artus HSV-1/2 QS-RGQ MDx Kit
Device Facts
| Record ID | K142738 |
|---|---|
| Device Name | artus HSV-1/2 QS-RGQ MDx Kit |
| Applicant | Qiagen |
| Product Code | OQO · Microbiology |
| Decision Date | Dec 19, 2014 |
| Decision | SESE |
| Submission Type | Traditional |
| Regulation | 21 CFR 866.3305 |
| Device Class | Class 2 |
| Attributes | Pediatric |
Intended Use
The artus HSV-1/2 QS-RGQ MDx Kit is an in vitro real-time PCR DNA amplification assay performed on the QIAsymphony RGQ MDx system for the direct qualitative detection and differentiation of herpes simplex virus (HSV-1 and HSV-2) DNA in genital or oral vesicular lesions from male and female patients suspected of HSV infection. The assay is intended for use as an aid in diagnosis of HSV infection in symptomatic patients. Warning: The artus HSV-1/2 QS-RGQ MDx Kit is not FDA-cleared for use with cerebrospinal fluid (CSF) or for prenatal screening.
Device Story
The artus HSV-1/2 QS-RGQ MDx Kit is an in vitro real-time PCR assay for qualitative detection and differentiation of HSV-1 and HSV-2 DNA. Input samples consist of genital or oral lesion swabs. The workflow utilizes the QIAsymphony SP/AS instrument for automated DNA extraction and PCR setup, followed by amplification and detection on the Rotor-Gene Q MDx (RGQ MDx) instrument. The assay uses fluorescently labeled oligonucleotide probes; signal generation is inversely proportional to target concentration. An internal control (synthetic plasmid) is added during sample preparation to monitor extraction and PCR inhibition. The Rotor-Gene AssayManager software automatically analyzes results, reporting 'Signal detected', 'No signal', or 'INVALID'. The device is intended for use in clinical laboratories by trained personnel. Results aid clinicians in diagnosing HSV infection in symptomatic patients.
Clinical Evidence
Prospective clinical study of 662 samples (510 genital, 152 oral) compared the device to ELVIS HSV ID and D3 Typing Test System. For genital samples (N=414 for HSV-1, N=510 for HSV-2), HSV-1 sensitivity was 95.8% and specificity 93.9%; HSV-2 sensitivity was 96.9% and specificity 91.1%. For oral samples (N=152), HSV-1 sensitivity was 93.8% and specificity 81.7%. Discordant analysis using alternative PCR and sequencing supported the device results. Contrived sample studies provided additional data for HSV-2 in oral samples.
Technological Characteristics
Real-time PCR assay; utilizes fluorescently labeled oligonucleotide probes for target detection. Instrumentation: QIAsymphony SP/AS for extraction/setup; Rotor-Gene Q MDx for amplification/detection. Software: Rotor-Gene AssayManager. Internal control: synthetic plasmid DNA. Storage: -30°C to -10°C. Connectivity: Integrated system workflow.
Indications for Use
Indicated for symptomatic male and female patients suspected of HSV infection. Used for qualitative detection and differentiation of HSV-1 and HSV-2 DNA in genital or oral vesicular lesions. Not indicated for CSF or prenatal screening.
Regulatory Classification
Identification
Herpes simplex virus serological assays are devices that consist of antigens and antisera used in various serological tests to identify antibodies to herpes simplex virus in serum. Additionally, some of the assays consist of herpes simplex virus antisera conjugated with a fluorescent dye (immunofluorescent assays) used to identify herpes simplex virus directly from clinical specimens or tissue culture isolates derived from clinical specimens. The identification aids in the diagnosis of diseases caused by herpes simplex viruses and provides epidemiological information on these diseases. Herpes simplex viral infections range from common and mild lesions of the skin and mucous membranes to a severe form of encephalitis (inflammation of the brain). Neonatal herpes virus infections range from a mild infection to a severe generalized disease with a fatal outcome.
Special Controls
*Classification.* Class II (special controls). The device is classified as class II (special controls). The special control for the device is FDA's revised guidance document entitled “Class II Special Controls Guidance Document: Herpes Simplex Virus Types 1 and 2 Serological Assays.” For availability of the guidance revised document, see § 866.1(e).
Predicate Devices
- MultiCode®-RTx Herpes Simplex Virus 1 & 2 Kit (K100336)
Related Devices
- K150962 — Simplexa HSV 1 & 2 Direct, Simplexa HSV 1 & 2 Positive Control Pack · Focus Diagnostics · Aug 28, 2015
- K142156 — SEEGENE ANYPLEX II HSV-1/2 ASSAY · Seegene · Feb 13, 2015
Submission Summary (Full Text)
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Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
QIAGEN KIMBERLY MAPP, Ph.D. MANAGER, REGULATORY AFFAIRS 1201 CLOPPER ROAD GAITHERSBURG MD 20878
December 19, 2014
Re: K142738
Trade/Device Name: artus® HSV-1/2 QS-RGQ MDx Kit Regulation Number: 21 CFR 866.3305 Regulation Name: Herpes simplex virus serological assays Regulatory Class: II Product Code: 000 Dated: September 23, 2014 Received: September 23, 2014
Dear Dr. Mapp:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food. Drug. and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21. Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
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If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to
http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.
Sincerely yours.
# Uwe Scherf -S for
Sally A. Hojvat. M.Sc., Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
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## Indications for Use
510(k) Number (if known) K142738
Device Name artus® HSV-1/2 QS-RGQ MDx Kit
#### Indications for Use (Describe)
The artus HSV-1/2 QS-RGQ MDx Kit is an in vitro real-time PCR DNA amplification assay performed on the QIAsymphony RGQ MDx system for the direct qualitative detection and differentiation of herpes simplex virus (HSV-1 and HSV-2) DNA in genital or oral vesicular lesions from male and female patients suspected of HSV infection.
The assay is intended for use as an aid in diagnosis of HSV infection in symptomatic patients.
Warning: The artus HSV-1/2 QS-RGQ MDx Kit is not FDA-cleared for use with cerebrospinal fluid (CSF) or for prenatal screening.
