ModifiedBlue Cross Blue Shield - LouisianaPolicy AHS - G2063

Testing for Diagnosis of Active or Latent Tuberculosis

Defines coverage criteria for laboratory and diagnostic testing used to detect active tuberculosis disease and latent tuberculosis infection (LTBI) for Blue Cross and Blue Shield of Louisiana members.

Policy Summary

PayerBlue Cross Blue Shield - Louisiana

PolicyTesting for Diagnosis of Active or Latent Tuberculosis

Policy CodePolicy AHS - G2063

Change TypeCoverage revisions and coding updates (removals and one addition)

Effective DateFeb 1, 2026

Next Review DateN/A

Key ActionDo not submit direct probe tests or the removed CPT codes; use current NAAT methods and document specimens and tests (including culture and NAAT) per policy.

SourceLink

POLICY UPDATE CHANGES

Direct probe testing is no longer available, resulting in removal of CC3 and reclassification of qualitative NAAT testing to CC2.c.

Removed CPT codes 87149, 87550, 87555, and 87560.

Added CPT code 0574U (off-cycle coding modification).

Replaced specific 'Hologic Amplified MTD' language with the broader term 'NAAT' in former CC4 (now CC3).

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

3specimens recommended

≥95%IGRA specificity

71%-82%TST sensitivity

Trek Health ingests and normalizes Transparency in Coverage data and payer policy updates to give provider organizations a clear view of how commercial reimbursement behaves across markets, payers, and services. Our platform transforms raw payer disclosures into structured intelligence that supports contract evaluation, payer negotiations, and service line strategy. By combining market benchmarks with ongoing policy visibility, Trek helps teams identify variability, risk, and opportunity in commercial reimbursement. The result is faster insight, stronger negotiating positions, and more informed financial decisions.

96% / 99%NAAT performance

Coverage Criteria

IGRA for LTBI screening

IGRA testing meets coverage criteria in the following circumstances:

IGRA meets coverage: IGRA MEETS COVERAGE CRITERIA when used to diagnose or screen for latent tuberculosis infection (LTBI) in: (a) individuals who are at risk for infection with Mycobacterium tuberculosis; OR (b) individuals who are unlikely to be infected with M. tuberculosis when screening is obliged by law or credentialing requirements.

Testing should be limited to persons who would benefit from treatment if positive; IGRA is not covered for diagnosis of active TB (see exclusions).

Tests that meet coverage criteria for suspected active TB

For suspected active tuberculosis, the following tests meet coverage criteria:

Active TB diagnostic tests covered: AFB smear/stain AND mycobacterial culture with culture-based drug susceptibility testing AND qualitative NAAT for Mycobacteria spp., M. tuberculosis, and M. avium complex MEET COVERAGE CRITERIA for evaluation of suspected active TB.

Culture is the microbiologic gold standard; NAAT complements smear and culture and must be interpreted with smear while culture is pending.

Molecular-based drug susceptibility testing coverage conditions

Molecular-based drug susceptibility testing meets coverage criteria when the individual is AFB smear positive or NAAT positive AND one of the listed risk conditions is met:

When molecular DST meets coverage: Individual is AFB smear positive OR NAAT positive; AND one or more of the following risk conditions are present:

Molecular DST is targeted to higher-risk scenarios.

Risk conditions for molecular DST: (a) prior treatment for TB; (b) born in or has lived ≥1 year in a foreign country with TB incidence ≥20 per 100,000 or with MDR-TB prevalence ≥2%; (c) contact of an individual with MDR-TB; (d) HIV infection.

Apply molecular DST (eg, rapid rifampin/isoniazid resistance assays) to inform initial therapy when criteria met.

Repeat drug susceptibility testing

Repeat DST meets coverage criteria in the following situations:

Indications for repeat DST: (a) Sputum cultures remain positive after 3 months of treatment; OR (b) Bacteriological reversion from negative to positive (culture conversion to relapse).

Repeat testing permits detection of acquired resistance or treatment failure and guides regimen changes.

Fluid testing in extrapulmonary disease

For suspected extrapulmonary TB with effusions or ascites, the following meet coverage criteria:

Fluid analysis covered: Cell counts AND protein AND glucose AND lactate dehydrogenase (LDH) concentrations measured on cerebrospinal, pleural, peritoneal, pericardial, and other relevant body fluids MEET COVERAGE CRITERIA when used in the evaluation of suspected extrapulmonary TB (eg, pleural effusion, pericardial effusion, ascites).

