CurrentBlue Cross Blue Shield - TennesseePolicy N/A

Testing for Diagnosis of Active or Latent Tuberculosis

Clinical coverage policy for laboratory testing used to diagnose active tuberculosis (TB) disease and screen for latent TB infection (LTBI) for Blue Cross Blue Shield of Tennessee members.

Policy Summary

PayerBlue Cross Blue Shield - Tennessee

PolicyTesting for Diagnosis of Active or Latent Tuberculosis

Policy CodePolicy N/A

Change TypeNo material change indicated

Effective DateN/A

Next Review DateN/A

Key ActionEnsure tests ordered align with listed covered indications to avoid non-coverage.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

CoveredIGRA for LTBI

AFB, culture, NAATCore TB tests

MultipleNot covered tests

Not coveredIGRA for active TB

3Specimens for sensitivity

96%/99%

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.

Coverage Criteria for TB Testing

Evidence References (informational)

Select evidence-based guidelines, consensus statements, and peer-reviewed studies that informed the coverage criteria are listed below for reference and further review.

Lewinsohn DM, et al. (2017). ATS/CDC/ERS/IDSA Clinical Practice Guidelines: diagnostic testing for tuberculosis — recommendations supporting AFB smear, culture, NAAT, and molecular DST.

World Health Organization (WHO). Multiple guidance documents (2015, 2018, 2021) regarding use of Xpert MTB/RIF, Xpert Ultra, Truenat, LPAs, LF-LAM, and recommendations against commercial serodiagnostic tests.

USPSTF (2023). Recommendation on screening for latent TB infection in persons at increased risk — supports targeted LTBI screening.

NTSC/NTCA (2023). Clinical recommendations for testing and treatment of LTBI in the United States — preference for IGRAs in many non–US-born and BCG-vaccinated individuals and guidance on serial/dual testing.

IDSA/ASM (2024). A Guide to Utilization of the Microbiology Laboratory for Diagnosis of Infectious Diseases — guidance on using NAATs as adjuncts to culture and laboratory validation requirements.

ATS/CDC/ERS/IDSA (Nahid et al., 2019). Guidance on molecular DST and repeat susceptibility testing for persistent positive cultures or bacteriologic reversion.

TBNET/RESIST-TB (Domínguez et al., 2016). Consensus on molecular resistance testing, limits of WGS interpretation, and the continued role of phenotypic DST.

NICE (2024). Recommendations for rapid diagnostic NAATs and rifampicin resistance testing and follow-up actions when tests are negative or positive.

Committee on Infectious Diseases, AAP Red Book (2021/2024). Pediatric-specific recommendations on TST vs IGRA by age and testing indications.

Peer-reviewed diagnostic performance studies and systematic reviews (e.g., Greco et al., 2006; Steingart et al., 2006; Mase et al., 2007; Pai et al., 2014) that inform sensitivity, specificity, and specimen handling considerations.

Zürcher K., et al. (2019). Multicentre cohort demonstrating impact of drug susceptibility testing on outcomes in high-burden settings.

Procedure Codes and Coding Notes

Applicable CPT/HCPCS Procedure Codes (section reference)mixed

No codes listed

Listed Laboratory and Test CPT/HCPCS Codes (part 1)CPT

81099	Unlisted urinalysis procedure.
81425	Genome (eg, unexplained constitutional or heritable disorder or syndrome); sequence analysis.
81426	Genome (eg, unexplained constitutional or heritable disorder or syndrome); sequence analysis, each comparator genome (eg, 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 (eg, synovial fluid, cerebrospinal fluid).
84311	Spectrophotometry, analyte not elsewhere specified.
86480	Tuberculosis test, cell mediated immunity antigen response measurement; gamma interferon.

1–10 of 13

1/2

Listed Laboratory and Test CPT/HCPCS Codes (part 2)CPT

87149	Culture, typing; identification by nucleic acid (DNA or RNA) probe, direct probe technique, per culture or isolate, each organism probed.
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 (eg, sequencing of the 16S rRNA gene).
87181	Susceptibility studies, antimicrobial agent; agar dilution method, per agent (eg, antibiotic gradient strip).
87184	Susceptibility studies; disk method, per plate (12 or fewer agents).
87185	Susceptibility studies; enzyme detection (eg, beta lactamase), per enzyme.
87187	Susceptibility studies; microdilution or agar dilution (minimum inhibitory concentration [MIC] or breakpoint), each multi-antimicrobial, per plate.
87188	Susceptibility studies; macrobroth dilution method, each agent.
87190	Susceptibility studies; mycobacteria, proportion method, each agent.
87206	Smear, primary source with interpretation; fluorescent and/or acid fast stain.