Type of Use (Select one or both, as applicable)
> Prescription Use (Part 21 CFR 801 Subpart D)
_ Over-The-Counter Use (21 CFR 801 Subpart C)
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Page 1 of 17
#### 510(k) SUMMARY
#### General Information
| Submitted by: | QIAGEN<br>19300 Germantown Road<br>Germantown, MD 20874 |
|------------------|----------------------------------------------------------------------------------------------------|
| Contact Person: | Kimberly Mapp, Ph.D.<br>Manager, Regulatory Affairs<br>1201 Clopper Road<br>Gaithersburg, MD 20878 |
| | Phone: 301.944.7817<br>Fax: 240.686.3847<br>Email: kimberly.mapp@qiagen.com |
| Date Prepared: | November 24, 2014 |
| Device Name: | <i>artus</i> ® HSV-1/2 QS-RGQ MDx Kit |
| Trade Name: | <i>artus</i> ® HSV-1/2 QS-RGQ MDx Kit |
| Common Name: | Herpes Simplex Virus detection assay |
| Classification: | Class II |
| Predicate Device | |
| Manufacturer | Product Name | 510(k) No. |
|--------------------|-----------------------------------------------|------------|
| Eragen Biosciences | MultiCode®-RTx Herpes Simplex Virus 1 & 2 Kit | K100336 |
#### Device Description
The artus HSV-1/2 QS-RGQ MDx Kit is an in vitro PCR assay for the qualitative detection and differentiation of nucleic acids encoding the Glycoprotein D and UL30 genes isolated from HSV-1 and HSV-2 DNA present in genital or oral lesions from male and female patients. Samples are extracted and prepared for PCR using the QIAsymphony SP/AS instrument with the QIAsymphony DSP Virus/Pathogen Mini Kit. Amplification and detection are carried out using the artus HSV-1/2 QS-RGQ MDx Kit with the Rotor-Gene O MDx (RGO MDx) and Rotor-Gene AssayManager software. The presence of a HSV-1 or HSV-2 target sequence is indicated by the fluorescent signal generated through the use of fluorescently labeled oligonucleotide probes. The probes do not generate a signal unless they are specifically bound to the amplified product. The
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amplification cycle at which fluorescent signal is detected by the RGQ MDx is inversely proportional to the HSV-1 and/or HSV-2 target concentration present in the original specimen. A plasmid construct containing DNA unrelated to HSV-1 and HSV-2 is introduced into each specimen during sample preparation to serve as an internal control. Run as a separate control, the positive control serves to demonstrate that the HSV-1/2 PCR reagents are functional. In addition, the positive control functions as a process control, to demonstrate that sample preparation has proceeded correctly during the run.
## Intended Use
The artus HSV-1/2 OS-RGO MDx Kit is an in vitro real-time PCR DNA amplification assay performed on the QIAsymphony RGQ MDx system for the direct qualitative detection and differentiation of herpes simplex virus (HSV-1 and HSV-2) DNA in genital or oral vesicular lesions from male and female patients suspected of HSV infection.
The assay is intended for use as an aid in diagnosis of HSV infection in symptomatic patients.
Warning: The artus HSV-1/2 QS-RGQ MDx Kit is not FDA-cleared for use with cerebrospinal fluid (CSF) or for prenatal screening.
## Comparison of the artus® HSV-1/2 QS-RGQ MDx Kit and the Predicate Device
The artus HSV-1/2 QS-RGQ MDx Kit is substantially equivalent to the predicate device:
- K100336: Eragen Biosciences MultiCode®-RTx Herpes Simplex Virus 1 & 2 Kit
Similarities and differences between the artus HSV-1/2 QS-RGQ MDx Kit and the predicate device are shown in Table 1.
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## Table 1: Comparison of the artus HSV-1/2 QS-RGQ MDx Kit with the predicate device
| Characteristic | Device | Predicate |
|----------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Name | artus® HSV-1/2 QS-RGQ MDx Kit | Eragen Biosciences MultiCode®- RTx Herpes Simplex Virus 1 & 2 Kit |
| Similarities | | |
| Intended Use | The artus HSV-1/2 QS-RGQ<br>MDx Kit is an <i>in vitro</i> real-time<br>PCR DNA amplification assay<br>performed on the QIAsymphony<br>RGQ MDx system for the direct<br>qualitative detection and<br>differentiation of herpes simplex<br>virus (HSV-1 and HSV-2) DNA<br>in genital or oral vesicular lesions<br>from male and female patients<br>suspected of HSV infection. | The MultiCode®-RTx Herpes<br>Simplex Virus 1 & 2 Kit is a<br>polymerase chain reaction<br>(PCR)-based qualitative <i>in vitro</i><br>diagnostic test for the detection<br>and typing of herpes simplex<br>virus (HSV1&2) DNA in<br>vaginal lesions. It is indicated<br>for use in the detection and<br>typing of HSV-1 or HSV-2 in<br>vaginal lesion swab specimens<br>from symptomatic female<br>patients as an aid in the<br>diagnosis of genital herpes<br>infection. |
| | The assay is intended for use as<br>an aid in diagnosis of HSV<br>infection in symptomatic patients. | |
| | Warning: The artus HSV-1/2 QS-<br>RGQ MDx Kit is not FDA-cleared for use with cerebrospinal<br>fluid (CSF) or for prenatal<br>screening. | Warning: The device is not<br>FDA cleared for the use with<br>cerebral spinal fluid (CSF) or<br>any lesions other than vaginal.<br>The assay is not intended to be<br>used for male penile specimens,<br>for prenatal screening, or<br>females under the age of 18<br>years. |
| Assay Targets | HSV-1<br>HSV-2 | HSV-1<br>HSV-2 |
| Amplification<br>and Detection<br>Technology | Real-time PCR DNA<br>amplification | Real-time PCR DNA<br>amplification |
| Assay Controls | Positive Control, Negative<br>Control and Internal Control<br>included in the kit. | Positive Control, Negative<br>Control and Internal Control<br>included in the kit. |
| | Differences | |
| Specimen Type | Male and female genital or oral<br>herpetic lesions | Female vaginal lesions |
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#### Performance Characteristics - Non-Clinical Studies
## Analytical Sensitivity (Limit of Detection)
The limit of detection (LoD) was assessed for the artus HSV-1/2 QS-RGQ MDx Kit using 2 strains of HSV-1 (MacIntyre and Isolate #15 from Zeptometrix™ Corporation. (ZMC)) and two strains of HSV-2 (MS and Isolate #2 from Zeptometrix™ Corporation). The LoD is defined as the HSV titer (TCID<0/mL) detected with a probability of 95% or greater and was determined by probit analysis. The results, representative of the analytical sensitivity of the artus HSV-1/2 QS-RGQ MDx Kit, are summarized in Table 2.