Policy excludes certain advanced fluid biomarkers (eg, ADA and IFN-γ in fluids are discussed elsewhere in guidance/exclusions).

Urine LAM testing in HIV-infected patients

Urine LAM meets coverage criteria in a limited HIV population:

Urine LAM covered: Urine-based detection of mycobacterial lipoarabinomannan (LAM) MEETS COVERAGE CRITERIA for HIV-infected individuals who have signs and symptoms of tuberculosis and a CD4 cell count ≤100 cells/microL.CD4 <=100 cells/microL

WHO guidance supports LF-LAM use primarily in hospitalized or seriously ill HIV-positive patients and recommends against use in asymptomatic persons or those with higher CD4 counts.

Covered diagnostic criteria and recommended test roles

Covered diagnostic approaches and when they are recommended (per cited public health guidance):

Complete clinical evaluation: All persons with signs/symptoms of TB disease or a positive IGRA/TST should receive a complete medical evaluation that includes: medical history, physical examination, test for TB infection (IGRA or TST), chest radiograph, and bacteriologic examination (smear microscopy, NAAT, culture, and drug susceptibility testing).

CDC-recommended five-component evaluation; culture is the gold standard for microbiologic confirmation.

Role of culture and NAAT: Culture is the diagnostic gold standard and required for isolate submission and phenotypic DST; rapid molecular NAATs (eg, Xpert MTB/RIF or Xpert Ultra) are recommended as initial diagnostic tests for symptomatic pulmonary TB and for many extrapulmonary specimens, with use tailored to clinical context and prior TB history.

WHO recommendations support NAAT as an initial test in many settings.

Smear microscopy: Perform smear microscopy (minimum two sputum specimens) as part of the diagnostic algorithm; LED fluorescence microscopy is preferred where available to increase sensitivity.

Coverage criteria from cited guidelines

Coverage aligned with clinical guidance: tests supported when clinical or risk-based indications exist.

Initial testing for suspected pulmonary TB: Perform AFB smear microscopy AND NAAT on the initial respiratory specimen; submit specimens for both liquid and solid mycobacterial culture; request rapid molecular DST for rifampin (and isoniazid when available) for patients who meet risk criteria.

Reflects ATS/IDSA/CDC, WHO, and NICE recommendations to combine rapid molecular testing with smear and culture.

Use of LPAs: Use first-line LPAs for detection of rifampicin and isoniazid resistance directly on smear-positive sputum or on cultured isolates; use SL-LPA for confirmed MDR/RR-TB to detect fluoroquinolone and second-line injectable resistance, recognizing LPAs do not obviate the need for culture-based DST for other agents.

WHO conditional recommendations and remarks.

LF-LAM use criteria: Use lateral-flow urine LAM to assist diagnosis of active TB in hospitalized or seriously ill HIV-positive patients with signs/symptoms of TB, and selectively in outpatients with low CD4 counts; do NOT use LF-LAM in HIV-positive persons without TB symptoms or with higher CD4 counts per WHO.

Diagnostic and screening coverage criteria

Covered testing and clinical approach when TB infection or disease is suspected

Pulmonary TB specimen submission: For persons capable of producing sputum suspected of pulmonary TB: submit at least two sputum specimens for microscopic examination and at least one specimen for rapid molecular testing for TB identification and drug resistance; send specimens for liquid culture and, if positive, perform culture-based DST in a quality-assured laboratory.

NICE recommends two+ sputum for microscopy and one for rapid molecular testing.

Extrapulmonary TB specimen submission: For presumed extrapulmonary TB, obtain appropriate specimens from suspected sites for microbiological testing (smear, NAAT, culture, species identification, DST) and for histopathology in quality-assured laboratories.

NICE guidance emphasizes site-appropriate specimen collection.

LTBI test selection: IGRAs are generally preferred for most non–US-born persons and in those with prior BCG vaccination; TST remains acceptable and test choice should consider age, availability, cost, and ability to return for reading.

NSTC/NTCA recommendations support IGRA preference in many non–US-born individuals.

