CAM 20410

Identification of Microorganisms Using Nucleic Acid Probes

Category:Laboratory   Last Reviewed:October 2019
Department(s):Medical Affairs   Next Review:October 2020
Original Date:July 1998    

Description: 
Nucleic acid hybridization technologies utilize complementary properties of the DNA double-helix structures to anneal together DNA fragments from different sources.  These techniques are utilized in polymerase chain reaction (PCR) and fluorescent resonance energy transfer (FRET) techniques to identify microorganisms (Khan, 2014).    

Regulatory Status 
As of 06/12/2019, a list of current U.S. Food and Drug Administration (FDA, 2019) approved or cleared nucleic acid-based microbial tests is available at: https://www.fda.gov/medical-devices/vitro-diagnostics/nucleic-acid-based-tests..

Policy 

  1. The status of nucleic acid identification using direct probe, amplified probe, or   quantification for the microorganism’s procedure codes is summarized in Table 1 below. "med nec" in the table below indicates that the test is considered MEDICALLY NECESSARY  No PA Required; while “inv” tests indicates that the test is investigational and/or unproven and therefore considered NOT MEDICALLY NECESSARY.

Microorganism

Direct Probe

Amplified Probe

Quantification

Bartonella henselae or quintana

 

87471(med nec)                            

87472 (inv)

 Candida species

 

87480 (med nec) for vaginitis 

87480 (inv) for all other situations except vaginitis 

87481 (inv) for all situations  

87482 (inv) for all situations 

Chlamydia pneumoniae

87485 (inv)

87486 (inv)

87487 (inv)

Clostridium difficile

87493 (med nec)

 

 

Cytomegalovirus

87495 (med nec)

87496 (med nec)

87497 (med nec)

Enterococcus, Vancomycin-resistant (e.g., enterococcus vanA, vanB)

 

87500 (med nec)

 

Enterovirus

 

87498 (med nec)

 

Gastrointestinal Pathogen Panel

 

87505-87507 (med nec)

 

Hepatitis B

 

87516 (med nec)

87517 (med nec)

Hepatitis G

87525 (inv)

87526 (inv)

87527 (inv)

Herpes virus-6

87531 (med nec)

87532 (inv)

87533 (med nec)

HIV-1

87534 (med nec)

87535 (med nec)

87536 (med nec)

HIV-2

87537 (med nec)

87538 (med nec)

87539 (med nec)

Legionella pneumophila

87540 (med nec)

87541 (med nec)

87542 (inv)

Mycoplasma pneumoniae

87580 (med nec)

87581 (med nec)

87582 (inv)

Respiratory virus panel

 

87631-87633 (med nec)

 

Staphylococcus aureus

 

87640 (med nec) 

 

Staphylococcus aureus, methicillin resistant 

 

87641 (med nec) 

 