#### Table 2: Limit of Detection
| Strain | LoD (95 % CI) TCID50/mL |
|------------------|---------------------------------------|
| HSV-1 Macintyre | 4.42 x 100 (2.81 x 100 - 9.14 x 100) |
| HSV-1 Isolate 15 | 1.82 x 101 (0.96 x 101 - 5.47 x 101) |
| HSV-2 MS | 9.78 x 10-1 (6.6 x 10-1 - 2.01 x 100) |
| HSV-2 Isolate 2 | 1.91 x 102 (1.26 x 102 - 3.55 x 102) |
## Analytical Reactivity
The analytical reactivity of the artus HSV-1/2 OS-RGO MDx Kit was assessed to determine whether the kit could detect a broad range of HSV-1 and HSV-2 strains. Strains were obtained from ZMC. A total of 39 strains (20 HSV-1 and 19 HSV-2) were diluted in M4RT viral transport medium to 2-3X LoD and tested with the artus HSV-1/2 QS-RGQ MDx Kit (Table 3). The intended HSV-1 or HSV-2 was detected in all strains tested.
| Organism | Part No. | Organism | Part No. |
|--------------------|-----------|--------------------|-----------|
| HSV-1, Isolate #2 | 0810183CF | HSV-2, Isolate #3 | 0810204CF |
| HSV-1, Isolate #3 | 0810184CF | HSV-2, Isolate #4 | 0810205CF |
| HSV-1, Isolate #4 | 0810185CF | HSV-2, Isolate #5 | 0810206CF |
| HSV-1, Isolate #5 | 0810186CF | HSV-2, Isolate #6 | 0810207CF |
| HSV-1, Isolate #6 | 0810187CF | HSV-2, Isolate #7 | 0810208CF |
| HSV-1, Isolate #7 | 0810188CF | HSV-2, Isolate #8 | 0810209CF |
| HSV-1, Isolate #8 | 0810189CF | HSV-2, Isolate #9 | 0810210CF |
| HSV-1, Isolate #9 | 0810190CF | HSV-2, Isolate #10 | 0810211CF |
| HSV-1, Isolate #10 | 0810191CF | HSV-2, Isolate #11 | 0810212CF |
| HSV-1, Isolate #11 | 0810192CF | HSV-2, Isolate #12 | 0810213CF |
| HSV-1, Isolate #12 | 0810193CF | HSV-2, Isolate #13 | 0810214CF |
Table 3: Strains Tested in Analytical Reactivity
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| Organism | Part No. | Organism | Part No. |
|--------------------|-----------|--------------------|-----------|
| HSV-1, Isolate #13 | 0810194CF | HSV-2, Isolate #14 | 0810215CF |
| HSV-1, Isolate #14 | 0810195CF | HSV-2, Isolate #15 | 0810216CF |
| HSV-1, Isolate #15 | 0810196CF | HSV-2, Isolate #16 | 0810217CF |
| HSV-1, Isolate #16 | 0810197CF | HSV-2, Isolate #17 | 0810218CF |
| HSV-1, Isolate #17 | 0810198CF | HSV-2, Isolate #18 | 0810219CF |
| HSV-1, Isolate #18 | 0810199CF | HSV-2, Isolate #19 | 0810220CF |
| HSV-1, Isolate #19 | 0810200CF | HSV-2, Isolate #20 | 0810221CF |
| HSV-1, Isolate #20 | 0810201CF | HSV-2, Isolate #21 | 0810222CF |
| HSV-1, Isolate #21 | 0810202CF | | |
#### Cross-Reactivity and Microbial Interference
A panel of microorganisms that may be present in patient specimens was tested to determine whether these microorganisms interfered with the detection of HSV-1 or HSV-2 or were cross-reactive with the artus HSV-1/2 QS-RGQ MDx Kit (Table 4). Organisms were tested at a target concentration of approximately 1 x 106 CFU/ml for bacteria (with the exception of Neisseria gonorrhea, which was tested at 3.5 x 10 CFU/mL due to the low titer of the stock culture) and fungi or ≥1 x 105 TCID50/ml for viruses separately in the presence of 2-3X LoD of each of three HSV strains: HSV-1 MacIntyre, HSV-1 Isolate #15, or HSV-2 MS. None of the potential interfering organisms cross-reacted or interfered with the detection of any of the HSV strains by the artus HSV-1/2 QS-RGQ MDx Kit.
