecular testing (NAAT) and send samples for liquid culture and culture-based DST in a quality-assured laboratory.

ERS/ECDC recommends >=2 sputum for microscopy and 1 for rapid molecular test; send for culture and DST if positive

Use of rapid NAAT on primary specimens: Request rapid diagnostic NAAT for M. tuberculosis complex on primary specimens when clinical suspicion exists and: the person has HIV; rapid species info would alter care; or contact-tracing implications are being explored.

NICE guidance

Rifampin resistance testing: For persons with clinically suspected TB and risk factors for MDR-TB (prior TB treatment, contact with known MDR-TB case, birth/residence in high MDR-TB prevalence country), request rapid NAAT for rifampin resistance; if NAAT is negative in high MDR-TB risk, obtain further specimens and use rapid rifampin resistance detection on positive cultures.

NICE guidance

NAAT and criteria renumbering

Coverage criteria updated to remove direct probe testing and to specify qualitative NAAT for Mycobacteria spp., M. tuberculosis, and M. avium complex.

Updated NAAT coverage: Qualitative NAAT for Mycobacteria spp., M. tuberculosis, and M. avium complex is specified as a covered testing category (CC2.c).

Reflects replacement of direct probe testing; former CC4 now CC3; former CC10 now CC8 with organism name update.

IGRA is explicitly excluded as a diagnostic test for individuals with active tuberculosis: the policy states IGRA DOES NOT MEET COVERAGE CRITERIA for individuals with active tuberculosis. In addition, a set of laboratory tests are identified as not meeting coverage criteria due to insufficient evidence, including quantitative NAAT, whole genome sequencing for drug resistance, genotyping, ADA and IFN-γ fluid testing for extrapulmonary TB, and serum protein biomarker panels.

The World Health Organization strongly recommends that commercial serodiagnostic (serological) tests not be used for diagnosis of pulmonary or extrapulmonary TB because currently available commercial assays produce inconsistent and imprecise results and do not improve patient outcomes.

WHO guidance notes that line probe assays (LPAs) are not recommended for direct testing of sputum smear–negative specimens; LPAs are intended for smear-positive specimens or cultured isolates and do not replace conventional culture-based DST for other agents.

WHO recommends against using LF-LAM to assist diagnosis in HIV-positive persons who do not have TB symptoms or who have unknown or higher CD4 counts in most outpatient settings. LF-LAM is recommended primarily for HIV-positive inpatients with symptoms or advanced immunosuppression and selected symptomatic outpatients with low CD4 counts.

Whole genome sequencing (WGS) provides comprehensive sequence data but results are limited by lack of validated correlation for many mutations; therefore WGS cannot currently be interpreted reliably for clinical decision-making across most resistance mutations and culture-based DST remains the reference standard for many drugs.

Direct probe testing has been removed from the policy because it is no longer available. As a result, pathways that previously allowed direct probe methods are excluded from coverage and have been eliminated in the criteria renumbering.

The policy identifies several tests that do not meet coverage criteria, including quantitative NAAT, whole genome sequencing for drug resistance, genotyping, ADA and IFN-γ fluid testing for extrapulmonary TB, and serum protein biomarker panels. These are listed as not meeting coverage criteria due to insufficient published evidence supporting their clinical utility.

WHO and the policy both state that IGRAs should not be used to diagnose active TB disease; IGRAs are inadequate to reliably rule in or rule out active TB and therefore are reserved for testing for latent infection rather than for diagnosing active disease.

Guidelines recommend against testing persons at low risk for M. tuberculosis infection and progression. USPSTF/ATS/IDSA/CDC and related guidance advise that testing for latent TB infection should be limited to persons at increased risk rather than applied universally to low-risk populations.

Because direct probe testing has been removed, the policy no longer permits claims that rely on performing two different NAAT types based on direct probe availability (previously reflected in CC9). Such claims are not supported and may be denied.