Revised Criteria Overview

Summary of revisions to coverage criteria from the 02/01/2026 review:

CC structure revision: Direct probe testing has been removed (no longer available); qualitative NAAT testing for Mycobacteria spp., M. tuberculosis, and M. avium complex is recorded as CC2.c. Proprietary 'Hologic Amplified MTD' language was replaced with the broader term 'NAAT.' CC9 was removed because, with removal of direct probes, there is no scenario permitting two types of NAAT. Several CPT codes were removed and CPT 0574U was added per coding updates.

Operational and coding changes summarized; full criteria text remains in policy sections cited elsewhere.

The policy lists several advanced or quantitative laboratory methods as not meeting coverage criteria due to insufficient published evidence. Specifically, quantitative nucleic acid testing (quantitative NAAT) for Mycobacterium spp., M. tuberculosis, and M. avium complex is identified as does not meet coverage criteria. Also listed as not meeting coverage are whole genome sequencing (WGS) of Mycobacterium spp. for detection of drug resistance, genotyping of Mycobacterium spp., and measurements of adenosine deaminase (ADA) and interferon-gamma (IFN-γ) levels in cerebrospinal, pleural, peritoneal, pericardial, and other fluids for extrapulmonary TB diagnosis. The policy additionally states that serum protein biomarker panels for TB detection are not covered.

The World Health Organization recommendation is summarized in the policy: commercial serodiagnostic (serological) tests should not be used to diagnose pulmonary or extrapulmonary TB. The rationale is that currently available commercial serologic assays provide inconsistent and imprecise findings, produce high proportions of false-positive and false-negative results, and there is no evidence they improve patient outcomes; therefore their use may harm patients through misdiagnosis.

The policy reflects guideline-based limitations on line probe assays and LF-LAM. For LPAs, WHO guidance allows their use as initial tests for sputum smear–positive specimens or cultured isolates to detect rifampicin and isoniazid resistance, but explicitly states that LPAs are not recommended for direct testing of sputum smear–negative specimens and do not eliminate the need for conventional culture-based drug susceptibility testing. For the lateral-flow urine lipoarabinomannan assay (LF-LAM), WHO strongly recommends LF-LAM to assist diagnosis of active TB in hospitalized HIV-positive persons with TB symptoms or who are seriously ill and provides conditional recommendations for selected outpatient use; conversely, WHO recommends against LF-LAM use in HIV-positive persons without assessment of TB symptoms or with higher/unknown CD4 counts.

When this policy conflicts with an applicable government coverage determination, the policy defers to the government policy. Specifically, if there is a conflict with Local Coverage Determinations (LCDs), National Coverage Determinations (NCDs), or state Medicaid rules, the government policy will be used to make the determination for the affected member.

The policy documents an operational change: direct probe testing is no longer available. As a result, the former direct-probe category was removed and related CPT codes were deleted; providers should not submit claims for removed direct-probe CPT codes. The revision also instructs providers and coders to align documentation and billing with currently allowed NAAT methods rather than legacy direct-probe terminology.

The policy states that IGRA is not covered for the diagnosis of active tuberculosis. In addition, the policy lists certain advanced or experimental tests as not covered, including quantitative NAAT, whole genome sequencing, genotyping, ADA/IFN-γ testing in fluids, and serum protein biomarker panels for detection or diagnosis of TB.

WHO guidance, as cited in the policy, emphasizes that IGRAs are inadequate as rule-in or rule-out tests for active TB. The WHO states there is no consistent evidence that IGRAs are more sensitive than TST for active disease and that studies show IGRAs add no meaningful diagnostic value beyond conventional microbiological tests; therefore, IGRAs should not be used to diagnose active TB disease.

The policy restricts LF-LAM use to populations and settings supported by WHO. LF-LAM is strongly recommended to assist diagnosis of active TB in hospitalized HIV-positive adults, adolescents, and children with TB symptoms or who are seriously ill, and is suggested selectively for outpatients with signs of TB or very low CD4 counts. The policy specifies that LF-LAM should not be used in HIV-positive persons without assessment of TB symptoms or with higher/unknown CD4 counts.

The policy removed the prior CC9 allowance that had permitted scenarios requiring two different NAAT methods. With the removal of direct probe testing, the policy notes there is no situation in which two types of NAAT would be permitted, and thus the CC9 scenarios have been eliminated.

