Description: 
Vaginitis is defined as inflammation of the vagina with symptoms of discharge, itching, and discomfort often due to a disruption of the vaginal microflora. The most common infections are bacterial vaginosis, Candida vulvovaginitis, and trichomoniasis.¹ Other causes include vaginal atrophy in postmenopausal women, cervicitis, foreign body, irritants, and allergens.²

Bacterial vaginosis (BV) is characterized by a shift in microbial species from the normally dominant hydrogen-peroxide producing Lactobacillus species to Gardnerella vaginalis and anaerobic commensals.^3-7

Vulvovaginal candidiasis (VVC) is usually caused by Candida albicans but can occasionally be caused by other Candida species.⁸ It is the second most common cause of vaginitis symptoms (after BV) and accounts for approximately one-third of vaginitis cases.^9,10

Trichomoniasis is caused by the flagellated protozoan Trichomonas vaginalis, which principally infects the squamous epithelium in the urogenital tract: vagina, urethra, and paraurethral glands.^11,12

Regulatory Status
A search of the term “vaginitis” on the FDA Device database on Jan. 29, 2021, yielded 145 records. Additionally, many labs have developed specific tests that they must validate and perform in house. These laboratory-developed tests (LDTs) are regulated by the Centers for Medicare & Medicaid Services (CMS) as high-complexity tests under the Clinical Laboratory Improvement Amendments of 1988 (CLIA ’88). The U.S. Food and Drug Administration has not approved or cleared this test as an LDT; however, FDA clearance or approval is not currently required for clinical use.

Policy:
Application of coverage criteria is dependent upon an individual’s benefit coverage at the time of the request. 

1. For individuals with signs and symptoms of vaginitis, testing of pH, testing for the presence of amines, measurement of sialidase activity, saline wet mount, potassium hydroxide (KOH) wet mount, and microscopic examination of vaginal fluids is considered MEDICALLY NECESSARY.
2. For individuals with signs and symptoms of vaginitis, direct probe DNA-based identification of Gardnerella, Trichomonas, and Candida (e.g., BD Affirm™ VPIII) is considered MEDICALLY NECESSARY.
3. For individuals with signs and symptoms of vaginitis but with negative findings on wet-mount preparations and a normal pH test, vaginal cultures for Candida species for the diagnosis of vulvovaginal candidiasis is considered MEDICALLY NECESSARY.
4. For individuals with signs and symptoms of vaginitis, nucleic acid amplification testing (NAAT) or polymerase chain reaction (PCR)-based identification of Trichomonas vaginalis is considered MEDICALLY NECESSARY. 
5. For individuals with risk factors for trichomoniasis (new or multiple partners; history of sexually transmitted infections (STIs), especially HIV; exchange of sex for payment; incarceration; injection drug use), screening for Trichomonas is considered MEDICALLY NECESSARY.
6. For individuals with complicated vulvovaginal candidiasis (VVC), polymerase chain reaction (PCR) based identification of Candida to confirm clinical diagnosis and identify non-albicans Candida is considered MEDICALLY NECESSARY. 
7. For individuals with signs and symptoms of bacterial vaginosis (BV), NAAT specific to the diagnosis of BV (e.g., Aptima® BV; OneSwab® BV Panel PCR with Lactobacillus Profiling by qPCR; SureSwab® Advanced BV, TMA) and single or multitarget PCR testing for the diagnosis of BV is considered MEDICALLY NECESSARY.
8. For individuals with signs and symptoms of vaginitis, NAAT panel testing designed to detect more than one type of vaginitis (VVC, BV, and/or trichomoniasis; e.g., BD MAX™ Vaginal Panel, NuSwab® VG, Xpert® Xpress MVP) is considered MEDICALLY NECESSARY. 
9. For asymptomatic individuals, including asymptomatic pregnant individuals at an average or high risk for premature labor, screening for trichomoniasis and bacterial vaginosis is considered NOT MEDICALLY NECESSARY.

The following does not meet coverage criteria due to a lack of available published scientific literature confirming that the test(s) is/are required and beneficial for the diagnosis and treatment of an individual’s illness.

10. For individuals with symptoms of vaginitis, rapid identification of Trichomonas by enzyme immunoassay is considered NOT MEDICALLY NECESSARY.
11. Testing for microorganisms involved in vaginal flora imbalance and/or infertility using molecular-based panel testing is considered NOT MEDICALLY NECESSARY.
12. All other tests for vaginitis not addressed above is considered NOT MEDICALLY NECESSARY.

Table of Terminology

Term	Definition
AAFP	American Academy of Family Physicians
ACOG	American College of Obstetrics and Gynaecology
ASM	American Society for Microbiology
AV	Aerobic vaginitis
BV	Bacterial vaginosis
BVAB	BV associated bacteria
CDC	Centers for Disease Control and Prevention
CLIA	Clinical Laboratory Improvement Amendments
CMS	Centers for Medicare and Medicaid
CT	Chlamydia
DNA	Deoxyribose nucleic acid
DOS	Date of service
HIV	Human Immunodeficiency Virus
IDSA	Infectious Diseases Society of America
LDTs	Laboratory developed tests
MDL	Medical Diagnostic Laboratories
NAAT	Nucleic acid amplification testing
NG	Gonorrhoea
NPV	Negative predictive value
OADS	Office of the Associate Director for Science
PCR	Polymerase chain reaction
PMNs	Polymorphonuclear cells
PPV	Positive predictive value
RTPCR	Real-time polymerase chain reaction
SOC	Standard of care
SOGC	Society Of Obstetricians and Gynaecologists of Canada
STDs	Sexually transmitted diseases
TMA	Transcription-mediated amplification
TV	Trichomonas vaginalis
USPSTF	U.S. Preventive Services Task Force
VVC	Vulvovaginal candidiasis

Rationale
Vaginitis is characterized by several symptoms including odor, itching, abnormal vaginal discharge, burning and irritation; this inflammatory ailment is considered the most common gynecologic diagnosis in primary care as most women experience vaginitis at least once in their lives.13 A diagnosis of vaginitis can be given based on a combination of symptoms, physical examination, and office or laboratory-based testing methods.

The squamous epithelium of the vagina in premenopausal women is rich in glycogen, a substrate for lactobacilli, which create an acidic vaginal environment (pH 4.0 to 4.5). This acidity helps maintain the normal vaginal flora and inhibits growth of pathogenic organisms. Disruption of the normal ecosystem by menstrual cycle, sexual activity, contraceptive, pregnancy, foreign bodies, estrogen level, sexually transmitted diseases, and use of hygienic products or antibiotics can lead to development of vaginitis. Bacterial vaginosis (BV), vulvovaginal candidiasis (VVC), and trichomoniasis are the three most common infections responsible for vaginitis. Other causes include: vaginal atrophy in postmenopausal women, cervicitis, foreign body, irritants and allergens.²

