LEARNING OBJECTIVES

Upon completion of this course, you will be able to:

• Discuss key concepts related to the transmission, symptoms, treatment, and prevention of seasonal influenza.

Influenza is an ancient disease. Its symptoms were described by Hippocrates more than 2,400 years ago. Since then, the disease has sickened and killed millions of people in local epidemics and global pandemics. The most famous and lethal pandemic began in 1918, when more than 50 million people died from what was called the Spanish flu. Then in 1957, the Asian flu swept around the world, killing millions, and in 1968, yet another pandemic named the Hong Kong flu infected and killed millions more.

The threat continues. In 2009, the World Health Organization declared a worldwide pandemic caused by a new type A, subtype H1N1, virus called "swine flu" because it was first discovered in pigs (CDC, 2009a). Fortunately, a specific vaccine has been developed to provide immunity to the virus and minimize its global threat (CDC, 2009b). Unfortunately, type A subtype H1N1 is not the only influenza virus that can sicken and kill. Other influenza viruses can make folks dreadfully ill. The seasonal influenza these viruses produce is the subject of this course.

MICROBIOLOGY OF INFLUENZA VIRUSES

All influenza viruses belong to the Orthomyxoviridae family of RNA virus and include viruses A, B, and C; only type A causes significant illness in humans. Each type contains two main surface antigens, or subtypes: hemagglutinin (HA) and neuraminidase (NA) (Cox, 2004). The HA antigen enables the virus to enter into cells, while the NA antigen facilitates cell-to-cell transmission. These subtypes are further subdivided by their surface antigens. When these antigens enter a human or animal, the body recognizes them as foreign substances and reacts in what is called an "immune response" by which the body creates antibodies against the foreign substance. Thus, when exposed to an influenza virus, people usually develop antibodies against the virus, lessening the severity of symptoms when and if they are infected again (Michael, 2009).

Influenza viruses continually change. They do this in two ways, called antigenic drift and antigenic shift. Antigenic drift is an ongoing process that occurs in both influenza A and B viruses when mutations occur within HA or NA genes. If this happens, antibodies may only partially recognize the resultant viruses or may not recognize them at all. In a given season, when such an antigen drift occurs, the current vaccine may not provide protection against disease. This is the reason seasonal influenza vaccines must be updated annually (AAPCID, 2009). Antigenic shift is uncommon, unpredictable, and can cause serious worldwide pandemics. It occurs only in influenza A viruses when new subtypes replace HA and sometimes NA, resulting in a new strain of virulent virus. When they do, a new vaccine must be made to combat the altered virus. For this reason, people must be vaccinated anew to protect themselves from the altered virus of seasonal influenza (Treanor, 2004).

COURSE OF THE DISEASE

According to the CDC, sick adults may be able to infect others beginning 1 day before symptoms appear and up to 5 to 7 days after they become ill. Sick children may be able to infect others beginning 1 day before symptoms appear and for more than 7 days after they become ill. Symptoms develop 1 to 4 days after the virus enters the body. That means that people may be able to pass on the flu virus to others even before they know they are sick. Any individual who has symptoms can infect others, as can some individuals who are infected with viruses but show no symptoms at all (CDC, 2009c).

SYMPTOMS AND SEVERITY

Influenza is a highly contagious infection of the respiratory tract. It can cause mild to severe illness and may lead to death. The incubation period is brief and the onset sudden, causing chills, fever, aching muscles, and general malaise. Symptoms include:

• Fever (usually high)
• Headache
• Extreme fatigue
• Dry cough
• Sore throat
• Runny or stuffy nose
• Muscle aches
• Nausea, vomiting, and diarrhea (more common in children than adults)

These indicators of influenza are referred to as "flu-like symptoms." For this reason, in the early stages of an infection, it may be difficult to distinguish between a common cold and influenza. However, the symptoms of flu are more severe and last longer than the common cold. The table below gives a comparison of the symptoms of typical seasonal influenza and those of the common cold.

SYMPTOMS OF INFLUENZA COMPARED TO THE COMMON COLD

Symptoms	Influenza	Common Cold
Onset	Brief, may be less than 24 hours after exposure	Gradual over several hours or days
Fever	Usually higher than 100° F (37.8° C)	Rare in adults and older children; infants and younger children may have higher fevers to 102° F
Headache	Sudden onset, may be severe	Rare
Muscle aches	Usual, often severe	Mild
Fatigue	Often extreme, may last 2 weeks or more	Never
Weakness	Often extreme, may last 2 weeks or more; children may show low activity level	Mild and, if present, of brief duration
Rhinitis and runny nose	Common	Common
Sneezing	Common	Common
Sore throat	May occur	Common
Nausea, vomiting, diarrhea	May occur in adults; more common in children	Never in adults
Cough	Hacking; may be severe and last for weeks after infection	Mild

SUSCEPTIBLE PEOPLE

Anyone can get the flu, but the disease is more severe for some people than others. The most vulnerable persons are young children; those 65 years of age and older; individuals with chronic medical conditions such as asthma, diabetes, or heart disease, regardless of age; and pregnant women. Pneumonia, bronchitis, and sinus and ear infections may complicate influenza, and the disease can make chronic health problems worse. For instance, persons with asthma may suffer asthma attacks while they have the flu, and people with chronic congestive heart failure may experience worsening symptoms caused by the accumulation of fluid in the lungs, abdominal organs, and peripheral tissues.

In a typical year in the United States, millions of people, about 5 to 20% of the population, get influenza. Most people who contract influenza recover in one to two weeks, but some develop life-threatening complications, particularly pneumonia. An average of 200,000 are admitted to hospitals, and 36,000 individuals die from influenza-related causes (CDC, 2009d).