Applicable Procedure Codes and Coding Changes

Applicable CPT/HCPCS Procedure Codesmixed

No codes listed

Applicable CPT Codes (part 1)CPT

81099	Unlisted urinalysis procedure.
81425	Genome (e.g., unexplained constitutional or heritable disorder or syndrome); sequence analysis.
81426	Genome (e.g., unexplained constitutional or heritable disorder or syndrome); sequence analysis, each comparator genome (e.g., parents, siblings) (List separately in addition to code for primary procedure).
81479	Unlisted molecular pathology procedure.
82945	Glucose, body fluid, other than blood.
83520	Immunoassay for analyte other than infectious agent antibody or infectious agent antigen; quantitative, not otherwise specified.
83615	Lactate dehydrogenase (LD), (LDH).
84157	Protein, total, except by refractometry; other source (e.g., synovial fluid, cerebrospinal fluid).
84311	Spectrophotometry, analyte not elsewhere specified.
86480	Tuberculosis test, cell mediated immunity antigen response measurement; gamma interferon.

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Applicable CPT Codes (part 2)CPT

87153	Culture, typing; identification by nucleic acid sequencing method, each isolate (e.g., sequencing of the 16S rRNA gene).
87181	Susceptibility studies, antimicrobial agent; agar dilution method, per agent (e.g., antibiotic gradient strip).
87184	Susceptibility studies, antimicrobial agent; disk method, per plate (12 or fewer agents).
87185	Susceptibility studies, antimicrobial agent; enzyme detection (e.g., beta lactamase), per enzyme.
87186	Susceptibility studies, antimicrobial agent; microdilution or agar dilution (minimum inhibitory concentration [MIC] or breakpoint), each multi- antimicrobial, per plate.
87187	Susceptibility studies, antimicrobial agent; microdilution or agar dilution, minimum lethal concentration (MLC), each plate (List separately in addition to code for primary procedure).
87188	Susceptibility studies, antimicrobial agent; macrobroth dilution method, each agent.
87190	Susceptibility studies, antimicrobial agent; mycobacteria, proportion method, each agent.
87206	Smear, primary source with interpretation; fluorescent and/or acid-fast stain for bacteria, fungi, parasites, viruses, or cell types.

Applicable CPT/HCPCS Codes (part 3)CPT/HCPCS

87551	Infectious agent detection by nucleic acid (DNA or RNA); Mycobacteria species, amplified probe technique.
87552	Infectious agent detection by nucleic acid (DNA or RNA); Mycobacteria species, quantification.
87556	Infectious agent detection by nucleic acid (DNA or RNA); Mycobacteria tuberculosis, amplified probe technique.
87557	Infectious agent detection by nucleic acid (DNA or RNA); Mycobacteria tuberculosis, quantification.
87561	Infectious agent detection by nucleic acid (DNA or RNA); mycobacteria avium-intracellulare, amplified probe technique.
87562	Infectious agent detection by nucleic acid (DNA or RNA); mycobacteria avium-intracellulare, quantification.
87564	Infectious agent detection by nucleic acid (DNA or RNA); Mycobacterium tuberculosis, rifampin resistance, amplified probe technique.
0574U	Mycobacterium tuberculosis, culture filtrate protein-10-kDa (CFP-10), serum or plasma, liquid chromatography mass spectrometry (LC-MS) Proprietary test: NanoDetect-TB™.

Policy coding changes (added and removed)CPT

0574U	CPT code added (effective 7/1/2025)
87564	CPT code added (effective 1/1/2025)
87149	CPT code removed
87550	CPT code removed
87555	CPT code removed
87560	CPT code removed

Provider Actions, Documentation, and Billing Notes

Prior Authorization

Coverage Contingent on Clinical Criteria

Coverage for TB diagnostic tests is conditional on meeting the clinical criteria outlined in this policy (for example: IGRA for individuals at risk or when screening is legally required; molecular testing and molecular-based DST when indicated by risk factors or positive AFB/NAAT). Verify individual member benefits at time of request.

Coverage contingent on clinical criteria (IGRA, NAAT, molecular DST)

Note

Prior Authorization

No specific prior authorization (PA) program/requirements are stated within the provided excerpts of this policy. Providers should confirm PA requirements with Medical Mutual prior to ordering when uncertain.

No PA specified in excerpts — verify with Medical Mutual for member-specific requirements

Background and Definitions

Mycobacterium tuberculosis infection ranges from asymptomatic latent infection to active pulmonary and extrapulmonary disease. The policy reiterates that culture (liquid and solid) is the diagnostic reference standard with the highest sensitivity and remains necessary for full drug susceptibility testing, while smear microscopy provides rapid initial information and NAAT offers rapid organism detection and some resistance markers but does not replace culture. For extrapulmonary disease, appropriate fluid studies and microbiologic/histopathologic testing are recommended.

inv-51: IGRA — Interferon gamma release assay (IGRA)

DefinitionInterferon gamma release assay (IGRA): blood tests measuring T-cell release of interferon-gamma in response to M. tuberculosis antigens, used to detect latent TB infection.

