Interim Recommendations for Clinical Use of Influenza Diagnostic Tests During the 2009-10 Influenza Season

From: www.cdc.com

September 29, 2009, 6:00 PM ET

Objective
To provide updated interim recommendations on influenza diagnostic testing for clinicians treating patients with suspected 2009 H1N1 influenza virus infection and to assist clinicians with testing decisions for the 2009-10 influenza season 1. These recommendations may be further revised as more information becomes available. These recommendations also can be adapted according to local epidemiologic and surveillance data and other state and local considerations. Clinical judgment is always an important part of testing and treatment decisions.

Summary Points
Most patients with clinical illness consistent with uncomplicated influenza who reside in an area where influenza viruses are circulating do not require diagnostic influenza testing for clinical management.
Patients who should be considered for influenza diagnostic testing include:
Hospitalized patients with suspected influenza
Patients for whom a diagnosis of influenza will inform decisions regarding clinical care, infection control, or management of close contacts.
Patients who died of an acute illness in which influenza was suspected.
When a decision is made to use antiviral treatment for influenza, treatment should be initiated as soon as possible without waiting for influenza test results. Antiviral treatment is most effective when administered as early as possible in the course of illness. (http://www.cdc.gov/h1n1flu/recommendations.htm)

Clinicians should be aware that the sensitivities of rapid influenza diagnostic tests (RIDTs) and direct immunofluorescence assays (DFAs) are lower than real-time reverse transcriptase polymerase chain reaction (rRT-PCR) tests and viral culture. A negative RIDT or DFA result does not rule out influenza virus infection. (http://www.cdc.gov/h1n1flu/guidance/rapid_testing.htm). Further, these tests cannot distinguish between 2009 H1N1 and seasonal H1N1 or H3N2 influenza A viruses.

If most circulating influenza viruses have similar antiviral susceptibilities (as is the case currently in the United States), information on the influenza A subtype may not be needed to inform clinical care.

If identification of 2009 H1N1 influenza virus infection is required, testing with a rRT-PCR assay specific for 2009 H1N1 influenza or viral culture should be performed.
Laboratory tests to diagnose 2009 H1N1 influenza, such as rRT-PCR, should be prioritized for hospitalized patients and immunocompromised persons with suspected influenza where RIDT or DFA testing is negative or to determine influenza A virus subtype in patients who have died from suspected or confirmed influenza A virus infection.

Information on testing of pathology specimens for suspected 2009 H1N1 influenza virus infection can be found at (http://cdc.gov/h1n1flu/tissuesubmission.htm).

Background
As of September 19, 2009, more than 99% of circulating influenza viruses identified in the United States were 2009 H1N1 influenza (previously referred to as novel influenza A (H1N1)). The clinical presentation of patients with uncomplicated 2009 H1N1 influenza virus infection is generally similar to seasonal influenza and includes abrupt onset of fever, cough, sore throat, myalgias, arthralgias, chills, headache and fatigue. Vomiting and diarrhea have been reported more often with 2009 H1N1 influenza than with seasonal influenza2. As with seasonal influenza, some patients with 2009 H1N1 influenza will present without fever. Clinical judgment and local surveillance data for influenza and other respiratory pathogens are important in considering the differential diagnosis of patients presenting with influenza-like illness.

CDC recommends early empiric antiviral treatment for suspected or confirmed influenza in hospitalized patients and in outpatients at higher risk for complications from influenza (see complete antiviral recommendations and list of high risk conditions: http://www.cdc.gov/h1n1flu/recommendations.htm). Empiric antiviral treatment, when indicated, should be initiated as early as possible and should not be delayed pending the results of influenza testing.

Influenza Diagnostic Tests
A number of diagnostic tests (Table 1) are available to detect the presence of influenza viruses in respiratory specimens. These tests differ in their sensitivity and specificity for detecting influenza viruses, commercial availability, processing time, approved clinical setting, and ability to distinguish between different influenza virus types (A versus B) and influenza A subtypes (e.g., 2009 H1N1 versus seasonal H1N1 versus seasonal H3N2 viruses).

Rapid influenza diagnostic tests (RIDTs) are widely available but have variable sensitivity3 (range 10 – 70%) for detecting 2009 H1N1 influenza when compared with real-time reverse transcriptase polymerase chain reaction (rRT-PCR), and a negative RIDT result does not rule out influenza virus infection4 . RIDTs have a high specificity5 (>95%6). Depending on which commercially available RIDT is used, the test can either i) detect and distinguish between influenza A and B viruses; or ii) detect both influenza A and B but not distinguish between influenza A and B viruses. More information on sensitivity, specificity and interpretation of RIDT results can be found at http://www.cdc.gov/h1n1flu/guidance/rapid_testing.htm.

Like RIDTs, direct immunofluorescence assays (DFAs) are widely available, have variable sensitivity (range 47 – 93%) for 2009 H1N1 influenza virus, and a high specificity (≥96%7). DFAs detect and distinguish between influenza A and B viruses but do not distinguish among different influenza A subtypes.

When influenza viruses are circulating in a community, the positive predictive value of the RIDT and DFA tests are generally high and a positive test result indicates that influenza virus infection is likely. However, as stated above, a negative test does not rule out influenza virus infection.

Nucleic acid amplification tests, including rRT-PCR, are the most sensitive and specific influenza diagnostic tests, but they may not be readily available, obtaining test results may take one to several days, and test performance depends on the individual rRT-PCR assay. As with any assay, false negatives can occur. Not all nucleic acid amplification assays can specifically differentiate 2009 H1N1 influenza virus from other influenza A viruses. If specific testing for 2009 H1N1 influenza virus is required, testing with an rRT-PCR assay specific for 2009 H1N1 influenza or viral culture should be performed.