| Organism | Source ID |
|--------------------------------------------|----------------------|
| Acinetobacter calcaceticus | ATCC 51432 |
| Acinetobacter lwoffi | ATCC 17925 |
| Adenovirus type 2 | ZMC 0810110CF |
| Bacteroides fragilis | ZMC 0601533 |
| Candida albicans | ATCC 10231 |
| Candida glabrata | ZMC Z007 |
| Candida guilliermondii | ZMC Z008 |
| Candida krusei | ZMC Z009 |
| Candida lustaniae | ATCC 42720 |
| Candida parapsilosis | ZMC Z011 |
| Candida tropicalis | ZMC Z012 |
| Chlamydia trachomatis | ATCC VR-885 |
| Cytomegalovirus | ZMC 0810003CF |
| Enterobacter cloacae | ATCC 13047 |
| Organism | Source ID |
| Enterovirus | ZMC 0810047CF |
| Epstein-Barr Virus | ZMC 0810008CF |
| Escherichia coli | ATCC 23571 |
| Fusobacterium nucleatum | ATCC 25586 |
| Gardnerella vaginalis | ATCC 14019 |
| Haemophilus ducreyi | ATCC 700724D-5 |
| Human Genomic DNA | Promega G3041 |
| Human Herpes Virus 6 | ZMC 0810003CF |
| Human Herpes Virus 7 | ZMC 0810071CF |
| Human papilloma virus 16 | ATCC 45113 |
| Human papilloma virus 18 | ATCC 45152 |
| Herpes Simplex Virus 1 (HSV-1), isolate 20 | 0810201CF |
| Herpes Simplex Virus 2 (HSV-2), isolate 20 | 0810221CF |
| Klebsiella pneumoniae | ATCC 13883 |
| Lactobacillus acidophilus | ATCC 4356 |
| Mobiluncus curtsii | ATCC 43063 |
| Mobiluncus mulieris | ATCC 35240 |
| Moraxella catarrhalis | ATCC 8176 |
| Mycoplasma hominis | ATCC 23114D |
| Neisseria gonorrhea | ATCC 9793 |
| Neisseria meningitides | ATCC 13077 |
| Prevotella melaninogenica | ATCC 25845 |
| Rubella Virus | ZMC 0810048CF |
| Simian Virus type 40 (SV40) | VRMC-2 |
| Staphylococcus aureus (MRSA) | ATCC 43300 |
| Staphylococcus aureus (MSSA) | ATCC 29213 |
| Staphylococcus epidermidis (MRSE) | ATCC 51625 |
| Staphylococcus saprophyticus | ATCC 15305 |
| Streptococcus mitis | ZMC Clinical isolate |
| Streptococcus mutans | ZMC Z072 |
| Streptococcus pneumoniae | ZMC 19F-Z022 |
| Streptococcus pyogenes | ATCC 8669 |
| Streptococcus salivarius | ATCC 13419 |
| Toxoplasma gondii | ZMC 0810007CF |
| Treponema pallidum | ATCC 632912 |
| Trichomonas vaginalis | ATCC PRA-98D |
| Varicella Zoster Virus (VZV) | ZMC 0810171CF |
Table 4: Organisms Tested in Cross Reactivity and Microbial Interference
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## Precision
The precision of the artus HSV-1/2 QS-RGQ MDx Kit was assessed using a sevenmember precision panel consisting of 2 strains of HSV: HSV-1 MacIntyre and HSV-2 MS, diluted in M4RT viral transport medium. Panel members were formulated with a single HSV strain present (HSV-1 or HSV-2) at three concentrations: Positive (~2-3X LoD), Low Positive (1X LoD), and High Negative (<1X LoD, targeting a 20-80% positivity rate). A seventh panel member (Negative) was prepared using M4RT viral transport medium only. The data obtained were used to determine the mean Cr, standard deviation (ST DEV) and the coefficient of variation (%CV) for each target and the internal control.
For the within laboratory repeatability study, the seven-member panel was tested in replicates of three, once a day for a total of twelve days. The testing was conducted by two alternating operators using one QIAsymphony RGQ MDx (QS-RGQ MDx) instrument platform and one reagent kit lot (Table 5).
| | HSV-1 | | | HSV-2 | | | IC | | | |
|---------------------------|------------|-----------|-------|------------|-----------|-------|------------|-----------|-------|--------------------|
| Sample | Mean<br>CT | ST<br>DEV | %CV | Mean<br>CT | ST<br>DEV | %CV | Mean<br>CT | ST<br>DEV | %CV | Detected/<br>Total |
| HSV-1<br>Positive | 32.56 | 0.32 | 0.97% | N/A | N/A | N/A | 31.79 | 0.64 | 2.00% | 35/35* |
| HSV-1 Low<br>Positive | 33.89 | 0.35 | 1.03% | N/A | N/A | N/A | 31.85 | 0.66 | 2.07% | 36/36 |
| HSV-1<br>High<br>Negative | 37.52 | 0.63 | 1.69% | N/A | N/A | N/A | 31.73 | 0.59 | 1.87% | 23/36 |
| HSV-2<br>Positive | N/A | N/A | N/A | 33.73 | 0.41 | 1.22% | 31.72 | 0.63 | 1.98% | 36/36 |
| HSV-2 Low<br>Positive | N/A | N/A | N/A | 36.73 | 1.05 | 2.86% | 31.69 | 0.63 | 2.00% | 36/36 |
| HSV-2<br>High<br>Negative | N/A | N/A | N/A | 38.35 | 1.01 | 2.64% | 31.82 | 0.57 | 1.80% | 9/36 |
| HSV<br>Negative | N/A | N/A | N/A | N/A | N/A | N/A | 31.88 | 0.52 | 1.64% | 0/36 |
Table 5: Within-Laboratory Repeatability Study Results
* Total number of samples is less than 36 due to exclusion of 1 invalid sample
To measure site-to-site reproducibility, the 7-member panel was run by 2 users at each of 3 external sites. Each of the 2 users performed 5 runs on alternating testing days for a total of 90 test results per panel member. Panel members were tested in replicates of 3 that were randomized and blinded to the user. A single OIAsymphony RGO MDx instrument platform and one lot of the artus HSV-1/2 QS-RGQ MDx Kit were used at each site to conduct the study (Table 6).
