Influenza is a viral infection often referred to as the flu. Influenza viruses are RNA viruses from the family Orthomyxoviridae, and are classified as either type A or type B, which contain specific viral nucleoproteins (NP). The viral genome consists of eight unique viral RNA segments that are associated with the NP in a ribonucleoprotein complex. The virus structure consists of a lipid envelope and a layer of matrix protein that surround the ribonucleoprotein complex. Two proteins, the viral hemagglutinin protein (HA) and neuraminidase (NA) protein, project outward from the lipid envelope. The HA protein is involved in entry of the virus into cells and is the primary antigen involved in the immune response to infection or vaccination.
Influenza A viruses are classified into subtypes based on combinations of different HA and NA proteins. Influenza type A strains that infect humans usually have one of three HA proteins (H1, H2, H3) and one of two NA proteins (N1, N2). H3N2 and H1N1 are the most common influenza virus subtypes that cause seasonal influenza. Influenza virus strains are also identified by the location where they were isolated, the isolate number and the year of isolation. For example, an H3N2 influenza type A virus isolated from the eighth individual from whom a clinical sample was obtained in Puerto Rico in 1934 is designated as A/PR/8/34 (H3N2). There are no subtypes of influenza B virus, but many different strains exist under two primary lineages of influenza B, namely the Victoria and Yamagata lineages.
Influenza A viruses infect many mammalian species and birds, including migratory birds that can spread strains of influenza across the globe. Certain avian influenza viruses such as the H5N1 and H7N9 viruses are highly pathogenic and are associated with a high mortality when they infect humans. Fortunately, these viruses, except in rare instances, cannot be transmitted from humans to other humans. The possibility that these viruses may mutate and acquire the ability to be efficiently transmitted among humans and cause a highly lethal pandemic, remains a serious concern among public health officials.
New virus strains are derived from two types of events. Co-infection of animals such as pigs with different influenza viruses can allow mixing of viral genomes and re-assortment of viral RNA segments thus creating new viruses. This phenomenon is called antigenic shift. In addition, influenza viruses rapidly mutate causing new viral antigens to appear. This is called antigen drift. These two phenomena cause new influenza viruses to circulate each season and can in some years lead to widespread infections across the world (pandemics) such as occurred during the 2009 novel H1N1 pandemic.
Influenza virus is transmitted via aerosols and infects cells of the respiratory tract. The time from infection until occurrence of symptoms (incubation period) is usually one to three days. Adults shed influenza virus for approximately seven days following infection, during which time they can spread the infection and thus are considered contagious. Children and individuals with a compromised immune system may be contagious for up to two weeks. The onset of flu symptoms is usually abrupt and characterized by:
- Fever (up to 104°F)
- Muscle aches
- Runny nose
- Lumbosacral backache
- Sore throat
- Dry cough
Fever usually lasts two to four days. Some symptoms, especially cough and malaise, may persist for up to two weeks. Unlike adults, children may present with vomiting and diarrhea. Signs seen on physical examination include conjunctivitis, nasal discharge, pharyngitis without exudate, cervical adenopathy and rarely rales.
Influenza occurs primarily during the winter months (November through April in the United States). According to the World Health Organization, influenza infections cause hospitalizations in about 3 to 5 million cases and between 290,000 to 650,000 deaths annually throughout the world. Influenza infection damages cells of the respiratory tract tissue, which predisposes infected individuals to a secondary bacterial infection. In healthy adults, bronchitis and pneumonia (primary viral and secondary bacterial) are the most common complications of influenza. The elderly, patients with heart and lung disease, and immunocompromised patients (cancer patients, those with HIV infection, transplant patients, etc.) are particularly susceptible to influenza. Other complications of influenza infection include encephalitis and meningitis. Children are susceptible to complications such as inner ear infections (otitis media), viral pneumonia, secondary bacterial pneumonia and Reye's syndrome, a potentially fatal complication that can be precipitated by aspirin therapy.
Vaccination is the primary means to protect individuals from influenza, and helps prevent the spread of disease in the population. An inactivated virus vaccine administered by intramuscular injection is 70 to 90 percent effective in preventing influenza in healthy adults. An intranasal live attenuated (weakened) vaccine (FluMist) is also effective for persons 2 to 49 years old. Vigilant hand washing and avoiding close contact with infected individuals also help prevent the spread of influenza. Annual influenza vaccination is recommended for everyone, but high-risk individuals who have the greatest potential of developing severe disease or complications should be vaccinated. These include:
- Children aged 6-23 months
- People aged 50 years and older
- People with chronic heart, lung or kidney disease, diabetes, immunosuppression or severe forms of anemia
- Residents of nursing homes or other chronic care facilities
- Women who will be over three months pregnant during the influenza season
- Children and teens receiving long-term aspirin therapy (these individuals may be at risk for developing Reye's syndrome following influenza infection)
- People who live or work with high-risk patients
The following individuals should also receive the vaccine because they have the greatest potential to transmit influenza to high-risk individuals:
- Healthcare workers
- Employees of nursing homes and other chronic care facilities
The vaccine is contraindicated in individuals with a prior allergic reaction to the vaccine and in individuals allergic to eggs. Recently, a non-egg cell-based vaccine (Flucelvax) was approved by the U.S. Food and Drug Administration. Individuals with an acute febrile illness should wait until their symptoms subside before receiving the vaccine.
Clinicians are not able to accurately diagnose influenza based on signs and symptoms alone. There are many other viruses that infect the respiratory tract and there is a large overlap of symptoms among these infections. Diagnostic tests performed on specimens taken from the respiratory tract provide a useful aid to the diagnosis of influenza. There are a number of methods available to laboratories to detect influenza virus in respiratory specimens from patients.
Traditionally, laboratories used viral culture to detect influenza virus and improvements in virus culture techniques allowed for results within 48 to 72 hours. The direct fluorescent antibody (DFA) method allows detection of virus within two to three hours but is labor intensive and requires considerable experience. Molecular methods such as reverse transcription polymerase chain reaction (RT-PCR)-based tests are the most accurate methods to detect influenza virus but are expensive and can only be done in laboratories that can afford expensive equipment and employ highly trained technologists. Rapid influenza diagnostic tests, such as lateral flow tests, can be performed at the site of patient care such as the physicians’ office or emergency department. These tests offer the possibility of identifying an infected patient early in the course of the disease and during the patient’s visit to the healthcare facility. Early diagnosis at the point of care can have a positive impact on the efficacy of therapy and other clinical management decisions.
Several anti-viral drugs are available which can decrease the severity and duration of flu symptoms if administered within 48 hours of the onset of symptoms. Rapid and accurate diagnosis of influenza at the point of care maximizes the benefit of these anti-viral medications. Supportive therapy that addresses the symptoms is an important aspect of treatment. Hospitalization may be required in serious cases and for high-risk patients especially if complications occur.