  1. PCR testing for Ebola is considered MEDICALLY NECESSARY and will currently be submitted with unspecified codes.
  2. The technique for quantification includes both amplification and direct probes; therefore, simultaneous coding for both amplification or direct probes is considered NOT MEDICALLY NECESSARY.
  3. PCR testing for the following microorganisms that do not have specific CPT codes is considered MEDICALLY NECESSARY(not an all-inclusive list):
    1. Actinomyces, for identification of actinomyces species in tissue specimens
    2. Adenovirus, to diagnose adenovirus myocarditis, and to diagnose adenovirus infection in immunocompromised hosts, including transplant recipients
    3. Avian influenza A virus, for diagnosis of avian influenza A (H5N1) in persons with both: (i) symptoms consistent with Avian influenza A virus; and (ii) a history of travel to or contact with persons or birds from a country with documented H5N1 avian influenza infections within 10 days of symptom onset. 
    4. Bacillus Anthracis
    5. BK polyomavirus in transplant recipients receiving immunosuppressive therapies and persons with immunosuppressive diseases
    6. Bordetella pertussis and B. parapertussis, for diagnosis of whooping cough in individuals with coughing
    7. Brucella spp., for members with signs and symptoms of Brucellosis, and history of direct contact with infected animals and their carcasses or secretions or by ingesting unpasteurized milk or milk products
    8. Burkholderia infections (including B. cepacia, B. gladioli), diagnosis
    9. Chancroid (Haemophilus ducreyi), for diagnosis of persons with genital ulcer disease
    10. Coxiella burnetii, for confirmation of acute Q fever
    11. Epidemic typhus (Rickettsia prowazekii), diagnosis 
    12. Epstein Barr Virus (EBV): for detection of EBV in post-transplant lymphoproliferative disorder; or for testing for EBV in persons with lymphoma; or for those who are immunocompromised for other reasons.
    13. Francisella tularensis, for presumptive diagnosis of tularemia
    14. Hantavirus, diagnosis
    15. Hemorrhagic fevers and related syndromes caused by viruses of the family Bunyaviridae (Rift Valley fever, Crimean-Congo hemorrhagic fever, hemorrhagic fever with renal syndromes), for diagnosis in acute phase in persons with clinical presentation suggestive of these conditions
    16. Hepatitis D virus, for confirmation of active infection in persons with anti-HDV antibodies
    17. Hepatitis E virus, for definitive diagnosis in persons with anti-HEV antibodies
    18. Human T Lymphotropic Virus type 1 and type 2 (HTLV-I and HTLV-II), to confirm the presence of HTLV-I and HTLV-II in the cerebrospinal fluid of persons with signs or symptoms of HTLV-I/HTLV-II
    19. Human metapneumovirus
    20. JC polyomavirus, in transplant recipients receiving immunosuppressive therapies, in persons with immunosuppressive diseases, and for diagnosing progressive multifocal leukoencephalopathy in persons with multiple sclerosis or Crohn's disease receiving natalizumab (Tysabri)
    21. Leishmaniasis, diagnosis
    22. Measles virus (Morbilliviruses), for diagnosis of measles
    23. Mumps
    24. Mycoplasma genitalium
    25. Neisseria meningitidis, to establish diagnosis where antibiotics have been started before cultures have been obtained
    26. Parvovirus, for detecting chronic infection in immunocompromised persons
    27. Psittacosis, for diagnosis of Chlamydophila (Chlamydia) psittaci infection
    28. Respiratory syncytial virus (RSV), for confirming the result of rapid antigen detection assay.
    29. Rubella, diagnosis
    30. Severe acute respiratory syndrome (SARS), for detection of SARS coronavirus RNA in persons with signs or symptoms of SARS who have traveled to endemic areas or have been exposed to persons with SARS
    31. Toxoplasma gondii, for detection of T. gondii infection in immunocompromised persons with signs and symptoms of toxoplasmosis, and for detection of congenital Toxoplasmagondii infection (including testing of amniotic fluid for toxoplasma infection)
    32. Varicella-Zoster infections
    33. Whipple's disease (T. whippeli), biopsy tissue from small bowel, abdominal or peripheral lymph nodes, or other organs of persons with signs and symptoms, to establish the diagnosis
    34. Yersinia Pestis
  4. Quantitative PCR testing for the following indications is considered MEDICALLY NECESSARY:
    1. Adenovirus viral load, to monitor response to antiviral therapy in infected immunocompromised hosts, including transplant recipients
    2. BK polyomavirus viral load, for diagnosis and monitoring response to therapy in infected kidney transplant recipients
    3. Cytomegalovirus (CMV) viral load, to monitor response to therapy
    4. EBV viral load, to monitor for EBV viral replication in solid organ transplant recipients
    5. Hepatitis B
    6. Hepatitis C
    7. Human herpesvirus type 6, to monitor response to therapy in immunocompromised hosts, including transplant recipients
    8. HIV RNA viral load testing, to monitor disease progression and response to therapy

Policy Guidelines
A discussion of every infectious agent that might be detected with a probe technique is beyond the scope of this policy. Many probes have been combined into panels of tests. For the purposes of this policy, other than the respiratory virus panel, only individual probes are reviewed..

Rationale
Nucleic acid hybridization technologies, including polymerase chain reaction (PCR), ligase- or helicase-dependent amplification, and transcription-mediated amplification, are beneficial tools for pathogen detection in blood culture and other clinical specimens due to high specificity and sensitivity (Khan, 2014). The use of nucleic acid-based methods to detect bacterial pathogens in a clinical laboratory setting offers “increased sensitivity and specificity over traditional microbiological techniques” due to its specificity, sensitivity, reduction in time, and high-throughput capability; however, “contamination potential, lack of standardization or validation for some assays, complex interpretation of results, and increased cost are possible limitations of these tests (Mothershed & Whitney, 2006)”.

Specific guidelines for testing of many organisms listed within the policy coverage criteria is found in the updated 2018 Infectious Diseases Society of America (IDSA) guidelines and recommendations titled, A Guide to Utilization of the Microbiology Laboratory for Diagnosis of Infectious Diseases: 2018 Update by the Infectious Diseases Society of America and the American Society for Microbiology (Miller et al., 2018).  “This document is organized by body system, although many organisms are capable of causing disease in >1 body system. There may be a redundant mention of some organisms because of their propensity to infect multiple sites. One of the unique features of this document is its ability to assist clinicians who have specific suspicions regarding possible etiologic agents causing a specific type of disease. When the term “clinician” is used throughout the document, it also includes other licensed, advanced practice providers. Another unique feature is that in most chapters, there are targeted recommendations and precautions regarding selecting and collecting specimens for analysis for a disease process. It is very easy to access critical information about a specific body site just by consulting the table of contents. Within each chapter, there is a table describing the specimen needs regarding a variety of etiologic agents that one may suspect as causing the illness. The test methods in the tables are listed in priority order according to the recommendations of the authors and reviewers (Miller et al., 2018).”