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| Panel<br>member | Site | HSV-1/HSV-2 | | | IC | | | Detected/<br>Total |
|---------------------------|---------|-------------|-----------|-------|------------|-----------|-------|--------------------|
| | | Mean<br>CT | ST<br>DEV | %CV | Mean<br>CT | ST<br>DEV | %CV | |
| HSV-1<br>Positive | Site 1 | 31.40 | 1.04 | 3.30% | 30.87 | 0.35 | 1.12% | 27/27 |
| | Site 2 | 31.44 | 0.35 | 1.10% | 30.80 | 0.37 | 1.19% | 29/29 |
| | Site 3 | 31.20 | 0.32 | 1.03% | 30.45 | 0.30 | 0.98% | 26/26 |
| | Overall | 31.35 | 0.66 | 2.09% | 30.71 | 0.38 | 1.24% | 82/82* |
| HSV-1<br>Low<br>Positive | Site 1 | 33.01 | 0.40 | 1.20% | 30.91 | 0.34 | 1.11% | 30/30 |
| | Site 2 | 32.78 | 0.44 | 1.34% | 30.76 | 0.38 | 1.24% | 30/30 |
| | Site 3 | 32.37 | 0.89 | 2.74% | 30.47 | 0.35 | 1.13% | 30/30 |
| | Overall | 32.72 | 0.66 | 2.03% | 30.71 | 0.40 | 1.29% | 90/90 |
| HSV-1<br>High<br>Negative | Site 1 | 36.34 | 0.88 | 2.41% | 30.85 | 0.29 | 0.93% | 19/30 |
| | Site 2 | 36.27 | 0.74 | 2.05% | 30.67 | 0.40 | 1.29% | 15/30 |
| | Site 3 | 36.77 | 1.06 | 2.88% | 30.44 | 0.30 | 1.00% | 17/30 |
| | Overall | 36.46 | 0.92 | 2.51% | 30.66 | 0.37 | 1.20% | 51/90 |
| HSV-2<br>Positive | Site 1 | 33.19 | 0.36 | 1.08% | 30.89 | 0.30 | 0.99% | 30/30 |
| | Site 2 | 32.85 | 0.35 | 1.05% | 30.75 | 0.35 | 1.15% | 30/30 |
| | Site 3 | 32.46 | 0.33 | 1.03% | 30.47 | 0.29 | 0.95% | 30/30 |
| | Overall | 32.83 | 0.45 | 1.38% | 30.70 | 0.36 | 1.17% | 90/90 |
| HSV-2<br>Low<br>Positive | Site 1 | 36.12 | 0.96 | 2.65% | 30.84 | 0.29 | 0.95% | 30/30 |
| | Site 2 | 35.53 | 0.66 | 1.85% | 30.73 | 0.32 | 1.04% | 30/30 |
| | Site 3 | 35.81 | 0.92 | 2.58% | 30.49 | 0.30 | 0.97% | 30/30 |
| | Overall | 35.82 | 0.88 | 2.46% | 30.69 | 0.33 | 1.08% | 90/90 |
| HSV-2<br>High<br>Negative | Site 1 | 38.09 | 0.55 | 1.44% | 30.91 | 0.31 | 0.99% | 5/30 |
| | Site 2 | 37.69 | 2.30 | 6.09% | 30.71 | 0.37 | 1.20% | 5/30 |
| | Site 3 | 37.27 | N/A | N/A | 30.50 | 0.32 | 1.04% | 1/30 |
| | Overall | 37.83 | 1.52 | 4.01% | 30.71 | 0.37 | 1.20% | 11/90 |
| HSV<br>Negative | Site 1 | N/A | N/A | N/A | 30.88 | 0.30 | 0.96% | 0/30 |
| | Site 2 | N/A | N/A | N/A | 30.72 | 0.36 | 1.16% | 0/30 |
| | Site 3 | N/A | N/A | N/A | 30.53 | 0.32 | 1.04% | 0/30 |
| | Overall | N/A | N/A | N/A | 30.71 | 0.35 | 1.14% | 0/90 |
### Table 6: Site-to-Site Reproducibility Study Results
* Total number of samples is less than 90 due to exclusion of invalid samples
## Target Carryover Study
Absence of carryover between samples for the entire workflow was demonstrated by performing 5 runs with alternating high positive (≥ 1.0 x 105 TCID56/mL) and negative samples. All samples were detected correctly, generating a carryover rate of 0.0%.
{11}------------------------------------------------
## Interfering Substances
A panel of 24 substances that may be present in oral/genital patient specimens was tested to determine whether these substances interfered with the performance of the artus HSV-1/2 QS-RGQ MDx Kit (Table 7). Two strains of HSV: HSV-1 MacIntyre and HSV-2 MS, were diluted to approximately 2-3X LOD in M4RT viral transport medium and spiked with each potentially inhibitory substance. None of the substances showed an inhibitory effect on the detection of HSV-1 or HSV-2 by the artus HSV-1/2 QS-RGQ MDx Kit.
| Substance | Potential Interferent/Active<br>Ingredient | Concentration<br>Of Substance<br>Added To<br>Reaction | Concentration Of<br>Active Ingredient<br>Added To<br>Reaction |
|-----------------------------------------------|----------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------|-------------------------------------------------------------------------------------|
| Whole blood<br>with EDTA | Hemoglobin, lactoferin | 100% | 5% v/v |
| Buffy coat | White blood cells | 100% | 5% v/v |
| Acyclovir | Acycloguanosine | 5 mg/ml | 5 mg/ml |
| Albumin | Albumin | 5 mg/ml | 5 mg/ml |
| Casein | Casein | 5 mg/ml | 5 mg/ml |
| Female urine* | Urea | 100% | Not listed |
| Male urine* | Urea | 100% | Not listed |
| K-Y® Brand<br>jelly | Glycerin, hydroxyethyl cellulose,<br>chlorhexidine, gluconate,<br>gluconolactone, methylparaben,<br>sodium hydroxide | 100% | Not listed |
| Douche* | Octoxynol-9, citric acid, sodium<br>benzoate, disodium EDTA | 100% | Not listed |
| Spermicide* | Nonoxynol-9 | 100% | 7% |
| Yeast Gard®* | Candida albicans ×27 HPUS†,<br>Candida parapsilosis ×27 HPUS,<br>Pulsatilla ×27 HPUS | 100% | Not listed |
| Monistat® 1* | Miconazole nitrate | 100% | 2% v/v |
| Vagisil®<br>Cream* | Benzocaine, resorcinol | 100% | Benzocaine 20%<br>Resorcinol 3% |
| Monistat 3* | Miconazole nitrate | 100% | 2% v/v |
| Triconazole 1* | Triconazole | 100% | 6.5% v/v |
| Substance | Potential Interferent/Active<br>Ingredient | Concentration<br>Of Substance<br>Added To<br>Reaction | Concentration Of<br>Active Ingredient<br>Added To<br>Reaction |
| Rite Aid<br>Feminine Wash,<br>Sensitive Skin* | Ammonium laureth sulfate,<br>ammonium lauryl sulfate, decyl<br>glucoside,cocamidopropyl betaine | 100% | Not listed |
| Clotrimazole-7<br>vaginal cream* | Clotrimazole | 100% | 1% v/v |
| Anti-itch<br>cream* | Benzocaine | 100% | 5% v/v |
| Listerine®<br>antiseptic<br>mouthwash* | Eucalyptol, menthol, methyl<br>salicylate, thymol | 100% | Eucalyptol 0.920%<br>Menthol 0.042%<br>Methyl salicylate<br>0.060%<br>Thymol 0.064% |
| Abreva®* | Docosanol | 100% | 10% v/v |
| Carmex® lip<br>balm* | Menthol, camphor, phenol | 100% | Menthol 0.7%<br>Camphor 1.7%<br>Phenol 0.4% |
| Releev® cold<br>sore treatment* | Benzalkonium chloride | 100% | 0.13% v/v |
| Lip Clear®<br>lysine+* | Zinc oxide | 100% | 1.2% v/v |
| Toothpaste* | Stannous fluoride | 100% | 0.454% v/v |
Table 7: Potentially Interfering Substances Tested
{12}------------------------------------------------
*: Applied directly to sample by swab.