1–10 of 16

1/2

No codes in references sectionmixed

No codes listed

inv-31: Foreign country residence risk threshold

Foreign residence thresholdLived ≥1 year in a country with TB incidence ≥20 per 100,000 or with MDR‑TB prevalence ≥2%

Applies to molecular DST coverageThis threshold is a qualifying criterion for molecular-based drug susceptibility testing to MEET coverage when sputum is AFB smear positive or MTD positive

Other qualifying exposuresContact of an individual with MDR‑TB or prior TB treatment also qualify for molecular DST coverage

inv-32: Specimen sensitivity improvement

Recommended number of specimensThree sputum specimens to achieve approximately 70% sensitivity

Provider Actions, Documentation, and Billing Guidance

Denial Risk

Align orders to covered indications — avoid non-coverage

Ensure tests ordered align with covered indications to avoid non-coverage. IGRA is for latent TB screening; NAAT, smear, culture align with covered indications for suspected TB. Ordering IGRA for active TB diagnosis or ordering simultaneous duplicate direct/amplified/quantitative tests for the same organism may trigger denial.

Denial triggers: Ordering IGRA for active TB diagnosis; simultaneous direct probe/amplified/quantitative testing for the same organism; repeating Xpert Ultra after an initial trace positive in adults may be inappropriate and could be denied.

Note

Use of in-home molecular testing

In-home molecular testing (for example, GeneXpert MTB/RIF) can provide same-day results and improve case detection among household contacts. Consider in-home testing for household contact investigations when feasible to reduce delays in diagnosis and linkage to care.

In-home molecular testing increases speed to result (median 0 days vs 16.5 days in a randomized study) and can increase yield of tested household contacts.

Background and Scope

Background: Mycobacterium tuberculosis infection exists on a spectrum from latent infection (LTBI), characterized by immune sensitization without clinical disease, to active pulmonary or extrapulmonary TB disease. Culture remains the gold standard for diagnosis because it provides isolates for species identification and drug susceptibility testing, while nucleic acid amplification tests (NAATs) enable rapid detection of M. tuberculosis complex and some resistance markers. Interferon‑gamma release assays (IGRAs) measure host immune response and are intended for LTBI screening rather than diagnosing active TB. Whole genome sequencing can provide detailed mutation data but currently has limited routine clinical interpretability for many resistance determinants.

Definitions and Test Descriptions

inv-55: IGRA — Interferon gamma release assay definition and use

DefinitionInterferon‑gamma release assay (IGRA): blood test measuring IFN‑γ release after stimulation with M. tuberculosis–specific antigens to detect TB infection (LTBI)

Primary useIntended to detect latent tuberculosis infection (LTBI); preferred in many non‑US‑born and BCG‑vaccinated individuals

Not for active TB diagnosisIGRA DOES NOT MEET COVERAGE CRITERIA for individuals with active tuberculosis

inv-56: AFB — Acid fast bacilli smear/stain definition and role

DefinitionAcid‑fast bacilli (AFB) smear/stain: rapid microscopic test for identifying AFB on respiratory or other clinical specimens

Role in diagnosisAFB smear microscopy is recommended in all patients suspected of TB and used alongside culture and NAATs

Policy Summary

PayerBlue Cross Blue Shield - Tennessee

PolicyTesting for Diagnosis of Active or Latent Tuberculosis

Policy CodePolicy N/A

Change TypeNo material change indicated

Effective DateN/A

Next Review DateN/A

Key ActionEnsure tests ordered align with listed covered indications to avoid non-coverage.