Bacterial vaginosis is caused by an imbalance of naturally occurring vaginal bacteria, characterized by both a change in the most common type of bacteria present, along with an increase in the total number of bacteria present. Normal vaginal microbiota is dominated by the species Lactobacilli, which are known to produce hydrogen peroxide and lactic acid, which help to keep the acidic vaginal environment below pH 4.5.^14,15 Though the origin of vaginal bacterial infections is still unclear, it is believed that most of such infections are the result of another bacteria, Gardnerella vaginalis, creating a biofilm which allows opportunistic bacteria to grow within the vagina, causing a decrease in the Lactobacilli and subsequent disruption of the pH of the system. An entire host of etiologic organisms have been identified as possible instigators and exacerbators, including Atopobium vaginae, Megasphaera phylotype 1 and 2, Leptotrichia aminionii, Mobiluncus spp, Prevotella spp, Mycoplasma hominis, Bacteroides spp, Sneathia, and BV-associated bacteria (BVAB) 1, 2, and 3, though as aforementioned the causative mechanism and the interaction between these species are still uncertain.¹⁴ 

Laboratory documentation of the etiology of vaginitis is important before initiating therapy, given the nonspecific nature and considerable overlap of the symptoms.^16-18 Diagnostic testing enables targeted treatment, increases therapeutic compliance, and increases the likelihood of partner notification.^2,9

Measurement of vaginal pH is the primary initial finding that drives the diagnostic. The pH of the normal vaginal secretions in premenopausal women with relatively high estrogen levels is 4.0 to 4.5. The pH of normal vaginal secretions in premenarchal and postmenopausal women in whom estrogen levels are low is ≥4.7. An elevated pH in a premenopausal woman suggests infections, such as BV (pH>4.5) or trichomoniasis (pH 5 to 6) and helps to exclude Candida vulvovaginitis (pH 4 to 4.5). Vaginal pH may also be altered by lubricating gels, semen, douches, intravaginal medications and in pregnant women, leakage of amniotic fluid.^2,17 

There are several challenging aspects to the diagnosis of the etiology of vaginitis based on clinical symptoms. Vaginitis is a global term for nonspecific syndrome and must be narrowed down to the distinct causative factors. Traditional methods have included microscopy, pH testing, amine ‘whiff’ test, and the Amsel criteria, depending on the suspected etiology. However, physicians may find in-office microscopy to be unavailable, time-consuming, and/or inconclusive in achieving a diagnosis – some estimates hold that misdiagnosis of vulvovaginitis approaches 50%.19 As another confounding factor, coinfections are common in vaginitis, adding difficulty in diagnosis of the three most common organisms if there is mixed vaginitis or coinfection.² 

Even though studies have shown that PCR methods have a higher specificity and sensitivity than culture and shorter turn-around time in identifying Candida,^20-23 their use may be adding to clinical non-specificity. Tabrizi, et al. (2006) reported that PCR “detected four additional Candida albicans, three Candida parapsilosis and one Candida tropicalis when compared with culture. All but one case additionally detected by PCR were found in patients with no VVC symptoms.”²² These data support the earlier findings by Giraldo, et al. (2000) where, unlike culture testing, “Candida was identified by PCR in a similar proportion of patients with previous recurrent vulvovaginal candidiasis (30%) and in controls (28.8%).” Taken together, these studies indicate that, even though PCR is more sensitive than culture, it may be identifying cases of Candida in asymptomatic women that are clinically irrelevant.

Overall, microscopy has lower sensitivities and negative predictive values for BV, candidiasis, and trichomoniasis, and yeast when compared to NAAT and culture, respectively.² The use of established molecular diagnostic tests as an alternative to traditional methods is an opportunity to improve the diagnosis and management of vaginitis; NAAT tests have already improved detection of trichomoniasis.² 

Proprietary Tests
DNA hybridization probe tests
As previously stated, microscopy, rather than bacterial culture, is the standard of care for diagnosing BV, and commercially available tests are available in the absence of microscopy but are not widely used. A study of 176 women using the Affirm VP III test (a DNA hybridization probe test that identifies high concentrations of G. vaginalis) reported comparable results to wet mount examination with no false positives and only three false negatives for T. vaginalis, and three false positives and four false negatives for G. vaginalis.²⁵ 

Trichomoniasis 
The OSOM Trichomonas vaginalis (TV) Rapid Test by Sekisui Diagnostics is “an antigen-detection test that uses immunochromatographic capillary flow dipstick technology that can be performed at the POC [point of care].”²⁶ The diagnostic accuracy of the OSOM TV Rapid assay was tested against the common laboratory-based Anyplex II STI-7 Detection in a South African cross-sectional study; all irregular results were further tested with the Fast Track Diagnostics (FTD) STD9 assay.²⁷ Vaginal swabs from 247 women were tested for this study. “The sensitivity and specificity of OSOM TV were 75.0% (45.0-100) and 100% (100-100),” respectively, showing a very high specificity and lower sensitivity.²⁷ 

Bacterial Vaginosis tests 
AMPLISwab™
The AMPLISwab™ by MedLabs is a comprehensive test created to assess the different organisms responsible for a variety of female genital tract infections, including causative pathogens for cervicitis, nongonococcal urethritis, pelvic inflammatory disease and infertility, sexually transmitted infections, and vaginitis (e.g., bacterial vaginosis, candidiasis and trichomoniasis). The test requires one swab to test for 23 total organisms, broken down into four categories (seven yeast, 12 bacteria and one reference bacteria, one parasite, and two types of herpes viruses), employing testing methodologies such as automated DNA/RNA extraction, transcription-mediated amplification,28 and real-time polymerase chain reaction (RT-PCR) for the quantification of select organisms implicated in bacterial vaginosis.²⁹ 

Aptima® BV 
The Aptima® Assay by Hologic is a NAAT that identifies BV. “NAAT detects 3x more mixed infections cases than clinical diagnosis with wet mount and Amsel’s criteria.”³⁰ The Aptima BV Assay is a NAAT that utilizes real time transcription-mediated amplification for the detection and quantification of ribosomal RNA from BV-associated bacteria: Lactobacillus (L. gasseri, L. crispatus, and L. jensenii), Gardnerella vaginalis, and Atopobium vaginae.²⁸ “The assay reports a qualitative result for BV and does not report results for individual organisms. The assay is intended to aid in the diagnosis of BV on the automated Panther system using clinician-collected and patient-collected vaginal swab specimens from females with a clinical presentation consistent with vaginitis and/or vaginosis.”³¹

OneSwab®
OneSwab® by Medical Diagnostic Laboratories (MDL) uses real-time PCR and qPCR to output a graphical representation of the relative concentrations of the microbial flora. The Bacterial Vaginosis (with Lactobacillus profiling) qPCR test results are then reported in a text based and graphical format. The graphic format includes a representation of the results of all the quantitative tests included in the panel. The relative ratios of DNA species in the give sample in proportion to one another reflect the relative concentrations of different bacteria in vaginal specimens. According to the website, the panel includes assays to detect Gardnerella vaginalis and Atopobium vaginae, which are established BV organisms. NAAT is 95% sensitive and 99% specific for these organisms. In addition, two new assays to detect Megasphaera species and Bacterial Vaginosis-Associated Bacterium 2 (BVAB2) are included in the Bacterial Vaginosis (with Lactobacillus profiling) panel. According to MDL, using NAAT to detect either of these two organisms is up to 99% sensitive and 94% specific for the diagnosis of BV when compared to Amsel Criteria and Nugent Score.³² Of note, the sensitivity and specificity just described are for the use of NAAT in detecting these microorganisms, as reported by Fredricks, et al. (2007), and are not necessarily the sensitivity and specificity of the MDL OneSwab® for BV. 

