Coverage Policy Manual
Policy #: 2016004
Category: Laboratory
Initiated: February 2016
Last Review: November 2023
  Lab Test: Identification of Microorganisms Using Nucleic Acid Probes

Description:
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, microbial identification using standard culture is difficult or impossible, and/or treatment decisions are based on quantitative results.
 
Nucleic Acid Probes
A nucleic acid probe is used to detect and identify species or subspecies of organisms by identifying nucleic acid sequences in a sample. Nucleic acid probes detect genetic materials, such as RNA or DNA, unlike other tests, which use antigens or antibodies to diagnose organisms.
 
The availability of nucleic acid probes has permitted the rapid direct identification of microorganisms’ DNA or RNA. Amplification techniques result in exponential increases in copy numbers of a targeted strand of microorganism-specific DNA. The most commonly used amplification technique is polymerase chain reaction (PCR) or reverse transcriptase (RT)-PCR. In addition to PCR, other nucleic acid amplification techniques have been developed such as transcription-mediated amplification, loop-mediated isothermal DNA amplification (LAMP), strand displacement amplification, nucleic acid sequence-based amplification, and branched chain DNA signal amplification. After amplification, target DNA can be readily detected using a variety of techniques. The amplified product can also be quantified to give an assessment of how many microorganisms are present. Quantification of the number of nucleic acids permits serial assessments of response to treatment; the most common clinical application of quantification is the serial measurement of HIV RNA (called viral load).
 
The direct probe technique, amplified probe technique, and probe with quantification methods vary in terms of the degree to which the nucleic acid is amplified and the method for measurement of the signal. The “direct probe” technique refers to detection methods in which nucleic acids are detected without an initial amplification step.
 
The “amplified probe” technique refers to detection methods in which either target, probe, or signal amplification is used to improve the sensitivity of the assay over direct probe techniques, without quantification of nucleic acid amounts.
 
    • Target amplification methods include PCR (including PCR using specific probes, nested or multiplex PCR), nucleic acid-based sequence amplification (NASBA), transcription-mediated amplification (TMA), and strand displacement amplification (SDA). NASBA and TMA involve amplification of an RNA (rather than a DNA) target.
    • Probe amplification method include ligase chain reaction (LCR).
    • Signal amplification methods include branched DNA probes (bDNA) and hybrid capture methods using an anti-DNA/RNA hybrid antibody.
 
The “probe with quantification” techniques refer to quantitative PCR (qPCR) or real-time PCR (rt-PCR) methods that use a reporter at each stage of the PCR to generate absolute or relative amounts of a known nucleic acid sequence in the original sample. These methods may use DNA-specific dyes (ethidium bromide or SYBR green), hybridization probes (cleavage-based [TaqMan] or displaceable), or primer incorporated probes.
 
Direct assays will generally have lower sensitivity than amplified probes. In practice, most commercially available probes are amplified, with a few exceptions. For the purposes of this evidence review, indications for direct and/or amplified probes without quantification are considered together, while indications for a probe with quantification are considered separately.
 
Classically, identification of microorganisms relies either on the culture of body fluids or tissues or identification of antigens, using a variety of techniques including direct fluorescent antibody technique and qualitative or quantitative immunoassays. These techniques are problematic when the microorganism exists in very small numbers or is technically difficult to culture. Indirect identification of microorganisms by immunoassays for specific antibodies reactive with the microorganism is limited by difficulties in distinguishing between past exposure and current infection.
 
Potential reasons for a nucleic acid probe to be associated with improved clinical outcomes compared with standard detection techniques include the following (note: in all cases, for there to be clinical utility, making a diagnosis should be associated with changes in clinical management, which could include initiation of effective treatment, discontinuation of other therapies, or avoidance of invasive testing):
 
    • Significantly improved speed and/or efficiency in making a diagnosis.
    • Improved likelihood of obtaining any diagnosis in cases where standard culture is difficult. Potential reasons for difficulty in obtaining standard culture include low numbers of the organisms (e.g., HIV), fastidious or lengthy culture requirements (e.g., Mycobacteria, Chlamydia, Neisseria species), or difficulty in collecting an appropriate sample (e.g., herpes simplex encephalitis).
    • There is no way to definitively make a diagnosis without nucleic acid testing.
    • The use of nucleic acid probe testing provides qualitatively different information than that available from standard cultures, such as information regarding disease prognosis or response to treatment. These include cases where quantification of viral load provides prognostic information or is used to measure response to therapy.
 
The risks of nucleic acid testing include false-positive and false-negative results, inaccurate identification of pathogens by the device, inaccurate interpretation of test results, or incorrect operation of the instrument.
 
    • False-positive results can lead to unnecessary treatment, with its associated toxicities and side effects, including allergic reaction. In addition, true diagnosis and treatment could be delayed or missed altogether.
    • False-negative results could delay diagnosis and initiation of proper treatment.
    • It is possible that these risks can be mitigated by the use of a panel of selected pathogens indicated by the clinical differential diagnosis while definitive culture results are pending.
 
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.
 
BK Polyomavirus
BK virus (BKV) is a double-stranded DNA, human polyomaviruses (Quest Diagnostics, 2005). More than 70 % of the adult population has antibodies to BKV and JCV, with primary infections typically occurring in childhood. Polymerase chain reaction testing detects the presence of the virus, not antibodies to the virus; thus, the detection of viral DNA may be indicative of an active infection (Randhawa et al, 2005). BK viruria increases in prevalence and magnitude (i.e., viral load) in immunocompromised patients. After kidney transplantation, high-level viruria, or shedding of urothelial or tubular epithelial cells with cytopathologic changes is seen in 30 to 60 percent of patients. However, only one-third of patients with BK viruria develop BK viremia and nephropathy (Hirsch et al, 2010; Sood et al, 2012).
 
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 2 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 5 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.
 
Chikungunya Virus
Chikungunya virus is transmitted by mosquitoes. Symptoms include, most commonly, fever and joint pain but may also include headache, muscle pain, joint swelling or rash. Symptoms can be severe, but infected individuals usually feel better within a week. In some people, joint pain may persist for months. Newborns infected around the time of birth, older adults (65 years and older) and people with medical conditions such as high blood pressure, diabetes, or heart disease are at risk for more severe disease. Once a person has been infected, he or she is likely to be protected from future infections.
 
Chlamydophila pneumoniae
Chlamydophila pneumoniae is an important cause of pneumonia, bronchitis, and sinusitis. Culture and isolation of the microorganism is difficult; a micro-immunofluorescence 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. 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. 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 RNA viruses. This group of viruses includes the polioviruses, coxsackieviruses, echoviruses, and other enteroviruses. In addition to 3 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 enteroviruses.
 
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 to monitor the response to direct-acting antiviral, interferon, and/or ribavirin therapy in patients with hepatitis C.
 
Herpes Simplex Virus
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 herpes simplex virus in the cerebrospinal fluid has been used to provide a rapid diagnosis of herpes virus encephalitis.
 
Human Herpesvirus 6
Human herpesvirus 6 (HHV-6) is the common collective name for HHV-6A and HHV-6B. These closely related viruses are 2 of the 9 herpesviruses known to have humans as their primary host. 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 (Yoshikawa, 2004).
 
HIV-1 and 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 to 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. Antiviral 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, intracellulare) after culture. In addition, amplification techniques for Mycobacterium tuberculosis may be used in patients who have a positive smear. The rapid identification of M. 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 below 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 M. pneumonia recover completely, although the course is sometimes prolonged for up to 4 weeks or more. Extrapulmonary complications of M. 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 HPV to identify patients at highest risk of progressing to invasive cervical carcinoma.
 
SARS-CoV-2
SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is the causative agent of COVID-19 and is of the genus Betacoronavirus. The virus primarily spreads between people through close contact and via respiratory droplets produced from coughs or sneezes.
 
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 streptococcal 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, group B streptococcus (GBS), is the most common cause of sepsis, meningitis, or death among newborns. Early-onset disease, within 7 days of birth, is related to exposure to GBS colonizing the mother’s anogenital tract during birth. The Centers for Disease Control and Prevention, the American College of Obstetrics and Gynecology, and the American Academy of Pediatricians 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 of 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.
 
West Nile Virus
West Nile virus (WNV), an infectious disease carried by mosquitoes, first appeared in the United States in 1999. Persons who get WNV usually have no symptoms or mild symptoms which include, headache, fever, skin rash, body aches and swollen lymph glands. Symptoms may last a few days to several weeks but usually go away on their own.
 
West Nile virus can cause encephalitis or meningitis and can be life-threatening.
 
Older people and those with weakened immune systems are most at risk. There are no specific vaccines or treatments for human WNV disease.
 
Regulatory Status
The U.S. Food and Drug Administration maintains a list of nucleic acid amplification tests (NAATs) that have been cleared by the Center for Devices and Radiological Health.
 
A list of current U.S. Food and Drug Administration (FDA)‒approved or cleared nucleic acid-based microbial tests is available at: http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/InVitroDiagnostics/ucm330711.htm
 
The Association of Molecular Pathology website also provides a list of current FDA approved tests for diagnosis of infectious diseases (available online at: http://www.amp.org/FDATable/FDATable.pdf).
 
The following tests are FDA-approved/cleared but do not have specific CPT codes:
Bacillus anthracis (Real-time PCR), Coxiella burnetii (Q fever) (Real-time PCR), Enterococcus faecalis (PNA 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 RT-PCR), Human metapneumovirus 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.

Policy/
Coverage:
Infectious disease testing ordered or performed as a panel, except as specifically listed in this policy as covered, does not meet primary coverage criteria or is considered not medically necessary. (See statement of non-coverage below.)
 
Effective August 2023
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
The use of nucleic acid testing using a direct or amplified probe technique (without quantification of viral load) meets member benefit certificate primary coverage criteria for the following microorganisms:
 
    • Anaplasma phagocytophilum
        • Amplified Probe: 87468
 
    • Babesia microti (Effective January 1, 2023)
        • Amplified Probe: 87469
 
    • Bartonella henselae or quintana
        • Direct Probe: N/A
        • Amplified Probe: 87471
 
    • Bordetella Pertussis and Bordetella Parapertussis (Effective April 2018)
        • Direct Probe: N/A
        • Amplified Probe: 87265
 
    • Borrelia burgdorferi (Effective August 2010)
        • Amplified Probe: 87476 (coverage per policy 2010035)
 
    • Borrelia miyamotoi
        • Amplified Probe: 87478
 
    • Candida species
        • Direct Probe: 87480
        • Amplified Probe: 87481
 
    • Chikungunya (Effective November 2018)
        • Direct Probe: N/A
        • Amplified Probe: 87798
 
    • Chlamydia trachomatis
        • Direct Probe: 87490
        • Amplified Probe: 87491
 
    • Clostridium difficile
        • Direct Probe: 87493
        • Amplified Probe: N/A
 
    • Enterococcus, Vancomycin-resistant (e.g., enterococcus vanA, vanB)
        • Direct Probe: N/A
        • Amplified Probe: 87500
 
    • Enterovirus
        • Direct Probe: N/A
        • Amplified Probe: 87498
 
    • Ehrlichia chaffeensis
        • Amplified Probe: 87484
 
    • Gardnerella vaginalis
        • Direct Probe: 87510
        • Amplified Probe: 87511
 
    • Herpes simplex virus
        • Direct Probe: 87528
        • Amplified Probe: 87529
 
    • Human papillomavirus
        • Direct Probe: N/A
        • Amplified Probe: 87623-87625
 
    • Legionella pneumophila
        • Direct Probe: 87540
        • Amplified Probe: 87541
 
    • Mumps rubulavirus (Effective February 2020)
        • Direct Probe: N/A
        • Amplified Probe: 87798
 
    • Mycobacterium species
        • Direct Probe: 87550
        • Amplified Probe: 87551
 
    • Mycobacterium tuberculosis
        • Direct Probe: 87555
        • Amplified Probe: 87556
 
    • Mycobacterium avium intracellulare
        • Direct Probe: 87560
        • Amplified Probe: 87561
 
    • Mycoplasma pneumoniae
        • Direct Probe: 87580
        • Amplified Probe: 87581
 
    • Neisseria gonorrhoeae
        • Amplified Probe: 87590
        • Direct Probe: 87591
 
    • Orthopox virus (monkeypox virus, cowpox virus, vaccinia virus)
        • Direct Probe: N/A
        • Amplified Probe: 87593 (Effective 07/26/2022)
 
    • Respiratory Syncytial Virus
        • Direct Probe: N/A
        • Amplified Probe: 87634
 
    • Respiratory Virus Panel
        • Direct Probe: N/A
        • Amplified Probe: 87631
        • 0240U (Effective March 1, 2021)
        • 0241U (Effective January 1, 2022)
        • Note: Effective 6/01/2018 87633 does not meet primary coverage criteria or is considered not medically necessary. (See statement of non-coverage below)
        • Note: Effective July 1, 2022, 87632 does not meet primary coverage criteria or is considered not medically necessary. (See statement of non-coverage below)
 
    • Rubeola (measles) (Effective April 2020)  
        • Direct Probe: N/A
        • Amplified Probe: 87798
 
    • SARS-CoV-2 (Effective July 2020)
        • Direct Probe: N/A
        • Amplified Probe: 87635
        • 87636 (Effective March 1, 2021)
        • 87637 (Effective January 1, 2022)
        • Note-For 0202U, 0223U, 0224U, 0225U, 0226U, 86413, and 87913 see statement of non-coverage below.
 
    • Staphylococcus aureus
        • Direct Probe: N/A
        • Amplified Probe: 87640
 
    • Staphylococcus aureus, methicillin resistant
        • Direct Probe: 87641
        • Amplified Probe: N/A
 
    • Streptococcus, group A
        • Direct Probe: 87650
        • Amplified Probe: 87651
 
    • Streptococcus, group B
        • Direct Probe: N/A
        • Amplified Probe: 87653
 
    • Trichomonas vaginalis
        • Direct Probe: 87660
        • Amplified Probe: 87661
 
    • West Nile (Effective November 2018)
        • Direct Probe: N/A
        • Amplified Probe: 87798
 
    • Zika Virus
        • Direct Probe: N/A
        • Amplified Probe: 87662
 
The use of nucleic acid testing using a direct or amplified probe technique (with or without quantification of viral load) meets member benefit certificate primary coverage criteria for the following microorganisms:
 
    • BK polyomavirus in renal transplant recipients receiving immunosuppressant therapy (Effective February 2019)
        • Direct Probe: 87797
        • Amplified Probe: 87798
        • Quantification: 87799 (Effective March 2021)
 
    • Cytomegalovirus
        • Direct Probe: 87495
        • Amplified Probe: 87496
        • Quantification: 87497
 
    • Hepatitis B virus
        • Direct Probe: N/A
        • Amplified Probe: 87516
        • Quantification: 87517
 
    • Hepatitis C virus
        • Direct Probe: 87520
        • Amplified Probe: 87521
        • Quantification: 87522
 
    • HIV-1
        • Direct Probe: 87534
        • Amplified Probe: 87535
        • Quantification: 87536
        • Note-For 0219U see statement of non-coverage below.
 
    • HIV-2
        • Direct Probe: 87537
        • Amplified Probe: 87538
        • Quantification: 87539
 
    • Human herpes virus
        • Direct Probe: 87531
        • Amplified Probe: 87532
        • Quantification: 87533
 
    • Influenza virus
        • Direct Probe: N/A
        • Amplified Probe: 87501-87503
        • Quantification: N/A
 
Note: The technique for quantification includes both amplification and direct probes; therefore, simultaneous coding for both quantification with either amplification or direct probes, is not warranted.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
Infectious disease testing ordered or performed as a panel except as specifically listed in this policy as covered (above), does not meet member benefit certificate primary coverage criteria of effectiveness in improving health outcomes and are noncovered services. For members with contracts without primary coverage criteria, use of infectious disease testing ordered or performed as a panel, except as specifically listed in this policy as covered (above), is considered not medically necessary. Not medically necessary services are considered contract exclusions in most member benefit certificates of coverage.
 