SourceLink

On This Page

First specimen sensitivity

First specimen sensitivity ≈53.8%

Incremental yieldSecond specimen increases sensitivity by ~11.1%; third adds an additional ~2–5%

Specimen timing and processingA first‑morning specimen increases sensitivity ~12%; concentrating specimens can increase sensitivity ~18%

inv-33: Mantoux induration threshold

Mantoux induration cutoff5 mm induration is considered positive for Mantoux (in some immunocompromised/adult contexts per NICE guidance)

Context for useIf Mantoux positive but active TB excluded, consider IGRA to decide on treatment

Concurrent testing in immunocompromisedFor severely immunocompromised adults (eg, HIV with CD4 <200) NICE advises offering IGRA with a concurrent Mantoux test

Documentation Required

Rapid molecular drug susceptibility testing recommended

Rapid molecular drug susceptibility testing (DST) for rifampin (and isoniazid when available) is recommended on initial respiratory specimens for patients with suspected TB, particularly when risk factors for drug resistance are present. Positive molecular rifampin-resistance findings should prompt immediate additional DST for first-line and second-line agents and confirmatory testing per public health guidance.

Perform rapid molecular DST for rifampin ± isoniazid on initial respiratory specimens when AFB smear positive or when meeting DST risk criteria (prior treatment, birth/residence in high-incidence setting, contact of MDR-TB case, HIV).
If molecular rifampin resistance is detected, perform molecular testing for second-line resistance and phenotypic DST; repeat resistance testing if cultures remain positive at/after 4 months or if recrudescence occurs.
Confirm initial commercial NAA-detected rifampin resistance with rpoB sequencing and phenotypic DST where indicated.

Billing Rule

Applicable procedure codes

Procedure and laboratory codes related to TB testing, molecular detection, culture, species identification, and susceptibility studies are listed in the applicable CPT/HCPCS code section. Use the listed codes for billing and consult payer guidance for completeness.

Referenced codes include (not exhaustive): 86480, 86481 (IGRA); 87116 (mycobacterial culture); 87149–87153 (nucleic acid probe/sequencing identification); 87550–87561 (infectious agent nucleic acid detection for Mycobacteria); 87181–87190 (susceptibility studies); 81099/81479/81425/81426 for unlisted/genomic procedures.
Procedure codes in policy are for reference and may not be all-inclusive; verify with current CPT/HCPCS resources.

Prior Authorization

Prior authorization — not specified in this section

This section does not specify prior authorization requirements. If prior authorization is required by the member's benefit plan or applicable government program, the government or plan-specific policy takes precedence.

Prior authorization: Not specified in this section; check member benefit plan and government policies (LCD/NCD/state Medicaid) for any authorization requirements.

Denial Risk

Risk of under-treatment from discordant DST

Be aware that discordant DST (local vs reference laboratory) can lead to under-treatment and increased mortality. When discordant or unexpected results occur, obtain confirmatory testing and consult public health/reference laboratories to guide therapy.

Risk: Discordant DST associated with higher odds of death and potential under-treatment; confirmatory testing with reference laboratory methods recommended.
Action: Repeat DST and obtain reference-laboratory confirmation when molecular and phenotypic results conflict or clinical response is not as expected.

Denial Risk

Repeated Xpert Ultra after trace positive

Repeating Xpert Ultra after an initial trace-positive result in adults is generally not recommended per WHO conditional guidance and may be considered inappropriate for coverage decisions. Follow WHO recommendations when interpreting trace results and consider clinical context.

In adults with an Xpert Ultra trace positive on initial test, repeated Xpert Ultra testing may not be used (conditional WHO recommendation).
Clinical correlation is required to determine next steps rather than routine repeat molecular testing.

Note

Government policy precedence

If a conflict exists between this policy and applicable government (e.g., LCDs, NCDs, state Medicaid) policy for a particular member, the government policy prevails and must be applied.

Government policy precedence: Local and federal coverage determinations override this policy where applicable.

Note

No explicit authorization or denial criteria in reference sections

This section contains supporting references and does not itself establish explicit authorization or denial criteria. Operational coverage decisions must be based on the medical necessity criteria and payer-specific authorization requirements.

Reference-only content: Scientific citations and guidelines provided as supporting evidence; not a substitute for operational coverage rules.

Documentation Required

Clinical correlation and reporting

Microbiologic and molecular testing results must be interpreted in the context of the patient's clinical presentation, exposure history, and imaging. NAAT/NAAT-based assays do not replace smear or culture; interpret NAAT results while culture is pending and correlate with AFB smear.

Clinical correlation: Interpret NAAT, smear, culture, and DST together with signs/symptoms and exposure risk.
NAAT limitations: NAAT more sensitive than smear but less sensitive than culture; >95% PPV in smear-positive specimens but variable in smear-negative specimens.