Committee on Infectious Diseases, American Academy of Pediatrics, 31st Edition (2018-2021, Red Book)
The Committee on Infectious Diseases released joint guidelines with the American Academy of Pediatrics. In it, they note that “the presumptive diagnosis of mucocutaneous candidiasis or thrush usually can be made clinically”. They also state that FISH probes may rapidly detect Candida species from positive blood culture samples, although PCR assays have also been developed for this purpose (Pediatrics, 2018).

References:

  1. FDA. (2019). Nucleic Acid Based Tests. Retrieved from https://www.fda.gov/medical-devices/vitro-diagnostics/nucleic-acid-based-tests
  2. Khan, A. (2014). Rapid Advances in Nucleic Acid Technologies for Detection and Diagnostics of Pathogens. J Microbiol Exp, 1(2). doi:10.15406/jmen.2014.01.00009
  3. Miller, J. M., Binnicker, M. J., Campbell, S., Carroll, K. C., Chapin, K. C., Gilligan, P. H., . . . Yao, J. D. (2018). A Guide to Utilization of the Microbiology Laboratory for Diagnosis of Infectious Diseases: 2018 Update by the Infectious Diseases Society of America and the American Society for Microbiology. Clinical Infectious Diseases, ciy381-ciy381. doi:10.1093/cid/ciy381
  4. Mothershed, E. A., & Whitney, A. M. (2006). Nucleic acid-based methods for the detection of bacterial pathogens: present and future considerations for the clinical laboratory. Clin Chim Acta, 363(1-2), 206-220. doi:10.1016/j.cccn.2005.05.050
  5. Pediatrics, C. o. I. D. A. A. o. (2018). Red Book® 2018. 

Coding Section

 Code          

 Number          

Description

CPT 

87471

Infectious agent detection by nucleic acid (DNA or RNA); Bartonella henselae and Bartonella quintana, amplified probe technique

 

87472

Infectious agent detection by nucleic acid (DNA or RNA); Bartonella henselae and Bartonella quintana, quantification

 

87480

Infectious agent detection by nucleic acid (DNA or RNA); Candida species, direct probe technique

 

87481

Infectious agent detection by nucleic acid (DNA or RNA); Candida species, amplified probe technique

 

87482

Infectious agent detection by nucleic acid (DNA or RNA); Candida species, quantification

 

87485

Infectious agent detection by nucleic acid (DNA or RNA); Chlamydia pneumoniae, direct probe technique

 

87486

Infectious agent detection by nucleic acid (DNA or RNA); Chlamydia pneumoniae, amplified probe technique

 

87487

Infectious agent detection by nucleic acid (DNA or RNA); Chlamydia pneumoniae, quantification

 

87493

Infectious agent detection by nucleic acid (DNA or RNA); Clostridium difficile, toxin gene(s), amplified probe technique

 

87495

Infectious agent detection by nucleic acid (DNA or RNA); cytomegalovirus, direct probe technique

 

87496

Infectious agent detection by nucleic acid (DNA or RNA); cytomegalovirus, amplified probe technique

 

87497

Infectious agent detection by nucleic acid (DNA or RNA); cytomegalovirus, quantification

 

87498

Infectious agent detection by nucleic acid (DNA or RNA); enterovirus, amplified probe technique, includes reverse transcription when performed

 

87500

Infectious agent detection by nucleic acid (DNA or RNA); vancomycin resistance (eg, enterococcus species van A, van B), amplified probe technique

 

87516

Infectious agent detection by nucleic acid (DNA or RNA); hepatitis B virus, amplified probe technique

 

87517

Infectious agent detection by nucleic acid (DNA or RNA); hepatitis B virus, quantification

 

87525

Infectious agent detection by nucleic acid (DNA or RNA); hepatitis G, direct probe technique

 

87526

Infectious agent detection by nucleic acid (DNA or RNA); hepatitis G, amplified probe technique

 

87527

Infectious agent detection by nucleic acid (DNA or RNA); hepatitis G, quantification

 

87531

Infectious agent detection by nucleic acid (DNA or RNA); Herpes virus-6, direct probe technique

 

87532

Infectious agent detection by nucleic acid (DNA or RNA); Herpes virus-6, amplified probe technique

 

