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Identification of Microorganisms Using Nucleic Acid Probes

Policy Number: MP-548

Latest Review Date: January 2019

Category: Medical

Policy Grade: B

POLICY:

Effective for dates of service on or after December 1, 2016:

The use of nucleic acid testing using a direct or amplified probe technique (without quantification of viral load) may be considered medically necessary for the following microorganisms (see Table 1 at end of this section for details on coding):

  • Bartonella henselae or quintana
  • Candida species
  • Chlamydia trachomatis
  • Clostridium difficile
  • Enterococcus, vancomycin-resistant (e.g., enterococcus vanA, vanB)
  • Enterovirus
  • Gardnerella vaginalis
  • Herpes simplex virus
  • Human papillomavirus
  • Legionella pneumophila
  • Mycobacterium species
  • Mycobacterium tuberculosis
  • Mycobacterium avium intracellulare
  • Mycoplasma pneumoniae
  • Neisseria gonorrhoeae
  • Respiratory virus panel
  • Staphylococcus aureus
  • Staphylococcus aureus, methicillin resistant
  • Streptococcus, group A
  • Streptococcus, group B
  • Trichomonas vaginalis

The use of nucleic acid testing using a direct or amplified probe technique (with or without quantification of viral load) may be considered medically necessary for the following microorganisms:

  • Cytomegalovirus
  • Hepatitis B virus
  • Hepatitis C virus
  • HIV-1
  • HIV-2
  • Human herpes virus 6
  • Influenza virus

The use of nucleic acid testing with quantification of viral load for microorganisms that are not included in the list of microorganisms are considered investigational and not medically necessary.

The use of nucleic acid testing using a direct or amplified probe technique with or without quantification of viral load is considered investigational and not medically necessary for the following microorganisms including but not limited to:

  • Chlamydophila pneumoniae
  • Hepatitis G virus
  • Human papillomavirus (low risk panel)
  • Gastrointestinal pathogen panel

CPT codes 87797, 87798, and 87799 describe the use of direct probe, amplified probe, and quantification, respectively, for infectious agents not otherwise specified. Testing submitted with these codes will be handled on a case by case basis. A discussion of every infectious agent that might be detected with a probe technique is beyond the scope of this policy. Table 1 provides a list of CPT codes for various nucleic acid probes.

A new PLA code will be effective 10/01/18 that represents the MYCODART Dual Amplification Real Time PCR Panel: 0068U Candida species panel (C. albicans, C. glabrata, C. parapsilosis, C. kruseii, C tropicalis, and C. auris), amplified probe technique with qualitative report of the presence or absence of each species.

A new PLA code will be effective 10/01/19 that represents MicroGenDX: 0112U - Infectious agent detection and identification, targeted sequence analysis (16S and 18S rRNA genes) with drug resistance gene. (Inv)

Table 1. CPT Codes for Nucleic Acid Probes

Pathogen

Direct Probe

Amplified Probe

Quantification

Bartonella henselae or quintana

87471 (Med Nec)

87472 (Inv)

Borrelia borgdorferia

87475 (Med Nec)

87476 (Med Nec)

Candida speciesb

87480 (Med Nec)

87481 (Med Nec)

87482 (Inv)

Chlamydia pneumoniae

87485(Inv)

87486 (Inv)

87487 (Inv)

Chlamydia trachomatis

87490 (Med Nec)

87491 (Med Nec)

87492 (Inv)

Clostridium difficile

87493 (Med Nec)

Cytomegalovirus

87495 (Med Nec)

87496 (Med Nec)

87497 (Med Nec)

Enterococcus, Vancomycin resistant

(e.g., enterococcus van A, van B)

87500 (Med Nec)

Enterovirus

87498 (Med Nec)

Gardnerella vaginalis

87510 (Med Nec)

87511 (Med Nec)

87512 (Inv)

Gastrointestinal Pathogen Panel

87505-87507 (Inv)

0097U (eff 07/01/19) (Inv)

Central nervous system pathogen panel

87483 (eff 01/01/17) (Med Nec)

Hepatitis B

87516 (Med Nec)

87517 (Med Nec)

Hepatitis C

87520 (Med Nec)

87521 (Med Nec)

87522 (Med Nec)

Hepatitis G

87525 (Inv)

87526 (Inv)

87527 (Inv)

Herpes simplex virus

87528 (Med Nec)

87529 (Med Nec)

87530 (Inv)

Human Herpes virus-6

87531 (Med Nec)

87532 (Med Nec)

87533 (Med Nec)

Human Immunodeficiency Virus 1 (HIV-1)

87534 (Med Nec)