Coding

No explicit billing codes in this excerptmixed

No codes listed

Miscellaneous laboratory procedure codesCPT

81099	Unlisted urinalysis 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.

Culture and susceptibility CPT codesCPTCovered

86480	Tuberculosis test, cell mediated immunity antigen response measurement; gamma interferon.
86481	Tuberculosis test, cell mediated immunity antigen response measurement; enumeration of gamma interferon-producing T-cells in cell suspension.
87070	Culture, bacterial; any other source except urine, blood, or stool, aerobic, with isolation and presumptive identification of isolates.
87077	Culture, bacterial; aerobic isolate, additional methods required for definitive identification, each isolate.
87116	Culture, tubercle, or other acid-fast bacilli (e.g., TB, AFB, mycobacteria) any source, with isolation and presumptive identification of isolates.
87150	Culture, typing; identification by nucleic acid (DNA or RNA) probe, amplified probe technique, per culture or isolate, each organism probed.
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.
87184	Susceptibility studies, antimicrobial agent; disk method, per plate.
87185	Susceptibility studies, antimicrobial agent; enzyme detection (e.g., beta lactamase), per enzyme.

1–10 of 13

1/2

NAAT, smear, and specialized TB test codesmixedCovered

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.
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™.

Coding guidancemixed

No codes listed

Added CPT CodesCPT

0574U

CPT code added (off-cycle modification)

Removed CPT CodesCPTNot Covered

87149	CPT code removed
87550	CPT code removed
87555	CPT code removed
87560	CPT code removed

Provider Actions and Operational Notes

Denial Risk

Non-covered tests may be denied

Non-covered tests listed in the policy (for example: quantitative NAAT, whole genome sequencing, genotyping, ADA/IFN-γ testing, and other assays explicitly stated as DOES NOT MEET COVERAGE CRITERIA) may be denied by the payer. Providers should order only tests that meet coverage criteria and document clinical necessity when requesting covered diagnostics.

Tests explicitly listed as DOES NOT MEET COVERAGE CRITERIA are subject to denial

Documentation Required

Complete clinical evaluation expected

A complete clinical evaluation for suspected TB is expected and is a prerequisite for appropriate coverage of diagnostic testing. The CDC-defined five-component evaluation should be performed and documented: 1) medical history, 2) physical examination, 3) test for TB infection (TST or IGRA), 4) chest radiograph, and 5) bacteriologic examination (sputum smear microscopy, NAAT, culture, and DST). Failure to complete and document this evaluation may lead to non-coverage of testing.

Background

Mycobacterium tuberculosis infection exists on a spectrum from asymptomatic latent infection to active pulmonary or extrapulmonary disease. The policy reiterates that culture is the diagnostic gold standard for confirmation, species identification, and phenotypic drug susceptibility testing. Rapid molecular tests (NAATs) provide timely identification of M. tuberculosis complex and can detect key resistance markers (for example, rifampin), but results should be interpreted alongside AFB smear microscopy and culture while culture remains pending.

Definitions

IGRA — definition and test description

DefinitionInterferon-gamma release assay (IGRA): blood tests that measure IFN-γ production by T‑cells after stimulation with M. tuberculosis–specific antigens (e.g., QuantiFERON, T‑SPOT).

Intended useDesigned as an aid to detect latent Mycobacterium tuberculosis infection (LTBI); FDA-cleared QuantiFERON assays are indicated for LTBI detection, not for diagnosing active TB disease.

MethodologyMeasures IFN‑γ concentration (ELISA) or enumerates IFN‑γ–secreting T cells (ELISPOT) after antigen stimulation (ESAT‑6, CFP‑10).

Clinical limitationIGRAs cannot distinguish latent infection from active TB and are inadequate alone to rule in or rule out active TB disease; they are used primarily for LTBI screening.

AFB smear — definition and characteristics

Definition

Revision History

2026-02-01criteria_revisionLatest

Reviewed and updated background, guidelines, and evidence references; removed direct probe testing, reclassified qualitative NAAT as CC2.c, renamed former CC4 to CC3 replacing proprietary 'Hologic Amplified MTD' with 'NAAT', and removed CC9 as redundant.

2025-07-01coding_update

Off-cycle coding modification added CPT code 0574U.