1: HPUS: Homeopathic Pharmacopeia of the United States.
#### Expected Values
Prevalence: The observed expected values for HSV-1 and HSV-2 during a multi-center clinical trial were calculated for the artus HSV-1/2 QS-RGQ MDx kit. The expected values for the patients ages 18 and older are shown for Genital lesion samples and for all ages for the oral samples. The observed prevalence rates for HSV-1 were estimated as 18.6% (91/489) for genital samples and 42.1% (64/152) for oral samples. The prevalence rates for HSV-2 were estimated as 26.2% (128/489) for genital samples and 0% (0/152) for oral samples. Gender and age distribution is provided in Table 8 and Table 9.
{13}------------------------------------------------
| Age<br>(Years) | Total # of<br>specimens | HSV-1<br>Positive | HSV-2<br>Positive | Negative |
|----------------|-------------------------|-------------------|-------------------|----------|
| 18-20 | 48 | 11 | 13 | 24 |
| 21-30 | 167 | 32 | 40 | 95 |
| 31-40 | 111 | 18 | 31 | 62 |
| 41-50 | 69 | 12 | 15 | 42 |
| 51-60 | 48 | 10 | 15 | 23 |
| 61-70 | 31 | 4 | 12 | 15 |
| 71-80 | 11 | 4 | 2 | 5 |
| 81-90 | 3 | 0 | 0 | 3 |
| 91-97 | 1 | 0 | 0 | 1 |
| Total | 489 | 91/489 | 128/489 | 270/489 |
### Table 8: Age Distribution for Genital Specimens
#### Table 9: Age Distribution for Oral Specimens
| Age (Years) | Total # of<br>specimens | HSV-1<br>Positive | HSV-2<br>Positive | Negative |
|-------------|-------------------------|-------------------|-------------------|----------|
| < 1 | 1 | 1 | 0 | 1 |
| 1-10 | 21 | 15 | 0 | 6 |
| 11-20 | 20 | 6 | 0 | 14 |
| 21-30 | 25 | 8 | 0 | 17 |
| 31-40 | 23 | 9 | 0 | 14 |
| 41-50 | 16 | 3 | 0 | 13 |
| 51-60 | 14 | 5 | 0 | 9 |
| 61-70 | 15 | 6 | 0 | 9 |
| 71-80 | 11 | 6 | 0 | 5 |
| 81-90 | 2 | 2 | 0 | 0 |
| 91-97 | 4 | 3 | 0 | 1 |
| Total | 152 | 64/152 | 0/152 | 88/152 |
Positive and Negative Predictive Value: Hypothetical positive and negative predictive values (PPV & NPV) for the artus HSV-1/2 QS-RGQ MDx kit are shown in Table 10. These calculations are based on hypothetical prevalence and overall sensitivity and specificity per specimen type as determined in the clinical study.
For HSV-1, these calculations are based upon an overall sensitivity and specificity of 96% and 94%, respectively, for genital swabs and 94% and 82%, respectively, for oral swabs.
For HSV-2, these calculations are based upon an overall sensitivity and specificity of 97% and 91%, respectively, for genital swabs and 0.0% and 100%, respectively, for oral swabs.
PPV was calculated using: (Sensitivity x Prevalence) / (Sensitivity x Prevalence + [1 -Specificity] x [1 - Prevalence]).
{14}------------------------------------------------
NPV was calculated using: (Specificity x [1 - Prevalence]) / ([1 - Sensitivity] x Prevalence + Specificity x [1 - Prevalence]).
| Prevalence (%) | Genital Swabs | | | | Oral Swabs | | | |
|----------------|---------------|---------|---------|---------|------------|---------|---------|---------|
| | HSV-1 | | HSV-2 | | HSV-1 | | HSV-2 | |
| | PPV (%) | NPV (%) | PPV (%) | NPV (%) | PPV (%) | NPV (%) | PPV (%) | NPV (%) |
| 2 | 24.6% | 99.9% | 18.0% | 99.9% | 9.6% | 99.9% | N/A | 98.0% |
| 5 | 45.7% | 99.8% | 36.2% | 99.8% | 21.6% | 99.6% | N/A | 95.0% |
| 10 | 64.0% | 99.5% | 54.5% | 99.6% | 36.7% | 99.2% | N/A | 90.0% |
| 20 | 80.0% | 98.9% | 72.9% | 99.2% | 56.6% | 98.2% | N/A | 80.0% |
| 30 | 87.3% | 98.2% | 82.2% | 98.6% | 69.1% | 97.0% | N/A | 70.0% |
| 40 | 91.4% | 97.2% | 87.8% | 97.8% | 77.7% | 95.3% | N/A | 60.0% |
| 50 | 94.1% | 95.9% | 91.5% | 96.8% | 83.9% | 93.2% | N/A | 50.0% |
Table10: Positive and Negative Predictive Values (PPV & NPV) for the artus assay based on sample type
N/A = Not Applicable
Mucocutaneous Lesions: A subset of samples from the clinical study was identified as mucocutaneous. Those classified as mucocutaneous included: oral, cervical, vaginal, rectal. Table 11 lists the specific locations for the mucocutaneous lesions that were reported as such in the study along with the total number of samples from each specific location and number of positives.