87535 (Med Nec)

87536 (Med Nec)

Human Immunodeficiency Virus 2 (HIV-2)

87537 (Med Nec)

87538 (Med Nec)

87539 (Med Nec)

Human Papillomavirus (HPV)

87623(Inv)

87624-87625 (Med Nec)

Influenza virus

87501 (Med Nec)

87502 (Med Nec)

87503 (Med Nec)

Legionella pneumophila

87540 (Med Nec)

87541 (Med Nec)

87542 (Inv)

Mycobacterium species

87550 (Med Nec)

87551(Med Nec)

87552 (Inv)

Mycobacterium tuberculosis

87555 (Med Nec)

87556 (Med Nec)

87557 (Inv)

Mycobacterium avium intracellulare

87560 (Med Nec)

87561 (Med Nec)

87562 (Inv)

Mycoplasma pneumoniae

87580 (Med Nec)

87581 (Med Nec)

87582 (Inv)

Neisseria gonorrhoeae

87590 (Med Nec)

87591 (Med Nec)

87592 (Inv)

Respiratory virus panel

87631-87634 (Med Nec)

0098U – 0100U (eff 07/01/19) (Med Nec)

0115U (eff 10/1/19) (Med Nec)

0151U (eff 1/1/2020) (Med Nec)

Staphylococcus aureus

87640 (Med Nec)

Staphylococcus aureus, methicillin resistant

87641 (Med Nec)

Streptococcus group Ac

87650 (Med Nec)

87651 (Med Nec)

87652 (Inv)

Streptococcus group Bd

87653 (Med Nec)

Trichomonas vaginalis

87660 (Med Nec)

87661 (Med Nec)

a Refer to medical policy #359, Intravenous Antibiotic Therapy and Associated Diagnostic Testing for Lyme Disease.

b For uncomplicated infections, testing for only one candida species, C albicans, may be considered medically necessary. For complicated infections, testing for multiple candida subspecies may be considered medically necessary. The Centers for Disease Control and Prevention classifies uncomplicated vulvovaginal candidiasis as being sporadic or infrequent or mild to moderate or likely to be C. albicans or in non-immunocompromised women. Complicated vulvovaginal candidiasis is classified as being recurrent or severe or not a C. albicans species or in women with uncontrolled diabetes, debilitation or immunosuppression.

c Antibiotic sensitivity of streptococcus A cultures is frequently not performed for throat cultures. However, if an antibiotic sensitivity is considered, then the most efficient method of diagnosis would be a combined culture and antibiotic sensitivity.

d In the evaluation of group B streptococcus, the primary advantage of a DNA probe technique compared to traditional culture techniques is the rapidity of results. This advantage suggests that the most appropriate use of the DNA probe technique is in the setting of impending labor, for which prompt results could permit the initiation of intrapartum antibiotic therapy.

Table 1 Key:

Med Necmeets medical criteria for coverage

Invdoes not meet medical criteria for coverage

For codes in use prior to January 1, 2015 please see Previous Coding section.

NOTE: Many probes have been combined into panels of tests. For the purposes of this policy, other than the gastrointestinal pathogen panel and the respiratory virus panel, only individual probes are reviewed.

____________________________________________________________________________

Effective for dates of service January 1, 2014 through November 30, 2016:

The status of nucleic acid identification using direct probe, amplified probe, or quantification for the microorganisms listed in the CPT book are summarized in the following table.

Key: Med Necmeets medical criteria for coverage

Invdoes not meet medical criteria for coverage

For codes in use prior to January 1, 2015 please see Previous Coding section.

Microorganism

Direct Probe

Amplified Probe

Quantification

Bartonella henselae or quintana

87470 (Inv)

87471 (Inv)

87472 (Inv)

Borrelia borgdorferia

87475 (Inv)

87476 (Inv)

87477 (Inv)

Candida speciesc

87480 (Med Nec)

87481 (Med Nec)

87482 (Inv)

Chlamydia pneumoniae

87485(Inv)

87486 (Inv)

87487 (Inv)

Chlamydia trachomatis

87490 (Med Nec)

87491 (Med Nec)

87492 (Inv)

Clostridium difficile

87493 (Med Nec)

Cytomegalovirus

87495 (Med Nec)

87496 (Med Nec)

87497 (Med Nec)

Enterococcus, Vancomycin resistant

(e.g., enterococcus van A, van B)

87500 (Med Nec)

Enterovirus

87498 (Inv)

Gardnerella vaginalis

87510 (Med Nec)

87511 (Inv)

87512 (Inv)

Gastrointestinal Pathogen Panel

87505-87507 (Inv)