2025-01-01

Policy Summary

PayerBlue Cross Blue Shield - Louisiana

PolicyTesting for Diagnosis of Active or Latent Tuberculosis

Policy CodePolicy AHS - G2063

Change TypeCoverage revisions and coding updates (removals and one addition)

Effective DateFeb 1, 2026

Next Review DateN/A

Key ActionDo not submit direct probe tests or the removed CPT codes; use current NAAT methods and document specimens and tests (including culture and NAAT) per policy.

SourceLink

On This Page

WHO/NICE guidance supports smear microscopy alongside NAAT and culture.

LTBI testing roles: Either TST or IGRA may be used for LTBI testing depending on age, BCG history, access, and ability to return; IGRAs are generally preferred in persons ≥5 years old in many scenarios (eg, prior BCG, non–US-born), while TST is suggested for some young children (<5 years).age-based

NTCA/NSTC and WHO guidance inform test selection.

Genotypic and phenotypic DST roles: LPAs and sequence-based assays can detect key resistance mutations and guide regimens; LPAs are recommended for direct testing of smear-positive specimens or cultured isolates but do not replace culture-based DST for other agents; WGS may help detect resistance but phenotypic DST remains necessary for confirmation for some drugs.

WHO guidance clarifies limitations and need for phenotypic DST for certain agents.

CD4 thresholds noted in guidance

WHO strong recommendations detail inpatient and outpatient thresholds.

LTBI testing preferences: Prefer IGRA over TST for individuals ≥5 years old in many scenarios (eg, prior BCG vaccination or inability to return); prefer TST in children <5 years when indicated; consider dual testing or two-step approaches in specific high-risk or serial-testing contexts.age-based

Guidance from ATS/IDSA/CDC, NTCA/NSTC, and pediatric recommendations.

Specimen handling for extrapulmonary TB: Obtain appropriate site-specific specimens for microscopy, NAAT, culture, and histopathology for suspected extrapulmonary TB; perform fluid chemistries and consider ADA/IFN-γ measurements where guideline-supported.

NICE and WHO recommend targeted specimen collection and testing in quality-assured labs.

Dual and serial testing: Dual testing (TST + IGRA) may be considered in immunocompromised patients or when concern exists about immune response; serial testing programs may use either IGRA or TST, with two-step TST required when TST is used for baseline.

NSTC/NTCA guidance on serial testing; IGRAs do not cause boosting.

Pre-biologic therapy screening: Screen all patients for latent TB infection prior to initiating TNF-α inhibitors or other immunosuppressive therapies; delay immunologic therapy until LTBI prophylaxis is completed when possible, or consider starting therapy after 1–2 months of prophylaxis if clinically necessary.

National Psoriasis Foundation guidance informs timing relative to biologic therapy.

Document each of the five CDC-required components of the TB medical evaluation

Note

Government policy precedence

When federal or state government policies (e.g., LCDs, NCDs, or state Medicaid rules) conflict with this policy, the applicable government policy takes precedence and will be used for coverage determinations. Providers should verify Medicare and Medicaid requirements for the member at the time of service.

If conflict exists, follow LCD/NCD/state Medicaid policy
Check CMS and state Medicaid resources for the latest guidance

Billing Rule

Coding-based denial risk

Use current, supported CPT/HCPCS codes. Use of removed or deprecated tests and coding (for example, direct probe methods and deleted CPT codes) may result in claim denials. Align laboratory test method documentation (e.g., current NAAT methods vs. discontinued direct probe assays) with submitted codes to reduce coding-based denial risk.

Avoid using deleted codes (see Review/Revision History)
Document the specific molecular method used (not 'direct probe' where removed)

Documentation Required

Specimen and reporting expectations

Submit appropriate specimens and report results to public health as required. Culture isolates identified as M. tuberculosis must be submitted to public health laboratories for confirmation and DST per jurisdictional requirements. Report positive cultures to public health authorities for case management.

Submit M. tuberculosis culture isolates to public health for confirmation and DST
Report positive cultures to public health authorities

Documentation Required

Required clinical and laboratory documentation

Ensure required clinical and laboratory documentation accompanies test orders and claims. Expected documentation includes clinical signs/symptoms, TB exposure or risk factors, prior TB treatment history, relevant immunosuppression status (e.g., HIV, planned biologic therapy), and the rationale for molecular DST when requested.

