Influenza Virus

The highly pathogenic avian influenza A H5N1 variant [HPAI A(H5N1)] is a zoonotic disease that largely affects birds and livestock, although infection is possible in humans and other animal populations. According to the CDC, testing for HPAI A(H5N1) should be performed in individuals who meet epidemiologic criteria and either clinical or public health response criteria.  Briefly, epidemiologic criteria include recent (within 10 days) exposure to HPAI A(H5N1)-infected live animals, animal products, animal waste, or live bird markets; close, unprotected exposure to individuals infected with HPAI A(H5N1); or laboratory exposure to HPAI A(H5N1) virus.  Clinical criteria include signs, symptoms, and unexplained complications of acute respiratory tract infection (lower or upper), conjunctivitis, and potentially, gastrointestinal symptoms.  Asymptomatic individuals who are workers at high risk of HPAI A(H5N1) exposure or who are close contacts of individuals with confirmed HPAI A(H5N1) infection meet public health response criteria.  Testing for public health response reasons should be performed in collaboration with local and state health authorities.  Refer to the CDC’s Highly Pathogenic Avian Influenza A(H5N1) Virus: Interim Recommendations for Prevention, Monitoring, and Public Health Investigations, for complete criteria. 

HPAI A(H5N1) testing may also be based on other influenza test results. Influenza testing is recommended in all individuals with suspected influenza, and viral subtyping should be expedited in hospitalized individuals (especially those in the intensive care unit [ICU]) if influenza A is detected.  HPAI A(H5N1) testing is appropriate when viral subtyping indicates the presence of an influenza A subtype that is not a seasonal influenza A subtype (specifically H1 or H3). 

When HPAI A(H5N1) testing is indicated, an H5N1-specific reverse-transcription polymerase chain reaction (RT-PCR) assay should be ordered.  Collection of a combined nasal/oropharyngeal swab specimen and a nasopharyngeal swab specimen are recommended, although a single swab is acceptable if necessary.  An additional conjunctival swab specimen is recommended if conjunctivitis is present.  If severe respiratory disease is present and collection is feasible, lower respiratory tract specimens should be collected.  Finally, collection of multiple respiratory tract specimens is recommended if an individual is severely ill.  Collection should be performed as quickly as possible after onset of symptoms in individuals who are ill. 
 

In most healthy individuals, the flu is self-limited and uncomplicated. In high-risk individuals (eg, immunocompromised persons, infants, elderly individuals, pregnant individuals, and residents of long-term care facilities), the flu can result in serious complications, including hospitalization and death.  The Infectious Diseases Society of America (IDSA) and the CDC recommend testing if the results will influence management decisions, such as whether to initiate antiviral therapy. If influenza has been documented in the area, testing is not necessary for otherwise healthy outpatients with signs and symptoms consistent with influenza.  Refer to the Indications for Testing section for specific testing recommendations.

The CDC recommends cotesting for SARS-CoV-2 and influenza in individuals with acute respiratory illness who require hospitalization. In an outpatient setting, testing is generally not indicated; however, cotesting can be considered when results would impact clinical management and disease control measures. 

Ideally, influenza testing should occur as soon as possible after illness onset, using respiratory specimens collected within 4 days of symptom onset. 

Influenza can be detected by polymerase chain reaction (PCR) tests, direct fluorescent antibody (DFA) stains, rapid influenza diagnostic tests (RIDTs), culture, and serology (which should only be used for retrospective epidemiologic investigations, not for primary diagnosis). PCR is preferred because of its increased sensitivity and specificity.  If influenza virus is the main concern, rapid molecular detection near the point of care is recommended. If other respiratory viruses are of concern, PCR panels are available that include testing for a spectrum of respiratory viruses, including influenza. 

Near-point-of-care polymerase chain reaction (PCR) testing offers a more rapid turnaround time than other molecular test types, as well as high sensitivity and specificity, although more complex assays provide greater sensitivity and specificity. Singleplex and multiplex PCR testing may also enable the detection of other respiratory viruses. Rapid influenza diagnostic tests (RIDTs) offer rapid results but low to moderate sensitivity and specificity. Direct fluorescent antibody (DFA) testing provides fairly quick turnaround time, but only moderate sensitivity and specificity compared with PCR testing.  Refer to the Comparison of Influenza Virus Testing Methodologies table for further information.