Hepatitis B

87515 (Med Nec)

87516 (Med Nec)

87517 (Med Nec)

Hepatitis C

87520 (Med Nec)

87521 (Med Nec)

87522 (Med Nec)

Hepatitis G

87525 (Inv)

87526 (Inv)

87527 (Inv)

Herpes simplex virus

87528 (Med Nec)

87529 (Med Nec)

87530 (Inv)

Human Herpesvirus-6

87531 (Inv)

87532 (Inv)

87533 (Inv)

Human Immunodeficiency Virus 1 (HIV-1)

87534 (Med Nec)

87535 (Med Nec)

87536 (Med Nec)

Human Immunodeficiency Virus 2 (HIV-2)

87537 (Med Nec)

87538 (Med Nec)

87539 (Med Nec)

Human Papillomavirus (HPV)

87623(Inv)

87624-87625 (Med Nec)

Influenza virus

87501 (Med Nec)

87502 (Med Nec)

87503 (Med Nec)

Legionella pneumophila

87540 (Inv)

87541 (Inv)

87542 (Inv)

Mycobacterium species

87550 (Med Nec)

87551(Inv)

87552 (Inv)

Mycobacterium tuberculosis

87555 (Med Nec)

87556 (Med Nec)

87557 (Inv)

Mycobacterium avium intracellulare

87560 (Med Nec)

87561 (Inv)

87562 (Inv)

Mycoplasma pneumoniae

87580 (Inv)

87581 (Inv)

87582 (Inv)

Neisseria gonorrhoeae

87590 (Med Nec)

87591 (Med Nec)

87592 (Inv)

Respiratory virus panel

87631-87633

(Med Nec)

Staphylococcus aureus

87640 (Med Nec)

Staphylococcus aureus, methicillin resistant

87641 (Med Nec)

Streptococcus group Ab

87650 (Med Nec)

87651 (Inv)

87652 (Inv)

Streptococcus group B

87653 (Med Nec)

Trichomonas vaginalis

87660 (Med Nec)

87661 (Med Nec)

a These probes are investigational except as noted in other policies. See Intravenous Antibiotic Therapy and Associated Diagnostic Testing for Lyme Disease, policy #359.

b The direct DNA probe test for streptococcus A is designed to be an alternative to a confirmatory culture. Therefore, the simultaneous use of confirmatory culture and DNA probe test does not meet medical criteria for coverage. Antibiotic sensitivity of streptococcus A cultures is frequently not performed for throat cultures. However, if an antibiotic sensitivity is considered, then the most efficient method of diagnosis would be a combined culture and antibiotic sensitivity.

c For uncomplicated infections, testing for only one candida species, C albicans, may be considered medically necessary. For complicated infections, testing for multiple candida subspecies may be considered medically necessary. The Centers for Disease Control and Prevention classifies uncomplicated vulvovaginal candidiasis as being sporadic or infrequent or mild to moderate or likely to be C. albicans or in non-immunocompromised women. Complicated vulvovaginal candidiasis is classified as being recurrent or severe or not a C. albicans species or in women with uncontrolled diabetes, debilitation or immunosuppression.

CPT codes 87797, 87798, and 87799 describe the use of direct probe, amplified probe, and quantification, respectively, for infectious agents not otherwise specified. 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 gastrointestinal pathogen panel and the respiratory virus panel, only individual probes are reviewed.

DESCRIPTION OF PROCEDURE OR SERVICE:

Nucleic acid probes are available for the identification of a wide variety of microorganisms. Nucleic acid probes can also be used to quantitate the number of microorganisms present. This technology offers advantages over standard techniques when rapid identification is clinically important, when microbial identification using standard culture is difficult or impossible, and/or when treatment decisions are based on quantitative results.

Microorganisms and Clinical Disease

Various bacteria, viruses, and fungi that can cause clinical disease and can be detected with various nucleic acid probe techniques are briefly outlined below.

Bartonella henselae or quintana

Bartonella henselae is responsible for cat scratch disease. In most patients (90-95%), the infection is a localized skin and lymph node disorder that occurs close to the site of inoculation, and is characterized by chronic regional lymphadenopathy that develops about two weeks after contact with a cat. Less commonly, Bartonella henselae infection may lead to disseminated infection, which can manifest as visceral organ involvement, often with fever and hepatosplenomegaly, a variety of ocular manifestations, and neurological manifestations (most commonly, encephalopathy).

Bartonella may also cause an opportunistic infection in HIV-infected patients, in whom it is characterized by an acute febrile bacteremic illness, evolving to an asymptomatic bacteremia and finally indolent vascular skin lesions. The organism is typically detected using culture techniques, although an incubation period of five to more than 30 days is required. DNA probe technology has been investigated as a diagnostic technique.