Primary useScreening for latent tuberculosis infection (LTBI) in individuals at increased risk or when screening is legally required.

Not for active TB diagnosisIGRAs should not be used to diagnose active tuberculosis; they are inadequate to rule in or rule out active disease.

Age considerationsGuidelines often prefer IGRA over TST in individuals ≥5 years, especially if prior BCG vaccination or inability to return for TST reading.

Policy Summary

Payermedical mutual - ohio

PolicyTesting for Diagnosis of Active or Latent Tuberculosis

Policy CodePolicy AHS - G2063

Change TypeMaterial updates to coverage criteria and coding

Effective DateFeb 1, 2026

Next Review DateSep 4, 2025

Key ActionUse updated qualitative NAAT nomenclature and verify coverage/PA for listed CPT/HCPCS codes when submitting claims.

SourceLink

On This Page

Denial Risk

Denial Risk for Non-Covered Tests

Tests explicitly listed as NOT meeting coverage criteria (e.g., quantitative NAAT, whole genome sequencing, genotyping, ADA/IFN-γ fluid testing, certain serum biomarker panels) are at heightened risk for denial when billed. Do not submit claims for these tests without documented medical necessity and prior authorization if applicable.

Denial risk for non-covered tests: quantitative NAAT, WGS, genotyping, ADA/IFN-γ fluid testing, serum biomarker panels

Documentation Required

Clinical and Public Health Reporting Documentation

Microbiologic test results and positive culture isolates are reportable and should be documented and submitted to public health authorities per jurisdictional requirements. Interpret laboratory results in the context of clinical signs, exposure history, and radiographic findings.

Report positive M. tuberculosis cultures to public health; document clinical correlation with lab results

Documentation Required

Specimen Testing and Documentation

Submit appropriate specimens for AFB smear, rapid molecular (NAAT) testing, mycobacterial culture, species identification, and drug susceptibility testing to quality-assured laboratories. Use both liquid and solid cultures when indicated to optimize sensitivity.

Specimen testing and documentation: AFB smear, NAAT, liquid and solid culture, species ID, DST in quality-assured labs

Note

Diagnostic Testing Sequence

Follow an algorithmic diagnostic testing sequence: perform AFB smear for rapid screening, submit multiple sputum specimens (including first morning specimens) to improve sensitivity, perform culture (gold standard) and NAAT for rapid identification and detection of resistance markers to guide therapy.

Diagnostic testing sequence: smear → NAAT (adjunct) → culture (reference standard); collect ≥3 specimens when possible

Documentation Required

Pre-biologic Therapy TB Screening

Prior to initiating immunosuppressive or biologic therapies (e.g., TNF-α inhibitors), screen for latent TB infection and consider delaying therapy until evaluation and appropriate prophylaxis are completed. Document screening results and any prophylactic treatment decisions in the medical record.

Pre-biologic therapy TB screening — screen for LTBI before starting immunosuppressive/biologic agents; delay therapy when indicated

inv-53: NAAT — Nucleic acid amplification techniques

DefinitionNucleic acid amplification techniques (NAAT) (e.g., MTD, Xpert MTB/RIF, Xpert Ultra, Truenat) for rapid detection of Mycobacterium tuberculosis and some resistance markers.

PerformanceReported NAAT sensitivity ~96% and specificity ~99%; >95% PPV when AFB smear-positive and can detect TB in 50-80% of smear-negative specimens.

Clinical roleRecommended as rapid initial tests in many scenarios (WHO/NICE); NAATs complement but do not replace culture for definitive species ID and full DST.

inv-54: Culture (liquid and solid)

DefinitionCulture (liquid and solid): microbiologic growth of M. tuberculosis; reference standard for TB diagnosis with higher sensitivity for liquid media and longer time-to-detection for solid media.

Performance and timingLiquid culture sensitivity 81.5–85.8% with average detection 13.2–15.2 days; solid media sensitivity ~76% with average detection ~25.8 days; combined methods increase sensitivity to ~87.7–89.7%.