SureSwab® Advanced Bacterial Vaginosis (BV), TMA
The SureSwab® (Quest Diagnostics, Inc.) Advanced Bacterial Vaginosis (BV), TMA uses real time TMA to screen for microorganisms involved in BV vaginal flora imbalances, including Lactobacillus species, Atopobium vaginae, and Gardnerella vaginalis from a single vaginal swab. It reports a qualitative result for BV and does not report results for individual organisms. The swab can be collected either by a physician or the patient.³⁴ 

OSOM® BVBlue®
The OSOM® BVBlue® chromogenic diagnostic point-of-care test is a CLIA-waived test with a reported 10 minute read time. The test detects “elevated vaginal fluid sialidase activity, an enzyme produced by bacterial pathogens associated with bacterial vaginosis including Gardnerella, Bacteroides, Prevotella, and Mobiluncus.” Sekisui Diagnostics reports that the test is “92.8% sensitive, 98% specific versus Gram Stain” with a “1-minute hands-on-time; 10 minute read time,” and “instant color change provides clear easy-to-read results.”³⁵

Combination panel tests for Vaginitis/Vaginosis
Aptima® CV/TV 
Aptima® CV/TV assays are NAAT tests that identify “bacterial vaginosis (BV), vulvovaginal candidiasis (Candida vaginitis or CV) and Trichomoniasis (Trichomonas vaginalis or TV) in symptomatic women from one vaginal sample. NAAT detects 3x more mixed infections cases than clinical diagnosis with wet mount and Amsel’s criteria.” These tests detect and qualitatively report results for the following organisms: Candida species group (C. albicans, C. tropicalis, C. parapsilosis, C. dubliniensis), Candida glabrata, Trichomonas vaginalis.³⁰

SureSwab®
SureSwab® Advanced Vaginitis, TMA is a test for bacterial vaginosis, vulvovaginal candidiasis (Candidiasis species), and trichomoniasis (Trichomonas vaginalis).³⁶ In an even more expansive combination test package, Quest offers a “SureSwab® Advanced Vaginitis Plus, TMA” assay which, in addition to detecting organisms associated with BV, trichomoniasis, and vulvovaginal candidiasis, also detects Chlamydia trachomatis and Neisseria gonorrhoeae.³⁷

BD MAX™ Vaginal Panel 
The BD MAX™ Vaginal Panel is “an automated qualitative in vitro diagnostic test for the direct detection of DNA targets from bacteria associated with BV (qualitative results reported based on detection and quantitation of targeted organism markers), Candida species associated with vulvovaginal candidiasis, and Trichomonas vaginalis from vaginal swabs in patients who are symptomatic for vaginitis/vaginosis. The test utilizes real-time PCR for the amplification of specific DNA targets and utilizes fluorogenic target-specific hybridization probes to detect and differentiate DNA.”³⁸ 

Analytical Validity
Microscopic examination of normal vaginal discharge reveals a predominance of squamous epithelial cells, rare polymorphonuclear leukocytes (PMNs), and Lactobacillus species. The primary goal of the examination is to look for candidal buds or hyphae, motile trichomonads, epithelial cells studded with adherent coccobacilli (clue cells), and increased numbers of PMNs.² The microscopic evaluation of BV is usually based on Amsel criteria.³⁹ Amsel criteria state that the presence of at least three out of the following four criteria are indicative of a BV diagnosis: increased homogeneous thin vaginal discharge, pH secretion > 4.5, amine odor when potassium hydroxide 10% solution is added to a vaginal secretion sample, and the presence of clue cells in wet preparations.39 If clinical criteria are used to define infection, then reported sensitivity may range from 62 to 100 percent.⁴⁰ Using Gram's stain as the standard for diagnosing BV, the sensitivity of Amsel criteria for diagnosis of BV is over 90 percent and specificity is 77 percent.¹⁶ The Nugent score is also available as a Gram staining scoring system to diagnose BV based on vaginal swab samples.⁴¹ Because BV represents complex changes in the vaginal flora, vaginal culture has no role in diagnosis. If microscopy is not available, commercial diagnostic testing methods (e.g., rapid antigen and nucleic acid amplification tests) are used for confirming the clinical suspicion of BV. Polymerase chain reaction (PCR)-based assays to quantify BV-associated bacteria^42,43 have good sensitivity and specificity compared with standard clinical tests.^44,45 However, they are expensive and of limited utility.⁷

Trichomoniasis can be diagnosed by the presence of motile trichomonads on wet mount, but it is identified in only 60 to 70 percent of culture-confirmed cases. Culture on Diamond's medium was considered the gold standard method for diagnosing a T. vaginalis infection⁹; however, nucleic acid amplification tests⁴⁶ have become the accepted gold standard for the diagnosis of T. vaginalis. One study found the sensitivities for T. vaginalis using wet mount, culture, rapid antigen testing, and transcription-mediated amplification testing were 65, 96, 90, and 98 percent, respectively.⁴⁷ Coexistence of T. vaginalis and BV pathogens is common, with coinfection rates of 60 to 80 percent.^11,48

Microscopy is negative in up to 50 percent of patients with culture-confirmed VVC.⁴⁹ Since there are no reliable point of care tests for Candida available in the United States,^50-55 culture must be obtained. PCR methods have high sensitivity and specificity and a shorter turn-around time than culture,^20-23 but they are costly and offer no proven benefit over culture in symptomatic women.¹⁰ 

Lynch, et al. (2019) collected vaginal swabs from 93 women in a cross-sectional study; results from microscopy were compared to two molecular approaches (a qPCR assay with a BV interpretive algorithm and a microbiome profiling test of the 16S rRNA gene produced by Illumina).⁵⁶ Results show that “Microscopy plus BV Nugent score had 76% overall agreement with the qPCR plus BV interpretive algorithm method”; further, “Microscopic identification of Candida versus that by qPCR had 94% agreement (9 positive, 78 negative).”⁵⁶ The qPCR assays gave additional information regarding the types of bacteria present, and the 16S microbiome analysis identified differentiating patterns between BV, aerobic vaginitis (AV), and Lactobacillus type infections.

Cartwright, et al. (2018) have published data regarding the clinical validity of a PCR-based assay for the detection of BV. This multicenter study included 1579 patients and compared PCR results to samples realized by both the Nugent gram stain and a clinical evaluation using Amsel criteria. Next-generation sequencing was used to confirm differing results. After the resolution of discordant test results using next-generation sequencing, the BV-PCR assay reported a sensitivity of 98.7%, a specificity of 95.9%, a positive predictive value of 92.9% and a negative predictive value of 96.9%.⁵⁷ These results show that this PCR-based assay can diagnose BV in symptomatic women efficiently.

