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Influenza Signs and Symptoms and the Role of Laboratory Diagnostics

Signs and Symptoms

The signs and symptoms of influenza can vary by age, immune status, and presence of underlying medication conditions. Uncomplicated influenza  can include any or all of these signs and symptoms: fever, muscle aches, headache, lack of energy, dry cough, sore throat, nasal congestion, and possibly runny nose. Fever is not always present, especially in elderly persons. The fever and body aches can last 3-5 days and the cough and lack of energy may last for 2 or more weeks, especially in elderly. Influenza can be difficult to diagnose based on clinical signs and symptoms alone because the signs and symptoms of influenza can be similar to those  caused by other infectious agents including, but not limited to, Mycoplasma pneumoniae, adenovirus, respiratory syncytial virus, rhinovirus, parainfluenza viruses, and Legionella spp.

Appropriate treatment of patients with respiratory illness depends on accurate and timely diagnosis. Early diagnosis of influenza can reduce the inappropriate use of antibiotics and provide the option of using antiviral therapy. However, because certain bacterial infections can produce signs and symptoms similar to influenza, bacterial infections should be considered and appropriately treated, if suspected. In addition, bacterial co-infection can occur as a complication of influenza.

Influenza surveillance information about the prevalence of circulating influenza viruses and diagnostic testing can aid clinical judgment and help guide treatment decisions. The accuracy of clinical diagnosis of influenza on the basis of signs and symptoms alone is limited because symptoms from illness caused by other pathogens can overlap considerably with influenza. Influenza surveillance by state and local health departments and CDC can provide information regarding the prevalence of influenza A and B viruses in the community. Surveillance can also identify the predominant circulating types, influenza A virus subtypes, and strains of influenza viruses.

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Laboratory Diagnostic Procedures

A number of tests can help in the diagnosis of influenza (see table). But, tests do not need to be done on all patients. For individual patients, tests are most useful when they are likely to yield clinically useful results that will help with diagnosis and treatment decisions. During a respiratory illness outbreak in a closed setting (e.g., hospitals, nursing home, cruise ship, boarding school, summer camp) however, testing for influenza can be very helpful in determining if influenza is the cause of the outbreak.

Preferred respiratory samples for influenza testing include nasopharyngeal or nasal swab, and nasal wash or aspirate, depending on which type of test is used (see table). Samples should be collected within the first 4 days of illness. Rapid influenza diagnostic tests provide results within approximately 15 minutes; viral culture provides results in 3-10 days. Most of the rapid influenza diagnostic tests that can be done in a physician’s office are approximately 50-70% sensitive for detecting influenza and approximately greater than 90% specific. Therefore, false negative results are more common than false positive results, especially during peak influenza activity.

Diagnostic tests available for influenza include viral culture, serology, rapid antigen testing, reverse transcription polymerase chain reaction (RT-PCR), immunofluorescence assays, and rapid molecular assays. Sensitivity and specificity of any test for influenza might vary by the laboratory that performs the test, the type of test used, the time from illness onset to specimen collection, and the type of specimen tested. Among respiratory specimens for viral isolation or rapid detection of human influenza viruses, nasopharyngeal specimens typically have higher yield than nasal or throat swab specimens. As with any diagnostic test, results should be evaluated in the context of other clinical and epidemiologic information available to health-care providers.

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Viral Culture

Despite the availability of rapid influenza diagnostic tests, collecting clinical specimens for viral culture is critical, because only culture isolates can provide specific information regarding circulating strains and subtypes of influenza viruses. This information is needed to compare current circulating influenza virus strains with vaccine strains, to guide decisions regarding influenza antiviral treatment and chemoprophylaxis, and to formulate vaccine for the coming year. Virus isolates also are needed to monitor the emergence of antiviral resistance and the emergence of novel influenza A viruses that might pose a pandemic threat.

During outbreaks of respiratory illness when influenza is suspected, some respiratory samples should be tested by both rapid influenza diagnostic tests and by viral culture. The collection of some respiratory samples for viral culture is essential for determining the influenza A subtypes and influenza A and B virus strains causing illness, and for surveillance of new strains that may need to be included in the next year’s influenza vaccine. During outbreaks of influenza-like illness, viral culture also can help identify other causes of illness.

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Commercial rapid influenza diagnostic tests are available that can detect influenza viruses within 20 minutes. Some tests are CLIA-waived and approved for use in any outpatient setting, whereas others must be used in a moderately complex clinical laboratory. These rapid influenza diagnostic tests differ in the types of influenza viruses they can detect and whether they can distinguish between influenza types. Different tests can detect 1) only influenza A viruses; 2) both influenza A and B viruses, but not distinguish between the two types; or 3) both influenza A and B and distinguish between the two.

None of the rapid influenza diagnostic tests provide any information about influenza A virus subtypes. The types of specimens acceptable for use (i.e., throat, nasopharyngeal, or nasal aspirates, swabs, or washes) also vary by test. The specificity and, in particular, the sensitivity of rapid influenza diagnostic tests are lower than for viral culture and RT-PCR and vary by test. Because of the lower sensitivity of the rapid influenza diagnostic tests, physicians should consider confirming negative tests with RT-PCR, viral culture or other means, especially in hospitalized patients or during suspected institutional influenza outbreaks because of the possibility of false-negative rapid test results, especially during periods of peak community influenza activity. In contrast, false-positive rapid test results are less likely, but can occur during periods of low influenza activity. Therefore, when interpreting results of a rapid influenza diagnostic test, physicians should consider the positive and negative predictive values of the test in the context of the level of influenza activity in their community. Package inserts and the laboratory performing the test should be consulted for more details regarding use of rapid influenza diagnostic tests.

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Serologic Testing

Routine serological testing for influenza requires paired acute and convalescent sera, does not provide results to help with clinical decision-making, is only available at a limited number of public health or research laboratories and is not generally recommended, except for research and public health investigations. Serological testing results for antibodies to human influenza viruses on a single serum specimen is not interpretable and is not recommended.

Influenza Diagnostic Table

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