Assay Sheet

Test ID

RV00 Respiratory Viral Panel (RVP)

CPT Code

87798   

Clinical Utility

The Respiratory Viral Panel is a comprehensive assay for the detection of a broad range of viruses and subtypes representing the majority of circulating respiratory disease-causing pathogens of particular importance to children, elderly, and immunocompromised patients. Detection of these pathogens will lead to more efficient management of patients with respiratory infections, play a key role in surveillance, and aid in limiting the spread of respiratory viruses through infection control practices.

Procedure

Viral nucleic acid is extracted from the specimen, which undergoes reverse transcription to generate complementary DNA (cDNA). The target cDNA is amplified using polymerase chain reaction (PCR), then analyzed with Luminex® xTag™ technology to detect the presence or absence of each virus in the panel. The Respiratory Viral Panel (RVP) has been cleared by the FDA for in vitro diagnostic use.

Specimens

* Nasopharyngeal swab (NP swab): sterile swab placed in 1-2 ml sterile saline or viral transport media; ship ambient.
**Nasopharyngeal aspirate (NP aspirate), tracheal aspirate, BAL: 2 ml; submitted in a sterile, screw-top tube; ship ambient.

Specificity

Detects 12 Respiratory viral targets: respiratory syncytial virus (RSV) A, respiratory syncytial virus (RSV) B, influenza A, influenza A subtype H1, influenza A subtype H3, influenza B, parainfluenza 1, parainfluenza 2, parainfluenza 3, human metapneumovirus (hMPV), rhinovirus, and adenovirus

Assay Range

Qualitative results (Positive/Not Detected) for: RSV A, RSV B, influenza A, influenza A subtype H1, influenza A subtype H3, influenza B, parainfluenza 1, parainfluenza 2, parainfluenza 3, hMPV, rhinovirus, and adenovirus

Turnaround Time

Within 24 hours of receiving specimen

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* NP swab has been cleared by the FDA for use in the RVP assay.
**In-house verification performed to establish as suitable specimen types.

Information derived from Respiratory Viral Panel Package Insert (Luminex Corporation).
Respiratory Viral Panel is a product of Luminex Corporation.
xTAG is a trademark of Luminex Corporation.
Luminex is a registered trademark of Luminex Corporation.
AS10-0108

Pathogen Overview

ABOUT THE INFLUENZA VIRUSES

The three types of influenza viruses, A, B, and C, are single-stranded RNA viruses of the Orthomyxoviridae family. Humans can be infected with all three types, though influenza C is rare compared to influenza A and B. Influenza A is classified into subtypes based on two surface antigens: hemagglutinin (HA) and neuraminidase (NA). Influenza B is not classified as subtypes, however, both influenza A and B are further classified into strains. Influenza viruses are highly dynamic and continuously evolve by antigenic drift or antigenic shift. Antigenic drift is a gradual evolution and occurs through point mutations in surface antigens, which produces new strains that may not be recognized by antibodies from previous strains. As a result, global surveillance is critical in monitoring the evolution of strains in effort to keep the influenza vaccine up-to-date. New strains are predicted and incorporated into the vaccine on a yearly basis. Both influenza A and B undergo antigenic drift and can cause human seasonal epidemics, though influenza A evolves more rapidly than influenza B. Human pandemics are associated with antigenic shifts, which is a sudden, major change that produces an entirely novel subtype of virus previously not in circulation. This can occur through direct animal (poultry)-to-human transmission or through genetic reassortment, the mixing of human virus and animal virus genes to create a new subtype. Only influenza A evolves through antigenic shift.

Influenza has caused three pandemics in the 20th century: 1918, 1957, and 1968. The 1918 Spanish flu pandemic had the highest mortality rate and resulted in approximately 50-100 million deaths. There is widespread concern that the next pandemic will be a result of avian influenza (H5N1). The first human case was reported in Hong Kong in 1997 during a poultry outbreak; 18 additional cases followed. Hundreds of millions of poultry were culled in efforts to contain the virus. Human cases of H5N1 infection seemingly ceased until 2003 when cases were reported in Azerbaijan, Cambodia, China, Djibouti, Egypt, Indonesia, Iraq, Laos, Nigeria, Thailand, Turkey and Vietnam. Over 200 confirmed cases have been reported since 2004. The World Health Organization (WHO) tracks the situation and monitors the threat of an influenza pandemic. Currently, avian influenza infection in humans is thought to result from direct contact with infected poultry, though there is some speculation that there may be limited human-to-human transmission. Avian influenza infection in humans is associated with a high mortality rate, 54%, especially in younger patients who are able to mount significant immunological responses, such as a cytokine storm. Interestingly, the 1918 pandemic mostly affected healthy young adults whose immune systems reacted to the infection with a cytokine storm.

INFLUENZA VIRUS CLINICAL MANIFESTATIONS

Influenza viruses are highly contagious and spread from person to person through respiratory droplet transmission. Infection is most serious in young children, the elderly, and immunocompromised persons. The incubation period is approximately 1-4 days. Adults can be infectious from the day before clinical presentation to 5 days afterwards and children greater than 10 days after the onset of symptoms. Prolonged viral shedding can occur in immunocompromised patients, lasting weeks to months.