Table 11: Mucocutaneous Lesion Sites
| Breakdown of<br>Mucocutaneous Samples | | HSV-1 | HSV-1 | HSV-1<br>Concordant | HSV-2<br>Culture | HSV-2<br>artus | HSV-2<br>Concordant |
|---------------------------------------|-------|------------------------------|----------------------------|---------------------------------|------------------------------|----------------------------|---------------------------------|
| Location | Total | Culture<br>Positive | artus<br>Positive | Positive | Positive | Positive | Positive |
| Bottom Lip | 1 | | | | | | |
| Cervical | 21 | 3 | 3 | 2 | 1 | 2 | 1 |
| Clitoral | 2 | | | | | | |
| Corners Of Lips | 1 | | | | | | |
| Penis foreskin | 1 | | | | | | |
| Genital | 8 | 2 | 3 | 2 | | 1 | |
| Groin Vesicles | 1 | | | | | | |
| In-Mouth | 1 | 1 | 1 | 1 | | | |
| Vaginal Introitus | 1 | | | | | | |
| L Nares | 1 | | | | | | |
| Labia | 47 | 3 | 5 | 3 | 9 | 12 | 9 |
| Breakdown of<br>Mucocutaneous Samples | | HSV-1<br>Culture<br>Positive | HSV-1<br>artus<br>Positive | HSV-1<br>Concordant<br>Positive | HSV-2<br>Culture<br>Positive | HSV-2<br>artus<br>Positive | HSV-2<br>Concordant<br>Positive |
| Location | Total | | | | | | |
| Labia Major | 1 | | | | 1 | 1 | 1 |
| Left Labia | 5 | | | | 1 | 1 | 1 |
| Left Outer Labia | 1 | | | | | | |
| Left Upper Palate | 1 | | | | | | |
| Left Vulvar | 1 | | | | | | |
| Lip | 31 | 17 | 20 | 17 | | | |
| Mons Pubic,<br>Clitoris | 1 | | | | | 1 | |
| Mouth | 35 | 10 | 14 | 10 | | | |
| Oral Blister | 3 | | 2 | | | | |
| Palate | 2 | 1 | | | | | |
| Penile Lesion | 2 | | | | | 1 | |
| Rectal | 3 | | | | 1 | 1 | 1 |
| Right Labia Papule | 2 | | | | 1 | 1 | 1 |
| Right Side Of<br>Mouth | 1 | 1 | 1 | 1 | | | |
| Throat | 7 | 2 | 1 | 1 | | | |
| Tongue | 6 | 2 | 3 | 2 | | | |
| Tooth | 1 | 1 | 1 | 1 | | | |
| Ulcer In Mouth | 1 | 1 | 1 | 1 | | | |
| Upper Hard Palate | 1 | | 1 | | | | |
| Upper Lip | 4 | 2 | 3 | 2 | | | |
| Urethral | 8 | | 1 | | 2 | 2 | 2 |
| Urogenital | 4 | 1 | 1 | 1 | | | |
| Vagina | 65 | 11 | 11 | 10 | 17 | 20 | 15 |
| Vaginal Rectal | 9 | 1 | 2 | 1 | | 1 | |
| Vesicle | 6 | | 2 | | | 1 | |
| Vulva | 34 | 7 | 9 | 7 | 6 | 8 | 6 |
| Total | 320 | 66 | 85 | 62 | 39 | 53 | 37 |
{15}------------------------------------------------
{16}------------------------------------------------
#### Performance Characteristics - Clinical Studies
Prospective Study: The performance of the artus HSV-1/2 QS-RGQ MDx Kit was evaluated at 3 testing sites in 2013-2014, using samples from 5 geographically diverse locations within the United States. A total of 662 male and female genital or oral lesion swabs (510 genital and 152 oral) prospectively collected from symptomatic patients were evaluated. Results from the artus HSV-1/2 QS-RGQ MDx Kit were compared to results obtained from the ELVIS® (Enzyme Linked Virus Inducible System) HSV ID and D3 Typing Test System (Diagnostic Hybrids, Athens, OH).
Ninety-six (96) prospective specimens identified as HSV-2 positive by ELVIS viral culture were removed from the initial 510 genital specimens for the calculation of the HSV-1 clinical performance. As a result, there were 566 samples (414 genital and 152 oral) used to determine clinical performance for HSV-1 (see Table 12 thru Table 15). The clinical performance for HSV-1 and HSV-2 mucocutaneous lesions was also assessed (Table 16 and Table 17). Prospectively collected samples that were classified as mucocutaneous included oral, cervical, vaginal, rectal, and any sample taken from a vesicle or lesion.
| | ELVIS | | | |
|-----------------------------------|---------------|-----|-------|-----|
| HSV-1 | POS | NEG | Total | |
| artus HSV-1/2 QS-<br>RGQ MDx Kit | POS | 69 | 21* | 90+ |
| | NEG | 3** | 321 | 324 |
| | TOTAL | 72 | 342 | 414 |
| | 95% CI | | | |
| Sensitivity – 95.8% (69/72) | 88.5% – 98.6% | | | |
| Specificity – 93.9% (321/342) | 90.8% – 96.0% | | | |
| Positive Predictive Value – 76.7% | 67.0% – 84.2% | | | |
| Negative Predictive Value – 99.1% | 97.3% – 99.7% | | | |
| Prevalence – 17.0% | 14.0% – 21.0% | | | |
Table 12: HSV-1 Results for Genital Samples (N=414)
*21 discordant specimens (artus HSV-1/2 QS-RGQ MDx Positive, ELVIS Negative) reported were analyzed by alternative PCR followed by bi-directional sequencing and the result was that 15 out of 21 were positive for HSV-1, agreeing with the artus HSV-1/2 QS-RGQ MDx result. **3 discordant specimens (artus HSV-1/2 QS-RGQ MDx Negative, ELVIS Positive) reported were analyzed by alternative PCR followed by bi-directional sequencing and the result was that all were negative for HSV-1, agreeing with the artus HSV-1/2 QS-RGQ MDx result. + 5 samples were undetermined for ELVIS out of a total of 95 HSV-1 artus positive genital samples. Therefore only the 90 samples that were both ELVIS and artus positive are listed.
{17}------------------------------------------------
| | ELVIS | | | |
|-----------------------------------|---------------|-----|-------|-----|
| HSV-2 | POS | NEG | Total | |
| artus HSV-1/2 QS-<br>RGQ MDx Kit | POS | 93 | 37* | 130 |
| | NEG | 3** | 377 | 380 |
| | TOTAL | 96 | 414 | 510 |
| <b>95% CI</b> | | | | |
| Sensitivity – 96.9% (93/96) | 91.2% – 98.9% | | | |
| Specificity – 91.1% (377/414) | 87.9% – 93.5% | | | |
| Positive Predictive Value – 71.5% | 63.3% – 78.6% | | | |
| Negative Predictive Value – 99.2% | 97.7% – 99.7% | | | |
| Prevalence – 19.0% | 16.0% – 22.0% | | | |
#### Table 13: HSV-2 Results for Genital Samples (N=510)
*32 discordant specimens (artus HSV-1/2 QS-RGQ MDx Positive, ELVIS Negative) reported were analyzed by alternative PCR followed by bi-directional sequencing and the result was that 27 out of 32 were positive for HSV-2, agreeing with the artus HSV-1/2 QS-RGQ MDx result. The remaining 5 samples were not available for discordant analysis.