Gaydos, et al. (2017) conducted a cross-sectional, multi-site study into the clinical validation of this system (n=1740 symptomatic women) reported a sensitivity and specificity of 90.9% and 94.1%, respectively for the Candida group and 90.5% sensitivity and 85.8% specificity for BV. For C. glabrata specifically, the assay had only 75.9% sensitivity but 99.7% specificity. For trichomoniasis, the sensitivity and specificity were 93.1% and 99.3%, respectively.⁵⁸ These researchers also compared the results of this test to clinician assessment. Again, to qualify for the study, the women must have at least one symptom of BV. Using Amsel’s criteria, the investigational test sensitivity was 92.7% as compared to the 75.6% sensitivity of the clinician assessment. The authors conclude, “The investigational test showed significantly higher sensitivity for detecting vaginitis, involving more than one cause, than did clinician diagnosis. Taken together, these results suggest that a molecular investigational test can facilitate accurate detection of vaginitis.”⁵⁹ It should be noted, however, that these studies only included symptomatic women, and, therefore, the possible clinical non-specificity (i.e., instances where an asymptomatic woman would test positive) is not addressed. Sherrard (2019) compared BV, candidiasis, and trichomoniasis diagnostic results from the BD MAX Vaginal Panel to a current test used in a UK specialist sexual health service center. The authors reported that the BD MAX Vaginal Panel had a sensitivity of 86.4% and specificity of 86.0% for Candida species, and a sensitivity of 94.4% and specificity of 79% for BV; the specificity for BV was lower in this study than what has been previously reported.⁶⁰

Sumeksri, et al. (2005) conducted a study correlated to the OSOM® BVBlue® test. The study included 173 pregnant women reported a sensitivity and specificity of 94% and 96% respectively, as compared to Gram stain score. These results were comparable to the previously reported values of 91.7% sensitivity and 97.8% specificity in an earlier, smaller study of non-menstruating women (n=57).⁶² A larger study (n=288 women) reported a sensitivity of 88% and specificity of 91% as compared to the Amsel criteria. The authors of this report concluded that women who “are not in settings where the conventional diagnostic methods are either practical or possible… would greatly benefit from access to rapid and reliable point-of-care tests to improve the diagnosis and management of BV.”⁶³

Clinical Utility and Validity
Anand, et al. (2020) investigated the accuracy of Papanicolaou smear to diagnose bacterial vaginosis infection in women with women with clinically evident genital infection using the Nugent score on Gram-stained smear as the gold standard. In a prospective blinded cross-sectional study of 254 nonpregnant women between the ages of 30 and 50 conducted between August 2016 and August 2018, the researchers found that using the Nugent score for diagnosing BV as the gold standard, the Pap smears showed sensitivity and specificity of 70.9% (CI: 61.5% - 79.2%) and 56.8% (CI: 48.2% - 65.2%), respectively. Moreover, they found that the positive percent value was 56.5% (CI: 47.8% - 64.9%), while the negative percent value was 71.2% (CI: 61.8% - 79.4%). These results indicated to the authors that though Pap smears are generally reserved for cervical cancer, the “Pap smear may serve as a means of diagnosing BV [bacterial vaginosis] infection in resource-constrained countries like India.”⁶⁴

Hilbert, et al. (2016) performed a prospective longitudinal study on the use of molecular assays for the accurate detection and diagnosis of bacterial vaginosis using MDL OneSwab®. The authors quantified nine organisms associated with vaginal health or disease (Gardnerella vaginalis, Atopobium vaginae, BV-associated bacteria 2 (BVAB2, an uncultured member of the order Clostridiales), Megasphaera phylotype 1 or 2, Lactobacillus iners, Lactobacillus crispatus, Lactobacillus gasseri, and Lactobacillus jensenii) in a total of 149 women were enrolled in the study. DNA was extracted from clinical specimens using mechanical disruption and the QIAamp mini-kit from Qiagen; qPCR assay was used to quantify BV microbes and Lactobacillus species. Though the authors evaluated a broad variety of organisms with the potential to be diagnostic markers, results from the study indicated a sensitivity of 92% and specificity of 95% for three that were predictive of diagnosis of BV: G. vaginalis, A. vaginae, and Megasphaera phylotypes 1 and 2; outcomes were 94% PPV, and 94% NPV for BV. The authors summarized their findings by describing the molecular assay as a highly specific laboratory test to identify bacterial vaginosis.⁶⁵

The Aptima BV and Aptima Candida/Trichomonas vaginitis (CV/TV) NAAT molecular tests detect and qualitatively report results using a proprietary algorithmic analysis. Pathogens addressed by the test include: Candida species group (C. albicans, C. tropicalis, C. parapsilosis, C. dubliniensis), Candida glabrata, Lactobacillus, Gardnerella vaginalis, Atopobium vaginae, and Trichomonas vaginalis.⁶⁶ Hologic announced the FDA approval of the Aptima BV and Aptima CV/TV vaginitis tests in 2019.⁶⁷ Schwebke, et al. (2020) performed a multicenter, prospective clinical study to validate the performance of the Aptima BV and Aptima CV/TV test for bacterial vaginosis, vulvovaginal candidiasis, and trichomonas vaginitis. A total of 1,519 subjects were enrolled in the study. The authors reported sensitivity and specificity for the investigational tests when it came to provider-collected samples at 95.0% and 89.6% for BV. When it came to Candida species, sensitivity and specificity was 91.7% and 94.9% respectively; C. glabrata sensitivity and specificity was 84.7% and 99.1%; 96.5% and 94.1% for T. vaginalis. Patient-collected samples showed similar ranges of sensitivity and specificity. In conclusion, the authors wrote, “In a secondary analysis, clinicians' diagnoses, in-clinic assessments, and investigational-assay results were compared to gold standard reference methods. Overall, the investigational assays had higher sensitivity and specificity than clinicians' diagnoses and in-clinic assessments, indicating that the investigational assays were more predictive of infection than traditional diagnostic methods.”²⁸ 

There has been increasing literature and reviews regarding both NAAT and DNA hybridization probe proprietary-based diagnostic performance in the identification of bacterial vaginosis. A study by Richter, et al. (2019) compared the performance of three molecular diagnostic assays. The assays included in the study were BD Affirm, Hologic ASR BV Assay, and the Aptima IVD BV Assay. A total of 111 women were enrolled in the study. Women had been given an Affirm test by their provider after describing symptoms that indicated a form of vaginitis. After the collection of additional specimens, samples were run on the different assays. As predicted by clinicians, BV was the most common outcome of diagnosis for 45 of the patients (71%). The sensitivity and specificity for the Hologic ASR assay (diagnosing BV) was 75.6% and 81.8%. The Affirm assay had a sensitivity and specificity of 86.7% and 60.6% for BV, while the Aptima BV IVD assay showed sensitivities and specificities of 84.4% and 86.3%. According to the study, of the three molecular assays that were evaluated, “Aptima BV IVD demonstrated the highest specificity, which may reflect value for the A. vaginae target unique to that assay.” The study also noted that “although assays that incorporate more bacterial targets are attractive since they reflect the bacterial diversity that has been reported in BV, it is uncertain whether they will provide better diagnostic accuracy to offset the higher cost usually charged for additional targets.”⁶⁸

One population health population study initiated by Kong, et al. (2021) noted that molecular testing is both a sensitive and specific approach to testing and also a welcome tool for providers using labor-intensive traditional practices. The authors address the issue of poor compliance by providers with established gold standard guidelines such as the Amsel criteria, as well as a varied and divergent approaches to office diagnostics. The widespread availability of molecular testing could help accomplish the diagnosis of vaginitis in a single visit. The authors conclude that “compared to CE, molecular tests offer high sensitivity and specificity that provide a precise treatment route. In addition to improved accuracy, recent evidence demonstrates that the combination of sensitive and specific laboratory testing as well as careful patient evaluation have the potential to reduce unnecessary follow-up visits and improve patient care.”⁶⁹