Any other use of nucleic acid testing with quantification of viral load (other than specifically listed above) does not meet member benefit certificate primary coverage criteria. For members with contracts without primary coverage criteria, the use of nucleic acid testing with quantification of viral load (other than specifically listed above) is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
The use of nucleic acid testing using a direct or amplified probe technique with or without quantification of viral load does not meet member benefit certificate primary coverage criteria, or for those members without primary coverage criteria, is considered investigational for the following microorganisms:
 
    • Atopobium vaginae (Effective January 1, 2021)
        • Quantification: 81513 (RNA)
        • Quantification: 81514 (DNA)
 
    • Bacterial Vaginosis Associated Bacteria 2 (BVAB 2) (Effective January 1, 2021)
        • Quantification: 81514 (DNA)
 
    • Chlamydia trachomatis
        • 0353U
 
    • Chlamydophila pneumoniae
        • Direct Probe: 87485
        • Amplified Probe: 87486
        • Quantification: 87487
 
    • Central Nervous System Panel (Effective 01/01/2018)
        • Direct Probe: N/A
        • Amplified Probe: 87483
        • 0323U
 
    • Gardnerella vaginalis (Effective January 1, 2021)
        • Quantification: 81513 (RNA)
        • Quantification: 81514 (DNA)
 
    • Gastrointestinal pathogen panel
        • Direct Probe: N/A
        • Amplified Probe: 87505-87507, 0097U
        • Quantification: N/A
 
    • Genitourinary pathogen panel
        • 0321U
 
    • Hepatitis B surface antigen (HBsAG), quantitative
        • 87467
 
    • Hepatitis G virus
        • Direct Probe: 87525
        • Amplified Probe: 87526
        • Quantification: 87527
 
    • HIV-1
        • 0219U (Effective October 1, 2020)
 
    • Lactobacillus species (Effective January 1, 2021)
        • Quantification: 81513 (RNA)
        • Quantification: 81514 (DNA)
 
    • Megasphaera type 1 (Effective January 1, 2021)
        • Quantification: 81514 (DNA)
 
    • MicroGenDX (qPCR + NGS) pathogen panel
        • 81479   
 
    • Mycoplasma Genitalium (Effective January 01, 2020)
        • Amplified Probe: 87563
 
    • Neisseria gonorrhoeae
        • 0353U
 
    • Respiratory Virus Panel
        • Amplified Probe: 87633 (Effective June 01, 2018)
        • 87632 (Effective July 1, 2022)
 
    • SARS-CoV-2
        • 0202U
        • 0223U
        • 0224U
        • 0225U
        • 0226U
        • 86413
        • 87913 (Effective February 21, 2022)
 
    • Streptococcus, group A
        • Quantification: 87652 (Effective January 01, 2020)
 
    • Vaginal Pathogen Panel
        • 0330U
 
    • Any other testing/Not otherwise specified
        • Direct Probe: 87797
        • Amplified Probe: 87798
        • Quantification: 87799
 
Effective January 2023 through July 2023
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
The use of nucleic acid testing using a direct or amplified probe technique (without quantification of viral load) meets member benefit certificate primary coverage criteria for the following microorganisms:
 
    • Anaplasma phagocytophilum
        • Amplified Probe: 87468
 
    • Babesia microti (Effecitve January 1, 2023)
        • Amplified Probe: 87469
 
    •   Bartonella henselae or quintana
        • Direct Probe: N/A
        • Amplified Probe: 87471
 
    • Bordatella Pertussis and Bordatella Parapertussis (Effective April 2018)
        • Direct Probe: N/A
        • Amplified Probe: 87265
 
    • Borrelia miyamotoi
        • Amplified Probe: 87478
 
    • Candida species
        • Direct Probe: 87480
        • Amplified Probe: 87481
 
    • Chikungunya (Effective November 2018)
        • Direct Probe: N/A
        • Amplified Probe: 87798
 
    • Chlamydia trachomatis
        • Direct Probe: 87490
        • Amplified Probe: 87491
 
    • Clostridium difficile
        • Direct Probe: 87493
        • Amplified Probe: N/A
 
    • Enterococcus, Vancomycin-resitant (eg, enterococcus vanA, vanB)
        • Direct Probe: N/A
        • Amplified Probe: 87500
 
    •  Enterovirus
        • Direct Probe: N/A
        • Amplified Probe: 87498
 
    • Ehrlichia chaffeensis
        • Amplified Probe: 87484
 
    • Gardnerella vaginalis
        • Direct Probe: 87510
        • Amplified Probe: 87511
 
    • Herpes simplex virus
        • Direct Probe: 87528
        • Amplified Probe: 87529
 
    • Human papillomavirus
        • Direct Probe: N/A
        • Amplified Probe: 87623-87625
 
    • Legionella pneumophila
        • Direct Probe: 87540
        • Amplified Probe: 87541
 
    • Mumps rubulavirus (Effective February 2020)
        • Direct Probe: N/A
        • Amplified Probe: 87798
 
    • Mycobacterium species
        • Direct Probe: 87550
        • Amplified Probe: 87551
 
    • Mycobacterium tuberculosis
        • Direct Probe: 87555
        • Amplified Probe: 87556
 
    • Mycobacterium avium intracellulare
        • Direct Probe: 87560
        • Amplified Probe: 87561
 
    • Mycoplasma pneumoniae
        • Direct Probe: 87580
        • Amplified Probe: 87581
 
    • Neisseria gonorrhoeae
        • Amplified Probe: 87590
        • Direct Probe: 87591
 
    • Orthopox virus (monkeypox virus, cowpox virus, vaccinia virus)
        • Direct Probe: N/A
        • Amplified Probe: 87593 (effective 07/26/2022)
 
    • Respiratory Syncytial Virus
        • Direct Probe: N/A
        • Amplified Probe: 87634
 
    • Respiratory Virus Panel
        • Direct Probe: N/A
        • Amplified Probe: 87631
        • 0240U (Effective March 1, 2021)
        • 0241U (Effective January 1, 2022)
        • Note: Effective 6/01/2018 87633 does not meet primary coverage criteria or is considered not medically necessary. (See statement of non-coverage below)
        • Note: Effective July 1, 2022, 87632 does not meet primary coverage criteria or is considered not medically necessary. (See statement of non-coverage below)
 
    • Rubeola (measles) (Effective April 2020)  
        • Direct Probe: N/A
        • Amplified Probe: 87798
 
    • SARS-CoV-2 (Effective July 2020)
        • Direct Probe: N/A
        • Amplified Probe: 87635
        • 87636 (Effective March 1, 2021)
        • 87637 (Effective January 1, 2022)
        • Note-For 0202U, 0223U, 0224U, 0225U, 0226U, 86413, and 87913 see statement of non-coverage below.
 
    • Staphylococcus aureus
        • Direct Probe: N/A
        • Amplified Probe: 87640
 
    • Staphylococcus aureus, methicillin resistant
        • Direct Probe: 87641
        • Amplified Probe: N/A
 
    • Streptococcus, group A
        • Direct Probe: 87650
        • Amplified Probe: 87651
 
    • Streptococcus, group B
        • Direct Probe: N/A
        • Amplified Probe: 87653
 
    • Trichomonas vaginalis
        • Direct Probe: 87660
        • Amplified Probe: 87661
 
    • West Nile (Effective November 2018)
        • Direct Probe: N/A
        • Amplified Probe: 87798
 
    • Zika Virus
        • Direct Probe: N/A
        • Amplified Probe: 87662
 
The use of nucleic acid testing using a direct or amplified probe technique (with or without quantification of viral load) meets member benefit certificate primary coverage criteria for the following microorganisms:
 
    • BK polyomavirus in renal transplant recipients receiving immunosuppressant therapy (Effective February 2019)
        • Direct Probe: 87797
        • Amplified Probe: 87798
        • Quantification: 87799 (Effective March 2021)
 
    • Cytomegalovirus
        • Direct Probe: 87495
        • Amplified Probe: 87496
        • Quantification: 87497
 
    • Hepatitis B virus
        • Direct Probe: N/A
        • Amplified Probe: 87516
        • Quantification: 87517
 
    • Hepatitis C virus
        • Direct Probe: 87520
        • Amplified Probe: 87521
        • Quantification: 87522
 
    • HIV-1
        • Direct Probe: 87534
        • Amplified Probe: 87535
        • Quantification: 87536
        • Note-For 0219U see statement of non-coverage below.
 
    • HIV-2
        • Direct Probe: 87537
        • Amplified Probe: 87538
        • Quantification: 87539
 
    • Human herpes virus
        • Direct Probe: 87531
        • Amplified Probe: 87532
        • Quantification: 87533
 
    • Influenza virus
        • Direct Probe: N/A
        • Amplified Probe: 87501-87503
        • Quantification: N/A
 
Note: The technique for quantification includes both amplification and direct probes; therefore, simultaneous coding for both quantification with either amplification or direct probes, is not warranted.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
Infectious disease testing ordered or performed as a panel except as specifically listed in this policy as covered (above), does not meet member benefit certificate primary coverage criteria of effectiveness in improving health outcomes and are noncovered services. For members with contracts without primary coverage criteria, use of infectious disease testing ordered or performed as a panel, except as specifically listed in this policy as covered (above), is considered not medically necessary. Not medically necessary services are considered contract exclusions in most member benefit certificates of coverage.
 
Any other use of nucleic acid testing with quantification of viral load (other than specifically listed above) does not meet member benefit certificate primary coverage criteria. For members with contracts without primary coverage criteria, the use of nucleic acid testing with quantification of viral load (other than specifically listed above) is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
The use of nucleic acid testing using a direct or amplified probe technique with or without quantification of viral load does not meet member benefit certificate primary coverage criteria, or for those members without primary coverage criteria, is considered investigational for the following microorganisms:
 
    • Atopobium vaginae (Effective January 1, 2021)
        • Quantification: 81513 (RNA)
        • Quantification: 81514 (DNA)
 
    • Bacterial Vaginosis Associated Bacteria 2 (BVAB 2) (Effective January 1, 2021)
        • Quantification: 81514 (DNA)
 
    • Chlamydia trachomatis
        • 0353U
 
    • Chlamydophila pneumoniae
        • Direct Probe: 87485
        • Amplified Probe: 87486
        • Quantification: 87487
 
    • Central Nervous System Panel (Effective 01/01/2018)
        • Direct Probe: N/A
        • Amplified Probe: 87483
        • 0323U
 
    • Gardnerella vaginalis (Effective January 1, 2021)
        • Quantification: 81513 (RNA)
        • Quantification: 81514 (DNA)
 
    • Gastrointestinal pathogen panel
        • Direct Probe: N/A
        • Amplified Probe: 87505-87507, 0097U
        • Quantification: N/A
 
    • Genitourinary pathogen panel
        • 0321U
 
    • Hepatitis B surface antigen (HBsAG), quantitative
        • 87467
 
    • Hepatitis G virus
        • Direct Probe: 87525
        • Amplified Probe: 87526
        • Quantification: 87527
 
    • HIV-1
        • 0219U (Effective October 1, 2020)
 
    • Lactobacillus species (Effective January 1, 2021)
        • Quantification: 81513 (RNA)
        • Quantification: 81514 (DNA)
 
    • Megasphaera type 1 (Effective January 1, 2021)
        • Quantification: 81514 (DNA)
 
  • MicroGendx (qPCR + NGS) pathogen panel
      • 81479   
 
  •  Mycoplasma Genitalium (Effective January 01, 2020)  
      • Amplified Probe: 87563
 
  • Neisseria gonorrhoeae
      • 0353U
 
  • Respiratory Virus Panel
      • Amplified Probe: 87633 (Effective June 01, 2018)
      • 87632 (Effective July 1, 2022)
 
    • SARS-CoV-2
        • 0202U
        • 0223U
        • 0224U
        • 0225U
        • 0226U
        • 86413
        • 87913 (Effective February 21, 2022)
 
    • Streptococcus, group A
        • Quantification: 87652 (Effective January 01, 2020)
 
    • Vaginal Pathogen Panel
        • 0330U
 
    • Any other testing/Not otherwise specified
        • Direct Probe: 87797
        • Amplified Probe: 87798
        • Quantification: 87799
 
Effective October 2022 through December 2022
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
The use of nucleic acid testing using a direct or amplified probe technique (without quantification of viral load) meets member benefit certificate primary coverage criteria for the following microorganisms:
 
        • Bartonella henselae or quintana
            • Direct Probe: N/A
            • Amplified Probe: 87471
 
        • Bordatella Pertussis and Bordatella Parapertussis (Effective April 2018)
            • Direct Probe: N/A
            • Amplified Probe: 87265
 
        • Candida species
            • Direct Probe: 87480
            • Amplified Probe: 87481
 
        • Chikungunya (Effective November 2018)
            • Direct Probe: N/A
            • Amplified Probe: 87798
 
        • Chlamydia trachomatis
            • Direct Probe: 87490
            • Amplified Probe: 87491
 
        • Clostridium difficile
            • Direct Probe: 87493
            • Amplified Probe: N/A
 
        • Enterococcus, Vancomycin-resitant (eg, enterococcus vanA, vanB)
            • Direct Probe: N/A
            • Amplified Probe: 87500
 
        •  Enterovirus
            • Direct Probe: N/A
            • Amplified Probe: 87498
 
        • Gardnerella vaginalis
            • Direct Probe: 87510
            • Amplified Probe: 87511
 
        • Herpes simplex virus
            • Direct Probe: 87528
            • Amplified Probe: 87529
 
        • Human papillomavirus
            • Direct Probe: N/A
            • Amplified Probe: 87623-87625
 
        • Legionella pneumophila
            • Direct Probe: 87540
            • Amplified Probe: 87541
 
        • Mumps rubulavirus (Effective February 2020)
            • Direct Probe: N/A
            • Amplified Probe: 87798
 
        • Mycobacterium species
            • Direct Probe: 87550
            • Amplified Probe: 87551
 
        • Mycobacterium tuberculosis
            • Direct Probe: 87555
            • Amplified Probe: 87556
 
        • Mycobacterium avium intracellulare
            • Direct Probe: 87560
            • Amplified Probe: 87561
 
        • Mycoplasma pneumoniae
            • Direct Probe: 87580
            • Amplified Probe: 87581
 
        • Neisseria gonorrhoeae
            • Amplified Probe: 87590
            • Direct Probe: 87591
 
        • Orthopox virus (monkeypox virus, cowpox virus, vaccinia virus)
            • Direct Probe: N/A
            • Amplified Probe: 87593 (effective 07/26/2022)
 
        • Respiratory Syncytial Virus
            • Direct Probe: N/A
            • Amplified Probe: 87634
 
        • Respiratory Virus Panel
            • Direct Probe: N/A
            • Amplified Probe: 87631
            • 0240U (Effective March 1, 2021)
            • 0241U (Effective January 1, 2022)
            • Note: Effective 6/01/2018 87633 does not meet primary coverage criteria or is considered not medically necessary. (See statement of non-coverage below)
            • Note: Effective July 1, 2022, 87632 does not meet primary coverage criteria or is considered not medically necessary. (See statement of non-coverage below)
 
        • Rubeola (measles) (Effective April 2020)  
            • Direct Probe: N/A
            • Amplified Probe: 87798
 
        • SARS-CoV-2 (Effective July 2020)
            • Direct Probe: N/A
            • Amplified Probe: 87635
            • 87636 (Effective March 1, 2021)
            • 87637 (Effective January 1, 2022)
            • Note-For 0202U, 0223U, 0224U, 0225U, 0226U, 86413, and 87913 see statement of non-coverage below.
 
        • Staphylococcus aureus
            • Direct Probe: N/A
            • Amplified Probe: 87640
 
        • Staphylococcus aureus, methicillin resistant
            • Direct Probe: 87641
            • Amplified Probe: N/A
 
        • Streptococcus, group A
            • Direct Probe: 87650
            • Amplified Probe: 87651
 
        • Streptococcus, group B
            • Direct Probe: N/A
            • Amplified Probe: 87653
 
        • Trichomonas vaginalis
            • Direct Probe: 87660
            • Amplified Probe: 87661
 
        • West Nile (Effective November 2018)
            • Direct Probe: N/A
            • Amplified Probe: 87798
 
        • Zika Virus
            • Direct Probe: N/A
            • Amplified Probe: 87662
 
The use of nucleic acid testing using a direct or amplified probe technique (with or without quantification of viral load) meets member benefit certificate primary coverage criteria for the following microorganisms:
 
        • BK polyomavirus in renal transplant recipients receiving immunosuppressant therapy (Effective February 2019)
            • Direct Probe: 87797
            • Amplified Probe: 87798
            • Quantification: 87799 (Effective March 2021)
 
        • Cytomegalovirus
            • Direct Probe: 87495
            • Amplified Probe: 87496
            • Quantification: 87497
 
        • Hepatitis B virus
            • Direct Probe: N/A
            • Amplified Probe: 87516
            • Quantification: 87517
 
        • Hepatitis C virus
            • Direct Probe: 87520
            • Amplified Probe: 87521
            • Quantification: 87522
 
        • HIV-1
            • Direct Probe: 87534
            • Amplified Probe: 87535
            • Quantification: 87536
            • Note-For 0219U see statement of non-coverage below.
 
        • HIV-2
            • Direct Probe: 87537
            • Amplified Probe: 87538
            • Quantification: 87539
 
        • Human herpes virus
            • Direct Probe: 87531
            • Amplified Probe: 87532
            • Quantification: 87533
 
        • Influenza virus
            • Direct Probe: N/A
            • Amplified Probe: 87501-87503
            • Quantification: N/A
 
Note: The technique for quantification includes both amplification and direct probes; therefore, simultaneous coding for both quantification with either amplification or direct probes, is not warranted.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
Infectious disease testing ordered or performed as a panel except as specifically listed in this policy as covered (above), does not meet member benefit certificate primary coverage criteria of effectiveness in improving health outcomes and are noncovered services. For members with contracts without primary coverage criteria, use of infectious disease testing ordered or performed as a panel, except as specifically listed in this policy as covered (above), is considered not medically necessary. Not medically necessary services are considered contract exclusions in most member benefit certificates of coverage.
 
Any other use of nucleic acid testing with quantification of viral load (other than specifically listed above) does not meet member benefit certificate primary coverage criteria. For members with contracts without primary coverage criteria, the use of nucleic acid testing with quantification of viral load (other than specifically listed above) is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
The use of nucleic acid testing using a direct or amplified probe technique with or without quantification of viral load does not meet member benefit certificate primary coverage criteria, or for those members without primary coverage criteria, is considered investigational for the following microorganisms:
 
        • Atopobium vaginae (Effective January 1, 2021)
            • Quantification: 81513 (RNA)
            • Quantification: 81514 (DNA)
 
        • Bacterial Vaginosis Associated Bacteria 2 (BVAB 2) (Effective January 1, 2021)
            • Quantification: 81514 (DNA)
 
        • Chlamydia trachomatis
          • 0353U
 
        • Chlamydophila pneumoniae
            • Direct Probe: 87485
            • Amplified Probe: 87486
            • Quantification: 87487
 
        • Central Nervous System Panel (Effective 01/01/2018)
            • Direct Probe: N/A
            • Amplified Probe: 87483
            • 0323U
 
        • Gardnerella vaginalis (Effective January 1, 2021)
            • Quantification: 81513 (RNA)
            • Quantification: 81514 (DNA)
 
        • Gastrointestinal pathogen panel
            • Direct Probe: N/A
            • Amplified Probe: 87505-87507, 0097U
            • Quantification: N/A
 
        • Genitourinary pathogen panel
            • 0321U
 
        • Hepatitis G virus
            • Direct Probe: 87525
            • Amplified Probe: 87526
            • Quantification: 87527
 
        • HIV-1
            • 0219U (Effective October 1, 2020)
 
        • Lactobacillus species (Effective January 1, 2021)
            • Quantification: 81513 (RNA)
            • Quantification: 81514 (DNA)
 
        • Megasphaera type 1 (Effective January 1, 2021)
            • Quantification: 81514 (DNA)
 
        • MicroGendx (qPCR + NGS) pathogen panel
            • 81479   
 
        •  Mycoplasma Genitalium (Effective January 01, 2020)  
            • Amplified Probe: 87563
 
        • Neisseria gonorrhoeae
          • 0353U
 
        • Respiratory Virus Panel
            • Amplified Probe: 87633 (Effective June 01, 2018)
            • 87632 (Effective July 1, 2022)
 
        • SARS-CoV-2
            • 0202U
            • 0223U
            • 0224U
            • 0225U
            • 0226U
            • 86413
            • 87913 (Effective February 21, 2022)
 
        • Streptococcus, group A
            • Quantification: 87652 (Effective January 01, 2020)
 
        • Vaginal Pathogen Panel
            • 0330U
 
        • Any other testing/Not otherwise specified
            • Direct Probe: 87797
            • Amplified Probe: 87798
            • Quantification: 87799
 