Bartonella quintana has classically been associated with “trench fever,” which is characterized by systemic symptoms (bone pain, malaise, headache), along with recurring fevers of varying durations. Among HIV-infected patients, B. quintana has been associated with bacillary angiomatosis.

Bartonella are fastidious organisms, making culture difficult. Histology of lesions affected by bacillary angiomatosis may be characteristic. Histology of affected lymph nodes or other tissue with B. henselae may demonstrate findings that are suggestive of cat-scratch disease, but which may be seen in other conditions. Two antigenic methods are available, one using indirect fluorescence assay (IFA) and one using enzyme immunosorbent assay (EIA), for both B. henselae and B. quintana infections. A positive serologic test is generally considered supportive, but not definitive, for Bartonella infection. Serologic methods may have limited yield in immunosuppressed patients.

Candida species

A commonly occurring yeast, Candida species normally can be found on diseased skin, throughout the entire gastrointestinal tract, expectorated sputum, the female genitalia, and in urine of patients with indwelling Foley catheters. Clinically significant Candida infections are typically diagnosed by clinical observation or by identification of the yeast forms on biopsy specimens. Candida species are a common cause of vaginitis.

Chlamydia pneumonia

Chlamydia pneumoniae is an important cause of pneumonia, bronchitis, and sinusitis. Culture and isolation of the microorganism is difficult; a microimmunofluorescence serum test may be used. The use of PCR amplification now offers a rapid diagnosis.

Chlamydia trachomatis

Chlamydia trachomatis is a significant intracellular pathogen causing, most prominently, urogenital disease (including pelvic inflammatory disease) and perinatal infections.

C. trachomatis is also responsible for lymphogranuloma venereum (LGV). Due to its prevalence and association with pelvic inflammatory disease and perinatal disease, widespread testing of chlamydia is recommended; routine chlamydia testing has been adopted as a quality measure by Healthcare Effectiveness Data and Information Set (HEDIS). This microorganism can be diagnosed by: 1) identifying the typical intracytoplasmic inclusions in cytology specimens; 2) isolation in tissue culture; 3) demonstration of chlamydial antigen by enzyme-linked immunosorbent assay or by immunofluorescent staining; or 4) demonstration of DNA using a direct probe or amplification technique.

Cytomegalovirus

Cytomegalovirus (CMV) is a common virus that infects many, but rarely causes clinical disease in healthy individuals. However, this virus can cause protean disease syndromes, most prominently in immunosuppressed patients, including transplant recipients or those infected with the HIV virus. CMV can also remain latent in tissues after recovery of the host from an acute infection. Diagnosis depends on demonstration of the virus or viral components or demonstration of a serologic rise. DNA probe techniques, including amplification, have also been used to identify patients at risk for developing CMV disease as a technique to triage antiviral therapy.

Clostridium difficile

Clostridium difficile is an anaerobic, toxin-producing bacteria present in the intestinal tract. It causes clinical colitis when the normal intestinal flora is altered and overgrowth of C difficile occurs. The common precipitant that disrupts the normal intestinal flora is previous treatment with antibiotics. The disorder has varying severity but can be severe and in extreme cases, life-threatening. C difficile is easily spread from person-to-person contact and is a common cause of hospital-acquired outbreaks. Hospital infection control measures, such as wearing gloves and handwashing with soap and water, are effective methods of reducing the spread of C difficile. The standard diagnosis is made by an assay for the C difficile cytotoxin or by routine culture methods.

Enterovirus

Enteroviruses are single-stranded ribonucleic acid (RNA) viruses. This group of viruses includes the polioviruses, coxsackievirus, echoviruses, and other enteroviruses. In addition to three polioviruses, there are more than 60 types of non-polio enteroviruses that can cause disease in humans. Most people who are infected with a non-polio enterovirus have no disease symptoms at all. Infected persons who develop illness usually develop either mild upper respiratory symptoms, flu-like symptoms with fever and muscle aches, or an illness with rash. Less commonly, enteroviruses can cause "aseptic" or viral meningitis, encephalitis, acute paralysis, and/or myocarditis. Enteroviral infections can cause life-threatening systemic infections in neonates, which are often associated with myocarditis or fulminant hepatitis. The use of amplified probe DNA test(s) can be used to detect enterovirus.