Evans, et al. (2024) studied the clinical utilization and costs of syndromic diagnostic testing for vaginitis. The study included data from 1,175,637 patients with ICD-10 codes indicating vaginitis between the years 2020 and 2023, pulled from the IQVIA PharMetrics® Plus database. Patients were divided into two cohorts: patients who did or did not receive a syndromic polymerase chain reaction (PCR) test within two days. “Patients who received a Syndromic Vaginitis PCR test had significantly fewer outpatient medical services in the 6 months following initial diagnosis compared to those who received no diagnostic test.” The authors attributed this result to decreased medical service visits. Patients who received a syndromic PCR saved an average of 2,067 dollars compared to patients who did not receive a syndromic PCR. The authors concluded that “Syndromic Vaginitis PCR testing may be an effective diagnostic tool for reducing costs associated with vaginitis infections.”⁷⁰

Centers for Disease Control and Prevention (CDC) 
The CDC published updated guidelines for diseases characterized by vulvovaginal itching, burning, irritation, odor or discharge in their Sexually Transmitted Infections Treatment Guidelines, 2021.⁷¹ These guidelines state that “obtaining a medical history alone has been reported to be insufficient for accurate diagnosis of vaginitis and can lead to inappropriate administration of medication…. Therefore, a careful history, examination, and laboratory testing to determine the etiology of any vaginal symptoms are warranted. Information regarding sexual behaviors and practices, sex of sex partners, menses, vaginal hygiene practices (e.g., douching), and self-treatment with oral and intravaginal medications or other products should be elicited.”⁷¹

The CDC notes that “in the clinician’s office, the cause of vaginal symptoms can often be determined by pH, a potassium hydroxide (KOH) test, and microscopic examination of a wet mount of fresh samples of vaginal discharge.” However, the guidelines conclude that “in settings where pH paper, KOH, and microscopy are unavailable, a broad range of clinical laboratory tests … can be used.”⁷¹

For the evaluation of BV, the CDC recommends that “BV can be diagnosed by the use of clinical criteria (i.e., Amsel’s Diagnostic Criteria) or by determining the Nugent score from a vaginal Gram stain.”⁷² Additional tests are available: “The Osom BV Blue test³⁵ detects vaginal sialidase activity. The Affirm VP III (Becton Dickinson) is an oligonucleotide probe test that detects high concentrations of G. vaginalis nucleic acids (>5 x 105 CFU of G. vaginalis/mL of vaginal fluid) for diagnosing BV, Candida species, and T. vaginalis. This test has been reported to be most useful for symptomatic women in conjunction with vaginal pH measurement and presence of amine odor. . . Finally, the FemExam Test Card (Cooper Surgical) measures vaginal pH, presence of trimethylamine (a metabolic by-product of G. vaginalis), and proline aminopeptidase. . . This test has primarily been studied in resource-poor settings, and although it has been reported to be beneficial compared with syndromic management, it is not a preferred diagnostic method for BV diagnosis.”⁷² The guidelines also state that due to insufficient evidence, “routine screening for BV among asymptomatic pregnant women at high or low risk for preterm delivery for preventing preterm birth is not recommended,”⁷² which is in compliance with the 2020 USPSTF recommendations and endorsed by the AAFP.⁷³

Regarding NAATs for BV, the CDC states that “BV NAATs should be used among symptomatic women only (e.g., women with vaginal discharge, odor, or itch) because their accuracy is not well defined for asymptomatic women. Despite the availability of BV NAATs, traditional methods of BV diagnosis, including the Amsel criteria, Nugent score, and the Affirm VP III assay, remain useful for diagnosing symptomatic BV because of their lower cost and ability to provide a rapid diagnosis. Culture of G. vaginalis is not recommended as a diagnostic tool because it is not specific. Cervical Pap tests have no clinical utility for diagnosing BV because of their low sensitivity and specificity.”⁷²

The CDC provides information on multiple BV NAATs that are available and notes that “these tests are based on detection of specific bacterial nucleic acids and have high sensitivity and specificity for BV (i.e., G. vaginalis, A. vaginae, BVAB2, or Megasphaera type 1) and certain lactobacilli (i.e., Lactobacillus crispatus, Lactobacillus jensenii, and Lactobacillus gasseri). They can be performed on either clinician- or self-collected vaginal specimens with results available in <24 hours, depending on the availability of the molecular diagnostic platform. Five quantitative multiplex PCR assays are available: Max Vaginal Panel (Becton Dickinson), Aptima BV (Hologic), NuSwab® VG (LabCorp), OneSwab® BV Panel PCR with Lactobacillus Profiling by qPCR (Medical Diagnostic Laboratories), and SureSwab® BV (Quest Diagnostics). Two of these assays are FDA cleared (BD Max Vaginal Panel and Aptima BV), and the other three are laboratory-developed tests. The Max Vaginal Panel provides results by an algorithmic analysis of molecular DNA detection of Lactobacillus species (L. crispatus and L. jensenii) in addition to G. vaginalis, A. vaginae, BVAB2, and Megasphaera type 1. This test has 90.5% sensitivity and 85.8% specificity for BV diagnosis, compared with Amsel criteria and Nugent score. It also provides results for Candida species and T. vaginalis. The Aptima BV detects G. vaginalis, A. vaginae, and certain Lactobacillus species including L. crispatus, L. jensenii, and L. gasseri, with sensitivity and specificity ranging from 95.0% to 97.3% and 85.8% to 89.6%, respectively (using either clinician- or patient-collected vaginal swabs). The three laboratory-developed tests (NuSwab® VG, OneSwab® BV Panel PCR with Lactobacillus Profiling by qPCR, and SureSwab® BV) have to be internally validated before use for patient care yet have good sensitivity and specificity, similar to FDA-cleared assays.”⁷²

For the evaluation of vulvovaginal candidiasis, the CDC recommends: “Examination of a wet mount with KOH preparation should be performed for all women with symptoms or signs of VVC, and women with a positive result should be treated. For those with negative wet mounts but existing signs or symptoms, vaginal cultures for Candida should be considered.”⁸ The most current guidelines for VVC diagnosis state that “vaginal culture or PCR should be obtained from women with complicated VVC to confirm clinical diagnosis and identify non–albicans Candida.”⁸