Effective July 2022 through September 2022
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
The use of nucleic acid testing using a direct or amplified probe technique (without quantification of viral load) meets member benefit certificate primary coverage criteria for the following microorganisms:
 
    • Bartonella henselae or quintana
      • Direct Probe: N/A
      • Amplified Probe: 87471
 
    • Bordatella Pertussis and Bordatella Parapertussis (Effective April 2018)
      • Direct Probe: N/A
      • Amplified Probe: 87265
 
    • Candida species
      • Direct Probe: 87480
      • Amplified Probe: 87481
 
    • Chikungunya (Effective November 2018)
      • Direct Probe: N/A
      • Amplified Probe: 87798
 
    • Chlamydia trachomatis
      • Direct Probe: 87490
      • Amplified Probe: 87491
 
    • Clostridium difficile
      • Direct Probe: 87493
      • Amplified Probe: N/A
 
    • Enterococcus, Vancomycin-resistant (eg, etnerococcus vanA, vanB)
      • Direct Probe: N/A
      • Amplified Probe: 87500
 
    • Enterovirus
      • Direct Probe: N/A
      • Amplified Probe: 87498
 
    • Gardnerella vaginalis
      • Direct Probe: 87510
      • Amplified Probe: 87511
 
    • Herpes simplex virus
      • Direct Probe: 87528
      • Amplified Probe: 87529
 
    • Human papillomavirus
      • Direct Probe: N/A
      • Amplified Probe: 87623-87625
 
    • Legionella pneumophila
      • Direct Probe: 87540
      • Amplified Probe: 87541
 
    • Mumps rubulavirus (Effective February 2020)
      • Direct Probe: N/A
      • Amplified Probe: 87798
 
    • Mycobacterium species
      • Direct Probe: 87550
      • Amplified Probe: 87551
 
    • Mycobacterium tuberculosis
      • Direct Probe: 87555
      • Amplified Probe: 87556
 
    • Mycobacterium avium intracellulare
      • Direct Probe: 87560
      • Amplified Probe: 87561
 
    • Mycoplasma pneumoniae
      • Direct Probe: 87580
      • Amplified Probe: 87581
 
    • Neisseria gonorrhoeae
      • Amplified Probe: 87590
      • Direct Probe: 87591
 
    • Orthopox virus (monkeypox virus, cowpox virus, vaccinia virus)
      • Direct Probe: N/A
      • Amplified Probe: 87593 (effective 07/26/2022)
 
    • Respiratory Syncytial Virus
      • Direct Probe: N/A
      • Amplified Probe: 87634
 
    • Respiratory Virus Panel
      • Direct Probe: N/A
      • Amplified Probe: 87631
      • 0240U (Effective March 1, 2021)
      • 0241U (Effective January 1, 2022)
      • Note: Effective 6/01/2018 87633 does not meet primary coverage criteria or is considered not medically necessary. (See statement of non-coverage below)
      • Note: Effective July 1, 2022, 87632 does not meet primary coverage criteria or is considered not medically necessary. (See statement of non-coverage below)
 
    • Rubeola (measles) (Effective April 2020)  
      • Direct Probe: N/A
      • Amplified Probe: 87798
 
    • SARS-CoV-2 (Effective July 2020)
      • Direct Probe: N/A
      • Amplified Probe: 87635
      • 87636 (Effective March 1, 2021)
      • 87637 (Effective January 1, 2022)
      • Note-For 0202U, 0223U, 0224U, 0225U, 0226U, 86413, and 87913 see statement of non-coverage below.
 
    • Staphylococcus aureus
      • Direct Probe: N/A
      • Amplified Probe: 87640
 
    • Staphylococcus aureus, methicillin resistant
      • Direct Probe: 87641
      • Amplified Probe: N/A
 
    • Streptococcus, group A
      • Direct Probe: 87650
      • Amplified Probe: 87651
 
    • Streptococcus, group B
      • Direct Probe: N/A
      • Amplified Probe: 87653
 
    • Trichomonas vaginalis
      • Direct Probe: 87660
      • Amplified Probe: 87661
 
    • West Nile (Effective November 2018)
      • Direct Probe: N/A
      • Amplified Probe: 87798
 
    • Zika Virus
      • Direct Probe: N/A
      • Amplified Probe: 87662
 
The use of nucleic acid testing using a direct or amplified probe technique (with or without quantification of viral load) meets member benefit certificate primary coverage criteria for the following microorganisms:
 
    • BK polyomavirus in renal transplant recipients receiving immunosuppressant therapy (Effective February 2019)
      • Direct Probe: 87797
      • Amplified Probe: 87798
      • Quantification: 87799 (Effective March 2021)
 
    • Cytomegalovirus
      • Direct Probe: 87495
      • Amplified Probe: 87496
      • Quantification: 87497
 
    • Hepatitis B virus
      • Direct Probe: N/A
      • Amplified Probe: 87516
      • Quantification: 87517
 
    • Hepatitis C virus
      • Direct Probe: 87520
      • Amplified Probe: 87521
      • Quantification: 87522
 
    • HIV-1
      • Direct Probe: 87534
      • Amplified Probe: 87535
      • Quantification: 87536
      • Note-For 0219U see statement of non-coverage below.
 
    • HIV-2
      • Direct Probe: 87537
      • Amplified Probe: 87538
      • Quantification: 87539
 
    • Human herpes virus
      • Direct Probe: 87531
      • Amplified Probe: 87532
      • Quantification: 87533
 
    • Influenza virus
      • Direct Probe: N/A
      • Amplified Probe: 87501-87503
      • Quantification: N/A
 
Note: The technique for quantification includes both amplification and direct probes; therefore, simultaneous coding for both quantification with either amplification or direct probes, is not warranted.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
For contracts without primary coverage criteria, infectious disease testing ordered or performed as a panel except as specifically listed in this policy as covered (above), do not meet member benefit certificate primary coverage criteria of effectiveness in improving health outcomes and are noncovered services. For contracts without primary coverage criteria, use of infectious disease testing ordered or performed as a panel, except as specifically listed in this policy as covered (above), is considered not medically necessary. Not medically necessary services are considered contract exclusions in most member benefit certificates of coverage.
 
Any other use of nucleic acid testing with quantification of viral load (other than specifically listed above) does not meet member benefit certificate primary coverage criteria. For members with contracts without primary coverage criteria, the use of nucleic acid testing with quantification of viral load (other than specifically listed above) is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
The use of nucleic acid testing using a direct or amplified probe technique with or without quantification of viral load does not meet member benefit certificate primary coverage criteria, or for those members without primary coverage criteria, is considered investigational for the following microorganisms:
 
    • Atopobium vaginae (Effective January 1, 2021)
      • Quantification: 81513 (RNA)
      • Quantification: 81514 (DNA)
 
    • Bacterial Vaginosis Associated Bacteria 2 (BVAB 2) (Effective January 1, 2021)
      • Quantification: 81514 (DNA)
 
    • Chlamydophila pneumoniae
      • Direct Probe: 87485
      • Amplified Probe: 87486
      • Quantification: 87487
 
    • Central Nervous System Panel (Effective 01/01/2018)
      • Direct Probe: N/A
      • Amplified Probe: 87483-*only to be performed on CSF sample
 
    • Gardnerella vaginalis (Effective January 1, 2021)
      • Quantification: 81513 (RNA)
      • Quantification: 81514 (DNA)
 
    • Gastrointestinal pathogen panel
      • Direct Probe: N/A
      • Amplified Probe: 87505-87507, 0097U
      • Quantification: N/A
 
    • Genitourinary pathogen panel
      • 0321U
 
    • Hepatitis G virus
      • Direct Probe: 87525
      • Amplified Probe: 87526
      • Quantification: 87527
 
    • HIV-1
      • 0219U (Effective October 1, 2020)
 
    • Lactobacillus species (Effective January 1, 2021)
      • Quantification: 81513 (RNA)
      • Quantification: 81514 (DNA)
 
    • Megasphaera type 1 (Effective January 1, 2021)
      • Quantification: 81514 (DNA)
      •  
    • MicroGendx (qPCR + NGS) pathogen panel
      • 81479   
 
    • Mycoplasma Genitalium (Effective January 01, 2020)  
      • Amplified Probe: 87563
 
    • Respiratory Virus Panel
      • Amplified Probe: 87633 (Effective June 01, 2018)
      • 87632 (Effective July 1, 2022)
 
    • SARS-CoV-2
      • 0202U
      • 0223U
      • 0224U
      • 0225U
      • 0226U
      • 86413
      • 87913 (Effective February 21, 2022)
 
    • Streptococcus, group A
      • Quantification: 87652 (Effective January 01, 2020)
 
    • Any other testing/Not otherwise specified
      • Direct Probe: 87797
      • Amplified Probe: 87798
      • Quantification: 87799
 
Due to the length of the policy, criteria for dates of service prior to July 1, 2022, is not online. If you would like a hardcopy print, please email: codespecificinquiry@arkbluecross.com

Rationale:
Bartonella henselae or quintana
Microbiologic detection of Bartonella henselae or quintana is difficult. A monoclonal antibody (mAb) to B.henselae has
become commercially available, along with several types of PCR testing. A single-step PCR-based assay which amplifies a fragment of the 16S-23S ribosomal RNA (rRNA) intergenic region conserved in Bartonella species had 80% and 100% sensitivity in feline samples with 10 to 30 CFU/mL bacteria and greater than 50 CFU/mL bacteria, respectively (Jensen, 2000). An earlier study  demonstrated high sensitivity of a PCR-based assay for the Bartonella riboflavin synthase gene in bacterial samples and samples from feline samples and human lymph node samples (Johnson, 2003). Another study reported high sensitivity of a PCR-based enzyme immunoassay in human lymph node samples (Sander, 1999).
 
In 2005, Hansmann et al reported on the diagnostic value of a PCR test for the B. henselae htrA gene in lymph node biopsy specimens or cytopunctures from 70 patients with suspected cat-scratch disease (Hansmann, 2005).Twenty-nine patients were considered to have definite cat-scratch disease based on clinical criteria; 16 were considered to have possible cat-scratch disease; and 26 subjects had an alternative diagnosis and served as controls. PCR analysis had specificity of 100%. In patients with definite cat-scratch disease, PCR testing was positive for 76% (95% confidence interval [CI], 56.5% to 89.7%); in those with possible cat-scratch disease, PCR testing was positive in 20% (95% CI, 4.3% to 48.1%).
 
A 2009 study by Caponetti et al (Capontetti, 2009) compared immunohistochemical analysis (IHC) for diagnosing B.henselae on surgical specimens with PCR detection and serologic testing. The study included 24 formalin-fixed, paraffin-embedded (FFPE) cases of lymphadenitis with histologic and/or clinical suspicion of B. henselae. Control cases included 14 cases of lymphadenopathy. FFPE tissue sections were evaluated with a mAb to B. henselae, Steiner silver stain (SSS), and PCR that targeted B. henselae and B. quintana. Positive cases were as follows: SSS, 11 (46%); PCR, 9 (38%); and IHC, 6 (25%). Only 2 cases (8%) were positive for all 3 techniques. All control cases were negative for IHC and PCR. The diagnostic sensitivity of these 3 tests is low for bartonellae. SSS seems to be the most sensitive test but is the least specific. PCR is more sensitive than IHC and may, therefore, serve as a helpful second-line test on all IHC negative cases.
 
B. henselae infections can cause a wide range of symptoms, from self-limited regional lymphadenopathy to disseminated infection involving visceral organs, the central nervous system, or the heart. B. henselae may also present with fever of unknown origin. Antibiotic therapy is not always needed for uncomplicated infections, but it is required for severe or systemic infections. In cases where B. Henselae is suspected and treatment will change as a result of a positive test, the use of Bartonella PCR testing has potential for clinical utility.
 
Candida Species
Candida infections are most commonly caused by Candida albicans but other species may be responsible. In complicated or severe cases, eg, candidemia and invasive focal infections, or in compromised patients, it may be necessary to identify the infecting Candida species for appropriate treatment planning. DNA probes are available to aid in the diagnosis of possible Candida species infections. Amplified peptide nucleic acid tests have demonstrated high sensitivity and specificity levels of up to 100% (Flahaut, 1998; Xia, 2012). Some tests have been able to detect up to 6 Candida species.9 A real-time qPCR assay, developed for the detection of the most common pathogenic Candida species using a single-reaction PCR assay targets a selected region of the 28S subunit of the fungal rDNA gene. In a 2012 study, the sensitivity and specificity of an assay based on quantitative real-time assay using duplex mutation primers were 100% and 97.4%, respectively (Xia, 2012). The data suggest that this assay may be appropriate for use in clinical laboratories as a simple, low-cost, and rapid screening test for the most frequently encountered Candida species.
 
Vulvovaginal candidiasis can typically be diagnosed by microscopy, and most cases are caused by C.albicans. Other species, such as Candida glabrata, may be responsible but are less common and may be difficult to detect by microscopy. Therefore, identification of Candida subspecies is not usually necessary and should be limited to use in complicated, recurrent or persistent cases that are resistant to azole/antifungal treatment. Additionally, symptomatic patients with negative microscopy may warrant subspecies testing (CDC, 2010).
 
Central Nervous System Bacterial and Viral Panel
The standard approach to the diagnosis of meningitis and encephalitis is culture and pathogen-specific PCR testing of cerebrospinal fluid (CSF) based on clinical characteristics. These techniques have a slow turnaround time, which can delay administration of effective therapies and lead to unnecessary empirical administration of broad-spectrum antimicrobials.
 
The FilmArray Meningitis/Encephalitis Panel (BioFire Diagnostics, Salt Lake City, UT) is a nucleic acid-based test that simultaneously detects multiple bacterial, viral, and yeast nucleic acids from CSF specimens obtained via lumbar puncture from patients with signs and/or symptoms of meningitis and/or encephalitis. The test has been cleared for marketing through the U.S. Food and Drug Administration 510(k) process. The test identifies 14 common organisms responsible for community-acquired meningitis or encephalitis:
 
Bacteria: Escherichia coli K1; Haemophilus influenzae; Listeria monocytogenes; Neisseria meningitides; Streptococcus agalactiae; Streptococcus pneumoniae; Viruses: Cytomegalovirus; Enterovirus; Herpes simplex virus 1; Herpes simplex virus 2; Human herpesvirus 6; Human parechovirus; Varicella zoster virus; Yeast: Cryptococcus neoformans/gattii.
Run-time is approximately 1 hour per specimen.
 
The clinical validity of the test has been analyzed using 1560 CSF specimens collected at 11 U.S. sites and several smaller studies. The following study selection criteria were used to assess whether the central nervous system panel is clinically valid: (1) eligibility and selection are described, and the study population represents the population of interest; (2) the test is compared with a credible reference standard; (3) studies report sensitivity, specificity, and preferably predictive values; studies that completely report true- and false-positive results are ideal. Several studies failed to meet selection criteria (Wootton, 2016; Launes, 2017; Messacar, 2016; Rhein, 2016; Arora, 2017; Lee, 2017).
 
In the largest study (Leber et al, 2016), 1560 samples were tested (Leber, 2016). The samples were from children and adults with available CSF but not limited to those with high pretest probability for an infectious cause for meningitis or encephalitis. Even the most prevalent organisms were present only a small number of times in the samples. The specificities ranged from 98% to 100% and, given the high number of true negatives, the specificities were estimated with tight precision. However, given the small number of true positives, the sensitivities to detect any given organism could not be estimated with precision. A total of 141 pathogens were detected in 136 samples with the FilmArray and 104 pathogens detected using comparator methods; 43 FilmArray results were “false-positive” compared with the comparator method and six were “false-negative.” For 21 of the 43 “false-positives,” repeat testing of the FilmArray, comparator, or additional molecular testing supported the FilmArray results. The remaining 22 “false-positives” (16% of all positives) were unresolved. Codetections were observed in 3.7% (5/136) positive specimens. All five included a bacterial and viral positive result, and all 5 specimens were found to have a false-positive result demonstrated by comparator testing. The investigators suggested that the discrepancies could have been due to specimen contamination or another problem with the assay configuration or testing process.
 
The smaller studies were consistent with Leber (2016) in estimating the specificities for all included pathogens to be greater than 98%. However, there were also a very low number of true positives for most pathogens in these studies and thus the estimates of sensitivities were imprecise.
 
In summary, the FilmArray ME Panel provides fast diagnoses compared with standard culture and pathogen-specific PCR and, because it combines multiple individual nucleic acid tests, clinicians can test for several potential pathogens simultaneously. The test uses only a small amount of CSF, leaving remaining fluid for additional testing if needed. The test is highly specific for the included organisms. However, due to the low prevalence of these pathogens overall, the sensitivity for each pathogen is not well-characterized. More than 15% of positives in the largest study were reported to be false-positives, which could cause harm if used to make clinical decisions. Also, a negative panel result does not exclude infection due to pathogens not included in the panel.
 
Chlamydophila pneumoniae or Chlamydia trachomatis
Probes are commercially available for the detection of Chlamydophila pneumoniae or Chlamydia trachomatis. A study by Stanek et al (Stanek, 2012) demonstrated a Chlamydia-specific real-time PCR which targeted the conserved 16S rRNA gene. The test can detect at least 5 DNA copies and shows very high specificity without cross-amplification from other bacterial DNA. The PCR was validated with 128 clinical samples positive or negative for C. trachomatis or C. pneumoniae. Of 65 positive samples, 61 (93.8%) were found to be positive with the new PCR. Another study (Marangoni, 2012) demonstrated the VERSANT® CT/GC DNA 1.0 Assay performed with 99.2% specificity for C. trachomatis detection and sensitivity of 100%.
 
C. trachomatis, microbial culture is technically difficult, and nucleic acid amplification tests for C.trachomatis are generally preferred over other diagnostic methods, including direct fluorescent antibody tests, enzyme immunoassays, and nucleic acid hybridization tests (CDC, 2014). Diagnosis of C. trachomatis has clinical utility in a variety of settings. Treatment of individuals with C. trachomatis genital infection prevents sexual transmission and complications, including pelvic inflammatory disease. Treatment of pregnant women will prevent the transmission of infection to infants during delivery. Antibiotic treatment is indicated in neonatal conjunctivitis caused by C. trachomatis.
 
PCR-based tests specific for C. pneumoniae have been described in the investigational setting (Tondella, 2002; Gaydos, 1994).
 