Document symptoms, exposure history, and prior TB treatment
Document HIV status and other immunosuppressive conditions when relevant
Provide rationale for molecular DST requests

Documentation Required

Specimen submission requirements

When pulmonary TB is suspected, submit at least two sputum specimens for microscopy and one specimen for rapid molecular testing (NAAT). For extrapulmonary disease, collect appropriate site-specific specimens for microscopy, NAAT, culture, species identification, and DST. Failure to submit recommended specimens may affect coverage.

At least two sputum specimens for microscopy and one for NAAT when pulmonary TB suspected
Obtain appropriate specimens from suspected extrapulmonary sites for microbiology and histopathology

Note

Testing algorithm relationship

NAAT should be used as part of an integrated testing algorithm with AFB smear and culture. Interpret NAAT results together with smear microscopy while awaiting culture; NAAT does not replace smear or culture but provides rapid detection and can guide early management decisions.

Use NAAT in conjunction with smear and culture; await culture for confirmation
Xpert/Xpert Ultra recommendations per WHO for initial diagnostic testing in many settings

Prior Authorization

Reflex resistance testing

When rifampin resistance is detected by a rapid molecular method, obtain additional molecular and phenotypic DST immediately for first-line drugs, fluoroquinolones, and aminoglycosides/amikacin/kanamycin/capreomycin as indicated. Repeat DST is indicated for persistent culture positivity or bacteriological reversion to positive.

Perform reflex molecular and culture-based DST immediately when rifampin resistance is detected
Repeat DST if sputum cultures remain positive after 3 months or if bacteriological reversion occurs

Note

Pre-immunosuppression TB screening

Screen patients for latent TB infection prior to initiating immunosuppressive or biologic therapy. Delay immunologic therapy until latent TB prophylaxis is completed when possible; if therapy must begin, coordinate with prophylactic treatment per specialty guidance and document timing and rationale.

Screen for LTBI before starting TNF-α inhibitors and other immunosuppressives
Prefer delaying immunologic therapy until LTBI prophylaxis completed; if not feasible, document prophylaxis and monitoring plan

Acid‑fast bacilli (AFB) smear/stain: a rapid microscopic technique to detect mycobacteria in clinical specimens using acid‑fast staining methods (e.g., Ziehl‑Neelsen or fluorescent stains).

RoleProvides rapid presumptive evidence of mycobacterial infection and informs initial infection control decisions; does not identify species or drug resistance.

Performance characteristicFaster but less sensitive than culture; used alongside NAAT and culture for diagnostic evaluation of suspected pulmonary TB.

Xpert MTB/RIF — description and rifampin-resistance detection

DescriptionXpert MTB/RIF: a qualitative, nested real‑time PCR assay on the GeneXpert platform that detects Mycobacterium tuberculosis complex DNA in sputum and related specimens.

Resistance detectionSimultaneously detects rifampin‑resistance–associated mutations in the rpoB gene, providing rapid molecular rifampin resistance information to guide management.

Recommended useWHO recommends Xpert MTB/RIF or Xpert Ultra as an initial diagnostic test for many patients with signs/symptoms of pulmonary or certain extrapulmonary TB presentations.

Culture (gold standard) — role in confirmation and phenotypic DST

DefinitionCulture (gold standard): isolation of Mycobacterium tuberculosis from clinical specimens for confirmation, species identification, and phenotypic drug susceptibility testing (pDST).

Role in confirmationPositive cultures confirm M. tuberculosis infection and are reportable to public health authorities; jurisdictions require submission of isolates for confirmation and DST.

Phenotypic DSTCulture isolates are used for conventional phenotypic DST to determine susceptibility to anti‑TB agents and to monitor emergence of additional resistance; pDST remains necessary for some drugs even when molecular tests are used.

Xpert MTB/RIF / Xpert Ultra — WHO‑recommended initial molecular assays

AssaysXpert MTB/RIF and Xpert Ultra are nucleic acid amplification tests (NAATs) recommended by WHO as initial molecular assays for detection of TB and rifampicin resistance in many clinical situations.

IndicationsRecommended as initial diagnostic tests for adults and children with signs/symptoms of pulmonary TB and for specific extrapulmonary specimens (e.g., CSF for TB meningitis).

Operational noteIn some clinical contexts Xpert assays may be used in lieu of smear/culture for immediate clinical decisions when supplementary tests are unavailable or would cause delay.

IGRA / TST — immune‑based tests for infection but inadequate alone for active TB diagnosis

DefinitionIGRA and TST are immune‑based tests used to detect infection with M. tuberculosis (latent infection) by assessing cell‑mediated immune responses.

