Influenza is a viral infection that attacks your respiratory system — your nose, throat and lungs. Influenza, commonly called the flu, is not the same as stomach “flu” viruses that cause diarrhea and vomiting.
For most people, influenza resolves on its own, but sometimes, influenza and its complications can be deadly. People at higher risk of developing flu complications include:
- Young children under 5, and especially those under 2 years
- Adults older than 65
- Residents of nursing homes and other long-term care facilities
- Pregnant women
- People with weakened immune systems
- People who have chronic illnesses, such as asthma, heart disease, kidney disease and diabetes
- People who are very obese, with a body mass index (BMI) of 40 or higher
Your best defense against influenza is to receive an annual vaccination.
The flu is caused by influenza virus types A, B, and C. Both type A and type B flu viruses are responsible for the seasonal outbreaks of flu. Type A flu viruses are found in many different animals, including ducks, chickens, pigs, and horses. Influenza B viruses circulate widely only among humans.
Flu viruses spread mainly from person to person, through coughing or sneezing by people infected with influenza. Sometimes people may become infected by touching a contaminated surface and then touching their mouth or nose. Healthy adults may be able to infect others beginning one day before symptoms develop and up to seven days after becoming sick. This means a person may be able to pass on the flu to someone else before ever knowing they are sick.
Influenza viruses are encapsulated, negative-sense, single-stranded RNA viruses of the family Orthomyxoviridae. The core nucleoproteins are used to distinguish the 3 types of influenza viruses: A, B, and C. Influenza A viruses cause most human and all avian influenza infections. The RNA core consists of 8 gene segments surrounded by a coat of 10 (influenza A) or 11 (influenza B) proteins. Immunologically, the most significant surface proteins include hemagglutinin (H) and neuraminidase (N).
Hemagglutinin and neuraminidase are critical for virulence, and they are major targets for the neutralizing antibodies of acquired immunity to influenza. Hemagglutinin binds to respiratory epithelial cells, allowing cellular infection. Neuraminidase cleaves the bond that holds newly replicated virions to the cell surface, permitting the infection to spread.
Major typing of influenza A occurs through identification of both H and N proteins. Nine H and 16 N types have been identified. All hemagglutinins and neuraminidases infect wild waterfowl, and the various combinations of H and N yield 144 potential subtypes of influenza.
The hemagglutinin and neuraminidase variants are used to identify influenza A virus subtypes. For example, influenza A subtype H3N2 expresses hemagglutinin 3 and neuraminidase 2. The most common subtypes of human influenza virus identified to date contain only hemagglutinins 1, 2, and 3 and neuraminidases 1 and 2. H3N2 and H1N1 are the most common prevailing influenza A subtypes that infect humans. Each year, the trivalent vaccine used worldwide contains influenza A strains from H1N1 and H3N2, along with an influenza B strain.
Because the viral RNA polymerase lacks error-checking mechanisms, the year-to-year antigenic drift is sufficient to ensure that there is a significant susceptible host population each year. However, the segmented genome also has the potential to allow reassortment of genome segments from different strains of influenza in a coinfected host.
In addition to humans, influenza also infects a variety of animal species. More than 100 types of influenza A infect most species of birds, pigs, horses, dogs, and seals. Influenza B has also been reported in seals, and influenza C has been reported, though rarely, in pigs.
Some of these influenza strains are species-specific. The species specificity of influenza strains is partly due to the ability of a given hemagglutinin to bind to different sialic acid receptors on respiratory tract epithelial cells. Avian influenza viruses generally bind to alpha-2,3-sialic acid receptors, whereas human influenza viruses bind to alpha-2,6-sialic acid receptors.
In this context, the term avian influenza (or “bird flu”) refers to zoonotic human infection with an influenza strain that primarily affects birds. Swine influenza refers to infections from strains derived from pigs.
New strains of influenza may spread from other animal species to humans, however. Alternatively, an existing human strain may pick up new genes from a strain that usually infects birds or pigs.
Antigenic drift and shift
Influenza A is a genetically labile virus, with mutation rates as high as 300 times that of other microbes. Changes in its major functional and antigenic proteins occur by means of 2 well-described mechanisms: antigenic drift and antigenic shift.
Antigenic drift is the process by which inaccurate viral RNA polymerase frequently produces point mutations in certain error-prone regions in the genes. These mutations are ongoing and are responsible for the ability of the virus to evade annually acquired immunity in humans. Drift can also alter the virulence of the strain. Drift occurs within a set subtype (eg, H2N2). For example, AH2N2 Singapore 225/99 may reappear with a slightly altered antigen coat as AH2N2 New Delhi 033/01.
Antigenic shift is less frequent than antigenic drift. In a shift event, influenza genes between 2 strains are reassorted, presumably during coinfection of a single host. Segmentation of the viral genome, which consists of 10 genes on 8 RNA molecules, facilitates genetic reassortment. Because pigs have been susceptible to both human and avian influenza strains, many experts believe that combined swine and duck farms in some parts of Asia may have facilitated antigenic shifts and the evolution of previous pandemic influenza strains.