Gaydos et al compared tissue culture, PCR/EIA, direct fluorescent antibody (DFA) stain, and serology for the diagnosis of C. pneumoniae in 56 patients with respiratory symptoms and 80 asymptomatic individuals (Gaydos, 1994). Determining test characteristics is limited by the lack of a true gold standard, given the difficulty in culturing C. pneumoniae. However, when culture- and/or DFA-positive results were used as a reference, PCR had a sensitivity and specificity of 76.5% and 99.0%, respectively. However, the use of PCR-based tests for C. pneumoniae in clinical practice has not been well defined.
 
Clostridium difficile
DNA probes for Clostridium difficile using PCR have been commercially available since 2009 (Barbut, 2011; Eastwood, 2009; Huang, 2009; Knetsch, 201).
 
Eastwood et al (Eastwood, 2009) compared the performance characteristics of numerous DNA probes with cytotoxic assays and cultures. The results demonstrated a mean sensitivity of 82.8% (range, 66.7%-91.7%) and a mean specificity of 95.4% (range, 90.9%-98.8%). Rapid identification of C. difficile allows for early treatment of the disease and timely institution of isolation measures to reduce transmission. Because of the advantages of early identification of C. difficile, the use of PCR-based testing for C. difficile has potential to improve health outcomes.
 
Cytomegalovirus
Diagnosis of CMV can be made by culture and/or serologies. However, CMV culture for establishing a diagnosis is limited by the slow growth of CMV and low sensitivity. Serologies provide indirect evidence of current and/or historical infection. A variety of tests to detect CMV DNA have been developed, including but not limited to Hybrid Capture (Digene Corp.), Amplicor CMV Monitor Tests (Roche Molecular Diagnostics), and TaqMan. The specific techniques used may vary by local availability, but studies have suggested that all provide complementary information (Boivin, 2000; Humar, 1999; Li, 2003; Razonable, 2003 Weinberg, 2000).
 
Clinically, molecular assays for CMV are primarily used to quantify CMV viral load, particularly to identify asymptomatic immunosuppressed patients (ie, transplant recipients) who would be candidates for preemptive antiviral therapy. For example, among transplant recipients, CMV infections account for about two-thirds of deaths in the immediate posttransplant period (ie, up to 50 days posttransplant), and thus, a variety of preventive therapies have been investigated. One strategy proposes that all at-risk patients (ie, seropositive patients, or seronegative patients receiving a seropositive organ) be treated prophylactically with antiviral therapy during the first 100 days after transplantation. While this strategy has been shown to be effective in reducing the risk of CMV disease, it results in a large number of patients being treated unnecessarily. Therefore, preemptive therapy has become an accepted option, in which antiviral therapy is initiated when a laboratory technique identifies an increasing viral load. Late CMV disease, defined as occurring after 100 days, is also a concern, and viral loads can also be monitored to prompt antiviral therapy.
 
Enterovirus
Amplified DNA probes are available for detecting this group of viruses including the polioviruses, coxsackieviruses, echoviruses, and other enteroviruses. In addition to 3 polioviruses, there are more than 60 types of non‒polio enteroviruses that can cause disease in humans. Several FDA-approved test kits are available including the GeneXpert Enterovirus Assay (GXEA), with a sensitivity, specificity, PPV, and NPV of 82.1%, 100%, 100%, and 96.2%, respectively. In this study, molecular assays were superior to viral culture for detecting enterovirus RNA in cerebrospinal fluid. GXEA showed a high specificity but a lower sensitivity for the detection of enterovirus RNA compared with the RT-qPCR assay.25 In at least clinical situations, the yield of virus identification with PCR has been shown to be higher than with viral culture (eg, suspected pediatric enteroviral encephalomyelitis) (Tsai, 2014).
 
Enteroviruses are associated with a wide spectrum of clinical symptoms, including exanthematous/enanthematous syndromes (eg, hand-foot-and-mouth disease, herpangina), viral meningitis and encephalitis, acute paralysis, and myocarditis. In neonates, enteroviruses can cause life-threatening systemic infections. In general, management is supportive and addresses symptoms. No antiviral medications are currently approved for the treatment of enterovirus infections. However, there are some situations in which PCR-based testing for enteroviruses allows for discontinuation of therapy for alternative diagnoses (eg, bacterial meningitis). For example, the use of enterovirus PCR testing has been associated with shorter hospital length of stay among febrile infants evaluated for serious bacterial infection with lumbar puncture (Dewan, 2010). Similarly, an observational study reported that the use of enterovirus PCR testing is associated with reduced hospital stay and reduced antibiotic duration in adults with aseptic Meningitis (Giulieri, 2015).
 
Vancomycin-Resistant Enterococcus
Probes are available for detecting vancomycin resistance of organisms (eg, for Enterococcus). These probes are able to detect vancomycin resistance in a rapid and accurate manner so that appropriate antibiotic selection can be made and infectious precautions, such as isolation, can be instituted (Appleman, 2004; Patel, 1997).
 
Gardnerella vaginalis
A 2006 study (Gazi, 2006) evaluated vaginal specimens from 321 symptomatic women that were analyzed for bacterial vaginosis, by both Gram stain using Nugent criteria and a DNA hybridization test (Affirm VPIII hybridization test). Of the 321 patients, 115 (35.8%) were Gram-positive for bacterial vaginosis and 126 (39.2%) were negative. A total of 80 patients (25.0%) demonstrated intermediate Gram staining that was also considered negative. The DNA hybridization test detected Gardnerella vaginalis in 107 (93.0%) of 115 vaginal specimens positive for bacterial vaginosis diagnosed by Gram stain. Compared with the Gram stain, the DNA hybridization test had a sensitivity of 87.7% and a specificity of 96.0%. PPVs and NPVs of the DNA hybridization test were 93.0% and 92.7%, respectively. The study concluded the Affirm VPIII hybridization test correlated well with Gram stain and may be used as a rapid diagnostic tool to exclude bacterial vaginosis in women with genital complaints.
 
Gastrointestinal Pathogen Panel
Infectious gastroenteritis may be caused by a broad spectrum of pathogens resulting in the primary symptom of diarrhea. Panels for gastrointestinal pathogens uses multiplex amplified probe techniques and multiplex reverse transcription for the simultaneous detection of many gastrointestinal pathogens such as C. difficile, Escherichia coli, Salmonella, Shigella, norovirus, rotavirus, and Giardia. Several studies of gastrointestinal pathogen panels demonstrate overall high sensitivities and specificities and indicate the panels may be useful for detecting causative agents for gastrointestinal infections (Claas, 2013; Khare, 2014; Onori, 2014).
 
Studies suggest that panels limited to bacterial pathogens have similarly high sensitivities and specificities compared with bacterial culture (Biswas, 2014). Beckmann et al reported findings on the use of a commercially available gastrointestinal pathogen panel (Luminex Molecular Diagnostics, Toronto, ON) in a group of 120 pediatric patients with suspected viral gastroenteritis and in a group of 151 adult and 25 pediatric patients (n=176) returning from the tropics with gastrointestinal symptoms (Beckmann, 2014). Positive results were detected in 21 samples from adults (11% of 185 samples) and in 66 pediatric samples (52% of samples).
 
Other studies have evaluated panels for bacteria associated with hemorrhagic diarrhea (Salmonella species, Shigella species, enterohemorrhagic E. coli, and Campylobacter species) and have reported high sensitivities and specificities (Al-Talib, 2014). Other panels are comprised of only viral infectious gastroenteritis pathogens (Jiang, 2014). The yield of testing is likely to vary based on panel composition (Khare, 2014). 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 there is suspicion for a specific pathogen, 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.
 
Hepatitis B
Hepatitis B genotyping has been used to predict response to various antiviral agents. In addition, viral load is used to determine which patients with hepatitis B are candidates for antiviral therapy. Guidelines from the National Institutes of Health (2009) (Sorrell, 2009)  and the American Association for the Study of Liver Diseases (Lok, 2009) include quantitative hepatitis B DNA levels in the diagnostic criteria for chronic and resolved hepatitis B and inactive hepatitis B carrier states.
 
Hepatitis C
Diagnostic tests for hepatitis C can be divided into 2 general categories: (1) serological assays that detect antibody to hepatitis C virus (anti-HCV); and (2) molecular assays that detect, quantify, and/or characterize HCV RNA genomes within an infected patient. Detection of HCV RNA in patient specimens by PCR provides evidence of active HCV infection and is used to confirm the diagnosis and monitor the response to antiviral therapy. The use of direct-acting antiviral agents (with or without interferon) has the potential to treat and cure chronic hepatitis C. Therapy-induced sustained virologic remission has been shown to reduce liver-related death, liver failure, and to a lesser extent, hepatocellular carcinoma.
 
Hepatitis G
It is possible that hepatitis C is part of a group of GB viruses, rather than just a single virus. It is unclear if hepatitis G causes a type of acute or chronic illness. When diagnosed, acute hepatitis G infection has usually been mild and brief and there is no evidence of serious complications, but it is possible that, like other hepatitis viruses, it can cause severe liver damage resulting in liver failure. The only method of detecting hepatitis G is by real-time PCR and direct sequencing for 4 randomly selected samples followed by phylogenetic analysis.
 
Herpes Simplex Virus
Typing of HSV isolates is required to identify the virus isolated in culture. The methods available for this include antigen detection by immunofluorescence (IF) assays and PCR. A 2009 cross-sectional study (Abraham, 2009) utilized 4 reference strains and 42 HSV isolates obtained from patients between September 1998 and September 2004. These were subjected to testing using a MAb-based IF test and a PCR that detects the polymerase (pol) gene of HSV isolates. The observed agreement of the MAb IF assay with the pol PCR was 95.7%. A total of 54.8% (23/42) of isolates tested by IF typing were found to be HSV-1, 40.5% (17/42) were HSV-2, and 2 (4.8%) were untypable using the MAb IF assay. The 2 untypable isolates were found to be HSV-2 using the pol PCR. According to the American Academy of Family Physicians, antiviral medications have expanded treatment options for the 2 most common cutaneous manifestations, HSV-1 and HSV-2. Acyclovir therapy remains an effective option; however, famciclovir and valacyclovir offer improved oral bioavailability and convenient oral dosing schedules but at a higher cost. Patients who have 6 or more recurrences of genital herpes per year can be treated with daily regimens which are effective in suppressing 70% to 80% of symptomatic recurrences.
 
Human Herpesvirus 6
Human herpesvirus 6 (HHV-6) can be detected with a number of immunoassays. The high rate of seropositivity in the general population makes interpreting positive results difficult. Historically, paired samples with a rise in antibody titer have been needed to diagnose an active infection. Qualitative and quantitative PCR tests are available for HHV-6 in blood and other samples. At least 1 evaluation of rt-PCR detecting viral mRNA transcripts in hematopoietic stem cell transplant (HSCT) subjects showed good analytic validity (Bressollette-Bodin, 2014).
 
Most often, in healthy patients, HHV-6 causes no symptoms or a mild-self-limited illness. In these cases, a definitive diagnosis of HHV-6 has little utility. However, primary HHV-6 infection can cause severe disease including thrombocytopenia, hepatitis, myocarditis, and meningoencephalitis. In immunosuppressed patients, particularly HSCT recipients, HHV-6 reactivation may cause a range of severe symptoms. A number of antiviral agents are active against HHV-6 (eg, ganciclovir, foscarnet). A variety of treatment strategies are used for immunosuppressed patients, which can be classified as prophylactic (all at-risk patients treated), preemptive (patients treated when viral replication is detected), and curative (patients treated when disease is confirmed) (Agut, 2015). The use of a quantitative HHV-6 assay may be used in treatment-related decisions.
 
Human Immunodeficiency Virus 1
Validated DNA probes are widely available for diagnosis and HIV-1 quantification. Quantification is standard of care to determine viral load in infected patients to monitor response to antiretroviral therapies.
 
Human Immunodeficiency Virus 2
DNA probes are available for diagnosis and quantification of HIV-2. HIV-2 is most commonly found in Western Africa, although it has been reported in the United States. Blood donations are routinely tested for HIV-2, but clinical testing for HIV-2 is typically limited to those in contact with persons in a country where HIV-2 is endemic or when clinical evaluation suggests HIV infection, but testing for HIV-1 is negative. HIV-2 quantification is regularly done to determine viral load in infected patients to monitor response to antiretroviral therapies.
 
Human Papillomavirus
There has also been research interest in exploring the relationship of human papilloma viral load and progression of low-grade cervical lesions to cervical cancer. While studies have reported that high-grade lesions are associated with higher viral loads,(Abba, 2003; Lorincz, 2002) clinical utility is based on whether or not the presence of increasing viral loads associated with low-grade lesions is associated with disease progression. For example, current management of cervical smears with “atypical cells of uncertain significance” suggests testing with HPV, and then, if positive, followed by colposcopy. It is hypothesized that colposcopy might be deferred if a low viral load were associated with a minimal risk. However, how treatment decisions may be tied to measurements of viral load is unclear (Josefsson, 2000; Schlecht, 2003; Ylitalo, 2000). Persistent infection with various HPV genotypes has also been linked with cervical lesions and may influence treatment decisions. HPV genotypes 16 and 18 have been most associated with carcinogenesis. Patients with high-risk HPV genotypes may warrant direct referral to colposcopy (Saslow, 2012; Wheeler, 2014).
 
Influenza Virus
Numerous different strains of influenza virus can be identified by DNA probes. Published studies indicate improved sensitivity of PCR for identifying influenza and distinguishing influenza from related viruses. Lassauniere et al (Lassauniere, 2010) used a multiplex RT-PCR probe to identify 13 respiratory viruses, including influenza A and B. Screening of 270 samples that were negative on immunofluorescence assays revealed the presence of a respiratory virus in 44.1%. Probes have also been developed to identify specific strains of influenza associated with epidemics, such as the H1N1 influenza virus (Wenzel, 2009). Because of the importance of early identification of outbreaks for infection-control purposes and of initiating antiviral therapy early in the course of illness (if indicated), there is clinical utility for the use of these tests.
 
Legionella pneumophila
Typically, methods to detect Legionella pneumophila, which is associated with 90% of culture-confirmed Legionella species infections, have included culture, serology, and/or urine antigen testing, which are limited by relatively low sensitivities and long turnaround times.
 
DNA probes for Legionella pneumophila have been developed. A 2010 study (Maurin, 2010) compared the usefulness of 2 quantitative RT-PCR assays (qrt-PCRmip targeting L. pneumophila, and qrt-PCR16S targeting all Legionella species) performed on lower respiratory tract (LRT) samples for diagnostic and prognostic purposes in 311 patients hospitalized for community-acquired pneumonia (CAP). The Now Legionella urinary antigen test from Binax (Portland, ME) was used as a reference test. One subset of 255 CAP patients admitted to Chambery hospital in 2005 and 2006 was evaluated and the sensitivities, specificities, PPVs and NPVs for both qrt-PCR tests were 63.6%, 98.7%, 77.7%, and 97.4%, respectively.
 
Diederen et al evaluated the use of an rt-PCR assay for Legionella species in 151 subjects with respiratory infections, 37 (25%) of whom fulfilled the European Working Group for Legionella Infections criteria for Legionella pneumonia and were considered to have Legionella pneumonia (Diederen, 2008). For a 16S rRNA-based PCR, the estimated sensitivity and specificity were 86% (95% CI, 72% to 95%) and 95% (95% CI, 90% to 98%), respectively. For a mip gene-based PCR, the estimated sensitivity and specificity were 92% (95% CI, 78% to 98%) and 98% (95% CI, 93% to 100%), respectively. Another study reported a significantly higher sensitivity for PCR versus culture in detecting L. pneumophila in samples taken within 2 days or less of hospitalization (94.7% vs 79.6%, respectively) or 3 to 14 days of hospitalization (79.3% and 47.8%, respectively) (Mentasti, 2012).
 
Delay in initiating appropriate antimicrobial therapy for Legionnaire’s disease is associated with increased mortality, which makes a strong indirect argument for improved early detection with nucleic acid probes.
 
Mycobacteria Species
DNA probes are available to distinguish between Mycobacterium species. In a recent study, (Choi, 2012) the extracted DNA specimens from Mycobacterium species and non-mycobacterial species were tested using peptide nucleic acid (PNA) probe-based RT-PCR assay to evaluate potential cross-reactivity. A total of 531 respiratory specimens (482 sputum specimens, 49 bronchoalveolar washing fluid specimens) were collected from 230 patients in July and August, 2011. All specimens were analyzed for the detection of Mycobacteria by direct smear examination, mycobacterial culture, and PNA probe-based RT-PCR assay. In cross-reactivity tests, no false-positive or false-negative results were evident. When the culture method was used as the criterion standard test for comparison, PNA probe-based RT-PCR assay for detection of Mycobacterium tuberculosis complex (MTBC) had a sensitivity and specificity of 96.7% (58/60) and 99.6% (469/471), respectively. Assuming the combination of culture and clinical diagnosis as the standard, the sensitivity and specificity of the RT-PCR assay for detection of MTBC were 90.6% (58/64) and 99.6% (465/467), respectively. The new RT-PCR for the detection of nontuberculous mycobacteria had a sensitivity and specificity of 69.0% (29/42) and 100% (489/489), respectively.
 
Mycobacterium tuberculosis
DNA probes are available to diagnose M. tuberculosis infection. In a recent study, (Seagar, 2012) an in-house IS6110 RT-PCR (IH IS6110), MTB Q-PCR Alert (Q-PCR) and GenoType® MTBDRplus (MTBDR) were compared for the direct detection of (MTBC in 87 specimens. This included 82 first smear-positive specimens and 3 smear-negative specimens. The sensitivities of IH IS6110, Q-PCR, MTBDR, and IH ITS for MTBC detection were 100%, 92%, 87%, and 87% respectively, compared with culture. Both IS6110-based RT-PCRs (in-house and Q-PCR) were similar in performance with 91.2% concordant results for MTBC detection. However, none of the RT-PCR assays tested provide drug resistance data. Detection and drug resistance profiling are necessary for successful treatment of infection.
 