Gardnerella vaginalis

A common microorganism, Gardnerella vaginalis is typically found in the human vagina and is usually asymptomatic. However, G vaginalis is found in virtually all women with bacterial vaginosis and is characterized by inflammation and perivaginal irritation. The microorganism is typically identified by culture. The role of G vaginalis in premature rupture of membranes and preterm labor is also under investigation.

Hepatitis B, C, and G

Hepatitis is typically diagnosed by a pattern of antigen and antibody positivity. However, the use of probe technology permits the direct identification of hepatitis DNA or RNA, which may also provide prognostic information. Quantification techniques are used as a technique for monitoring the response to direct acting antiviral, interferon and/or ribavirin therapy in patients with hepatitis C.

Herpes simplex virus (HSV)

Herpes simplex infection of the skin and mucous membranes is characterized by a thin-walled vesicle on an inflammatory base typically in the perioral, ocular, or genital area, although any skin site may be involved. The diagnosis may depend on pathologic examination of cells scraped from a vesicle base or by tissue culture techniques. Herpes simplex encephalitis is one of the most common and serious sporadic encephalitides in immunocompetent adults. The PCR technique to detect HSV in the cerebrospinal fluid has been used to provide a rapid diagnosis of herpes virus encephalitis.

Human Herpes virus-6

Human herpesvirus 6 (HHV-6) is the common collective name for HHV-6A and HHV-6B. These closely related viruses are two of the nine herpes viruses known to have humans as their primary host. Human herpes virus-6 (HHV-6) is widespread in the general population. In immunocompetent hosts, HHV-6 primary infection typically causes a mild, self-limited illness in childhood, often roseola. HHV-6 may also cause meningitis and encephalitis in children and adults. Diagnosis is typically based on rising serologic titers.

In immunosuppressed patients, HHV-6 reactivation may cause meningitis, encephalitis, pneumonitis, and/or bone marrow suppression.

HIV-1, HIV-2

DNA probe technology for HIV-1 is widely disseminated, and HIV-1 quantification has become a standard laboratory test in HIV-1 infected patients. HIV-2 can result in severe immunosuppression and the development of serious opportunistic diseases. Although HIV-2 has been reported in the United States, it is most commonly found in Western Africa. Blood donations are routinely tested for HIV-2, but due to its rarity in this country, clinical testing for HIV-2 is typically limited to those in contact with persons in a country where HIV-2 is endemic or when the clinical picture suggests HIV infection, but testing for HIV-1 is negative.

Influenza virus

Influenza virus is a very common pathogen that accounts for a high burden of morbidity and mortality, especially in elderly and immunocompromised patients. The most common means of identifying influenza is by viral culture, which takes 48-72 hours to complete. Influenza is highly contagious and has been the etiology of numerous epidemics and pandemics. Identification of outbreaks is important so that isolation measures may be undertaken to control the spread of disease. Anti-viral treatment can be effective if instituted early in the course of disease. Therefore, rapid identification of influenza virus is important in making treatment decisions for high-risk patients and in instituting infection control practices.

Legionella pneumophila

Legionella pneumophila is among the most common microbial etiologies of community-acquired pneumonia. Laboratory diagnosis depends on culture, direct fluorescent antibody tests, urinary antigens, or DNA probe. DNA probe techniques have also been used in epidemiologic investigations to identify the source of a Legionella outbreak.

Mycobacteria species

Although mycobacterium can be directly identified in sputum samples, (i.e., acid fast bacilli) these organisms may take 9 to 16 days to culture. DNA probes have also been used to identify specific mycobacterial groups (i.e., mycobacterial tuberculosis, avian complex, or intracellulare) after culture. In addition, amplification techniques for mycobacterium tuberculosis may be used in patients who have a positive smear. The rapid identification of Mycobacteria tuberculosis permits prompt isolation of the patient and identification of the patient’s contacts for further testing.

Mycoplasma pneumoniae

Mycoplasma pneumoniae is an atypical bacterium that is a common cause of pneumonia. It is most prevalent in younger patients, younger than age 40 years and in individuals who live or work in crowded areas such as schools or medical facilities. The infection is generally responsive to antibiotics of the macrolide or quinolone class. Most patients with mycoplasma pneumonia recover completely, although the course is sometimes prolonged for up to four weeks or more. Extra-pulmonary complications of mycoplasma pneumonia occur uncommonly, including hemolytic anemia and the rash of erythema multiforme.

Neisseria gonorrhoeae

Isolation by culture is the conventional form of diagnosis for this common pathogen, but culture requires specific sampling and plating techniques. Direct DNA probes and amplification techniques have also been used. Neisseria is often tested for at the same time as Chlamydia.