Both influenza A and B infections present as fever, myalgia, headache, malaise, nonproductive cough, sore throat, and rhinitis. Otitis media, nausea, and vomiting are commonly seen in children. Less common in children are symptoms that resemble bacterial sepsis with high fevers and febrile seizures. Influenza infections can lead to primary viral pneumonia or secondary bacterial pneumonia, especially in patients with pulmonary or cardiac disease. Influenza B virus infections require hospitalization about fourfold less than influenza A; though myositis, Reye’s syndrome, and gastrointestinal symptoms are more common with influenza B. Uncomplicated influenza infection in immunocompetent individuals typically resolves within 3-7 days without treatment, though cough and malaise can persist for greater than 2 weeks.

Influenza infection in immunocompromised patients can lead to severe and sometimes fatal disease, especially in solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients. Clinical presentation in immunocompromised patients is comparable to that in immunocompetent persons. However, progression from an upper respiratory tract infection to pneumonia is more common. Other complications, such as bacterial superinfection, CNS involvement, myocarditis, and graft dysfunction or rejection are also more common in the immunocompromised host. The incidence of influenza infection among transplant patients varies depending upon the type of transplantation, though lung transplant recipients seem to be at higher risk. Prognosis is worse the closer the infection occurs following transplantation. It is unclear whether there are substantial differences in clinical presentations or outcomes if a transplant patient is infected with influenza A versus influenza B.

INFLUENZA VIRUS LABORATORY DIAGNOSIS

Viral culture is a common method of influenza detection, though it is time consuming, taking 3-14 days. Fluorescent antibody techniques are more timely, though poor negative predictive values are a significant limitation of this method. The need for a rapid and highly sensitive diagnostic method is significant. Polymerase Chain Reaction (PCR) is coming to the forefront as it has been shown to be a rapid, sensitive and specific method for detecting influenza.

INFLUENZA VIRUS TREATMENT

Influenza is mainly a community acquired infection, though nosocomial spread does occur. Spread of infection can be prevented with hand hygiene practices, isolation measures, and yearly vaccination. The standard inactivated intramuscular vaccine is recommended for transplant patients; the live attenuated intranasal vaccine is not recommended. However, transplant patients may not be able to mount an appropriate immune response to the vaccination or may not be able to receive the vaccine; prophylaxis is recommended in these cases.

Amantadine and rimantadine are no longer used in the treatment or prophylaxis of influenza A due to drug resistance. Oseltamivir and zanamivir are neuraminidase inhibitors now used in the treatment and prophylaxis of influenza infection, though some cases of oseltamivir resistance have been reported. Transplant patients with severe influenza may benefit from aerosolised ribavirin, in addition to neuraminidase inhibitor therapy. The potential benefits of many treatment options in transplant patients remain unclear, such as administration of prophylaxis during the entire influenza season versus only post-exposure, administration of a higher dosage of vaccination, or repeat vaccination, among others.

Selected References

Avian Influenza Infection in Humans. Centers for Disease Control and Prevention Web site. http://www.cdc.gov/flu/avian/gen-info/avian-flu-humans.htm. Updated August 9, 2006. Accessed September 12, 2007.

Englund JA. Diagnosis and epidemiology of community-acquired respiratory virus infections in the immunocompromised host. Biol Blood Marrow Transplant. 2001;7 Suppl:2S-4S.

Influenza Viruses. Centers for Disease Control and Prevention Web site. http://www.cdc.gov/flu/avian/gen-info/flu-viruses.html. Updated November 18, 2005. Accessed August 29, 2007.

Knipe D, Howley P. Fields Virology. 5th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2006.

Lee I, Barton TD. Viral respiratory tract infections in transplant patients: epidemiology, recognition and management. Drugs. 2007;67(10):1411-1427.

Mahoney J, Chong S, Merante F, et al. Development of a respiratory virus panel (RVP) test for the detection of twenty human respiratory viruses using multiplex PCR and a fluid microbead-based assay.

J Clin Microbiol. 2007;45(9):2965-2970.

Prevention and Control of Influenza: Recommendations of the Advisory Committee on Immunization Practices (ACIP) (MMWR 2006 Jul 28;55(RR10):1-42.

PAO-20-0907

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Collection & Shipping

PCR tests are performed pursuant to a license agreement with Roche Molecular Systems Inc.
ImmuKnow is a registered trademark of Cylex Incorporated.
Respiratory Viral Panel is a product of Luminex Corporation.

Abstracts & Publications

Avian Influenza Infection in Humans. Centers for Disease Control and Prevention Web site. http://www.cdc.gov/flu/avian/gen-info/avian-fluhumans.htm. Updated August 9, 2006. Accessed September 12, 2007.

Englund JA. Diagnosis and epidemiology of community-acquired respiratory virus infections in the immunocompromised host. Biol Blood Marrow Transplant. 2001;7 Suppl:2S-4S.

Influenza Viruses. Centers for Disease Control and Prevention Web site. http://www.cdc.gov/flu/avian/gen-info/flu-viruses.html. Updated November 18, 2005. Accessed August 29, 2007.

Knipe D, Howley P. Fields Virology. 5th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2006.

Lee I, Barton TD. Viral respiratory tract infections in transplant patients: epidemiology, recognition and management. Drugs. 2007;67(10):1411-1427.

Mahoney J, Chong S, Merante F, et al. Development of a respiratory virus panel (RVP) test for the detection of twenty human respiratory viruses using multiplex PCR and a fluid microbead-based assay. J Clin Microbiol. 2007;45(9):2965-2970.

Prevention and Control of Influenza: Recommendations of the Advisory Committee on Immunization Practices (ACIP) (MMWR 2006 Jul 28;55(RR10):1-42.