Mycobacterium avium and Mycobacterium intracellulare
DNA probes are available to diagnose Mycobacterium avium and Mycobacterium intracellulare infection. One study (Bicmen, 2011) evaluated the performance of the GenoType Mycobacteria Direct (GTMD) test for rapid molecular detection and identification of the MTBC and 4 clinically important nontuberculous mycobacteria (M. avium, M. intracellulare, M. kansasii, M. malmoense) in smear-negative samples. A total of 1570 samples (1103 bronchial aspiration, 127 sputum, 340 extrapulmonary samples) were analyzed. When evaluated, the performance criteria in combination with a positive culture result and/or the clinical outcome of the patients, the overall sensitivity, specificity, and PPVs and NPVs were found to be 62.4%, 99.5%, 95.9%, and 93.9%, respectively, whereas they were 63.2%, 99.4%, 95.7%, and 92.8%, respectively, for pulmonary samples and 52.9%, 100%, 100%, and 97.6%, respectively, for
extrapulmonary samples. Among the culture-positive samples which had Mycobacterium species detectable by the GTMD test, 3 samples were identified to be M. intracellulare and 1 sample was identified to be M. avium. However, 5 M. intracellulare samples and an M. kansasii sample could not be identified by the molecular test and were found to be negative. The GTMD test is a reliable, practical, and easy tool for rapid diagnosis of smear-negative pulmonary and extrapulmonary tuberculosis so that effective precautions may be taken and appropriate treatment may be initiated.
 
Mycoplasma pneumoniae
Probes for Mycoplasma pneumoniae have been developed (Chalker, 2011; Peuchangt, 2009). In 1 study using probes, a very high sensitivity and specificity for M. pneumoniae infection was reported (99.1% and 100%, respectively) (Ishiguro, 2015). Chalker et al (Chalker, 2011) tested 3987 nose and throat swabs from patients presenting with symptoms of a respiratory tract infection. Mycoplasma DNA was present in 1.7% of patients overall and was more common in children aged 5 to 14 years, in whom 6.0% of samples were positive. Probes have also been developed to test for mycoplasma strains with macrolide resistance. Peuchant et al (Peuchant, 2009) found that 9.8% (5/51) of mycoplasma strains were macrolide resistant.
 
In many cases, management of M. pneumoniae infection does not require definitive diagnosis (eg, community-acquired pneumonia). However, there are some cases where M. Pneumoniae is associated with severe illnesses that can have a variety of causes, in which definitive diagnosis may make a difference in treatment. M. pneumoniae PCR can be used to detect M. pneumoniae in patients with Stevens-Johnson syndrome (Olson, 2015) and refractory/severe pneumonia (Miyashita, 2015). At least 1 study suggests that inappropriate antibiotic use may worsen fulminant mycoplasma infection, and patients benefit from early administration of appropriate antimycoplasmal drugs with steroids (Izumikawa, 2014).
 
Neisseria gonorrhoeae
Probes for Neisseria gonorrhoeae have been developed for commercial use. These probes are often a combination test with C. trachomatis. A 2012 study (Hopkins, 2012) demonstrated the PPV of the screening PCR (Cobas 4800 CT/NG PCR screening assay) in urine specimens remained high (98.75%) even though the prevalence of gonorrhoeae was low. Another study12 demonstrated the VERSANT® CT/GC DNA 1.0 assay performed with 99.4% and 99.2% of specificity for N. gonorrhoeae and C. trachomatis detection, respectively, whereas sensitivity was 100% both for C. trachomatis and N. gonorrhoeae. As a comparator, culture methods were 100% specific, but far less sensitive. As a clinical consideration, patients accept antibiotic treatment before their infection status has been confirmed.
 
Respiratory Viral Panel
A broad spectrum of pathogens is causative for respiratory tract infections, but symptoms are mostly similar. The identification of the causative viruses is only feasible using multiplex PCR or several monoplex PCR tests in parallel. Several studies of various respiratory viral panels,(Mansuy, 2012; Dabisch-Ruthe, 2012); Pierce, 2012) demonstrate the multiplex assay detected clinically important viral infections in a single genomic test and thus, may be useful for detecting causative agents for respiratory tract disorders. A 2011 study by Brittain-Long (Brittain-Long, 2011) on a randomized population of 406 patients with access to a rapid, multiplex-PCR assay used to detect 13 viruses had lower antibiotic prescription rates (4.5% vs 12.3%, respectively) versus delayed identification with no significant difference in outcome at follow-up (p=0.359). Access to a rapid method for etiologic diagnosis of respiratory tract infections may reduce antibiotic prescription rates at the initial visit in an outpatient setting.
 
Staphylococcus aureus and Methicillin-Resistant Staphylococcus aureus
Probes are available for the detection of Staphylococcus aureus (Kaplan, 2005; Zhang, 2004). These probes are able to not only distinguish between coagulase-negative Staphylococcus and S. aureus, they can also detect methicillin-resistant species (MRSA) with high accuracy (Patel, 1997; Claas, 2013). Given the importance of establishing an early and accurate diagnosis in clinical situations in which an S. aureus infection is likely and there is substantial likelihood of MRSA, there is clinical utility for testing in these situations.
 
Streptococcus, Group A
While group A Streptococcus pyogenes (group A Streptococcus [GAS]) can cause a variety of clinical symptoms including impetigo, pharyngitis, and more invasive infections (eg, necrotizing fasciitis, pneumonia), most of the focus of rapid detection methods is on the diagnosis of GAS pharyngitis. Patients with confirmed acute GAS pharyngitis are typically treated with antibiotics, which shorten the duration of symptoms modestly and help prevent acute rheumatic fever. The diagnosis of GAS pharyngitis can be made by culture, which has a sensitivity of 90% to 95%, but is limited by a slow turnaround time (1-2 days), which may hamper decisions about initiating antibiotic therapy. Point-of-care rapid antigen detection tests (RADTs) are widely used to diagnose GAS pharyngitis. RADTs are characterized by high specificity (approximately 95%) but poor sensitivity (70%-90%) compared with culture (Shulman, 2012).
 
Several nucleic acid probes that detect either unamplified or amplified nucleotides have been developed. Typically, these tests have a shorter turnaround time than culture, and some are intended to be used as point-of-care tests.
 
In most studies of the amplified PCR assays, the sensitivity and specificity of the probes are very high. Upton et al reported lower sensitivity and lower PPV for the Illumigene assay than previous studies using this assay (Upton, 2015). The authors hypothesize that the lower PPV may be related to the fact that the study was conducted in a population of children attending school, lowering the pretest probability of actual GAS infection. Alternatively, the PCR assay may be detecting isolates of other Streptococcus species that carry the GAS pyrogenic exotoxin B gene, which is detected by the assay.
 
The high NPV of nucleic acid-based assays for GAS suggests that as point-of-care tests, they offer improved accuracy over the current standard, RADTs. The high sensitivity, approaching that of standard culture, suggests that it may be reasonable to use them as an alternative to culture.
 
Streptococcus, Group B
Several different rapid PCR-based tests for group B Streptococcus (GBS) have been developed, with reported sensitivities and specificities similar to that of conventional culture. DNA probes have also been developed to identify GBS from cultured specimens (Bergeron, 2001; Bergeron, 2000). The use of intrapartum antibiotic therapy for GBS is recommended in patients who are known to be carriers for GBS. The postpartum management of newborn infants to prevent early-onset GBS infection is affected by whether the maternal GBS status is positive, negative, or unknown, and whether antibiotic prophylaxis is administered. The availability of rapid testing in peripartum women allows initiation or discontinuation of peripartum antibiotic prophylaxis to prevent vertical transmission of GBS.
 
Trichomonas vaginalis
Nye et al87 compared the performance characteristics of PCR testing for Trichomonas with wet prep microscopy and culture in 296 female and 298 male subjects. In both women and men, DNA probe testing of vaginal swabs was more sensitive than culture. However, in men, wet prep testing was more sensitive than DNA probe testing. Munson et al (Munson, 2010) compared DNA probe testing and culture in 255 vaginal saline preparations. The DNA probe identified Trichomonas in 9.4% (24/255) of specimens that were negative on culture. This probe offers the ability to better distinguish between causes of vaginitis, which can be difficult clinically and using standard culture methods. Nucleic acid amplification tests have demonstrated higher clinical sensitivity than culture and wet mount microscopy,(Nye, 2009) as well as single-probe nonamplified testing in general. A 2011 prospective multicenter study of 1025 asymptomatic and symptomatic women found nucleic acid amplification testing had clinical sensitivity of 100% for both vaginal and endocervical swabs while urine specimen sensitivity was 95.2% (Schwebke, 2011). Specificity levels ranged from 98.9% to 99.6%. Other studies have also reported similar results (Andrea, 2011). PCR amplification tests have higher clinical sensitivity and are considered the standard of care for diagnosing Trichomonas vaginalis when culturing is not an option.
 
Summary of Evidence
The evidence for the use of nucleic acid probes for Chlamydophila pneumoniae or hepatitis G virus in individuals with suspected C. pneumoniae or with hepatitis, respectively, 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 for both types of organisms. For C. pneumoniae, 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 based 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.
 
The evidence for the use of a nucleic acid-based gastrointestinal pathogen panel in individuals who have signs and/or symptoms of gastroenteritis 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.
 
2019 Update
Annual policy review completed with a literature search using the MEDLINE database through October 2019. No new literature was identified that would prompt a change in the coverage statement.
 
 2020 Update
Annual policy review completed with a literature search using the MEDLINE database through October 2020. No new literature was identified that would prompt a change in the coverage statement. The key identified literature is summarized below.
 
In 2020, the Infectious Diseases Society of America (IDSA) established a panel composed of 8 members including frontline clinicians, infectious diseases specialists and clinical microbiologists who were members of the IDSA, American Society for Microbiology (ASM), Society for Healthcare Epidemiology of America (SHEA), and the Pediatric Infectious Diseases Society (PIDS). Panel members represented the disciplines of adult and pediatric infectious diseases, medical microbiology, as well as nephrology and gastroenterology. The panel created a COVID-19 Diagnosis guideline using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach for evidence assessment; and, given the need for rapid response to an urgent public health crisis, the methodological approach was modified according to the GIN/McMaster checklist for development of rapid recommendations. The panel published recommendations for COVID-19 Diagnosis in an online format, as when substantive new information becomes available the recommendations will require frequent updating (IDSA, 2020). The current recommendations (published May 6, 2020) support SARS-CoV-2 nucleic acid testing for the following groups:
 
        • all symptomatic individuals suspected of having COVID-19;
        • asymptomatic individuals with known or suspected contact with a COVID-19 case;
        • asymptomatic individuals without known exposure when the results will impact isolation/quarantine/personal protective equipment (PPE) usage decisions, dictate eligibility for surgery, or inform administration of immunosuppressive therapy.
 
The IDSA panel further recommends the following:
 
        • collecting nasopharyngeal, or mid-turbinate or nasal swabs rather than oropharyngeal swabs or saliva alone for SARS-CoV-2 RNA testing in symptomatic individuals with upper respiratory tract infection (URTI) or influenza like illness (ILI) suspected of having COVID-19 (conditional recommendation, very low certainty of evidence).
        • nasal and mid-turbinate (MT) swab specimens may be collected for SARS-CoV-2 RNA testing by either patients or healthcare providers, in symptomatic individuals with upper respiratory tract infection (URTI) or influenza like illness (ILI) suspected of having COVID-19 (conditional recommendation, low certainty of evidence).
        • a strategy of initially obtaining an upper respiratory tract sample (e.g., nasopharyngeal swab) rather than a lower respiratory sample for SARS-CoV-2 RNA testing in hospitalized patients with suspected COVID-19 lower respiratory tract infection. If the initial upper respiratory sample result is negative, and the suspicion for disease remains high, the IDSA panel suggests collecting a lower respiratory tract sample (e.g., sputum, bronchoalveolar lavage fluid, tracheal aspirate) rather than collecting another upper respiratory sample (conditional recommendations, very low certainty of evidence)
        • performing a single viral RNA test and not repeating testing in symptomatic individuals with a low clinical suspicion of COVID-19 (conditional recommendation, low certainty of evidence).
        • repeating viral RNA testing when the initial test is negative (versus performing a single test) in symptomatic individuals with an intermediate or high clinical suspicion of COVID-19 (conditional recommendation, low certainty of evidence).
 
The IDSA panel makes no recommendations for or against using rapid (i.e., test time 1hour) versus standard RNA testing in symptomatic individuals suspected of having COVID-19 (knowledge gap).
 
2021 Update
Annual policy review completed with a literature search using the MEDLINE database through October 2021. No new literature was identified that would prompt a change in the coverage statement. The key identified literature is summarized below.
 
Kosai et al evaluated the Verigene Pathogens Nucleic Acid Test (Luminex Corporation), testing 268 clinical stool samples for bacteria and toxins and 167 samples for viruses (Kosai, 2021). Of these samples, 256 and 160 samples, respectively, (95.5% and 95.8%) had fully concordant results between the Verigene EP test and the reference methods (which were culture for bacteria and toxins and xTAG GPP for viral detection). Overall sensitivity and specificity were 97.0% and 99.3%, respectively. Sensitivity for individual pathogens ranged from 87.5% to 100%, and specificity ranged from 98.7% to 100%. A total of 13 false-positive and 6 false-negative results were reported.
 
American Society for Microbiology
7.1 In 2020, the American Society for Microbiology updated the 2010 guidelines on detecting and identifying GBS that were originally published by the CDC (Filkins, 2020). The guidelines state that "intrapartum NAAT without enrichment has an unacceptably high false negative rate...As such we do not recommend the use of intrapartum NAAT without enrichment to rule out the need for prophylaxis." All GBS screening specimens should be incubated in selective enrichment broth prior to agar media plating or NAAT. " Nucleic acid amplification-based identification of GBS from enrichment broth is acceptable" for GBS screening, "but not sufficient for all patients" due to high false-negative rates.
 
2022 Update
Annual policy review completed with a literature search using the MEDLINE database through October 2022. No new literature was identified that would prompt a change in the coverage statement. The key identified literature is summarized below.
 
The CDC published updated guidelines on Zika virus testing (Zika Virus: Testing Guidance, 2019). Routine testing for Zika virus in asymptomatic pregnant patients is not recommended, but NAAT testing may still be considered for asymptomatic pregnant women with recent travel to an area with risk of Zika outside the U.S. and its territories. Symptomatic pregnant patients should receive NAAT testing if they have recently traveled to areas with a risk of Zika virus or if they have had sex with someone who lives in or recently traveled to areas with risk of Zika virus. If a pregnant woman (with risk of Zika virus exposure) has a fetus with prenatal ultrasound findings consistent with congenital Zika virus infection, Zika virus NAAT and IgM testing should be performed on maternal serum and NAAT on maternal urine. If amniocentesis is being performed as part of clinical care, Zika virus NAAT testing of amniocentesis specimens should also be performed.
 
2.1 The National Institute of Health (NIH), CDC, and HIV Medicine Association of the Infectious Diseases Society of America (IDSA) published guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV (NIH Guidelines, 2022). The most recent update took place in 2022. In these guidelines, NAATs are discussed in the following situations:
 
2.1.1 Bartonella species
For patients with suspected bacillary angiomatosis, serologic tests are the standard of care and the most accessible test for diagnosing Bartonella infection. There are PCR methods that have been developed for identification and speciation of Bartonella and are becoming increasingly available through private laboratories, as well as the CDC and may aid in diagnosis of Bartonella in freshly biopsied tissue samples or whole blood.
 
2.1.2 Clostridioides (Clostridium) difficile
Detection of either the C. difficile toxin B gene, using NAAT, or the C. difficile toxin B protein, using an enzyme immunoassay, is required for diagnosis. PCR assays have high sensitivity and can detect asymptomatic carriers.
 
2.1.3 Cytomegalovirus
For patients with suspected CMV disease, diagnosis is based on clinical symptoms and the presence of CMV in cerebral spinal fluid (CSF) or brain tissue, most often evaluated with PCR. “Viremia can be detected by PCR” however, "a negative serum or plasma PCR assay does not rule out CMV end-organ disease."
 
2.1.4 Hepatitis B
The CDC, the United States Preventive Services Task Force, and the American Association for the Study of Liver Disease (AASLD) recommend that patients with HIV infection should be tested for hepatitis B; however, NAATs are not recommended for initial testing in patients with HIV.
 
2.1.5 Hepatitis C
Patients with HIV are recommended to undergo routine hepatitis C screening, initially “performed using the most sensitive immunoassays licensed for detection of antibody to HCV in blood.” The use of NAATs are not mentioned for initial testing in patients with HIV.
 
2.1.6 Herpes Simplex Virus
“HSV DNA PCR and viral culture are preferred methods for diagnosis of mucocutaneous lesions potentially caused by HSV.”
 
2.1.7 Mycobacterium tuberculosis infection and disease
“NAA tests provide rapid diagnosis of TB, and some assays also provide rapid detection of drug resistance.”
"NAA assays, if positive, are highly predictive of TB disease when performed on Acid-Fast Bacillus (AFB) smear-positive specimens. However, because nontuberculous mycobacterial infections (NTM) may occur in people with HIV with advanced immunodeficiency, negative NAA results in the setting of smear-positive specimens may indicate NTM infection and can be used to direct therapy and make decisions about the need for respiratory isolation."
"NAA tests are more sensitive than AFB smear, being positive in 50% to 80% of smear negative, culture-positive specimens and up to 90% when three NAA tests are performed. Therefore, it is recommended that for all patients with suspected pulmonary TB, a NAA test be performed on at least one specimen. NAA tests also can be used on extrapulmonary specimens with the caveat that the sensitivity is often lower than with sputum specimens."
 
The thirty-second edition of the American Academy of Pediatrics (AAP) Red Book describes the diagnostic and treatment options for many infectious diseases in the pediatric population (Kimberlin, 2021). Their diagnostic test recommendations for the pediatric population is listed below.
 