Papillomavirus

Papillomavirus species are common pathogens that produce epithelial tumors of the skin and mucous membranes, most prominently the genital tract. Physical examination is the first diagnostic technique. Direct probe and amplification procedures have been actively investigated in the setting of cervical lesions. The ViraPap test is an example of a commercially available direct probe technique for identifying papillomavirus. There has also been interest in evaluating the use of viral load tests of papilloma virus to identify patients at highest risk of progressing to invasive cervical carcinoma.

Streptococcus, Group A

Also referred to as Streptococcus pyogenes, this pathogen is the most frequent cause of acute bacterial pharyngitis. It can also give rise to a variety of cutaneous and systemic conditions, including rheumatic fever and post-streptococcal glomerulonephritis. Throat culture is the preferred method for diagnosing Streptococcus pharyngitis. In addition, a variety of commercial kits are now available that use antibodies for the rapid detection of group A carbohydrate antigen directly from throat swabs. While very specific, these kits are less sensitive than throat cultures, so a negative test may require confirmation from a subsequent throat culture. DNA probes have also been used for direct identification of streptococcus and can be used as an alternative to a throat culture as a back-up test to a rapid, office-based strep test.

Streptococcus, group B

Also referred to as Streptococcus agalactiae, GBS is the most common cause of sepsis, meningitis, or death among newborns. Early-onset disease, within seven days of birth, is related to exposure to GBS colonizing the mother’s anogenital tract during birth. The Centers for Disease Control and Prevention (CDC), the American College of Obstetrics and Gynecology (ACOG), and the American Academy of Pediatricians (AAP) recommend either maternal risk assessment or screening for GBS in the perinatal period. Screening consists of obtaining vaginal and anal specimens for culture at 35 to 37 weeks’ gestation. The conventional culture and identification process requires 48 hours. Therefore there has been great interest in developing rapid assays using DNA probes to shorten the screening process, so that screening could be performed in the intrapartum period with institution of antibiotics during labor.

Trichomonas vaginalis

Trichomonas is a single-cell protozoan that is a common cause of vaginitis. The organism is sexually transmitted and can infect the urethra or vagina. The most common way of diagnosing trichomonas is by clinical signs and by directly visualizing the organism by microscopy in a wet prep vaginal smear. Culture of trichomonas is limited by poor sensitivity. Treatment with metronidazole results in a high rate of eradication. The disease is usually self-limited without sequelae, although infection has been associated with premature birth and higher rates of HIV transmission, cervical cancer, and prostate cancer.

KEY POINTS:

The most recent literature review was conducted for the period through October 18, 2018.

Summary of Evidence

For individuals who have suspected Chlamydophila pneumoniae who receive a nucleic acid probe for C. pneumoniae, the evidence includes prospective and retrospective evaluations of the tests’ sensitivity and specificity. Relevant outcomes are test accuracy and validity, other test performance measures, symptoms, and change in disease status. The body of evidence is limited One study was identified that reported relatively high sensitivity and specificity for a polymerase chain reaction‒based test. However, the total number of patients in this study was small (N=56), and most other studies were conducted in the investigational setting. In addition to the limitations in the evidence base on test characteristics, the clinical implications of these tests are unclear. The evidence is insufficient to determine the effects of the technology on health outcomes.

For individuals who have hepatitis who receive a nucleic acid probe for hepatitis G, the evidence is lacking. Relevant outcomes are test accuracy and validity, other test performance measures, symptoms, and change in disease status. The clinical implications of this test are unclear. The evidence is insufficient to determine the effects of the technology on health outcomes.

For individuals who have signs and/or symptoms of gastroenteritis who receive nucleic acid-based gastrointestinal pathogen panel testing, the evidence includes prospective and retrospective evaluations of the tests’ sensitivity and specificity. Relevant outcomes include test accuracy and validity, other test performance measures, symptoms, and change in disease status. The evidence suggests that gastrointestinal pathogen panels are likely to identify both bacterial and viral pathogens with high sensitivity, compared with standard methods. Access to a rapid method for etiologic diagnosis of gastrointestinal infections may lead to more effective early treatment and infection-control measures. However, in most instances, when a specific pathogen is suspected, individual tests could be ordered. There may be a subset of patients with an unusual presentation who would warrant testing for a panel of pathogens at once, but that subset has not been well defined. The evidence is insufficient to determine the effects of the technology on health outcomes.