For the evaluation of trichomoniasis, the CDC recommends: “Diagnostic testing for T. vaginalis should be performed for women seeking care for vaginal discharge… Wet-mount microscopy traditionally has been used as the preferred diagnostic test for T. vaginalis among women because it is inexpensive and can be performed at the POC; however, it has low sensitivity (44%–68%) compared with culture. . . More highly sensitive and specific molecular diagnostic options are available, which should be used in conjunction with a negative wet mount when possible. NAATs are highly sensitive, detecting more T. vaginalis infections than wet-mount microscopy among women. . . The OSOM® trichomonas rapid test³⁵ is an antigen-detection test that uses immunochromatographic capillary flow dipstick technology that can be performed at the POC by using clinician-obtained vaginal specimens. Results are available in approximately 10–15 minutes, with sensitivities of 82%–95% and specificity of 97%–100%, compared with wet mount, culture, and transcription-mediated amplification . . . The Solana trichomonas assay (Quidel) is another rapid test for the qualitative detection of T. vaginalis DNA and can yield results <40 minutes after specimen collection. . . The Amplivue trichomonas assay (Quidel) is another rapid test providing qualitative detection of T. vaginalis that has been FDA cleared for vaginal specimens from symptomatic and asymptomatic women”²⁶ and “the Affirm VP III (Becton Dickinson) is an oligonucleotide probe test that detects high concentrations of G. vaginalis nucleic acids (>5 x 105 CFU of G. vaginalis/mL of vaginal fluid) for diagnosing BV, Candida species, and T. vaginalis. This test has been reported to be most useful for symptomatic women in conjunction with vaginal pH measurement and presence of amine odor (sensitivity of 97%); specificity is 81% compared with Nugent.”⁷² 

In the updated Sexually Transmitted Infections Treatment Guidelines, the CDC also mentions the FDA-cleared Aptima T. vaginalis assay that may be used for detection of T. vaginalis from symptomatic or asymptomatic women.²⁶

American Academy of Family Physicians (AAFP) 
The AAFP published an article on the diagnosis of vaginitis which states that: “Physicians traditionally diagnose vaginitis using the combination of symptoms, physical examination, pH of vaginal fluid, microscopy, and the whiff test. When combined, these tests have a sensitivity and specificity of 81 and 70 percent, respectively, for BV; 84 and 85 percent for vulvovaginal candidiasis; and 85 and 100 percent for trichomoniasis when compared with the DNA probe standard…A cost-effectiveness analysis of diagnostic strategies for vaginitis undiagnosed by pelvic examination, wet-mount preparation, and related office tests showed that the least expensive strategy was to perform yeast culture, gonorrhea and chlamydia probes at the initial visit, and Gram stain and Trichomonas culture only when the vaginal pH exceeded 4.9. Other strategies cost more and increased duration of symptoms by up to 1.3 days.”⁷⁴

In 2018, the AAFP published the following guidelines:

• “Symptoms alone cannot differentiate between the causes of vaginitis. Office-based or laboratory testing should be used with the history and physical examination findings to make the diagnosis. (C evidence rating)
• Do not obtain culture for the diagnosis of bacterial vaginosis because it represents a polymicrobial infection. (C evidence rating)
• Nucleic acid amplification testing is recommended for the diagnosis of trichomoniasis in symptomatic or high-risk women. (C evidence rating).”¹³

U.S. Preventive Services Task Force Recommendations
In 2020, the USPSTF published recommendations discouraging the use of screening for BV in pregnancy: “The USPSTF recommends against screening for bacterial vaginosis in pregnant persons not at increased risk for preterm delivery.” On a similar note, the USPSTF maintains its 2008 recommendation stating “that the current evidence is insufficient to assess the balance of benefits and harms of screening for bacterial vaginosis in pregnant persons at increased risk for preterm delivery.”⁷⁵

American College of Obstetrics and Gynecology (ACOG) 
The ACOG published in 2020 Practice Bulletin Number 215 on vaginitis in nonpregnant patients. These guidelines were reaffirmed in 2022. In these guidelines, the ACOG made these recommendations for diagnostic testing based on good and consistent scientific evidence (Level A):

• “The use of Amsel clinical criteria or Gram stain with Nugent scoring is recommended for the diagnosis of bacterial vaginosis.”
• “Nucleic acid amplification testing is recommended for the diagnosis of trichomoniasis.”
• “In a symptomatic patient, diagnosis of vulvovaginal candidiasis requires one of the following two findings: 1) visualization of spores, pseudohyphae, or hyphae on wet-mount microscopy or 2) vaginal fungal culture or commercial diagnostic test results positive for Candida species.”

The ACOG also published recommendations based on limited or inconsistent scientific evidence (Level B), along with a series of recommendations based on consensus and expert opinion (Level C). Those relating to diagnostic testing are reported below:

• “Patients should be retested within 3 months after treatment for T vaginalis because of the high rates of infection recurrence” (Level B).
• “Pap tests are not reliable for the diagnosis of vaginitis. Diagnostic confirmation is recommended for incidental findings of vulvovaginal candidiasis, bacterial vaginosis, or trichomoniasis on a Pap test” (Level B).
• “A complete medical history, physical examination of the vulva and vagina, and clinical testing of vaginal discharge (i.e. pH testing, a potassium hydroxide [KOH] “whiff test”, and microscopy) are recommended for the initial evaluation of patients with vaginitis symptoms” (Level C).

The ACOG mentions in Bulletin Number 215 that an advanced single-swab panel test that combines multiplex PCR and DNA probe technology could be a promising alternative to microscopy for BV, trichomoniasis, and candidiasis.⁷⁶

Infectious Diseases Society of America (IDSA) Clinical Practice Guidelines 
The IDSA has published an updated clinical guideline⁷⁷ for the management of candidiasis in which recommendations include diagnosing vulvovaginal candidiasis before proceeding with empiric antifungal therapy. The usual diagnosis is clinical based on signs and symptoms of vaginitis such as pruritus, irritation, vaginal soreness, vulvar edema, erythema and many others. Clinical signs and symptoms are nonspecific and could be attributed to causes other than vulvovaginal candidiasis. Therefore, authors recommend confirming clinical diagnosis by a wet -mount preparation with saline and 10% KOH to demonstrate the presence of yeast and a normal pH. In cases where signs and symptoms are suggestive of vulvovaginal candidiasis, but microscopic findings and pH are negative, culture testing confirms the diagnosis according to published guidelines. The IDSA also discusses the possible use of PCR in diagnosing invasive candidiasis, even though the guidelines later state that “Cultures of blood or other samples collected under sterile conditions have long been considered diagnostic gold standards for invasive candidiasis…The role of PCR in testing samples other than blood is not established.”⁷⁷

In the 2024 IDSA Guide to Utilization of the Microbiology Laboratory for Diagnosis of Infectious Diseases, the IDSA states that like “the initial investigations of NAATs compared to culture for CT [chlamydia] and NG [gonorrhoea], the SOC [standard of care] reference methods for vaginitis limit the validity of interpretation of the new multiplex vaginal panels. Basically, the vaginal Gram stain (Nugent) and Amsel's criteria do not align with each other on either sensitivity or specificity.” The IDSA notes “there are 3 FDA-cleared microbiome-based multiplex vaginal NAATs, BD Max™ Vaginal Panel (Becton Dickinson) (for use in women ≥18 years old), Aptima® BV and CV/TV (Hologic) (both approved for use in ≥14 years of age), and the Xpert® Xpress Multiplex vaginal panel (MVP) test (Cepheid) (approved for use in women ≥18 years old).” 

