Influenza: How serious is it?

Flu virus particles on red blood cells, as shown on colored scanning electron micrograph.
Flu virus particles on red blood cells, as shown on colored scanning electron micrograph.

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Seasonal influenza virus is one of the most common viral respiratory infections and primarily occurs in the winter season in the United States.1 It is a highly contagious airborne disease that infects the nose, throat, and lungs. At times, the infection can lead to hospitalization or even death secondary to a fatal pulmonary condition.1 Yearly, this infection accounts for approximately 226,000 hospitalizations and 36,000 deaths.2 The influenza virus is a negative-strand RNA virus representing three of the five types of the Orthomyxoviridae family.3,4 Every season, the virus may present differently and may mutate. The best prevention against this infection and its associated complications is the seasonal influenza vaccine that is administered annually.2 Health care providers should take the opportunity to educate their patients on the prevalence of influenza, its potential complications, and available prevention options. Providers should offer the influenza vaccine as soon as it is available to all eligible patients.

Pathophysiology

The influenza virus is a single-stranded RNA virus. The main nucleoproteins are used to differentiate among the three types of influenza virus (A, B, and C). Although all three types of influenza virus have the capacity to infect humans, the most pathogenic are types A and B.5 Influenza A is responsible for all avian infections and most of the infections in humans,6 whereas influenza B and C primarily infect humans.3 Influenza C may cause some mild respiratory conditions.5

All three viruses share a common genetic origin; however, they are genetically different through the exchange of RNA segments or reassortment.4 Each of the three groups has negative RNA segments that are used as a template for production of two types of positive RNA, messenger RNA (mRNA) and complementary RNA (cRNA); mRNA is used for production of protein and cRNA is used for replication of the virus.3

Influenza A is identified by two proteins: hemagglutinin (H) and neuraminidase (N). These proteins play a key role in causing the influenza virus by neutralizing antibodies of the obtained immunity. The H protein binds to respiratory epithelial cell receptors and facilitates entry of the virus, causing cellular infection. The N protein facilitates the spread of the infection as it cleaves sialic acid from glycoproteins.6,7 These two proteins are used in the typing of influenza A. There are 16 distinct genetic subtypes for the H protein and 9 subtypes for the N protein; of these, only three types of the H protein (H1, H2, and H3) and two types from the N protein (N1 and N2) are capable of infecting humans.4 This virus causes a moderate-to-severe illness and can affect any age group.8

Influenza A and B virus are structurally similar under a microscope; both are spherical and filamentous in shape.4 However, unlike influenza A virus, influenza B contains four envelope proteins: H and N (similar to influenza A), plus NB and BM2.4 The NB protein is encoded by RNA segment 6. Although it is not essential for influenza B virus replication in cell culture, the NB protein is a protein that is incorporated into virus particles, and its function is currently unknown.9 The BM2 protein is encoded by RNA segment 7 and is essential for virus uncoating.9,10 Influenza B infection is less severe than influenza A infection and commonly affects children.8 Influenza B has less antigenic drift, which makes it more stable than influenza A.8 This means that annual vaccinations are more effective against influenza B virus than influenza A.

Influenza C structurally differs from types A and B because it has one major surface glycoprotein, the hemagglutinin-esterase-fusion protein.4 This protein has a similar function to H and N, seen in types A and B, and another minor envelope protein, CM2.4 Although the function of the CM2 protein in viral replication is not clearly understood, it has been proposed that it plays a potential role in genome packaging and the uncoating process of the replication.11 Influenza C virus infection is very mild and is rarely reported.

Epidemiology and transmission

There are many factors that make influenza seasons unpredictable. According to the Centers for Disease Control and Prevention (CDC), it is very difficult to predict what virus will appear, when it will start, how bad the season will be, and how long it will last. Influenza is an acute but highly infectious disease that contributes to significant morbidity and mortality during epidemic seasons.12 Every year 5% to 20% (15 to 61 million) of the U.S. population contract it; more than 200,000 individuals are hospitalized13 and 36,000 die.2 This number varies each year based on the rate of vaccination and the success of matching the vaccine to that year's mutating strain.13 Serious complications from the influenza virus are seen mostly among those with underlying medical conditions and elderly individuals aged more than 65 years.12,13 Although the elderly frequently have immunologic memory against influenza virus infection, their advanced age reduces their ability to fight off the infection.13

Yearly, new influenza viruses evolve through mutation or reassortment. Mutation may cause some changes in the H and N antigens of the virus, causing drift.14 This constant antigenic drift is responsible for causing an epidemic.15 Antigenic drift changes the virus' gene gradually, and ultimately, these changes result in viruses that are antigenically different enough that the immune system fails to recognize them.

The mode of transmission for influenza is primarily through respirable droplets.12 The distribution of transmission during an epidemic of influenza is estimated to be 30% within households, 33% in the community, and 37% at school or in the workplace.12 According to the CDC, an individual with influenza may spread it to another person who is 6 feet away via coughing, sneezing, or talking.16 Influenza virus can be transmitted from one person to another, from 1 day prior to up to 7 days after symptom development.16

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