For individuals who have signs and/or symptoms of meningitis and/or encephalitis who receive a nucleic acid-based central nervous system pathogen panel, the evidence includes retrospective evaluations of the tests’ sensitivity and specificity. Relevant outcomes include test accuracy and validity, other test performance measures, symptoms, and change in disease status. Access to a rapid method that can simultaneously test for multiple pathogens may lead to the faster initiation of more effective treatment and conservation of cerebrospinal fluid. The available central nervous system panel is highly specific for the included organisms, but the sensitivity for each pathogen is not well-characterized. More than 15% of positives in the largest clinical validity study were false-positives. A negative panel result does not exclude infection due to pathogens not included in the panel. The evidence is insufficient to determine the effects of the technology on health outcomes.

For other nucleic acid probes discussed in this review, the tests’ clinical utility was evaluated based on whether there is demonstrated clinical validity, along with either direct evidence of improved outcomes or a chain of evidence indicating that changes in management leading to improved outcomes are likely to occur with testing. For example, for group A Streptococcus, use of nucleic acid−based testing can result in a reduction in antibiotic use as a result of not needing to initiate empirical antibiotics pending culture results. In many cases, clinical input has indicated that nucleic acid−based testing is considered the standard of care (e.g., hepatitis B and C, HIV-1 and -2, and cytomegalovirus in the post transplant setting).

Practice Guidelines and Position Statements

No guidelines or statements were identified.

U.S. Preventive Services Task Force Recommendations

Nucleic acid probe testing is not a preventive service.

APPROVED BY GOVERNING BODIES:

A list of current U.S. Food and Drug Administration (FDA)-approved or cleared nucleic acid-based microbial tests is available online. The below table lists tests that are FDA-approved/cleared but do not have specific CPT codes.

Table. FDA-Approved/Cleared Tests without CPT Codes

FDA Approved/Cleared Diagnostic Test

Test Type

Bacillus anthracis

Real-time PCR

Coxiella Burnetii (Q fever)

Real-time PCR

Enterococcus faecalis

PNA (Peptide nucleic acid) FISH

Escherichia coli and Pseudomonas aeruginosa

PNA FISH

Escherichia coli and/or Klebsiella pneumoniae and Pseudomonas aeruginosa

PNA FISH

Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa

PNA FISH

Francisella tularensis

Real-time PCR

Leishmania

Real-Time PCR

Yersinia pestis

Real-time PCR

Adenovirus

Multiplex Real-time RT-PCR

Avian Flu

Real-time PT-PCR

Human meta-pneumovirus

Multiplex Real-time RT-PCR

Influenza virus A/H5

Real-time RT-PCR

Influenza virus H1N1

Real-time RT-PCR

Dengue virus

Real-time RT-PCR

Gram-positive/gram-negative bacteria panel

Multiplex nucleic acid amplification

FDA: Food and Drug Administration; FISH: fluorescence in situ hybridization; PCR: polymerase chain reaction; PNA: peptide nucleic acid; RT: reverse transcriptase.

KEY WORDS:

Bartonella henselae or quintana, Borrelia burgdorferi, Candida species, Chlamydia pneumonia or trachomatis, Clostridium difficile, Cytomegalovirus (CMV), Enterovirus, Vancomycin-resistant Enterococcus, Gardnerella vaginalis, Hepatitis B, Hepatitis C, Hepatitis G, Herpes simplex virus, Herpes virus-6, Human immunodeficiency virus 1 (HIV-1), Human immunodeficiency virus (HIV-2), Human papillomavirus (HPV), Influenza virus, Legionella pneumophila, Mycobacterium species, Mycobacterium tuberculosis, Mycobacterium avium, Mycobacterium intracellulare, Mycoplasma pneumonia, Neisseria gonorrhoeae, Respiratory Viral Panel, Staphylococcus aureus, Methicillin-resistant Staphylococcus aureus, Streptococcus, Group A, Streptococcus, Group B, Trichomonas vaginalis, Human Herpes virus-6, MicroGenDX, MYCODART, BioFire, FilmArray GI Panel, FilmArray Respiratory Panel, GI panel, Respiratory Panel, ePlex

BENEFIT APPLICATION:

Coverage is subject to member’s specific benefits. Group specific policy will supersede this policy when applicable.

ITS: Home Policy provisions apply.

FEP: Special benefit consideration may apply. Refer to member’s benefit plan. FEP does not consider investigational if FDA approved and will review for medical necessity.