“Several commercial labs offer testing for vaginitis, often requiring a specific swab. Providers need to be aware that targets may vary depending on assay platform used. Tests offered vary from FDA-cleared platforms to lab developed (LDTs). FDA-cleared tests have been validated in several publications. All tests are for use in women with symptoms consistent with vaginitis/vaginosis with either a single self-collected or clinician-collected vaginal swab specimen. Importantly, these multiplex tests are not intended for screening asymptomatic patients. They are also not to be used for prognostic purposes or to be used as a test of cure. In general, multiplex tests have provided more accurate diagnoses for causes of vaginitis, consistently demonstrating higher sensitivity and negative predictive value than clinician diagnosis or POCTs. In addition, a statistically higher overall percent agreement with each of the reference methods than SOC POCTs performed on site demonstrated statistically higher sensitivity for detecting coinfections, most commonly, BV and VVC.”

“BV targets and interpretation algorithms differ for each product, but all use multiple vaginal microbiota species for determination of a positive result, making the tests specific for BV. Candida species are identified in groups relative to likelihood of fluconazole susceptibility (fluconazole susceptible, eg, C. albicans, C. tropicalis, C. parapsilosis, C. dubliniensis vs fluconazole resistant, eg, C. glabrata, C. krusei). In addition, NAATs have been more accurate in identifying mixed and coinfections, both among vaginitis entities (BV, VVC, TV) as well as with CT and NG. Outcome data from both prospective and retrospective review of claims data and studies shows that primary testing with NAATs results in fewer repeat visits, more directed therapy, and less overall cost as the primary testing choice compared to current SOC POC, despite NAAT results compared were not available at the POC. Overall, data suggest that the need for consistent, more accurate diagnosis and directed treatment is needed. A transition to accurate diagnostic testing for vaginitis by multiplex NAATs needs to be thoroughly addressed in future guidelines.”⁷⁸

Society of Obstetricians and Gynecologists of Canada (SOGC) 
The SOGC published guidelines for the screening and management of BV in pregnancy. These guidelines state that the following:

• “In symptomatic pregnant women, testing for and treatment of bacterial vaginosis is recommended for symptom resolution. Diagnostic criteria are the same for pregnant and non-pregnant women (I-A).
• Asymptomatic women and women without identified risk factors for preterm birth should not undergo routine screening for or treatment of bacterial vaginosis (I-B).
• Women at increased risk for preterm birth may benefit from routine screening for and treatment of bacterial vaginosis (I-B).
• Testing should be repeated one month after treatment to ensure that cure was achieved (III-L).”⁷⁹

The SOGC also published guidelines regarding the screening and management of trichomoniasis, VVC, and BV. These guidelines state that “Bacterial vaginosis should be diagnosed using either clinical (Amsel’s) or laboratory (Gram stain with objective scoring system) criteria (II-2A).”⁸⁰

Australian STI Management Guidelines for Use in Primary Care
The Australian STI Management Guidelines for Use in Primary Care recommends testing for bacterial vaginitis when symptoms of “abnormal vaginal discharge and/or malodor” are present. The guidelines recommend for specimen collection: “clinician collection ensures visualisation of secretions and measurement of vaginal pH; microscopy can be performed on self-collected or clinician collected swabs smeared on a slide.” Overall, “Clinical diagnosis is made using Amsel criteria (see below); if 3 or 4 of the following criteria are present, presumptive treatment can be offered.

1. Thin white/grey homogenous discharge on speculum examination
2. Elevated vaginal pH (pH > 4.5)
3. Whiff test: malodour with addition of potassium hydroxide to vaginal secretions, or if not available, genital malodour on examination
4. Clue cells on microscopy of Gram stain of high vaginal swab.”

The guidelines also note that “Isolation of Gardnerella vaginalis (by NAAT) is reported by some laboratories but cannot be used to diagnose bacterial vaginosis as this organism can also be isolated in people with an optimal vaginal microbiota and no bacterial vaginosis. If your laboratory uses NAAT testing, speak to your pathology provider about its comparative performance. Scoring of the vaginal Gram stain (i.e. Nugent score, Ison-Hay method), are increasingly only used in specialised services.”⁸¹

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68. Richter SS, Otiso J, Goje OJ, et al. Prospective Evaluation of Molecular Assays for Diagnosis of Vaginitis. Journal of clinical microbiology. Dec 23 2019;58(1)doi:10.1128/jcm.01264-19
69. Kong AM, Jenkins D, Troeger KA, Kim G, London RS. Diagnostic Testing of Vaginitis: Improving the Value of Care. Population Health Management. 2021/08/01 2021;24(4):515-524. doi:10.1089/pop.2021.0143
70. Evans A, Fragala MS, Upadhyay P, French A, Goldberg SE, Reddy J. Utilization of Syndromic Vaginitis Diagnostic Testing Reduces 6-Month Follow-Up Outpatient Service Healthcare Costs-A Real-World Data Analysis. Healthcare (Basel). Nov 5 2024;12(22)doi:10.3390/healthcare12222204
71. CDC. Diseases Characterized by Vulvovaginal Itching, Burning, Irritation, Odor or Discharge. Updated July 22, 2021. https://www.cdc.gov/std/treatment-guidelines/vaginal-discharge.htm
72. CDC. Bacterial Vaginosis. Updated July 22, 2021. https://www.cdc.gov/std/treatment-guidelines/bv.htm
73. USPSTF. Bacterial Vaginosis in Pregnant Persons to Prevent Preterm Delivery: Screening. 2020;
74. Hainer BL, Gibson MV. Vaginitis: Diagnosis and Treatment. American Family Physician. 2011;83(7):807-815. 
75. Owens DK, Davidson KW, Krist AH, et al. Screening for Bacterial Vaginosis in Pregnant Persons to Prevent Preterm Delivery: US Preventive Services Task Force Recommendation Statement. Jama. Apr 7 2020;323(13):1286-1292. doi:10.1001/jama.2020.2684
76. ACOG. Vaginitis in Nonpregnant Patients: ACOG Practice Bulletin, Number 215. Obstetrics and gynecology. Jan 2020;135(1):e1-e17. doi:10.1097/AOG.0000000000003604
77. Pappas PG, Kauffman CA, Andes DR, et al. Clinical Practice Guideline for the Management of Candidiasis: 2016 Update by the Infectious Diseases Society of America. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. Feb 15 2016;62(4):e1-50. doi:10.1093/cid/civ933
78. Miller JM, Binnicker MJ, Campbell S, et al. Guide to Utilization of the Microbiology Laboratory for Diagnosis of Infectious Diseases: 2024 Update by the Infectious Diseases Society of America (IDSA) and the American Society for Microbiology (ASM) ∗. Clinical Infectious Diseases. 2024;doi:10.1093/cid/ciae104
79. Yudin MH, Money DM. No. 211-Screening and Management of Bacterial Vaginosis in Pregnancy. J Obstet Gynaecol Can. Aug 2017;39(8):e184-e191. doi:10.1016/j.jogc.2017.04.018
80. van Schalkwyk J, Yudin MH. Vulvovaginitis: screening for and management of trichomoniasis, vulvovaginal candidiasis, and bacterial vaginosis. J Obstet Gynaecol Can. Mar 2015;37(3):266-274. doi:10.1016/s1701-2163(15)30316-9
81.  Australian STI Management Guidelines for Use in Primary Care. Bacterial vaginosis. 2024;
82. FDA. 510(k) Substantial Equivalence Determination Decision Summary: BD MAX Vaginal Panel, BD MAX System. https://www.accessdata.fda.gov/cdrh_docs/reviews/K191957.pdf

