Diagnosis of Influenza

Symptom-based diagnosis is fairly accurate in otherwise healthy individuals during seasonal epidemics, and in pneumonia, acute respiratory distress syndrome (ARDS), sepsis, or if encephalitis, myocarditis, or muscle tissue failure occurs case should be suspected.Because influenza resembles other viral respiratory illnesses, laboratory diagnosis is required to confirm the diagnosis. Common methods of collecting samples for testing include nasal and throat swabs.Samples may be collected from the lower airway if the infection has cleared the upper airway but not the lower airway.Influenza testing is recommended for anyone who is hospitalized with flu-like symptoms during flu season or is associated with a flu case.For severe cases, early diagnosis improves patient outcomes.

Diagnostic methods that can identify influenza include viral cultures, antibody and antigen detection tests, and nucleic acid-based tests.

Viruses can be grown in mammalian cell or embryonated egg cultures for 3-10 days to monitor cytopathic effects.Final confirmation can then be performed by antibody staining,hemoadsorption using red blood cells,or immunofluorescence microscopy.Shell vial culture allows identification of infection by immunostaining before cytopathic effects appear,is more sensitive than traditional culture, and results are available in 1-3 days.Cultures can be used to characterize novel viruses,observe susceptibility to antiviral drugs, and monitor antigenic drift, but they are relatively slow and require specialized skills and equipment.Serological assays can be used to detect antibody responses to influenza after natural infection or vaccination.Common serological tests include hemagglutination inhibition tests to detect HA-specific antibodies,virus neutralization tests to check whether antibodies have neutralized the virus, and enzyme-linked immunosorbent assays.These methods tend to be relatively cheap and quick, but are not as reliable as nucleic acid-based tests.Direct fluorescent or immunofluorescent antibody (DFA/IFA) testing involves staining respiratory epithelial cells in a sample with a fluorescently labeled influenza-specific antibody, followed by examination under a fluorescent microscope.They can distinguish between IAV and IBV, but not IAV.The Rapid Influenza Diagnostic Test (RIDT) is a simple method to obtain laboratory results, with low cost and quick results in less than 30 minutes, so it is widely used, but it cannot distinguish IAV from IBV or IAV subtypes,which is not as good as nucleic acid-based test sensitive.Nucleic acid-based tests (NATs) amplify and detect viral nucleic acids.Most of these tests take several hours,but rapid molecular testing is as fast as RIDT.Among NATs, reverse transcription-polymerase chain reaction (RT-PCR) is the most traditional and is considered the gold standard for diagnosing influenza because it is fast and can subtype IAV, but relatively Expensive and more prone to false positives.Culture Other NATs that have been used include loop-mediated isothermal amplification-based assays, simple amplification-based assays, and nucleic acid sequence-based amplification.Nucleic acid sequencing methods can identify infections by obtaining nucleic acid sequences of virus samples, thereby identifying viruses and antiviral drug resistance.The traditional method is Sanger sequencing, but it has largely been replaced by next-generation methods with higher sequencing speed and throughput. 

Treatment

In cases of mild or moderate illness, treatment of influenza is supportive and includes administration of fever-reducing medications such as acetaminophen and ibuprofen,adequate fluid intake to avoid dehydration, and rest at home.Cough suppressants and throat sprays may be beneficial for sore throats.It is recommended to avoid alcohol and smoking while you have the flu.Aspirin is not recommended for the treatment of influenza in children due to the increased risk of Reye syndrome.Corticosteroids are also not recommended except when treating septic shock or an underlying medical condition, such as exacerbation of chronic obstructive pulmonary disease or asthma, as they are associated with increased mortality.If a secondary bacterial infection develops, treatment with antibiotics may be required.

Antivirals

Antiviral drugs are mainly used to treat seriously ill patients, especially those with compromised immune systems.Antiviral drugs are most effective when started within the first 48 hours after symptoms appear.Late dosing may still be beneficial for those with underlying immune deficiencies,those with more severe symptoms,or those at higher risk of complications if those people are still shedding the virus.Antiviral treatment is also recommended if a person is hospitalized with suspected flu rather than waiting for test results to come back and symptoms worsen.Most antiviral drugs against influenza fall into two classes: neuraminidase (NA) inhibitors and M2 inhibitors.A notable exception is baloxavir marboxil, which targets the endonuclease activity of viral RNA polymerase and can be used as an alternative to NA and M2 inhibitors of IAV and IBV.NA inhibitors target the enzymatic activity of the NA receptor, mimicking the binding of sialic acid in the NA active site to IAV and IBV virions,resulting in impaired virus release and viral replication rates from infected cells.NA inhibitors include oseltamivir, which is taken orally as a prodrug and is converted to the active form in the liver, and zanamivir, which is a nasally inhaled powder.Oseltamivir and zanamivir are effective for prophylaxis and post-exposure prophylaxis, and overall studies have shown that NA inhibitors are effective in reducing complication rates,hospitalization, and mortality as well as disease course.Furthermore the earlier the NA inhibitor is given, the better the outcome,although delayed dosing can still be beneficial in severe cases.Other NA inhibitors include laninamivir and peramivir, which can be used as an alternative to oseltamivir in those who cannot tolerate or absorb.

Amantadine and rimantadine are oral agents that block the M2 ion channel of influenza virus,preventing viral uncoating.These drugs are only effective against IAV,but are no longer recommended due to widespread IAV resistance to them.Adamantane resistance first appeared in H3N2 in 2003 and spread globally by 2008.Oseltamivir resistance is no longer prevalent, as the 2009 pandemic H1N1 strain (H1N1 pdm09) was resistant to adamantanes and appeared to displace circulating resistant strains.Since the 2009 pandemic, oseltamivir resistance has been observed primarily in treated patients,especially immunocompromised children.Oseltamivir resistance is commonly reported in H1N1 but less frequently in H3N2 and IBV.Because of this,oseltamivir is recommended as the drug of choice for immunocompetent people,while for immunocompromised people, oseltamivir is recommended for anti-H3N2 and IBV, and zanamivir for anti-H1N1 pdm09.Resistance to zanamivir was observed less frequently and may be resistant to peramivir and baloxavir.