CURRENT CODING:

CPT Codes: See Policy Section

PREVIOUS CODING:

87470

Infectious agent detection by nucleic acid (DNA or RNA); Bartonella henselae and Bartonella quintana, direct probe technique (deleted effective 1/1/18)

87477

Infectious agent detection by nucleic acid (DNA or RNA); Borrelia burgdorferi, quantification (deleted effective 1/1/18)

87515

Infectious agent detection by nucleic acid (DNA or RNA); hepatitis B virus, direct probe technique (deleted effective 1/1/18)

REFERENCES:

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POLICY HISTORY:

Medical Policy Panel, September 2013

Medical Policy Group, November 2013 (2): New Policy

Medical Policy Administration Committee, November 2013

Available for comment November 20, 2013 through January 4, 2014

Medical Policy Panel, September 2014

Medical Policy Group, September 2014 (1): Updated Description, Policy statement, Key Points, Coding and References related to adding gastrointestinal pathogen panel (new CPT codes 87505-87507) as investigational, and adding new HPV probe CPT codes 87623-87625, which are considered medically necessary, all new codes effective 1/1/15. For Annual coding, placed deleted codes under Previous coding section.

Medical Policy Administration Committee, October 2014

Medical Policy Panel, February 2016

Medical Policy Group, May 2017 (3): Updates to Description, Key Points, Key Words, Approved Governing Bodies, & References; multiple coverage changes added to Policy statements

Medical Policy Administration Committee, June 2017

Available for comment May 23 through July 6, 2017

Medical Policy Group, July 2017 (3): Updated CPT code 87476 as medically necessary on coverage table under Policy Section

Medical Policy Panel, December 2017

Medical Policy Group, January 2018 (3): Updates to Description, Key Points & References; removed Previous Coding section for codes deleted 12/31/14; added central nervous system pathogen panel, ENT/pulmonary panel & nail panel to list of tests considered investigational; no change in intent of policy statements.

Medical Policy Panel, December 2018

Medical Policy Group, January 2019 (9): 2019 Updates to Description, Key Points & References. Added previous coding section for codes: 87470, 87477, 87515-deleted 1/1/18 and removed them from Table 1, added PLA code 0068u-new code effective 10/1/18. Added key word: MYCODART. Removed the following from investigational policy statement: Central nervous system pathogen panel, ENT/pulmonary panel, Nail panel. Added to Table 2 (CPT Codes for Nucleic Acid Probes): Central nervous system pathogen panel, CPT code 87483 to amplified probe column.

Medical Policy Group, June 2019: July 2019 quarterly coding update. Added new CPT codes 0097U and 0098U – 0100U to Table 1 under Policy section. Added Key Words BioFire, FilmArray GI Panel, FilmArray Respiratory Panel, GI panel, Respiratory Panel.

Medical Policy Group, July 2019 (9): Added CPT code 87634 to Table 1 under Policy section for Respiratory Virus Panel.

Medical Policy Group, September 2019: October 2019 quarterly coding update.  Added new CPT codes 0112U and 0115U to the Policy section. Added Key Word ePlex.

Medical Policy Group, November 2019: 2020 Annual Coding Update. Added new CPT code 0151U code to the Policy section.


This medical policy is not an authorization, certification, explanation of benefits, or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All medical policies are based on (i) research of current medical literature and (ii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.

This policy is intended to be used for adjudication of claims (including pre-admission certification, pre-determinations, and pre-procedure review) in Blue Cross and Blue Shield’s administration of plan contracts.

The plan does not approve or deny procedures, services, testing, or equipment for our members. Our decisions concern coverage only. The decision of whether or not to have a certain test, treatment or procedure is one made between the physician and his/her patient. The plan administers benefits based on the member’s contract and corporate medical policies. Physicians should always exercise their best medical judgment in providing the care they feel is most appropriate for their patients. Needed care should not be delayed or refused because of a coverage determination.

As a general rule, benefits are payable under health plans only in cases of medical necessity and only if services or supplies are not investigational, provided the customer group contracts have such coverage.

The following Association Technology Evaluation Criteria must be met for a service/supply to be considered for coverage:

1. The technology must have final approval from the appropriate government regulatory bodies;

2. The scientific evidence must permit conclusions concerning the effect of the technology on health outcomes;

3. The technology must improve the net health outcome;

4. The technology must be as beneficial as any established alternatives;

5. The improvement must be attainable outside the investigational setting.

Medical Necessity means that health care services (e.g., procedures, treatments, supplies, devices, equipment, facilities or drugs) that a physician, exercising prudent clinical judgment, would provide to a patient for the purpose of preventing, evaluating, diagnosing or treating an illness, injury or disease or its symptoms, and that are:

1. In accordance with generally accepted standards of medical practice; and

2. Clinically appropriate in terms of type, frequency, extent, site and duration and considered effective for the patient’s illness, injury or disease; and

3. Not primarily for the convenience of the patient, physician or other health care provider; and

4. Not more costly than an alternative service or sequence of services at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of that patient’s illness, injury or disease.