Red Book Diagnostic Test Recommendations for the Pediatric Population:
Bartonella henselae
    • EIA
    • IFA
    • NAAT (PCR)
Candida species
    • Clinical evaluation microscopy
    • PNA FISH probes and PCR assays developed for rapid detection directly from positive blood cultures
Chlamydia pneumoniae
    • NAATs (PCR) are the preferred method for diagnosis of acute infection
    • Serologic antigen test is an option, but is technically complex and interpretation is subjective
Chlamydia trachomatis
    • NAATs are recommended for C trachomatis urogenital infections and in postpubescent individuals. They are not recommended for diagnosing C trachomatis conjunctivitis or pneumonia or in the evaluation of prepubescent children for possible sexual assault.
Clostridioides (Clostridium) difficile
    • NAATs detect genes responsible for the production of toxins A and B, rather than free toxins A and B in the stool, which are detected by EIA
    • NAAT could be considered alone if a policy in place to screen symptoms; if no policy in place, multi-step algorithms involving EIA, GDH, NAAT plus toxin is recommended
Coronaviruses (including SARS-CoV-2 and MERS-CoV)
    • RT-PCR
    • Direct antigen testing
Cytomegalovirus
    • Saliva PCR is the preferred diagnostic tool for screening.
Enterovirus
    • RT-PCR and culture from a variety of specimens
Gardnerella vaginalis
    • Microscopy
    • Numerous NAATs have been recommended when microscopy is unavailable
Hepatitis B
    • Serologic antigen tests
    • NAATs
Hepatitis C
    • IgG antibody enzyme immunoassays
    • NAATs
Herpes simplex virus
    • Cell culture
    • NAATs- diagnostic method of choice for neonates with CNS infections, older children, and adults with HSE
Human herpesvirus 6
    • Few developed assays are available commercially and do not differentiate between new, past, and reactivated infection. Therefore, these tests “have limited utility in clinical practice:”
    • Serologic tests;
    • PCR- the assays are not sensitive in younger children.
HIV 1
    • HIV DNA PCR or RNA PCR- preferred test to diagnose HIV infection in infants and children younger than 18mo; highly sensitive and specific by 2 weeks of age and available
Human papillomavirus
    • “Detection of HPV infection is based on detection of viral nucleic acid.”
Influenza virus
    • RT-PCR, viral culture tests, and rapid influenza molecular assays are available options for testing; optimal choice of influenza test depends on the clinical setting.
Legionella pneumophila
    • BCYE media
    • Legionella antigen in urine
    • Direct IFA
    • Genus-specific PCR reaction-based assays
Meningitis
    • Cultures of blood and CSF
    • NAATs- “useful in patients who receive antimicrobial therapy before cultures are obtained.”
Mycobacteria species
    • M tuberculosis disease:
    • Chest radiography and physical examination
    • Several NAATs are cleared for rapid detection of M tuberculosis, but expert consultation is recommended for interpretation of results
    • NTM: “definite diagnosis of NTM disease requires isolation of the organism.”
Mycoplasma pneumoniae
    • PCR tests for M pneumoniae are available commercially and increasing replacing other tests, because PCR tests performed on respiratory tract specimens have sensitivity and specifically between 80% and 100%, yield positive results earlier in the course of illness than serologic tests, and are rapid.
Neisseria gonorrhoeae
    • “NAATs are far superior in overall performance compared with other N gonorrhoeae culture and nonculture diagnostic methods to test genital and nongenital specimens", but performance varies by NAAT type.
Staphylococcus aureus
    • NAATS are approved for detection and identification of S aureus, including MRSA, in positive blood cultures.
Streptococcus, group A
    • “Children with pharyngitis and obvious viral symptoms should not be tested or treated for group A streptococcal infection...Laboratory confirmation before initiation of antimicrobial treatment is required for cases in children without viral symptoms… culture on sheep blood agar can confirm group A streptococcal infection.”
Streptococcus, group B
    • “Gram-positive cocci in pairs or short chains from a normally sterile body fluid provides presumptive evidence of infection.”
Trichomonas vaginalis
    • Microscopy
    • NAATs are the most sensitive mean of diagnosing T vaginalis infection and is encouraged for detection in females and males.
Vancomycin-resistant Enterococcus
    • "Selective agars are available for screening of vancomycin-resistant enterococcus from stool specimens. Molecular assays are available for direct detection of vanA and vanB genes from rectal and blood specimens to identify vancomycin-resistant enterocci"
Zika virus
    • NAATs
    • Trioplex real-time PCR assay
    • Serologic testing  
 
2023 Update
Annual policy review completed with a literature search using the MEDLINE database through October 2023. No new literature was identified that would prompt a change in the coverage statement. The key identified literature is summarized below.
 
Meltzer et al conducted a single-center RCT investigating antibiotic use in patients with moderate to severe suspected infectious diarrhea presenting to the emergency department (Meltzer, 2022). Patients were randomized to receive multiplex PCR testing with the BioFire FilmArray GI panel (n=38) or standard care (usual testing or no testing; n=36). In the PCR arm, subjects received antibiotics in 87% of bacterial or protozoal diarrheal infections (13/15) compared to 46% (6/13) in the control arm (p=.042). No significant differences were found between groups in follow-up symptoms as assessed on days 2, 7, and 30, or emergency department length of stay. The study was terminated early due to the COVID-19 pandemic and thus was underpowered. Additional limitations include potential antibiotic prescribing at subsequent healthcare visits that was not captured and lack of a standardized reference test for the control arm.
 
The RCT conducted by Darie et al was excluded as the Unyvero Hospitalized Pneumonia panel is not currently commercially available in the United States (Darie, 2022).
 
Clark et al conducted a systematic review and meta-analysis of the impact of multiplex PCR testing among individuals with a suspected acute respiratory tract infection in the hospital setting (Clark, 2023). Twenty-seven studies representing 17,321 patients were identified for analysis. Multiplex testing was associated with a reduction in both time to results (-24.22 h; 95% CI, -28.70 to -19.74 h) and hospital length of stay (-0.82 days; 95% CI, -1.52 to -0.11). Antivirals were more likely to be prescribed among influenza positive individuals (RR, 1.25; 95% CI, 1.06 to 1.48) as was use of an appropriate infection control facility (RR, 1.55; 95% CI, 1.16 to 2.07).

CPT/HCPCS:
0086UInfectious disease (bacterial and fungal), organism identification, blood culture, using rRNA FISH, 6 or more organism targets, reported as positive or negative with phenotypic minimum inhibitory concentration (MIC) based antimicrobial susceptibility
0096UHuman papillomavirus (HPV), high risk types (ie, 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68), male urine
0097UGastrointestinal pathogen, multiplex reverse transcription and multiplex amplified probe technique, multiple types or subtypes, 22 targets (Campylobacter [C. jejuni/C. coli/C. upsaliensis], Clostridium difficile [C. difficile] toxin A/B, Plesiomonas shigelloides, Salmonella, Vibrio [V. parahaemolyticus/V. vulnificus/V. cholerae], including specific identification of Vibrio cholerae, Yersinia enterocolitica, Enteroaggregative Escherichia coli [EAEC], Enteropathogenic Escherichia coli [EPEC], Enterotoxigenic Escherichia coli [ETEC] lt/st, Shiga like toxin producing Escherichia coli [STEC] stx1/stx2 [including specific identification of the E. coli O157 serogroup within STEC], Shigella/Enteroinvasive Escherichia coli [EIEC], Cryptosporidium, Cyclospora cayetanensis, Entamoeba histolytica, Giardia lamblia [also known as G. intestinalis and G. duodenalis], adenovirus F 40/41, astrovirus, norovirus GI/GII, rotavirus A, sapovirus [Genogroups I, II, IV, and V])
0098URespiratory pathogen, multiplex reverse transcription and multiplex amplified probe technique, multiple types or subtypes, 14 targets (adenovirus, coronavirus, human metapneumovirus, influenza A, influenza A subtype H1, influenza A subtype H3, influenza A subtype H1 2009, influenza B, parainfluenza virus, human rhinovirus/enterovirus, respiratory syncytial virus, Bordetella pertussis, Chlamydophila pneumoniae, Mycoplasma pneumoniae)
0099URespiratory pathogen, multiplex reverse transcription and multiplex amplified probe technique, multiple types or subtypes, 20 targets (adenovirus, coronavirus 229E, coronavirus HKU1, coronavirus, coronavirus OC43, human metapneumovirus, influenza A, influenza A subtype, influenza A subtype H3, influenza A subtype H1 2009, influenza, parainfluenza virus, parainfluenza virus 2, parainfluenza virus 3, parainfluenza virus 4, human rhinovirus/enterovirus, respiratory syncytial virus, Bordetella pertussis, Chlamydophila pneumonia, Mycoplasma pneumoniae)
0100URespiratory pathogen, multiplex reverse transcription and multiplex amplified probe technique, multiple types or subtypes, 21 targets (adenovirus, coronavirus 229E, coronavirus HKU1, coronavirus NL63, coronavirus OC43, human metapneumovirus, human rhinovirus/enterovirus, influenza A, including subtypes H1, H1 2009, and H3, influenza B, parainfluenza virus 1, parainfluenza virus 2, parainfluenza virus 3, parainfluenza virus 4, respiratory syncytial virus, Bordetella parapertussis [IS1001], Bordetella pertussis [ptxP], Chlamydia pneumoniae, Mycoplasma pneumoniae)
0112UInfectious agent detection and identification, targeted sequence analysis (16S and 18S rRNA genes) with drug resistance gene
0140UInfectious disease (fungi), fungal pathogen identification, DNA (15 fungal targets), blood culture, amplified probe technique, each target reported as detected or not detected
0141UInfectious disease (bacteria and fungi), gram positive organism identification and drug resistance element detection, DNA (20 gram positive bacterial targets, 4 resistance genes, 1 pan gram negative bacterial target, 1 pan Candida target), blood culture, amplified probe technique, each target reported as detected or not detected
0142UInfectious disease (bacteria and fungi), gram negative bacterial identification and drug resistance element detection, DNA (21 gram negative bacterial targets, 6 resistance genes, 1 pan gram positive bacterial target, 1 pan Candida target), amplified probe technique, each target reported as detected or not detected
0151UInfectious disease (bacterial or viral respiratory tract infection), pathogen specific nucleic acid (DNA or RNA), 33 targets, real time semi quantitative PCR, bronchoalveolar lavage, sputum, or endotracheal aspirate, detection of 33 organismal and antibiotic resistance genes with limited semi quantitative results
0202UInfectious disease (bacterial or viral respiratory tract infection), pathogen-specific nucleic acid (DNA or RNA), 22 targets including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), qualitative RT-PCR, nasopharyngeal swab, each pathogen reported as detected or not detected
0219UInfectious agent (human immunodeficiency virus), targeted viral next-generation sequence analysis (ie, protease [PR], reverse transcriptase [RT], integrase [INT]), algorithm reported as prediction of antiviral drug susceptibility
0223UInfectious disease (bacterial or viral respiratory tract infection), athogenspecific nucleic acid (DNA or RNA), 22 targets including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), qualitative RT-PCR, nasopharyngeal swab, each pathogen reported as detected or not detected
0224UAntibody, severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) (Coronavirus disease [COVID-19]), includes titer(s), when performed
0225UInfectious disease (bacterial or viral respiratory tract infection) pathogen-specific DNA and RNA, 21 targets, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), amplified probe technique, including multiplex reverse transcription for RNA targets, each analyte reported as detected or not detected
0226USurrogate viral neutralization test (sVNT), severe acute respiratory syndrome coronavirus 2 (SARS CoV 2) (Coronavirus disease [COVID 19]), ELISA, plasma, serum
0240UInfectious disease (viral respiratory tract infection), pathogen-specific RNA, 3 targets (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2], influenza A, influenza B), upper respiratory specimen, each pathogen reported as detected or not detected
0241UInfectious disease (viral respiratory tract infection), pathogen-specific RNA, 4 targets (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2], influenza A, influenza B, respiratory syncytial virus [RSV]), upper respiratory specimen, each pathogen reported as detected or not detected
0301UInfectious agent detection by nucleic acid (DNA or RNA), Bartonella henselae and Bartonella quintana, droplet digital PCR (ddPCR);
0302UInfectious agent detection by nucleic acid (DNA or RNA), Bartonella henselae and Bartonella quintana, droplet digital PCR (ddPCR); following liquid enrichment
0323UInfectious agent detection by nucleic acid (DNA and RNA), central nervous system pathogen, metagenomic nextgeneration sequencing, cerebrospinal fluid (CSF), identification of pathogenic bacteria, viruses, parasites, or fungi
0330UInfectious agent detection by nucleic acid (DNA or RNA), vaginal pathogen panel, identification of 27 organisms, amplified probe technique, vaginal swab
81479Unlisted molecular pathology procedure
81513Infectious disease, bacterial vaginosis, quantitative real time amplification of RNA markers for Atopobium vaginae, Gardnerella vaginalis, and Lactobacillus species, utilizing vaginal fluid specimens, algorithm reported as a positive or negative result for bacterial vaginosis
81514Infectious disease, bacterial vaginosis and vaginitis, quantitative real time amplification of DNA markers for Gardnerella vaginalis, Atopobium vaginae, Megasphaera type 1, Bacterial Vaginosis Associated Bacteria 2 (BVAB 2), and Lactobacillus species (L. crispatus and L. jensenii), utilizing vaginal fluid specimens, algorithm reported as a positive or negative for high likelihood of bacterial vaginosis, includes separate detection of Trichomonas vaginalis and/or Candida species (C. albicans, C. tropicalis, C. parapsilosis, C. dubliniensis), Candida glabrata, Candida krusei, when reported
86413Severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) Coronavirus disease [COVID-19]) antibody, quantitative
87154Culture, typing; identification of blood pathogen and resistance typing, when performed, by nucleic acid (DNA or RNA) probe, multiplexed amplified probe technique including multiplex reverse transcription, when performed, per culture or isolate, 6 or more
87467Hepatitis B surface antigen (HBsAg), quantitative
87468Infectious agent detection by nucleic acid; Anaplasma phagocytophilum
87469Infectious agent detection by nucleic acid; Babesia microti
87471Infectious agent detection by nucleic acid (DNA or RNA); Bartonella henselae and Bartonella quintana, amplified probe technique
87476Infectious agent detection by nucleic acid (DNA or RNA); Borrelia burgdorferi, amplified probe technique
87478Infectious agent detection by nucleic acid; Borrelia miyamotoi
87480Infectious agent detection by nucleic acid (DNA or RNA); Candida species, direct probe technique
87481Infectious agent detection by nucleic acid (DNA or RNA); Candida species, amplified probe technique
87483Infectious agent detection by nucleic acid (DNA or RNA); central nervous system pathogen (eg, Neisseria meningitidis, Streptococcus pneumoniae, Listeria, Haemophilus influenzae, E. coli, Streptococcus agalactiae, enterovirus, human parechovirus, herpes simplex virus type 1 and 2, human herpesvirus 6, cytomegalovirus, varicella zoster virus, Cryptococcus), includes multiplex reverse transcription, when performed, and multiplex amplified probe technique, multiple types or subtypes, 12 25 targets
87484Infectious agent detection by nucleic acid; Ehrlichia chaffeensis
87485Infectious agent detection by nucleic acid (DNA or RNA); Chlamydia pneumoniae, direct probe technique
87486Infectious agent detection by nucleic acid (DNA or RNA); Chlamydia pneumoniae, amplified probe technique
87487Infectious agent detection by nucleic acid (DNA or RNA); Chlamydia pneumoniae, quantification
87490Infectious agent detection by nucleic acid (DNA or RNA); Chlamydia trachomatis, direct probe technique
87491Infectious agent detection by nucleic acid (DNA or RNA); Chlamydia trachomatis, amplified probe technique
87492Infectious agent detection by nucleic acid (DNA or RNA); Chlamydia trachomatis, quantification
87493Infectious agent detection by nucleic acid (DNA or RNA); Clostridium difficile, toxin gene(s), amplified probe technique
87495Infectious agent detection by nucleic acid (DNA or RNA); cytomegalovirus, direct probe technique
87496Infectious agent detection by nucleic acid (DNA or RNA); cytomegalovirus, amplified probe technique
87497Infectious agent detection by nucleic acid (DNA or RNA); cytomegalovirus, quantification
87498Infectious agent detection by nucleic acid (DNA or RNA); enterovirus, amplified probe technique, includes reverse transcription when performed
87500Infectious agent detection by nucleic acid (DNA or RNA); vancomycin resistance (eg, enterococcus species van A, van B), amplified probe technique
87501Infectious agent detection by nucleic acid (DNA or RNA); influenza virus, includes reverse transcription, when performed, and amplified probe technique, each type or subtype
87502Infectious agent detection by nucleic acid (DNA or RNA); influenza virus, for multiple types or sub types, includes multiplex reverse transcription, when performed, and multiplex amplified probe technique, first 2 types or sub types
87503Infectious agent detection by nucleic acid (DNA or RNA); influenza virus, for multiple types or sub types, includes multiplex reverse transcription, when performed, and multiplex amplified probe technique, each additional influenza virus type or sub type beyond 2 (List separately in addition to code for primary procedure)
87505Infectious agent detection by nucleic acid (DNA or RNA); gastrointestinal pathogen (eg, Clostridium difficile, E. coli, Salmonella, Shigella, norovirus, Giardia), includes multiplex reverse transcription, when performed, and multiplex amplified probe technique, multiple types or subtypes, 3 5 targets
87506Infectious agent detection by nucleic acid (DNA or RNA); gastrointestinal pathogen (eg, Clostridium difficile, E. coli, Salmonella, Shigella, norovirus, Giardia), includes multiplex reverse transcription, when performed, and multiplex amplified probe technique, multiple types or subtypes, 6 11 targets
87507Infectious agent detection by nucleic acid (DNA or RNA); gastrointestinal pathogen (eg, Clostridium difficile, E. coli, Salmonella, Shigella, norovirus, Giardia), includes multiplex reverse transcription, when performed, and multiplex amplified probe technique, multiple types or subtypes, 12 25 targets
87510Infectious agent detection by nucleic acid (DNA or RNA); Gardnerella vaginalis, direct probe technique
87511Infectious agent detection by nucleic acid (DNA or RNA); Gardnerella vaginalis, amplified probe technique
87516Infectious agent detection by nucleic acid (DNA or RNA); hepatitis B virus, amplified probe technique
87517Infectious agent detection by nucleic acid (DNA or RNA); hepatitis B virus, quantification
87520Infectious agent detection by nucleic acid (DNA or RNA); hepatitis C, direct probe technique
87521Infectious agent detection by nucleic acid (DNA or RNA); hepatitis C, amplified probe technique, includes reverse transcription when performed
87522Infectious agent detection by nucleic acid (DNA or RNA); hepatitis C, quantification, includes reverse transcription when performed
87525Infectious agent detection by nucleic acid (DNA or RNA); hepatitis G, direct probe technique
87526Infectious agent detection by nucleic acid (DNA or RNA); hepatitis G, amplified probe technique
87527Infectious agent detection by nucleic acid (DNA or RNA); hepatitis G, quantification
87528Infectious agent detection by nucleic acid (DNA or RNA); Herpes simplex virus, direct probe technique
87529Infectious agent detection by nucleic acid (DNA or RNA); Herpes simplex virus, amplified probe technique
87531Infectious agent detection by nucleic acid (DNA or RNA); Herpes virus 6, direct probe technique
87532Infectious agent detection by nucleic acid (DNA or RNA); Herpes virus 6, amplified probe technique
87533Infectious agent detection by nucleic acid (DNA or RNA); Herpes virus 6, quantification
87534Infectious agent detection by nucleic acid (DNA or RNA); HIV 1, direct probe technique
87535Infectious agent detection by nucleic acid (DNA or RNA); HIV 1, amplified probe technique, includes reverse transcription when performed
87536Infectious agent detection by nucleic acid (DNA or RNA); HIV 1, quantification, includes reverse transcription when performed
87537Infectious agent detection by nucleic acid (DNA or RNA); HIV 2, direct probe technique
87538Infectious agent detection by nucleic acid (DNA or RNA); HIV 2, amplified probe technique, includes reverse transcription when performed
87539Infectious agent detection by nucleic acid (DNA or RNA); HIV 2, quantification, includes reverse transcription when performed
87540Infectious agent detection by nucleic acid (DNA or RNA); Legionella pneumophila, direct probe technique
87541Infectious agent detection by nucleic acid (DNA or RNA); Legionella pneumophila, amplified probe technique
87550Infectious agent detection by nucleic acid (DNA or RNA); Mycobacteria species, direct probe technique
87551Infectious agent detection by nucleic acid (DNA or RNA); Mycobacteria species, amplified probe technique
87555Infectious agent detection by nucleic acid (DNA or RNA); Mycobacteria tuberculosis, direct probe technique
87556Infectious agent detection by nucleic acid (DNA or RNA); Mycobacteria tuberculosis, amplified probe technique
87560Infectious agent detection by nucleic acid (DNA or RNA); Mycobacteria avium intracellulare, direct probe technique
87561Infectious agent detection by nucleic acid (DNA or RNA); Mycobacteria avium intracellulare, amplified probe technique
87563Infectious agent detection by nucleic acid (DNA or RNA); Mycoplasma genitalium, amplified probe technique
87580Infectious agent detection by nucleic acid (DNA or RNA); Mycoplasma pneumoniae, direct probe technique
87581Infectious agent detection by nucleic acid (DNA or RNA); Mycoplasma pneumoniae, amplified probe technique
87590Infectious agent detection by nucleic acid (DNA or RNA); Neisseria gonorrhoeae, direct probe technique
87591Infectious agent detection by nucleic acid (DNA or RNA); Neisseria gonorrhoeae, amplified probe technique
87593Infectious agent detection by nucleic acid (DNA or RNA); orthopoxvirus (eg, monkeypox virus, cowpox virus, vaccinia virus), amplified probe technique, each
87623Infectious agent detection by nucleic acid (DNA or RNA); Human Papillomavirus (HPV), low risk types (eg, 6, 11, 42, 43, 44)
87624Infectious agent detection by nucleic acid (DNA or RNA); Human Papillomavirus (HPV), high risk types (eg, 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68)
87625Infectious agent detection by nucleic acid (DNA or RNA); Human Papillomavirus (HPV), types 16 and 18 only, includes type 45, if performed
87631Infectious agent detection by nucleic acid (DNA or RNA); respiratory virus (eg, adenovirus, influenza virus, coronavirus, metapneumovirus, parainfluenza virus, respiratory syncytial virus, rhinovirus), includes multiplex reverse transcription, when performed, and multiplex amplified probe technique, multiple types or subtypes, 3 5 targets
87632Infectious agent detection by nucleic acid (DNA or RNA); respiratory virus (eg, adenovirus, influenza virus, coronavirus, metapneumovirus, parainfluenza virus, respiratory syncytial virus, rhinovirus), includes multiplex reverse transcription, when performed, and multiplex amplified probe technique, multiple types or subtypes, 6 11 targets
87633Infectious agent detection by nucleic acid (DNA or RNA); respiratory virus (eg, adenovirus, influenza virus, coronavirus, metapneumovirus, parainfluenza virus, respiratory syncytial virus, rhinovirus), includes multiplex reverse transcription, when performed, and multiplex amplified probe technique, multiple types or subtypes, 12 25 targets
87634Infectious agent detection by nucleic acid (DNA or RNA); respiratory syncytial virus, amplified probe technique
87635Infectious agent detection by nucleic acid (DNA or RNA); severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (Coronavirus disease [COVID-19]), amplified probe technique
87636Infectious agent detection by nucleic acid (DNA or RNA); severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (Coronavirus disease [COVID-19]) and influenza virus types A and B, multiplex amplified probe technique
87637Infectious agent detection by nucleic acid (DNA or RNA); severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (Coronavirus disease [COVID-19]), influenza virus types A and B, and respiratory syncytial virus, multiplex amplified probe technique
87640Infectious agent detection by nucleic acid (DNA or RNA); Staphylococcus aureus, amplified probe technique
87641Infectious agent detection by nucleic acid (DNA or RNA); Staphylococcus aureus, methicillin resistant, amplified probe technique
87650Infectious agent detection by nucleic acid (DNA or RNA); Streptococcus, group A, direct probe technique
87651Infectious agent detection by nucleic acid (DNA or RNA); Streptococcus, group A, amplified probe technique
87652Infectious agent detection by nucleic acid (DNA or RNA); Streptococcus, group A, quantification
87653Infectious agent detection by nucleic acid (DNA or RNA); Streptococcus, group B, amplified probe technique
87660Infectious agent detection by nucleic acid (DNA or RNA); Trichomonas vaginalis, direct probe technique
87661Infectious agent detection by nucleic acid (DNA or RNA); Trichomonas vaginalis, amplified probe technique
87662Infectious agent detection by nucleic acid (DNA or RNA); Zika virus, amplified probe technique
87797Infectious agent detection by nucleic acid (DNA or RNA), not otherwise specified; direct probe technique, each organism
87798Infectious agent detection by nucleic acid (DNA or RNA), not otherwise specified; amplified probe technique, each organism
87799Infectious agent detection by nucleic acid (DNA or RNA), not otherwise specified; quantification, each organism
87913Infectious agent genotype analysis by nucleic acid (DNA or RNA); severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (coronavirus disease [COVID-19]), mutation identification in targeted region(s)