The reassortment of an avian strain with a mammalian strain may produce a chimeric virus that is transmissible between mammals; such mutation products may contain H or N proteins that are unrecognizable to the immune systems of mammals. This antigenic shift results in a much greater population of susceptible individuals in whom more severe disease is possible.
Such an antigenic shift can result in a virulent strain of influenza that possesses the triad of infectivity, lethality, and transmissibility and can cause a pandemic. Three major influenza pandemics have been recorded:
- The Spanish influenza pandemic of 1918 (H1N1)
- The pandemic of 1957 (H2N2)
- The pandemic of 1968 (H3N2)
- Smaller outbreaks occurred in 1947, 1976, 1977, and 2009.
Transmission and infection
Transmission of influenza from poultry or pigs to humans appears to occur predominantly as a result of direct contact with infected animals. The risk is especially high during slaughter and preparation for consumption; eating properly cooked meat poses no risk. Avian influenza can also be spread through exposure to water and surfaces contaminated by bird droppings.
Influenza viruses spread from human to human via aerosols created when an infected individual coughs or sneezes. Infection occurs after an immunologically susceptible person inhales the aerosol. If not neutralized by secretory antibodies, the virus invades airway and respiratory tract cells.
Once the virus is within host cells, cellular dysfunction and degeneration occur, along with viral replication and release of viral progeny. As in other viral infections, systemic symptoms result from release of inflammatory mediators.
The incubation period of influenza ranges from 1 to 4 days. Aerosol transmission may occur 1 day before the onset of symptoms; thus, it may be possible for transmission to occur via asymptomatic persons or persons with subclinical disease, who may be unaware that they have been exposed to the disease.
Viral shedding occurs at the onset of symptoms or just before the onset of illness (0-24 hours). Shedding continues for 5-10 days. Young children may shed virus longer, placing others at risk for contracting infection. In highly immunocompromised persons, shedding may persist for weeks to months.
H5N1 avian influenza
To date, avian influenza (H5) remains a zoonosis. The vast majority of cases of avian influenza have been acquired from direct contact with live poultry, with no sustained human-to-human transmission. Hemagglutinin type 5 attaches well to avian respiratory cells and thus spreads easily among avian species. However, attachment to human cells and resultant infection is more difficult.
Avian viruses tend to prefer sialic acid alpha(2-3) galactose, which, in humans, is found in the terminal bronchi and alveoli. Conversely, human viruses prefer sialic acid alpha(2-6) galactose, which is found on epithelial cells in the upper respiratory tract. Although this results in a more severe respiratory infection, it probably explains why few, if any, definite human-to-human transmissions of avian influenza have been reported: infection of the upper airways is probably required for efficient spread via coughing and sneezing.
Most human deaths from bird flu have occurred in Indonesia. Sporadic outbreaks among humans have continued elsewhere, including China, Egypt, Thailand, and Cambodia.
In theory, however, mutation of the hemagglutinin protein through antigenic drift could result in a virus capable of binding to upper and lower respiratory epithelium, creating a strain that is easily transferred from human to human and thus could cause a worldwide pandemic.
Initially, the flu may seem like a common cold with a runny nose, sneezing and sore throat. But colds usually develop slowly, whereas the flu tends to come on suddenly. And although a cold can be a nuisance, you usually feel much worse with the flu.
Common signs and symptoms of the flu include:
- Fever over 100 F (38 C)
- Aching muscles, especially in your back, arms and legs
- Chills and sweats
- Dry, persistent cough
- Fatigue and weakness
- Nasal congestion
- Sore throat
The most important step in flu prevention is getting vaccinated each year with a flu shot. Avoid close contact with people who are sick, stay home when you are sick, cover your mouth and nose when you cough or sneeze, wash your hands, avoid touching your eyes, nose or mouth, get plenty of sleep, and drink plenty of fluids. In certain situations, antiviral drugs can be used to prevent seasonal influenza.
Usually, you’ll need nothing more than bed rest and plenty of fluids to treat the flu. But in some cases, your doctor may prescribe an antiviral medication, such as oseltamivir (Tamiflu) or zanamivir (Relenza). If taken soon after you notice symptoms, these drugs may shorten your illness by a day or so and help prevent serious complications.
Oseltamivir is an oral medication. Zanamivir is inhaled through a device similar to an asthma inhaler and shouldn’t be used by anyone with respiratory problems, such as asthma and lung disease.
Antiviral medication side effects may include nausea and vomiting. These side effects may be lessened if the drug is taken with food. Oseltamivir has also been associated with delirium and self-harm behaviors in teenagers.
Some researchers recommend further study on both of these drugs because of uncertainty about their effects beyond a slight reduction in the time of illness. Some studies have suggested that these medications can also help reduce the severity of complications. The Centers for Disease Control and Prevention still recommends their use for some people, however.
An additional concern is that some strains of influenza have become resistant to oseltamivir, amantadine and rimantadine (Flumadine), which are older antiviral drugs.