87533

Infectious agent detection by nucleic acid (DNA or RNA); Herpes virus-6, quantification

 

87534

Infectious agent detection by nucleic acid (DNA or RNA); HIV-1, direct probe technique

 

87535

Infectious agent detection by nucleic acid (DNA or RNA); HIV-1, amplified probe technique, includes reverse transcription when performed

 

87536

Infectious agent detection by nucleic acid (DNA or RNA); HIV-1, quantification, includes reverse transcription when performed

 

87537

Infectious agent detection by nucleic acid (DNA or RNA); HIV-2, direct probe technique

 

87538

Infectious agent detection by nucleic acid (DNA or RNA); HIV-2, amplified probe technique, includes reverse transcription when performed

 

87539

Infectious agent detection by nucleic acid (DNA or RNA); HIV-2, quantification, includes reverse transcription when performed

 

87540

Infectious agent detection by nucleic acid (DNA or RNA); Legionella pneumophila, direct probe technique

 

87541

Infectious agent detection by nucleic acid (DNA or RNA); Legionella pneumophila, amplified probe technique

 

87542

Infectious agent detection by nucleic acid (DNA or RNA); Legionella pneumophila, quantification

 

87580

Infectious agent detection by nucleic acid (DNA or RNA); Mycoplasma pneumoniae, direct probe technique

 

87581

Infectious agent detection by nucleic acid (DNA or RNA); Mycoplasma pneumoniae, amplified probe technique

 

87582

Infectious agent detection by nucleic acid (DNA or RNA); Mycoplasma pneumoniae, quantification

 

87634

Infectious agent detection by nucleic acid (DNA or RNA); respiratory syncytial virus, amplified probe technique

 

87640

Infectious agent detection by nucleic acid (DNA or RNA); Staphylococcus aureus, amplified probe technique

 

87641

Infectious agent detection by nucleic acid (DNA or RNA); Staphylococcus aureus, methicillin resistant, amplified probe technique 

 

87797

Infectious agent detection by nucleic acid (DNA or RNA), not otherwise specified; direct probe technique, each organism

 

87798

Infectious agent detection by nucleic acid (DNA or RNA), not otherwise specified; amplified probe technique, each organism

 

87799

Infectious agent detection by nucleic acid (DNA or RNA), not otherwise specified; quantification, each organism

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each Policy. They may not be all-inclusive. 

This medical policy was developed through consideration of peer-reviewed medical literature generally recognized by the relevant medical community, U.S. FDA approval status, nationally accepted standards of medical practice and accepted standards of medical practice in this community, Blue Cross and Blue Shield Association technology assessment program (TEC) and other non-affiliated technology evaluation centers, reference to federal regulations, other plan medical policies, and accredited national guidelines.

"Current Procedural Terminology © American Medical Association.  All Rights Reserved" 

History From 2014 Forward     

10/29/2019 

Annual review, no change to policy intent. Reformatting for clarity. Updating coding.

09/25/2019 

Corrected formatting. No other changes made. 

05/29/2019 

Corrected Typo. No change to policy intent. 

11/27/2018 

Major rewrite of this policy related to adoption of diagnostic testing of most common sexually transmitted infections, B-Hemolytic Streptococcus Testing, and testing for mosquito or tick-related infections. All four policies will be implemented on 02012019. 

12/7/2017 

Updating policy with 2018 coding. No other changes. 

11/28/2017 

Annual review. Updating background, description, reg status, policy, guidelines, references and coding.

04/25/2017 

Updated category to Laboratory. No other changes. 

01/10/2017 

Annual Review. No significant changes.

11/30/2016 

Updated coding section with 2017 codes. 

05/09/2016 

Interim review, updating Human herpes virus 6 testing to indicate that direct probe and quantification can be considered medically necessary, but, that amplified probe (87532) is considered investigational. No other changes. 

01/21/2015 

Returning Borrelia burgdorferi as medically necessary with reference to see policy 50108. 

01/05/2016 

Interim review with the following policy intent changes: Medically necessary statement added for non-quantified nucleic acid-based testing for enterovirus, Legionella pneumophila, Mycoplasma pneumoniae, and Bartonella spp, and for quantified testing for human herpesvirus 6. Borrelia, major revision in the visual look of the policy, but, only the content listed has been altered in intent. Updating background, description, guidelines, verbiage, rationale and references, and coding. 

11/24/2015 

Annual review, no changes made. 

3/16/2015 

Removed the word "archived" in table 1 on Candida species, Gardnerella vaginalis and  Human Papillomavirus lines. No other changes.

10/27/2014

Annual review. Added description and coding. Updated background, policy, rationale and references. New CPT codes(8751xx 1-3 and 876xx 3-5 added.


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