References: Package Insert, GenProbe.(2015) Group A Streptococcus Direct Test. Quidel. LyraDirect Strep Assay. https://www.quidel.com/sites/default/files/product/documents/PIM112001EN00.pdf. Accessed December 1, 2015.

Abba MC, Mouron SA, Gomez MA, et al.(2003) Association of human papillomavirus viral load with HPV16 and high-grade intraepithelial lesion. Int J Gynecol Cancer. Mar-Apr 2003;13(2):154-158. PMID 12657116

Abraham AM, Babu M, Kavitha S, et al.(2009) A molecular method for typing Herpes simplex virus isolates as an alternative to immunofluorescence methods. Indian J Med Microbiol. Jan-Mar 2009;27(1):22-26. PMID 19172054

Agut H, Bonnafous P, Gautheret-Dejean(2015) A. Laboratory and clinical aspects of human herpesvirus 6 infections. Clin Microbiol Rev. Apr 2015;28(2):313-335. PMID 25762531

Al-Talib H, Latif B, Mohd-Zain Z.(2014) Pentaplex PCR assay for detection of hemorrhagic bacteria from stool samples. J Clin Microbiol. Sep 2014;52(9):3244-3249. PMID 24958797

Anderson NW, Buchan BW, Mayne D, et al.(2013) Multicenter clinical evaluation of the illumigene group A Streptococcus DNA amplification assay for detection of group A Streptococcus from pharyngeal swabs. J Clin Microbiol. May 2013;51(5):1474-1477. PMID 23447639

Andrea SB, Chapin KC.(2011) Comparison of Aptima Trichomonas vaginalis transcription-mediated amplification assay and BD affirm VPIII for detection of T. vaginalis in symptomatic women: performance parameters and epidemiological implications. J Clin Microbiol. Mar 2011;49(3):866-869. PMID 21248097

Appleman MD, Citron DM, Kwok R.(2004) Evaluation of the Velogene genomic assay for detection of vanA and vanB genes in vancomycin-resistant Enterococcus species. J Clin Microbiol. Apr 2004;42(4):1751-1752. PMID 15071039

Arora HS, Asmar BI, Salimnia H, et al.(2017) Enhanced identification of group B Streptococcus and Escherichia Coli in young infants with meningitis using the Biofire Filmarray Meningitis/Encephalitis Panel. Pediatr Infect Dis J. Jul 2017;36(7):685-687.

Barbut F, Monot M, Rousseau A, et al(2011) Rapid diagnosis of Clostridium difficile infection by multiplex real-time PCR. Eur J Clin Microbiol Infect Dis. Apr 13 2011;30(10):1279-1285. PMID 21487764

Beckmann C, Heininger U, Marti H, et al.(2014) Gastrointestinal pathogens detected by multiplex nucleic acid amplification testing in stools of pediatric patients and patients returning from the tropics. Infection. Dec 2014;42(6):961-970. PMID 25015433

Bergeron MG, Ke D, Menard C, et al.(2000) Rapid detection of group B streptococci in pregnant women at delivery. N Engl J Med. Jul 20 2000;343(3):175-179. PMID 10900276

Bergeron MG, Ke D.(2001) New DNA-based PCR approaches for rapid real-time detection and prevention of group B streptococcal infections in newborns and pregnant women. Expert Rev Mol Med. Nov 2001;3(27):1-14. PMID 14585149

Bicmen C, Gunduz AT, Coskun M, et al.(2011) Molecular detection and identification of mycobacterium tuberculosis complex and four clinically important nontuberculous mycobacterial species in smear-negative clinical samples by the genotype mycobacteria direct test. J Clin Microbiol. Aug 2011;49(8):2874-2878. PMID 21653780

Biswas JS, Al-Ali A, Rajput P, et al.(2014) A parallel diagnostic accuracy study of three molecular panels for the detection of bacterial gastroenteritis. Eur J Clin Microbiol Infect Dis. Nov 2014;33(11):2075-2081. PMID 24935616

Boivin G, Belanger R, Delage R, et al.(2000) Quantitative analysis of cytomegalovirus (CMV) viremia using the pp65 antigenemia assay and the COBAS AMPLICOR CMV MONITOR PCR test after blood and marrow allogeneic transplantation. J Clin Microbiol. Dec 2000;38(12):4356-4360. PMID 11101564

Boyanton BL, Jr., Darnell EM, Prada AE, et al.(2015) Evaluation of the Lyra Direct Strep Assay to Detect Group A Streptococcus and beta-Hemolytic Groups C/G Streptococcus from Pharyngeal Specimens. J Clin Microbiol. Oct 21 2015. PMID 26491174

Bressollette-Bodin C, Nguyen TV, Illiaquer M, et al.(2014) Quantification of two viral transcripts by real time PCR to investigate human herpesvirus type 6 active infection. J Clin Virol. Feb 2014;59(2):94-99. PMID 24380721

Brittain-Long R, Westin J, Olofsson S, et al.(2011) Access to a polymerase chain reaction assay method targeting 13 respiratory viruses can reduce antibiotics: a randomised, controlled trial. BMC Med. 2011;9:44. PMID 21521505

Caponetti GC, Pantanowitz L, Marconi S, et al.(2009) Evaluation of immunohistochemistry in identifying Bartonella henselae in cat-scratch disease. Am J Clin Pathol. Feb 2009;131(2):250-256. PMID 19141385

Centers for Disease C, Prevention.(2014) Recommendations for the laboratory-based detection of Chlamydia trachomatis and Neisseria gonorrhoeae--2014. MMWR Recomm Rep. Mar 14 2014;63(RR-02):1-19. PMID 24622331

Centers for Disease Control and Prevention (CDC).(2010) Diseases characterized by vaginal discharge. In: Sexually transmitted diseases treatment guidelines. MMWR. Dec 2010;59(RR-12):56-63.http://www.cdc.gov/mmwr/PDF/rr/rr5912.pdf. Accessed April, 2015.

Centers for Disease Control and Prevention (CDC).(2015) Diseases characterized by vaginal discharge. In: Sexually transmitted diseases treatment guidelines. MMWR. Dec 2010;59(RR-12):56-63. http://www.cdc.gov/mmwr/PDF/rr/rr5912.pdf. Accessed April, 2015.

Centers for Disease Control and Prevention.(2018) Chikungunya Virus https://www.cdc.gov/chikungunya/symptoms/index.html Accessed Nov. 9, 2018.

Chalker VJ, Stocki T, Mentasti M, et al.(2011) Mycoplasma pneumoniae infection in primary care investigated by realtime PCR in England and Wales. Eur J Clin Microbiol Infect Dis. Jul 2011;30(7):915-921. PMID 21311941

Choi YJ, Kim HJ, Shin HB, et al.(2012) Evaluation of peptide nucleic acid probe-based real-time PCR for detection of Mycobacterium tuberculosis complex and nontuberculous mycobacteria in respiratory specimens. Ann Lab Med. Jul 2012;32(4):257-263. PMID 22779066

Claas EC, Burnham CA, Mazzulli T, et al.(2013) Performance of the xTAG(R) gastrointestinal pathogen panel, a multiplex molecular assay for simultaneous detection of bacterial, viral, and parasitic causes of infectious gastroenteritis. J Microbiol Biotechnol. 2013;23(7):1041-1045. PMID 23711521

Clark TW, Lindsley K, Wigmosta TB, et al.(2023) Rapid multiplex PCR for respiratory viruses reduces time to result and improves clinical care: Results of a systematic review and meta-analysis. J Infect. May 2023; 86(5): 462-475. PMID 36906153

Cohen DM, Russo ME, Jaggi P, et al.(2015) Multicenter Clinical Evaluation of the Novel Alere i Strep A Isothermal Nucleic Acid Amplification Test. J Clin Microbiol. Jul 2015;53(7):2258-2261. PMID 25972418

Dabisch-Ruthe M, Vollmer T, Adams O, et al.(2012) Comparison of three multiplex PCR assays for the detection of respiratory viral infections: evaluation of xTAG respiratory virus panel fast assay, RespiFinder 19 assay and RespiFinder SMART 22 assay. BMC Infect Dis. 2012;12:163. PMID 22828244

Darie AM, Khanna N, Jahn K, et al.(2022) Fast multiplex bacterial PCR of bronchoalveolar lavage for antibiotic stewardship in hospitalised patients with pneumonia at risk of Gram-negative bacterial infection (Flagship II): a multicentre, randomised controlled trial. Lancet Respir Med. Sep 2022; 10(9): 877-887. PMID 35617987

Das S, Brown TM, Kellar KL, et al.(2006) DNA probes for the rapid identification of medically important Candida species using a multianalyte profiling system. FEMS Immunol Med Microbiol. Mar 2006;46(2):244-250. PMID 16487306

de Crom SC, Obihara CC, van Loon AM, et al.(2012) Detection of enterovirus RNA in cerebrospinal fluid: comparison of two molecular assays. J Virol Methods. Jan 2012;179(1):104-107. PMID 22024398

Dewan M, Zorc JJ, Hodinka RL, et al.(2010) Cerebrospinal fluid enterovirus testing in infants 56 days or younger. Arch Pediatr Adolesc Med. Sep 2010;164(9):824-830. PMID 20819964

Diederen BM, Kluytmans JA, Vandenbroucke-Grauls CM, et al.(2008) Utility of real-time PCR for diagnosis of Legionnaires' disease in routine clinical practice. J Clin Microbiol. Feb 2008;46(2):671-677. PMID 18094136

Eastwood K, Else P, Charlett A, et al.(2009) Comparison of nine commercially available Clostridium difficile toxin detection assays, a real-time PCR assay for C. difficile tcdB, and a glutamate dehydrogenase detection assay to cytotoxin testing and cytotoxigenic culture methods. J Clin Microbiol. Oct 2009;47(10):3211-3217. PMID 19710274

Egli A, Helmersen DS, Taub K, et al(2010) Renal failure five years after lung transplantation due to polyomavirus BK-associated nephropathy Am J Transplant 2010; 10:2324

Faron ML, Ledeboer NA, Granato P, et al.(2015) Detection of Group A Streptococcus in Pharyngeal Swab Specimens Using the AmpliVue GAS Isothermal Helicase-Dependent Amplification Assay. J Clin Microbiol. May 13 2015. PMID 25972419

Filkins L, Hauser J, Robinson-Dunn B, Tibbetts R, Boyanton B, Revell P.(2020) Guidelines for the Detection and Identification of Group B Streptococcus. American Society for Microbiology. Published 3/10/20. https://asm.org/ASM/media/Policy-and-Advocacy/images/ASM-GBS-guideline-031020.pdf?ext=.pdf. Accessed May 5, 2021.

Flahaut M, Sanglard D, Monod M, et al(1998) Rapid detection of Candida albicans in clinical samples by DNA amplification of common regions from C. albicans-secreted aspartic proteinase genes. J Clin Microbiol. Feb 1998;36(2):395-401. PMID 9466748

Gaydos CA, Roblin PM, Hammerschlag MR, et al.(1994) Diagnostic utility of PCR-enzyme immunoassay, culture, and serology for detection of Chlamydia pneumoniae in symptomatic and asymptomatic patients. J Clin Microbiol. Apr 1994;32(4):903-905. PMID 8027341

Gazi H, Degerli K, Kurt O, et al.(2006) Use of DNA hybridization test for diagnosing bacterial vaginosis in women with symptoms suggestive of infection. APMIS. Nov 2006;114(11):784-787. PMID 17078859

Giulieri SG, Chapuis-Taillard C, Manuel O, et al.(2015) Rapid detection of enterovirus in cerebrospinal fluid by a fully-automated PCR assay is associated with improved management of aseptic meningitis in adult patients. J Clin Virol. Jan 2015;62:58-62. PMID 25542472

Hansmann Y, DeMartino S, Piemont Y, et al.(2005) Diagnosis of cat scratch disease with detection of Bartonella henselae by PCR: a study of patients with lymph node enlargement. J Clin Microbiol. Aug 2005;43(8):3800-3806. PMID 16081914

Henson AM, Carter D, Todd K, et al.(2013) Detection of Streptococcus pyogenes by use of Illumigene group A Streptococcus assay. J Clin Microbiol. Dec 2013;51(12):4207-4209. PMID 24048538

Hirsch HH, Randhawa P, AST Infectious Diseases Community of Practice(2013) BK polyomavirus in solid organ transplantation Am J Transplant 2013; 13 Suppl 4:179

Hirsch HH, Vincenti V, Friman S, et al(2010) Risk factors of polyomavirus BKV high-level viruria and viremia in de novo renal transplantation: a multivariate analysis from the DIRECT Study comparing cyclosporine and tacrolimus (Abstract #1664) Transplantation 2010

Hologic.(2015) Gen-Probe Group A Streptococcus Direct Test. http://www.hologic.com/sites/default/files/package%20inserts/103887RevP.pdf. Accessed December 1, 2015.

