Influenza is a communicable viral disease that affects the upper respiratory tract including upper and lower respiratory passages. It is caused by a wide spectrum of influenza viruses. Some of these viruses can infect humans, and some are specific to different species. These viruses are transmissible through respiratory droplets expelled from the mouth and respiratory system during coughing, talking, and sneezing. The influenza viruses can be transmitted by touching inanimate objects soiled with the virus and touching the nose or eye. Influenza can be transmitted before the patient is symptomatic and until 5 to 7 days after infection. After infection, it takes a few days for most of the healthy patients to recover fully, but complications that include pneumonia and death are common in certain high-risk groups. These groups include young children, elderly, immunocompromised, and pregnant females. Symptoms of influenza include a runny nose, high fever, cough, and sore throat. Influenza spreads rapidly and efficiently in seasonal epidemics. Flu epidemics occur every autumn and winter in temperate regions and affect a significant portion of adults and children, but seasons differently impact age groups and severity.
There are four types of influenza viruses, A, B, C and D. Influenza types A and B cause human infection annually during the epidemic season. Influenza A has several subtypes according to the combination of hemagglutinin (H) and the neuraminidase (N) proteins that are expressed on the surface of the viruses. There are 18 different hemagglutinin subtypes and 11 different neuraminidase subtypes (H1-18 and N1-11). Influenza A viruses can be characterized by the H and N types such as H1N1 and H3N2. Influenza B viruses are classified into lineages and strains. Influenza B viruses that have circulated in recent influenza seasons belong to one of two lineages, influenza B Yamagata and influenza B Victoria. Influenza viruses have receptors responsible for making them species specific. The animal influenza viruses can cause infections in humans if the antigenic characters of the virus change. When this happens, transmission from person-to-person is usually inefficient. Influenza pandemics like 1918 and 2009 can occur if the transmission from person-to-person becomes efficient. Avian influenza, or Bird Flu, is an infectious disease of birds caused by a variety of influenza A viruses including A(H5N1), A(H5N8), and H7N9 viruses. These viruses are worrisome as they can change to develop the ability for transmissibility from person-to-person and start a severe pandemic. A good example of animal origin influenza is the 2009 Pandemic influenza, which is an animal influenza virus that likely started in South America in early 2009 and developed the ability to spread from person-to-person and spread globally.
Researchers isolated Influenza A in 1933, seven years later, they isolated influenza B. Influenza viruses in certain geographic regions of the northern and southern hemispheres are called an influenza epidemic which occurs every year during the winter seasons. The severity, length of influenza, and age groups that are highly impacted and complication rates such as hospitalizations and deaths differ significantly during different influenza seasons. When H3N2 viruses predominate, the season tends to be more severe especially among children and elderly. World Health Organization (WHO) conducts global influenza virologic surveillance that indicates influenza viruses are isolated every month from humans in a geographic region. In temperate regions, influenza activity peaks during the winter months. In the Northern Hemisphere, influenza outbreaks and epidemics typically occur between October and March, whereas in the Southern Hemisphere, influenza activity occurs between April and August. In the tropical belt, influenza circulates year-round.
Influenza is an acute disease that targets upper respiratory tract and causes inflammation of upper respiratory tree and trachea. The acute symptoms persist for seven to ten days, and the disease is self-limited in most healthy individuals. The immune reaction to the viral infection and the interferon response are responsible for the viral syndrome that includes high fever, coryza, and body aches. High-risk groups who have chronic lung diseases, cardiac disease and pregnancy are more prone to severe complications such as primary viral pneumonia, secondary bacterial pneumonia, hemorrhagic bronchitis, and death. These severe complications can develop in as little as 48 hours from the beginning of symptoms. The virus replicates in the upper and lower respiratory passages starting from the time of inoculation and peaking after 48 hours, on average.
Influenza viruses replicate in the epithelial cell lining of the upper and lower respiratory tracts. The pathology does not differ between natural or experimental infection. Definitive diagnosis of influenza needs serologic, immunologic, and molecular testing through RT-PCR for upper or lower respiratory tract specimens. Mild cases show pathological changes in the respiratory tracts, but severe cases show clear evidence of pathologic changes of pneumonia. The tracheobronchial changes due to influenza infection can be summarized as redness and inflammation with mucous and purulent discharge macroscopically, and desquamation and destruction of the pseudostratified epithelium of the trachea and bronchi with only the basal layer remained viable but inflamed microscopically.
The clinical presentation of influenza ranges between mild to severe depending on the age, co-morbidities, vaccination status, and natural immunity to the virus. Usually, patients who received the seasonal vaccine present with milder symptoms, and they are less likely to develop complications.
Signs and symptoms of influenza in mild cases include a cough, fever, sore throat, myalgia, headache, runny nose, and congested eyes. A frontal or retro-orbital headache is a common presentation with selected ocular symptoms that include photophobia and pain with different qualities. The cause of ocular pain is related to the viral tropism that is associated with certain types and subtypes. Severe cases may progress to shortness of breath, tachycardia, hypotension, and need for supportive respiratory interventions in as little as 48 hours.
Diagnosis of influenza can be reached clinically especially during the influenza season. Most of the cases will recover without medical treatment, and they would not need laboratory test for the diagnosis. In high-risk cases, initiation of treatment should not be delayed until test results are obtained. Influenza laboratory tests should be ordered for cases where testing would inform clinical action or public health interventions such as the outbreak situations where the diagnosis of the causative agent is necessary for therapeutic and prophylactic recommendations.
Laboratory tests available for diagnosis of influenza are rapid antigen detection, a rapid molecular assay for the detection of viral RNA, immunofluorescence direct and indirect antibody staining for detection of viral antigen, real-time PCR test, and cell culture.
Influenza infection is self-limited and mild in most healthy individuals who do not have other co-morbidities. No antiviral treatment is needed during mild infections in healthy individuals. Antiviral medications can be used to treat or prevent influenza infection especially during the outbreaks in healthcare settings such as hospitals and residential institutions. Oseltamivir, zanamivir, and peramivir belong to the neuraminidase inhibitors family and can be used for the treatment of influenza A and B. The adamantanes antiviral family has two medications, amantadine, and rimantadine. Amantadine and rimantadine are effective against influenza A, but not influenza B. During recent influenza seasons, high rates of resistance have been identified in influenza A for the adamantanes antivirals, and they are not recommended for treatment or prophylaxis against influenza A. Resistance to the neuraminidase inhibitors has been low in recent influenza seasons, but the virus may mutate and develop resistance at any time. Resistance can develop in some patients following treatment, especially in immunocompromised patients. Oseltamivir can be used for chemoprophylaxis for individuals one year and older in cases of outbreaks and exposure in high-risk groups. The side effects of oseltamivir include skin reactions that might be severe and sporadic transient neuropsychiatric events; these side effects form a barrier to the use of oseltamivir in elderly and individuals that are at higher risk of developing these side effects. The only contraindication to zanamivir is an allergy to eggs.