Verigene® Respiratory Virus Nucleic Acid TestSP (RVNATSP)

For in vitro Diagnostic Use

Overview

  • FDA-Cleared
  • Sample-to-result automation
  • CLIA "Moderately Complex" designation
  • On-demand, random access testing
  • Scalable workflow
  • "Detected" or "Not Detected" results for 3 common respiratory viruses in a single test cartridge:
    • Influenza A (reactive with 2009 H1N1 cultured isolates*)
    • Influenza B
    • RSV A/B
RVNAT
Figure 1. Verigene® System with Verigene® Reader (left), two Verigene® Processor SP's (right), and various Verigene® Test Cartridges (front).

*Although this test has been shown to detect 2009 Influenza A H1N1 from four clinical cultured isolates in analytical studies, the performance characteristics of this device with patient specimens that are positive for the 2009 Influenza A H1N1 have not been established. The RVNATSP can distinguish between Influenza A and B viruses, but it cannot differentiate influenza subtypes. See package insert for detailed performance characteristics.


Background

Each year in the United States, nearly 12 million patients present to emergency departments with respiratory illnesses1. The two leading causes of respiratory illness are infection with influenza or respiratory syncytial virus (RSV). Most patients with these infections can be safely discharged with little or no treatment, however, as many as 325,000 will need to be admitted for further care (primarily the young, elderly, and otherwise immunocompromised patients)2,3. In a hospital setting, influenza and RSV outbreaks can be catastrophic, as both pathogens are highly contagious. Consequently, the rapid identification of patients infected with these viruses has become a focus of busy emergency departments, clinical laboratories, and medical centers as a whole. Rapid antigen tests are capable of detecting respiratory viruses in less than 30 minutes. However, the sensitivity of these tests can be as low as 10% in the clinical setting4. RT-PCR tests, on the other hand, have demonstrated excellent sensitivity, but the complexity of these tests has prevented many laboratories from offering them.

Influenza
The influenza virus is a contagious respiratory pathogen known to cause mild to severe illness in people of all ages. Influenza type A is the most common type of seasonal influenza, and can also cause non-seasonal epidemics. The other major type of influenza, type B, is less common and generally leads to milder disease. Seasonal influenza occurs primarily in the fall, winter, and early spring, and will infect 5% to 20% of the population in a given year5. In the United States, influenza infections are responsible for over 200,000 hospitalizations and 36,000 deaths each year. Symptoms include fever, headache, congestion, and general malaise. Influenza can also lead to serious complications, such as pneumonia, bronchitis, sinus infections, and encephalitis.

RSV
Respiratory syncytial virus can cause upper and lower respiratory tract infections in children and, less commonly, in adults with weakened immune systems. It is the leading cause of bronchiolitis and pneumonia in children under one year of age in the United States6, and leads to between 75,000 and 125,000 hospitalizations each year2. Similar to influenza, RSV outbreaks occur seasonally in the US in the fall, winter, and early spring. Symptoms include coughing, sneezing, runny nose, fever, and decrease in appetite.

Performance Characteristics – Semi-Automated Test

The Verigene® Respiratory Virus Nucleic Acid Test (VRNAT)‡ is a semi-automated predecessor to the automated Verigene® Respiratory Virus Nucleic Acid TestSP (RVNATSP). The test combines external nucleic acid extraction and RT-PCR with Nanosphere's proprietary nanoparticle hybridization technology for detection and identification of Influenza A, Influenza B, and RSV on the Verigene® System.

‡The VRNAT is not currently available for commercial sale. The test is not intended to detect influenza C virus. The test is intended to be used on the Verigene® System. Negative results do not preclude influenza or RSV infection and should not be used as the sole basis for treatment or other management decisions. It is recommended that negative RSV results be confirmed by culture.

Table 1 - VRNAT vs Culture/DFA with Bi-Directional Sequencing for Discordant Results7

  VRNAT vs Culture/DFA VRNAT vs Culture/DFA with Bi-Directional Sequencing for Discordant Results
  Sensitivity Specificity Sensitivity Specificity
Influenza A 99.2% 90.1% 100% 99.8%
Influenza B 96.8% 98.5% 100% 99.1%
RSV 89.8% 91.5% 95.7% 98.2%

VRNAT performance versus culture/DFA and bi-directional sequencing (to resolve discordant results) for 720 nasopharyngeal specimens. See package insert for detailed information of discordant analysis and other performance characteristics.

Performance Characteristics - Verigene® RVNATSP


The Verigene® RVNATSP is an automated version of the semi-automated VRNAT assay. It utilizes the new Verigene® Processor SP (Figure 1) to automate sample preparation and test processing. This FDA-cleared test requires only one user pipetting step and less than 5 minutes of hands-on time for a sample-to-result turnaround time of about 3.5 hours. A method comparison was performed to demonstrate equivalency between the automated Verigene® RVNATSP and semi-automated VRNAT tests.