Public health requirementPositive M. tuberculosis cultures should be identified per CLSI/ASM guidance and submitted to public health jurisdictions for confirmation and DST.

inv-55: ADA and IFN-γ in body fluids

DefinitionAdenosine deaminase (ADA) and interferon-gamma (IFN-γ) levels in cerebrospinal, pleural, peritoneal, and pericardial fluids have been studied as biomarkers for extrapulmonary TB diagnosis.

Test characteristicsReported ADA sensitivity ~79% and specificity ~83%; IFN-γ sensitivity ~89% and specificity ~97% in relevant fluids.

Diagnostic limitationNeither ADA nor IFN-γ levels alone provide a definitive diagnosis of TB disease and should be interpreted with other clinical and laboratory data.

inv-56: NAAT/rapid molecular tests

DefinitionNAAT/rapid molecular tests (e.g., Xpert, Xpert Ultra, Truenat, LPAs) used for rapid detection of M. tuberculosis and some resistance markers; recommended as initial tests in certain clinical scenarios but should complement, not replace, culture for full DST.

Use for resistanceXpert/Xpert Ultra and Truenat may provide rapid rifampin (and in some contexts isoniazid) resistance information to guide initial treatment decisions.

LimitationsMolecular resistance tests may miss some mutations; positive molecular rifampin resistance in low-prevalence settings should be confirmed by a second molecular test or phenotypic DST; culture-based DST remains necessary for many agents.

inv-57: LF-LAM — Lateral flow urine lipoarabinomannan assay

DefinitionLF-LAM (lateral flow urine lipoarabinomannan assay): a point-of-care urine test to assist diagnosis of active TB in certain HIV-positive populations.

WHO recommendations - inpatientStrongly recommended in HIV-positive inpatients with TB symptoms or who are seriously ill, and for those with advanced HIV or CD4 <200 cells/mm3.

WHO recommendations - outpatientSuggested for selected HIV-positive outpatients with TB symptoms or CD4 <100 cells/mm3; not recommended for HIV-positive persons without TB symptoms or with higher/unknown CD4 counts in most outpatient scenarios.

inv-58: Phenotypic DST

DefinitionPhenotypic drug susceptibility testing (culture-based DST): culture-based methods to determine antimicrobial susceptibility, regarded as the gold standard for many drugs.

Discordance with molecular methodsMolecular and phenotypic DST results can discord; some molecular tests do not cover all resistance-conferring mutations, so phenotypic confirmation remains important.

Guidance on useWhen rifampin resistance is detected molecularly, additional phenotypic and molecular DST for first- and second-line agents should be obtained to guide therapy.

inv-59: WGS limitations

DefinitionWhole genome sequencing (WGS) provides the complete genome sequence of M. tuberculosis isolates but many detected mutations lack validated correlation with phenotypic resistance or clinical outcomes.

Interpretation limitationBecause most mutations currently cannot be reliably interpreted for clinical decision-making, WGS cannot fully replace phenotypic DST for many drugs.

Role in practiceWGS can help rule-in resistance for some mutations but results often require confirmation and expert interpretation; it is not sufficient alone for many treatment decisions.

inv-60: NAAT (rapid)

DefinitionRapid NAATs for M. tuberculosis complex and rifampin resistance (e.g., Xpert, Xpert Ultra, Truenat) are used on primary specimens when results would alter clinical care or when MDR-TB risk exists.

When to orderRequest rapid NAAT when clinical suspicion exists and the person has HIV, rapid species info would alter care, or large contact-tracing is needed; order rifampin-resistance testing when MDR risk factors are present.

Adjunct to cultureNAAT should be used while culture is pending and must not replace culture for species identification and full DST; laboratories must validate non–FDA-cleared NAATs.

inv-61: Qualitative NAAT

DefinitionQualitative NAAT: nucleic acid amplification testing specified as qualitative assays for Mycobacteria spp., M. tuberculosis, and M. avium complex after removal of direct probe testing.

Policy change noteRevision removed direct probe testing and designated qualitative NAAT as the covered NAAT category (CC2.c); former direct-probe pathways were eliminated.

Organism nomenclaturePolicy updated organism naming to use 'M. avium complex' in place of older terminology (e.g., M. avium intracellulare).