Coding Section 

Code	Number	Description
CPT	81513 (effective 01/01/2021)	Infectious 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
	81514 (effective 01/01/2021)	Infectious 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
	81515 (effective 01/01/2025)	Infectious disease, bacterial vaginosis and vaginitis, real-time PCR amplification of DNA markers for Atopobium vaginae, Atopobium species, Megasphaera type 1, and Bacterial Vaginosis Associated Bacteria-2 (BVAB-2), utilizing vaginal-fluid specimens, algorithm reported as positive or negative for high likelihood of bacterial vaginosis, includes separate detection of Trichomonas vaginalis and Candida species (C. albicans, C. tropicalis, C. parapsilosis, C. dubliniensis), Candida glabrata/Candida krusei, when reported
	82120	Amines, vaginal fluid, qualitative
	83986	Ph; body fluid, not otherwise specified
	87070	Culture, bacterial; any other source except urine, blood or stool, aerobic, with isolation and presumptive identification of isolates
	87149	Culture, typing; identification by nucleic acid (DNA or RNA) probe, direct probe technique, per culture or isolate, each organism probed
	87150	Culture, typing; identification by nucleic acid (DNA or RNA) probe, amplified probe technique, per culture or isolate, each organism probed
	87210	Smear, primary source with interpretation; wet mount for infectious agents (e.g., saline, India ink, KOH preps)
	87480	Infectious agent detection by nucleic acid (dna or rna); candida species, direct probe technique
	87481	Infectious agent detection by nucleic acid (dna or rna); candida species, amplified probe technique
	87482	Infectious agent detection by nucleic acid (dna or rna); candida species, quantification technique
	87510	Infectious agent detection by nucleic acid (dna or rna); gardnerella vaginalis, direct probe technique
	87511	Infectious agent detection by nucleic acid (DNA or RNA); Gardnerella vaginalis, amplified probe technique
	87512	Infectious agent detection by nucleic acid (DNA or RNA); Gardnerella vaginalis, quantification
	87515
	87660	Infectious agent detection by nucleic acid (dna or rna); trichomonas vaginalis, direct probe technique
	87661	Infectious agent detection by nucleic acid (dna or rna); trichomonas vaginalis, amplified probe technique
	87797	Infectious agent detection by nucleic acid (DNA or RNA), not otherwise specified; direct probe technique, each organism
	87798	Infectious agent detection by nucleic acid (DNA or RNA), not otherwise specified; amplified probe technique, each organism
	87799	Infectious agent detection by nucleic acid (DNA or RNA), not otherwise specified; quantification, each organism
	87800	Infectious agent detection by nucleic acid (dna or rna), multiple organisms; direct probe(s) technique
	87801	Infectious agent detection by nucleic acid (DNA or RNA), multiple organisms; amplified probe(s) technique
	87808	Infectious agent antigen detection by immunoassay with direct optical observation; trichomonas vaginalis
	87905	Infectious agent enzymatic activity other than virus (e.g., sialidase activity in vaginal fluid)
	0330U	Infectious agent detection by nucleic acid (DNA or RNA), vaginal pathogen panel, identification of 27 organisms, amplified probe technique, vaginal swab Proprietary test: Bridge Women's Health Infectious Disease Detection Test Lab/Manufacturer: Bridge Diagnostics/ThermoFisher and Hologic Test Kit on Panther Instrument
	0505U	Infectious disease (vaginal infection), identification of 32 pathogenic organisms, swab, real-time PCR, reported as positive or negative for each organism Proprietary test: Vaginal Infection Testing Lab/Manufacturer: NxGen MDx LLC
	Q0111	Wet mounts, including preparations of vaginal, cervical or skin specimens
ICD-10-CM	A56.11	Chlamydial female pelvic inflammatory disease
	A59	Trichomoniasis
	A59.0	Urogenital trichomoniasis
	A59.00	Urogenital trichomoniasis, unspecified
	A59.01	Trichomonal vulvovaginitis
	B37.3	Candidiasis of vulva and vagina
	B96.89	Other specified bacterial agents as the cause of diseases classified elsewhere [Gardnerella vaginitis]
	F11.10-F11.99	Opioid related disorders [injecting drug users]
	F13.10-F13.99	Sedative, hypnotic, or anxiolytic related disorders [injecting drug users]
	F14.10-F14.99	Cocaine related disorders [injecting drug users]
	F15.10-F15.99	Other stimulant related disorders [injecting drug users]
	L29.0	Pruritus ani
	L29.2	Pruritus vulvae
	L29.8	Other pruritus
	L29.9	Pruritus, unspecified
	N72	Inflammatory disease of cervix uteri
	N73	Other female pelvic inflammatory diseases
	N73.9	Female pelvic inflammatory disease, unspecified
	N76	Other inflammation of vagina and vulva
	N76.0	Acute vaginitis
	N76.1	Subacute and chronic vaginitis
	N76.2	Acute vulvitis
	N76.3	Subacute and chronic vulvitis
	N76.89	Other specified inflammation of vagina and vulva
	N77.1	Vaginitis, vulvitis and vulvovaginitis in diseases classified elsewhere
	N89.0	Mild vaginal dysplasia
	N89.1	Moderate vagina dysplasia
	N89.8	Other specified noninflammatory disorders of vagina
	N90.89	Other specified noninflammatory disorders of vulva and perineum
	N93	Other abnormal uterine and vaginal bleeding
	N94.11	Superficial (introital) dyspareunia
	N94.89	Other specified conditions associated with female genital organs and menstrual cycle
	O09.211	Suprvsn of preg w history of pre-term labor, first trimester
	O09.212	Suprvsn of preg w history of pre-term labor, second tri
	O09.213	Suprvsn of preg w history of pre-term labor, third trimester
	O09.219	Suprvsn of preg w history of pre-term labor, unsp trimester
	R10.2	Pelvic and perineal pain
	Z01.411	Encounter for gynecological examination (general) (routine) with abnormal findings
	Z11.2	Encounter for screening for other bacterial diseases
	Z11.3	Encounter for screening for infections with a predominantly sexual mode of transmission
	Z11.8	Encounter for screening for other infectious and parasitic diseases [High risk screening for Trichomonas only]
	Z13.89	Encounter for screening for genitourinary disorders
	Z20.2	Contact with and (suspected) exposure to infections with a predominantly sexual mode of transmission
	Z20.9	Contact with and (suspected) exposure to unspecified communicable disease
	Z33.1	Pregnant state, incidental
	Z72.5	High risk sexual behavior
	Z86.19	Personal history of other infectious and parasitic diseases

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

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

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

History From 2024 Forward     

04/01/2025	Annual review, updating coverage criteria #1 to include measurement of sialidase activity and potassium hydroxide (KOH) wet mount. Removing coverage critieria # 4 as it is addressed in newly updated criteria #1. Also updating description, table of terminology, rationale, guidelines/recommendations, references. Removing code 0352U and Adding code 0505U.
11/22/2024	Updating CPT coding. Code 81515 to be effective on 01/01/2025.
08/26/2024	Interim review. Added PLA code 0505U to coding section.
04/18/2024	Annual review, no change to policy intent.
01/01/2024	New Policy.