Table 2 - Verigene® RVNATSP vs VRNAT Method Comparison8

  VRNAT (Semi-Automated)    
    Positive Negative Total  
Verigene® RVNATSP (Automated) Positive 191 0 191 PPA 97.9%
(95% CI=94.8%-99.0%)
Negative 4a 363 367 NPA 100.0%
(95%CI=99.0% - 100.0%)
  Total 195 363 558  

Method comparison of automated Verigene® RVNATSP vs semi-automated VRNAT using 62 unique samples run at three separate sites. The 62 samples provided a total of 186 decisions, as each test delivered a 'Detected' or 'Not Detected' result for each of the 3 viruses: Influenza A, Influenza B, and RSV. Of the 62 samples, 3 samples had dual infections where 2 viruses were present. See package insert for detailed performance characteristics.

a All discordant samples were Influenza A low positive. Repeat tests were positive and gave the expected result.


Ordering Information

The Verigene® RVNATSP is now available as an FDA-cleared product For in vitro Diagnostic Use. For more information on ordering or to arrange a system demonstration please contact Nanosphere at 1-888-VERIGENE (837-4436) or IDtesting@nanosphere.us.

Coming Soon

Nanosphere is working hard to deliver a broad menu of innovative clinical microbiology and infectious disease tests for use on the Verigene® System. For more information on influenza A subtyping (in development), expanded respiratory virus panel (in development), and rapid bloodstream infection ID (in development) tests, please contact Nanosphere at IDtesting@nanosphere.us.

Literature Cited

  1. Centers for Disease Control and Prevention. National Hospital Ambulatory Medical Care Survey: 2006 Emergency Department Summary, 2006. National Health Statistics Reports: Number 7; August 6, 2008.
  2. Shay DK, Holman RC, Newman RD, Liu LL, Stout JW, Anderson LJ. Bronchiolitis-associated hospitalizations among U.S. children, 1980--1996. JAMA 1999;282:1440-6.
  3. Centers for Disease Control and Prevention. Seasonal Influenza-Associated Hospitalizations in the United States. Reviewed September 18, 2006. Retrieved June 23, 2009 from www.cdc.gov/flu/about/qa/hospital.htm.
  4. Hurt AC, Alexander R, Hibbert J, Deed N, Barr IG. Performance of six influenza rapid tests in detecting human influenza in clinical specimens. J Clin Virol 2007; 39:132-5.
  5. Centers for Disease Control and Prevention. Key Facts About Seasonal Influenza (Flu). Reviewed March 12, 2009. Retrieved June 24, 2009 from www.cdc.gov/flu/keyfacts.htm.
  6. Centers for Disease Control and Prevention. Respiratory Syncytial Virus Infection (RSV): Infection and Incidence. Reviewed October 17, 2008. Retrieved June 24, 2009 from www.cdc.gov/rsv/about/infection.html.
  7. Jannetto PJ, Vaughan K, Prokhorova A, Brener D, Lonosky PM, Sonpatki VM, Marla SS, Cork WH, Guaring-Angulo N, Pathak N, Saad R, Ledeboer NA. Nanoparticle probes for the detection and discrimination of influenza A/B and RSV A/B in respiratory specimens, abstract M10. 2009; 25th Clinical Virology Symposium, April 19-22, Daytona Beach, FL.
  8. Verigene® Respiratory Virus Nucleic Acid TestSP Package Insert.
The Verigene® Reader is protected by US patent 7,110,585, and other pending US and foreign patent applications. The Verigene® Processor and Verigene® Processor SP are protected by US patent 7,396,677, and other pending US and foreign patent applications. The Verigene® Test Cartridge is protected by one or more of the following US patents: 6,506,564; 6,602,669; 6,645,721; 6,673,548; 6,677,122;6,720,147; 6,730,269; 6,750,016; 6,767,702; 6,759,199; 6,812,334; 6,818,753, 6,903,207; 6,962,786; 6,986,989; and other pending US and foreign patent applications.
Methods for analysis of results by the Verigene® Reader is made possible under license of US Patent Nos. 5,599,668 and 5,843,651 owned by Abbott Laboratories.
The use of this product in relation to the manufacture or use of nucleic acid arrays may be covered by one or more of the following patents owned by Oxford Gene Technology Limited or Oxford Genet Technology IP Limited (together "OGT"): US Patent Nos. 6,054,270, 5,700,637; European Patent No. 0,373,203; Japan Patent No. 3,393,528 and 3,386,391 and pending patents. The purchase of this product does not confer the purchaser any rights or licenses under any of OGT's patents.
This product is sold under licensing arrangements between Nanosphere, Inc. and Life Technologies Corporation IP Holdings, Inc. The purchase of this product conveys to the buyer limited, nontransferable rights to use the Platinum® Tfi One-Step q-RT PCR SuperMix (which includes SuperScript® III Reverse Transcriptase) and UDG decontamination technology owned by Life Technologies, wherein both the Platinum® Tfi One-Step q-RT PCR SuperMix and the UDG decontamination technology are solely for activities by the purchaser in detection of respiratory infectious agents, including, but not limited to, influenza A, influenza B, and respiratory syncytial viruses A and B, parainfluenza viruses, and metapneumoviruses within the field of human diagnostics. No other rights are conveyed.
Further information on purchasing licenses may be obtained by contacting the Licensing Department, Life Technologies Corporation, 5791 Van Allen Way, Carlsbad, CA 92008. Email: outlicensing@invitrogen.com
Verigene® and Nanosphere are registered trademarks of Nanosphere, Inc. Platinum® and SuperScript® are registered trademarks of Life Technologies Corporation.