Use caseBoth tests are used for LTBI screening; either may be used depending on age, BCG history, availability, and local guidance, but neither alone can diagnose active TB.

Limitations for active TBWHO and other guidance note IGRAs (and TST) are inadequate to rule in or rule out active TB disease and should not be used alone to diagnose active TB.

IGRA — recommended contexts and preference statements from guidelines

Preferred contextsIGRA is generally preferred over TST in individuals ≥5 years old who warrant LTBI testing—especially those with prior BCG vaccination or unlikely to return for TST reading.

Children and special casesTST is suggested over IGRA for healthy children <5 years when testing is indicated; dual testing or confirmatory second tests may be considered in selected high‑risk situations.

Serial testingFor serial screening programs, IGRAs do not cause boosting and thus do not require initial two‑step testing; two‑step TST is recommended when TST is used for baseline in serial programs.

LPA — line probe assay definition and typical usage

DefinitionLine probe assay (LPA): a commercial molecular test that detects resistance‑associated mutations (first‑line LPAs for rifampicin and isoniazid; SL‑LPAs for fluoroquinolones and second‑line injectables).

Typical usageLPAs may be used directly on sputum smear‑positive specimens or on cultured isolates to detect resistance and guide initial regimen selection in MDR/RR‑TB cases.

LimitationLPAs are not recommended for direct testing of smear‑negative specimens and do not replace conventional culture‑based DST for all agents.

LF‑LAM — lateral flow urine LAM assay and WHO‑recommended use in hospitalized HIV‑positive patients

DefinitionLateral flow urine lipoarabinomannan assay (LF‑LAM): a point‑of‑care urine test that detects mycobacterial LAM antigen to assist diagnosis of active TB in specific populations.

WHO‑recommended useWHO strongly recommends LF‑LAM to assist diagnosis of active TB in hospitalized HIV‑positive adults, adolescents, and children with TB symptoms or serious illness; selective use is suggested in some outpatient scenarios based on CD4 count and symptoms.

LimitationsWHO recommends against using LF‑LAM in HIV‑positive persons without assessing TB symptoms or in those with higher CD4 counts (e.g., ≥200 cells/mm3) or unknown CD4 without symptoms.

IGRA — restated IGRA definition for preferred testing populations

Restated definitionIGRA: blood‑based assays measuring T‑cell release of IFN‑γ to M. tuberculosis antigens; generally preferred in many adults and in persons with prior BCG vaccination or non‑US birth.

Preference rationaleIGRAs offer greater specificity than TST in persons with prior BCG vaccination or non‑tuberculous mycobacterial exposure and are preferred for most non–US‑born individuals.

Confirmatory testing noteWhen testing individuals 5 years or older who are unlikely to be infected but must be tested by law, IGRA is suggested over TST and a second diagnostic test may be suggested if initial test is positive.

Two‑step TST — definition and recommended scenarios

DefinitionTwo‑step TST: an initial tuberculin skin test followed by a second TST 1–3 weeks later to detect boosting and establish a baseline when serial testing is anticipated.

Recommended scenariosRecommended when serial TST testing is anticipated (e.g., baseline for healthcare personnel) to distinguish boosting from recent conversion.

Operational detailWhen two‑step testing is used, follow timing recommendations relative to live vaccines (wait ≥28 days after live vaccine before TB testing when vaccine given first).

NAAT — definition and replacement of previous 'direct probe' terminology

DefinitionNucleic acid amplification testing (NAAT): molecular methods for detecting Mycobacteria spp. DNA/RNA; replaces prior 'direct probe' terminology in this policy context.

ScopeIncludes assays such as Xpert MTB/RIF, Xpert Ultra, Truenat, and other validated NAATs used for rapid identification of M. tuberculosis and some resistance markers.

Policy implicationQualitative NAAT for Mycobacteria spp., M. tuberculosis, and M. avium complex is placed as a covered category (CC2.c) and direct probe assays have been removed from coverage as they are no longer available.

Reviewed and updated background, guidelines, and references; made clarity edits (verb tense fixes) and added CPT code 87564 without modifying coverage criteria.

2026-02-01coding_removal

Removed CPT codes 87149, 87550, 87555, and 87560 as part of the 02/01/2026 revisions.