** 3 discordant specimens (artus HSV-1/2 QS-RGQ MDx Negative, ELVIS Positive) reported were analyzed by alternative PCR followed by bi-directional sequencing and the result was that all were negative for HSV-2, agreeing with the artus HSV-1/2 QS-RGQ MDx result.
| HSV-1 | | ELVIS | | |
|-----------------------------------|-------|---------------|-----|-------|
| | | POS | NEG | Total |
| artus HSV-1/2 QS-<br>RGQ MDx Kit | POS | 45 | 19* | 64 |
| | NEG | 3** | 85 | 88 |
| | TOTAL | 48 | 104 | 152 |
| 95% CI | | | | |
| Sensitivity – 93.8% (45/48) | | 83.2% – 97.9% | | |
| Specificity – 81.7% (85/104) | | 73.2% - 88.0% | | |
| Positive Predictive Value – 70.3% | | 58.2% - 80.1% | | |
| Negative Predictive Value – 96.6% | | 90.5% - 98.8% | | |
| Prevalence – 32.0% | | 25.0% - 39.0% | | |
#### Table 14: HSV-1 Results for Oral Samples (N=152)
* 19 discordant specimens (artus HSV-1/2 QS-RGQ MDx Positive, ELVIS Negative) reported were analyzed by alternative PCR followed by bi-directional sequencing and the result was that 13 out of 19 were positive for HSV-1, agreeing with the artus HSV-1/2 QS-RGQ MDx result. **2 discordant specimens (artus HSV-1/2 QS-RGQ MDx Negative, ELVIS Positive) reported were analyzed by alternative PCR followed by bi-directional sequencing and the result was that 2 out of 2 were negative for HSV-1, agreeing with the artus HSV-1/2 QS-RGQ MDx result. The remaining 1 specimen was unavailable for discordant analysis testing.
{18}------------------------------------------------
Page 16 of 17
| Table 15: HSV-2 Results for Oral Samples (N=152) | | | | |
|--------------------------------------------------|-------|----------------|-----|-------|
| HSV-2 | | ELVIS | | |
| | | POS | NEG | Total |
| artus HSV-1/2 QS-<br>RGQ MDx Kit | POS | 0 | 0 | 0 |
| | NEG | 0 | 152 | 152 |
| | TOTAL | 0 | 152 | 152 |
| | | 95% CI | | |
| Sensitivity – N/A | | N/A | | |
| Specificity – 100.0% (152/152) | | 97.5% – 100.0% | | |
| Positive Predictive Value – N/A | | N/A | | |
| Negative Predictive Value – 100.0% | | 97.5% – 100.0% | | |
| Prevalence – 0.0% | | 0.0% – 2.0% | | |
# Table 15: HSV-2 Results for Oral Samples (N-152)
Table 16: HSV-1 Mucocutaneous Samples (N=281)
| HSV-1 | | ELVIS | | |
|-----------------------------------|-------|---------------|-----|-------|
| | | POS | NEG | Total |
| artus HSV-1/2 QS-<br>RGQ MDx Kit | POS | 62 | 23 | 85 |
| | NEG | 4 | 192 | 196 |
| | TOTAL | 66 | 215 | 281 |
| 95% CI | | | | |
| Sensitivity – 93.9% (62/66) | | 85.4% – 97.6% | | |
| Specificity – 89.3% (192/215) | | 84.5% – 92.8% | | |
| Positive Predictive Value – 72.9% | | 62.7% – 81.2% | | |
| Negative Predictive Value – 98.0% | | 94.9% – 99.2% | | |
| Prevalence – 23.0% | | 19.0% – 29.0% | | |
| | | | | Table 17: HSV-2 Mucocutaneous Samples (N=320) | | | |
|--|--|--|--|-----------------------------------------------|--|--|--|
|--|--|--|--|-----------------------------------------------|--|--|--|
| HSV-2 | | ELVIS | | |
|-----------------------------------|---------------|--------|-----|-------|
| | | POS | NEG | Total |
| | POS | 37 | 16 | 53 |
| artus HSV-1/2 QS-<br>RGQ MDx Kit | NEG | 2 | 265 | 267 |
| | TOTAL | 39 | 281 | 320 |
| | | 95% CI | | |
| Sensitivity – 94.9% (37/39) | 83.1% – 98.6% | | | |
| Specificity – 94.3% (265/281) | 91.0% – 96.5% | | | |
| Positive Predictive Value – 69.8% | 56.5% – 80.5% | | | |
| Negative Predictive Value – 99.3% | 97.3% – 99.8% | | | |
| Prevalence – 12.0% | 9.0% – 16.0% | | | |
{19}------------------------------------------------
## HSV-2 Oral Retrospective Sample Study and Contrived Sample Study:
A retrospective study was conducted using oral samples for HSV2 detection. A total of 38 oral retrospective specimens were tested with the artus HSV-1/2 QS-RGQ MDx assay and ELVIS HSV ID and D3 Typing Test System. There were no HSV-2 positive specimens detected in 38 oral specimens.
A contrived specimen study was performed to provide additional performance data for detection of HSV-2 in oral samples. A panel of seventy (70) individual samples consisting of 15 HSV-1/2 negative oral samples, 10 HSV-1 positive oral samples and 45 HSV-1/2 negative oral samples spiked with HSV-2 at a concentration from 3X LoD to 1000X LoD and tested with the artus HSV-1/2 QS-RGQ MDx Kit. The HSV-1 positive oral samples and HSV-1/2 negative oral samples obtained from the method comparison study were used to make the panel. All samples were randomized and blinded to the operator prior to testing. HSV-2 was detected in all 45 contrived samples at all concentrations tested, supporting the claim for detection of HSV-2 in oral samples by the artus HSV-1/2 QS-RGQ MDx Kit.