Hopkins MJ, Smith G, Hart IJ, et al.(2012) Screening tests for Chlamydia trachomatis or Neisseria gonorrhoeae using the cobas 4800 PCR system do not require a second test to confirm: an audit of patients issued with equivocal results at a sexual health clinic in the Northwest of England, U.K. Sex Transm Infect. Nov 2012;88(7):495-497. PMID 22661631

Huang H, Weintraub A, Fang H, et al.(2009) Comparison of a commercial multiplex real-time PCR to the cell cytotoxicity neutralization assay for diagnosis of clostridium difficile infections. J Clin Microbiol. Nov 2009;47(11):3729-3731. PMID 19741082

Humar A, Gregson D, Caliendo AM, et al.(1999) Clinical utility of quantitative cytomegalovirus viral load determination for predicting cytomegalovirus disease in liver transplant recipients. Transplantation. Nov 15 1999;68(9):1305-1311. PMID 10573068

Infectious Diseases Society of America(2020) Guidelines on the Diagnosis of COVID-19. Published May 6, 2020. https://www.idsociety.org/practice-guideline/covid-19-guideline-diagnostics/. Accessed on May 27, 2020.

Ishiguro N, Koseki N, Kaiho M, et al.(2015) Sensitivity and Specificity of a Loop-Mediated Isothermal Amplification Assay for the Detection of Mycoplasma Pneumonia from Nasopharyngeal Swab Samples Compared with those of Real-time PCR. Clin Lab. 2015;61(5-6):603-606. PMID 26118195

Izumikawa K, Izumikawa K, Takazono T, et al.(2014) Clinical features, risk factors and treatment of fulminant Mycoplasma pneumoniae pneumonia: a review of the Japanese literature. J Infect Chemother. Mar 2014;20(3):181-185. PMID 24462437

Jensen WA, Fall MZ, Rooney J, et al.(2000) Rapid identification and differentiation of Bartonella species using a single-step PCR assay. J Clin Microbiol. May 2000;38(5):1717-1722. PMID 10790087

Jiang Y, Fang L, Shi X, et al.(2014) Simultaneous detection of five enteric viruses associated with gastroenteritis by use of a PCR assay: a single real-time multiplex reaction and its clinical application. J Clin Microbiol. Apr 2014;52(4):1266-1268. PMID 24478418

Johnson G, Ayers M, McClure SC, et al.(2003) Detection and identification of Bartonella species pathogenic for humans by PCR amplification targeting the riboflavin synthase gene (ribC). J Clin Microbiol. Mar 2003;41(3):1069-1072. PMID 12624031

Josefsson AM, Magnusson PK, Ylitalo N, et al.(2000) Viral load of human papilloma virus 16 as a determinant for development of cervical carcinoma in situ: a nested case-control study. Lancet. Jun 24 2000;355(9222):2189-2193. PMID 10881891

Kaplan S, Marlowe EM, Hogan JJ, et al.(2005) Sensitivity and specificity of a rapid rRNA gene probe assay for simultaneous identification of Staphylococcus aureus and detection of mecA. J Clin Microbiol. Jul 2005;43(7):3438-3442. PMID 16000472

Khare R, Espy MJ, Cebelinski E, et al.(2014) Comparative evaluation of two commercial multiplex panels for detection of gastrointestinal pathogens by use of clinical stool specimens. J Clin Microbiol. Oct 2014;52(10):3667-3673. PMID 25100818

Khare R, Espy MJ, Cebelinski E, et al.(2014) Multiplex Detection of Gastrointestinal Pathogens: A Comparative Evaluation of Two Commercial Panels Using Clinical Stool Specimens. J Clin Microbiol. Aug 6 2014. PMID 25100818

Kimberlin DW, Barnett ED, Lynfield R, et al.(2021) Red Book: 2021 Report on the Committee on Infectious Diseases, 32nd Edition. American Academy of Pediatrics: 2021

Knetsch CW, Bakker D, de Boer RF, et al. (2011) Comparison of real-time PCR techniques to cytotoxigenic culture methods for diagnosing Clostridium difficile infection. J Clin Microbiol. Jan 2011;49(1):227-231. PMID 20980562

Knowles WA, Pillay D, Johnson MA, et al(1993) Prevalence of long-term BK and JC excretion in HIV-infected adults and lack of correlation with serological markers J Med Virol 1999; 59:474

Kosai K, Suzuki H, Tamai K, et al.(2021) Multicenter evaluation of Verigene Enteric Pathogens Nucleic Acid Test for detection of gastrointestinal pathogens. Sci Rep. Feb 04 2021; 11(1): 3033. PMID 33542335

Lassauniere R, Kresfelder T, Venter M.(2010) A novel multiplex real-time RT-PCR assay with FRET hybridization probes for the detection and quantitation of 13 respiratory viruses. J Virol Methods. May 2010;165(2):254-260. PMID 20153377

Launes C, Casas-Alba D, Fortuny C, et al.(2017) Utility of FilmArray meningitis/encephalitis panel during outbreak of brainstem encephalitis caused by enterovirus in Catalonia in 2016. J Clin Microbiol. Jan 2017;55(1):336-338.

Leber AL, Everhart K, Balada-Llasat JM, et al.(2016) Multicenter evaluation of biofire filmarray meningitis/encephalitis panel for detection of bacteria, viruses, and yeast in cerebrospinal fluid specimens. J Clin Microbiol. Sep 2016;54(9):2251-2261.

Lee CK, Chiu L, Yan G, et al.(2017) False negative results caused by erroneous automated result interpretation algorithm on the FilmArray 2.0 instrument. Clin Chem Lab Med. Aug 01 2017.

Li H, Dummer JS, Estes WR, et al.(2003) Measurement of human cytomegalovirus loads by quantitative real-time PCR for monitoring clinical intervention in transplant recipients. J Clin Microbiol. Jan 2003;41(1):187-191. PMID 12517846

Li H, Dummer JS, Estes WR, et al.(2003) Measurement of human cytomegalovirus loads by quantitative real-time PCR for monitoring clinical intervention in transplant recipients. J Clin Microbiol. Jan 2003;41(1):187-191. PMID 12517846

Lok AS, McMahon BJ.(2009) Chronic Hepatitis B: Update 2009. AASLD Practice Guideline Update 2009; http://www.aasld.org/sites/default/files/guideline_documents/ChronicHepatitisB2009.pdf. Accessed July 21, 2015.

Lok AS, McMahon BJ.(2015) Chronic Hepatitis B: Update 2009. AASLD Practice Guideline Update 2009; http://www.aasld.org/sites/default/files/guideline_documents/ChronicHepatitisB2009.pdf. Accessed July 21, 2015.

Lorincz AT, Castle PE, Sherman ME, et al.(2002) Viral load of human papillomavirus and risk of CIN3 or cervical cancer. Lancet. Jul 20 2002;360(9328):228-229. PMID 12133661

Mansuy JM, Mengelle C, Da Silva I, et al.(2012) Performance of a rapid molecular multiplex assay for the detection of influenza and picornaviruses. Scand J Infect Dis. Dec 2012;44(12):963-968. PMID 22830610

Marangoni A, Foschi C, Nardini P, et al.(2012) Evaluation of the new test VERSANT CT/GC DNA 1.0 assay for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae in urine specimens. J Clin Lab Anal. Feb 2012;26(2):70-72. PMID 22467321

Markowitz RB, Thompson HC, Mueller JF, et al(1993) Incidence of BK virus and JC virus viruria in human immunodeficiency virus-infected and -uninfected subjects J Infect Dis 1993; 167:13

Maurin M, Hammer L, Gestin B, et al.(2010) Quantitative real-time PCR tests for diagnostic and prognostic purposes in cases of legionellosis Clin Microbiol Infect. Apr 2010;16(4):379-384. PMID 19519843

Meltzer AC, Newton S, Lange J, et al.(2022) A randomized control trial of a multiplex gastrointestinal PCR panel versus usual testing to assess antibiotics use for patients with infectious diarrhea in the emergency department. J Am Coll Emerg Physicians Open. Feb 2022; 3(1): e12616. PMID 35072157

Mentasti M, Fry NK, Afshar B, et al.(2012) Application of Legionella pneumophila-specific quantitative real-time PCR combined with direct amplification and sequence-based typing in the diagnosis and epidemiological investigation of Legionnaires' disease. Eur J Clin Microbiol Infect Dis. Aug 2012;31(8):2017-2028. PMID 22278293

Messacar K, Breazeale G, Robinson CC, et al.(2016) Potential clinical impact of the film array meningitis encephalitis panel in children with suspected central nervous system infections. Diagn Microbiol Infect Dis. Sep 2016;86(1):118-120.

Miyashita N, Kawai Y, Inamura N, et al.(2015) Setting a standard for the initiation of steroid therapy in refractory or severe Mycoplasma pneumoniae pneumonia in adolescents and adults. J Infect Chemother. Mar 2015;21(3):153-160. PMID 25533771

Munson E, Napierala M, Basile J, et al.(2010) Trichomonas vaginalis transcription-mediated amplification-based analyte-specific reagent and alternative target testing of primary clinical vaginal saline suspensions. Diagn Microbiol Infect Dis. Sep 2010;68(1):66-72. PMID 20727473

NIH Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV.(2022) Updated April 12, 2022. https://clinicalinfo.hiv.gov/en/guidelines/adult-and-adolescent-opportunistic-infection/whats-new-guidelines. Accessed on May 10, 2022.

Nye MB, Schwebke JR, Body BA.(2009) Comparison of APTIMA Trichomonas vaginalis transcription-mediatedamplification to wet mount microscopy, culture, and polymerase chain reaction for diagnosis of trichomoniasis in men and women. Am J Obstet Gynecol. Feb 2009;200(2):188 e181-187. PMID 19185101

Olson D, Watkins LK, Demirjian A, et al.(2015) Outbreak of Mycoplasma pneumoniae-Associated Stevens-Johnson Syndrome. Pediatrics. Aug 2015;136(2):e386-394. PMID 26216320

Onori M, Coltella L, Mancinelli L, et al.(2014) Evaluation of a multiplex PCR assay for simultaneous detection of bacterial and viral enteropathogens in stool samples of paediatric patients. Diagn Microbiol Infect Dis. Jun 2014;79(2):149-154. PMID 24656922

Patel R, Uhl JR, Kohner P, et al.(1997) Multiplex PCR detection of vanA, vanB, vanC-1, and vanC-2/3 genes in enterococci. J Clin Microbiol. Mar 1997;35(3):703-707. PMID 9041416

Peuchant O, Menard A, Renaudin H, et al.(2009) Increased macrolide resistance of Mycoplasma pneumoniae in France directly detected in clinical specimens by real-time PCR and melting curve analysis. J Antimicrob Chemother. Jul 2009;64(1):52-58. PMID 19429926

Pierce VM, Hodinka RL.(2012) Comparison of the GenMark Diagnostics eSensor respiratory viral panel to real-time PCR for detection of respiratory viruses in children. J Clin Microbiol. Nov 2012;50(11):3458-3465. PMID 22875893

Quest Diagnostics(2005) BK and JC virus DNA, real-time PCR Test Summary Lyndhurst, NJ: Quest Diagnostics; 2005

Quidel. LyraDirect Strep Assay. https://www.quidel.com/sites/default/files/product/documents/PIM112001EN00.pdf. Accessed December 1, 2015.

Randhawa P, Shapiro R, Vatas A(2005) Quantitation of DNA of polyomaviruses BK and JC in human kidneys J Infect Dis 2005;192:504-509

Razonable RR, van Cruijsen H, Brown RA, et al.(2003) Dynamics of cytomegalovirus replication during preemptive therapy with oral ganciclovir. J Infect Dis. Jun 1 2003;187(11):1801-1808. PMID 12751039

Rhein J, Bahr NC, Hemmert AC, et al.(2016) Diagnostic performance of a multiplex PCR assay for meningitis in an HIV-infected population in Uganda. Diagn Microbiol Infect Dis. Mar 2016;84(3):268-273.

Sander A, Penno S.(1999) Semiquantitative species-specific detection of Bartonella henselae and Bartonella quintana by PCR-enzyme immunoassay. J Clin Microbiol. Oct 1999;37(10):3097-3101. PMID 10488160

Saslow D, Solomon D, Lawson HW, et al.(2012) American Cancer Society, American Society for Colposcopy and Cervical Pathology, and American Society for Clinical Pathology screening guidelines for the prevention and early detection of cervical cancer. Am J Clin Pathol. Apr 2012;137(4):516-542. PMID 22431528

Schlecht NF, Trevisan A, Duarte-Franco E, et al.(2003) Viral load as a predictor of the risk of cervical intraepithelial neoplasia. Int J Cancer. Feb 10 2003;103(4):519-524. PMID 12478669

Schwebke JR, Hobbs MM, Taylor SN, et al.(2011) Molecular testing for Trichomonas vaginalis in women: results from a prospective U.S. clinical trial. J Clin Microbiol. Dec 2011;49(12):4106-4111. PMID 21940475

Seagar AL, Neish B, Laurenson IF.(2012) Comparison of two in-house real-time PCR assays with MTB Q-PCR Alert and GenoType MTBDRplus for the rapid detection of mycobacteria in clinical specimens. J Med Microbiol. Oct 2012;61(Pt 10):1459-1464. PMID 22790204

Shulman ST, Bisno AL, Clegg HW, et al.(2012) Clinical practice guideline for the diagnosis and management of group A streptococcal pharyngitis: 2012 update by the Infectious Diseases Society of America. Clin Infect Dis. Nov 15 2012;55(10):e86-102. PMID 22965026

Shulman ST, Bisno AL, Clegg HW, et al.(2015) Clinical practice guideline for the diagnosis and management of group A streptococcal pharyngitis: 2012 update by the Infectious Diseases Society of America. Clin Infect Dis. Nov 15 2012;55(10):e86-102. PMID 22965026

Slinger R, Goldfarb D, Rajakumar D, et al.(2011) Rapid PCR detection of group A Streptococcus from flocked throat swabs: a retrospective clinical study. Ann Clin Microbiol Antimicrob. 2011;10:33. PMID 21888649

Sood P, Senanayake S, Sujeet K, et al(2012) Management and outcome of BK viremia in renal transplant recipients: a prospective single-center study Transplantation 2012; 94:814

Sorrell MF, Belongia EA, Costa J, et al.(2009) National Institutes of Health Consensus Development Conference Statement: management of hepatitis B. Ann Intern Med. Jan 20 2009;150(2):104-110. PMID 19124811

Stanek G, Wormser GP, Gray J, et al.(2012) Lyme borreliosis. Lancet. Feb 4 2012;379(9814):461-473. PMID 21903253

Tondella ML, Talkington DF, Holloway BP, et al.(2002) Development and evaluation of real-time PCR-based fluorescence assays for detection of Chlamydia pneumoniae. J Clin Microbiol. Feb 2002;40(2):575-583. PMID 11825973

Tondella ML, Talkington DF, Holloway BP, et al.(2002) Development and evaluation of real-time PCR-based fluorescence assays for detection of Chlamydia pneumoniae. J Clin Microbiol. Feb 2002;40(2):575-583. PMID 11825973

Tsai JD, Tsai HJ, Lin TH, et al.(2014) Comparison of the detection rates of RT-PCR and virus culture using a combination of specimens from multiple sites for enterovirus-associated encephalomyelitis during enterovirus 71epidemic Jpn J Infect Dis. 2014;67(5):333-338. PMID 25241681

U.S. National Library of Medicine.(2018) West Nile Virus. https://medlineplus.gov/westnilevirus.html. Accessed Nov. 9, 2018

Upton A, Bissessor L, Farrell E, et al.(2015) Comparison of illumigene Group A Streptococcus assay with culture of throat swabs from children with sore throats in the New Zealand school-based rheumatic fever prevention program. J Clin Microbiol. Nov 11 2015. PMID 26560542

Weinberg A, Hodges TN, Li S, et al.(2000) Comparison of PCR, antigenemia assay, and rapid blood culture for detection and prevention of cytomegalovirus disease after lung transplantation. J Clin Microbiol. Feb 2000;38(2):768-772. PMID 10655383

Wenzel JJ, Walch H, Bollwein M, et al.(2009) Library of prefabricated locked nucleic acid hydrolysis probes facilitates rapid development of reverse-transcription quantitative real-time PCR assays for detection of novel influenza A/H1N1/09 virus. Clin Chem. Dec 2009;55(12):2218-2222. PMID 19797710

Wheeler CM, Hunt WC, Cuzick J, et al.(2014) The influence of type-specific human papillomavirus infections on the detection of cervical precancer and cancer: A population-based study of opportunistic cervical screening in the United States. Int J Cancer. Aug 1 2014;135(3):624-634. PMID 24226935

Wootton SH, Aguilera E, Salazar L, et al.(2016) Enhancing pathogen identification in patients with meningitis and a negative Gram stain using the BioFire FilmArray((R)) Meningitis/Encephalitis panel. Ann Clin Microbiol Antimicrob. Apr 21 2016;15:26.

Xia QF, Liu JB, Liu P, et al.(2012) Development of a novel quantitative real-time assay using duplex mutation primers for rapid detection of Candida species. Mol Med Rep. Jan 2012;5(1):207-210. PMID 21964617

Ylitalo N, Sorensen P, Josefsson AM, et al.(2000) Consistent high viral load of human papillomavirus 16 and risk of cervical carcinoma in situ: a nested case-control study. Lancet. Jun 24 2000;355(9222):2194-2198. PMID 10881892

Yoshikawa T.(2004) Human herpes virus 6 infection in hematopoietic stem cell transplant patients. Br J Haematol. Feb 2004;124(4):421-432. PMID 14984492

Zhang K, Sparling J, Chow BL, et al.(2004) New quadriplex PCR assay for detection of methicillin and mupirocin resistance and simultaneous discrimination of Staphylococcus aureus from coagulase-negative staphylococci. J Clin Microbiol. Nov 2004;42(11):4947-4955. PMID 15528678

Zika Virus: Testing Guidance. Center for Disease Control and Prevention.(2019) https://www.cdc.gov/zika/hc-providers/testing-guidance.html. Last Reviewed December 9, 2019. Accessed May 11, 2022.


Group specific policy will supersede this policy when applicable. This policy does not apply to the Wal-Mart Associates Group Health Plan participants or to the Tyson Group Health Plan participants.
CPT Codes Copyright © 2023 American Medical Association.