Documentation Required

Submission and reporting of M. tuberculosis isolates

All culture isolates identified as Mycobacterium tuberculosis must be submitted to U.S. public health jurisdictions for confirmation of identification and drug susceptibility testing. Positive cultures should be reported to public health authorities for oversight and case management.

Submission requirement: Submit M. tuberculosis isolates to jurisdictional public health labs for confirmatory ID and DST per local requirements.
Reporting: Positive cultures must be reported to public health for case management and contact investigations.

Documentation Required

Required diagnostic documentation

Perform and document AFB smear microscopy, both liquid and solid mycobacterial cultures, and NAAT on initial respiratory specimens for suspected pulmonary TB. For extrapulmonary disease, submit appropriate specimens for microscopy, NAAT, culture, species identification, and DST as clinically indicated.

Required diagnostics on initial respiratory specimens: AFB smear, NAAT (rapid molecular test), and both liquid and solid cultures.
Extrapulmonary specimens: Obtain and document appropriate site-specific testing (microscopy, NAAT, culture, species identification, DST) and histopathology when indicated.
Document specimen types, collection dates/times, and test results in the medical record to support medical necessity.

Documentation Required

Specimen submission and testing documentation

Submit at least two sputum specimens for smear microscopy and one specimen for rapid molecular testing for persons suspected of pulmonary TB. First-morning and concentrated specimens increase sensitivity; follow guidance for specimen volume and transport to quality-assured laboratories.

Specimen submission: At minimum, submit two sputum specimens for smear and one for rapid molecular testing; obtain first-morning specimens when possible.
Documentation: Record specimen source, collection dates/times, and handling/transport conditions; ensure samples sent for liquid culture and, if positive, for culture-based DST in quality-assured labs.

Note

Supporting scientific references

This section includes supporting scientific references and guideline citations (WHO, CDC, ATS/IDSA, ERS/ECDC, NICE, TBNET/RESIST-TB, and peer-reviewed studies) that inform the diagnostic recommendations and medical necessity determinations.

Use provided references when documenting medical necessity, but operational coverage and billing decisions should follow the policy criteria and applicable payer or government requirements.

Documentation Required

Resistance testing sequence

When molecular detection of rifampin resistance is positive or MDR-TB is suspected, perform rapid testing for resistance to second-line drugs and follow up with phenotypic DST as needed. Repeat resistance testing if cultures remain positive during therapy or if bacteriologic reversion occurs.

Resistance testing sequence: Rapid molecular DST for rifampin → if positive, immediate testing for first-line, fluoroquinolones, and injectables → molecular testing for second-line resistance and phenotypic DST in reference labs.
Repeat testing: Repeat DST when sputum cultures remain positive at/after 4 months of treatment or become positive again ≥1 month after culture conversion.

Step Therapy

No step therapy rules are described here

No step-therapy rules, quantity limits, or step edits are described in this section. Clinical guidelines and references are provided for diagnostic practice but do not establish step therapy requirements.

No step therapy rules described: This section contains guidelines and bibliographic references only; check other policy sections or payer systems for any step edits.

Specimen guidancePerform AFB smear on initial respiratory specimens and document results while culture is pending

inv-57: NAAT / PCR / Xpert MTB/RIF — NAAT definition and role

NAAT definitionNucleic acid amplification test (NAAT): molecular assays (eg, Amplified MTD, Xpert MTB/RIF/Ultra) that rapidly detect M. tuberculosis complex and some resistance markers

Clinical roleNAATs are more sensitive than smear but less sensitive than culture; provide rapid species detection and rifampin resistance information

PerformanceReported NAAT sensitivity ~96% and specificity ~99% in cited studies

inv-58: NAAT — Nucleic acid amplification techniques description and examples

Technique descriptionNucleic acid amplification techniques amplify target mycobacterial DNA/RNA for rapid detection (examples include Amplified MTD and Xpert MTB/RIF/Ultra)

ExamplesAmplified Mycobacterium tuberculosis Direct (MTD), Xpert MTB/RIF, Xpert Ultra

Interpretation noteNAAT does not replace smear or culture; results should be interpreted with AFB smear and culture pending

inv-59: WGS — Whole genome sequencing definition and role in resistance prediction

WGS definitionWhole‑genome sequencing (WGS): sequence‑based assay providing the complete bacterial genome to identify mutations associated with drug resistance

Clinical utilityWGS can predict resistance more accurately than probe‑based assays and guide regimen design, with rapid turnaround compared with phenotypic DST

LimitationsWGS currently has limited correlation for many mutations with phenotypic DST and clinical outcomes; interpret with expert reference labs

inv-60: Urine LAM — Point-of-care urine lipoarabinomannan assay description and indications

Urine LAM definitionPoint‑of‑care assay detecting mycobacterial lipoarabinomannan (LAM) in urine to assist TB diagnosis in HIV‑infected patients

IndicationsMeets coverage for HIV‑infected individuals with CD4 ≤100 cells/µL who have signs/symptoms of TB and for seriously ill HIV‑infected patients

PerformanceReported sensitivity ~67.9% and specificity ~97.6% in patients with CD4 <100

inv-61: LF-LAM — Lateral flow urine lipoarabinomannan assay definition and inpatient/outpatient indications

LF‑LAM definitionLateral‑flow urine LAM (LF‑LAM): a rapid lateral‑flow assay detecting lipoarabinomannan to assist TB diagnosis in HIV‑positive patients

Inpatient recommendationWHO strongly recommends LF‑LAM for HIV‑positive inpatients with TB signs/symptoms, seriously ill patients, or advanced HIV (CD4 <200)

Outpatient recommendationWHO suggests LF‑LAM for certain outpatients with symptoms or CD4 <100; WHO recommends against use without TB symptoms or with CD4 ≥200

inv-62: Xpert MTB/RIF and Xpert Ultra — Molecular NAAT descriptions and guidance on repeated testing

Xpert descriptionsXpert MTB/RIF and Xpert Ultra are cartridge‑based molecular NAATs for M. tuberculosis detection and rifampin resistance; used as initial diagnostic tests in many settings per WHO

Repeated testing guidanceWHO advises against repeated Xpert Ultra testing in adults after an initial 'trace' positive; repeated testing recommendations vary by age and pretest probability

Role versus cultureXpert/Xpert Ultra may be used as initial tests to guide immediate treatment decisions when culture is unavailable or delayed, but culture remains important

inv-63: WGS (whole genome sequencing) — Additional WGS definition note (limited clinical interpretability currently)

WGS additional noteWGS provides complete genome sequence data but currently many detected mutations lack clear clinical interpretability; WGS should be used cautiously and with confirmatory phenotypic testing where needed

Use in regimen designWGS can be used to 'rule in' resistance and help design regimens for complex resistant strains but pDST remains necessary for some drugs

Reference recommendationSend extended molecular or WGS testing to experienced reference laboratories for interpretation and confirmatory testing

inv-64: IGRA / TST — IGRA and tuberculin skin test comparison and indications

IGRA vs TSTIGRA: blood‑based assays preferred in many non‑US‑born and BCG‑vaccinated persons; TST preferred in children <2 years per AAP/NICE guidance

When to use eachFor adults severely immunocompromised, consider IGRA with concurrent Mantoux; for others IGRA alone or with Mantoux may be considered

Serial testingIGRAs do not cause boosting and are acceptable for serial testing in healthcare personnel; TST requires two‑step baseline when used serially

inv-65: Interferon-gamma release assays (IGRAs) — Supporting definitions and references

IGRA definition and evidenceInterferon‑gamma release assays (IGRAs): blood tests detecting immune response to M. tuberculosis antigens; multiple guideline and meta‑analysis references support use for LTBI screening

Commercial assaysCommercially available IGRAs include QuantiFERON‑TB Gold and related assays

Guideline supportATS/IDSA/CDC, AAP, NSTC/NTCA and USPSTF guidance cited regarding preferred use and indications

inv-66: Nucleic acid amplification tests (NAATs) / GeneXpert — NAATs definition with cited performance guidance

NAATs / GeneXpert descriptionNucleic acid amplification tests (NAATs), including GeneXpert (Xpert MTB/RIF/Ultra), are rapid molecular assays that detect M. tuberculosis and some resistance markers (eg, rifampin)

Performance noteNAATs are more sensitive than smear but less sensitive than culture; reported pooled sensitivity ~96% and specificity ~99%

Clinical recommendationPerform NAAT on initial respiratory specimens when clinical suspicion exists; NAAT does not replace culture and should be combined with smear and culture