DIAGNOSIS

When people shows signs and symptoms of influenza in regions with few or no H1N1 influenza cases, the CDC recommends that state and local health departments, hospitals, and clinicians consider collecting a swab specimen of nasal or pharynx exudate from such individuals in order to identify the specific cause of the illness (CDC, 2009d). The technique for collecting such a specimen is critical to the accurate identification of the causative agent. The box below describes the technique for obtaining a specimen.

TREATMENT

Comfort and Care

People young and old who are infected with the virulent viruses of flu are desperately ill. Their throats are sore, their eyes irritated and watery. They sneeze and cough, and copious mucus runs from their noses. Their muscles ache, their head aches, and they feel extreme fatigue. It is not unusual for children to be nauseated or have diarrhea. The sick one may curl up in bed, shiver with chills and fever, and feel too sick to talk or even cry. Such seriously ill people need rest, comfort, sleep, and extra fluids and may benefit from analgesics and antipyretic medications such as aspirin and acetaminophen. (However, to avoid the development of Reye's syndrome, an acute encephalopathy and fatty infiltration of the liver that tends to follow some acute viral infection, children younger than 18 years of age should NOT receive salicylates such as acetylsalicylic acid or aspirin [Merck Manual, 2006].) In spite of the misery for the first few days, most children and adults gradually recover without complications or antiviral medications in one to two weeks.

Antiviral Medications

Antiviral medications are recommended for individuals who exhibit more critical symptoms, chronic conditions, or influenza-related complications such as pneumonia (CDC, 2009e). These include:

• People with severe illness who have been hospitalized
• People younger than 19 years of age who are receiving long-term aspirin therapy
• People with suspected or confirmed influenza who are at higher risk for complications, such as:
  • Children younger than 2 years of age
  • Adults 65 years and older
  • Pregnant women
  • People with certain chronic medical and immunosuppressive conditions

ANTIVIRAL DRUGS FOR ADULTS

The CDC recommends two antiviral drugs for both seasonal and H1N1 influenza in adults who are sick enough to be hospitalized, especially if they have difficulty breathing or show signs of lower respiratory tract illness. The two recommended drugs are:

• Oseltamivir (Tamiflu) capsules, 75 mg twice a day for five days
• Zanamivir (Relenza), an inhaled powder administered to the respiratory tract via an oral disk inhaler device provided by the drug company

Either antiviral drug should be administered within 48 hours of the onset of symptoms without waiting for laboratory confirmation of the disease. Treatment should continue for a minimum of 5 days (CDC, 2009e). 

ANTIVIRAL DRUGS FOR CHILDREN

The CDC recommends two antiviral drugs for both seasonal and H1N1 influenza, as follows:

• Oseltamivir (Tamiflu) was approved for treatment in July 2009 by the Food and Drug Administration for use in children, even younger than 1 year of age (CDC, 2009e).
• Zanamivir (Relenza) is approved for treatment in children 7 years of age or older but is licensed only for use in people WITHOUT underlying respiratory disease, asthma, or heart disease, including people with asthma. The drug is an inhaled powder that comes with a disk inhaler (CDC, 2009e).

Either antiviral drug should be administered within 48 hours of the onset of symptoms without waiting for laboratory confirmation of the disease, and treatment should continue for a minimum of 5 days. Further, the benefits of antiviral treatment in children are that such treatment reduces the incidence of ear infections and the need for antibiotic medications in children between the ages of 1 and 12 years (CDC, 2009e). In addition, the American Academy of Pediatrics (AAP) recommends antiviral drugs to treat influenza in children who are at high risk of serious flu-related complications and who have moderate to severe influenza (AAP, 2007).

PREVENTION

Because influenza produces such serious symptoms, in September 2009 the CDC issued the following recommendations to the public:

INFLUENZA VACCINES: COMPOSITION AND RECOMMENDATIONS

There are two types of seasonal influenza vaccine:

• Live attenuated influenza vaccine (LAIV), containing live but weakened influenza virus, which is sprayed into the nostrils.
• Inactivated injectable influenza vaccine, or trivalent inactivated vaccines (TIVs), called the "flu shot."

Because influenza viruses constantly change, vaccines must be updated every year. To be better protected, individuals must be vaccinated every year. They need to understand that it takes two weeks to develop immunity after the vaccination.

Each year, experts from the Centers for Disease Control and Prevention (CDC), World Health Organization (WHO), U.S. Food and Drug Administration (FDA), and other institutions study virus samples and patterns in an effort to identify strains that are most likely to cause illness in the upcoming season. Based on those forecasts, the FDA determines three strains which manufacturers should include in their vaccines for the U.S. population. The vaccine for the 2009–2010 seasonal influenza contains:

• an A/Brisbane/59/2007 (H1N1)-like virus
• an A/Brisbane/10/2007 (H3N2)-like virus
• a B/Brisbane/60/2008-like virus

Six influenza virus vaccines were approved for the 2009–2010 influenza season: five trivalent inactivated vaccines (TIVs) with brand names Fuzone, Fluvirin, FluLaval, Fluarix, and Afluria; and one live attenuated influenza vaccine (LAIV) with the brand name FluMist. The table below shows the dosage charts for these vaccines.

SEASONAL INFLUENZA VACCINES

Trivalent Inactivated Vaccine (TIV) Injectable
Trade Name	Age	Dose/Presentation	Number of Doses
Source: CDC, 2009 (http://www.cdc.gov/FLU/freeresources/2009-10/pdf/dosagechart.pdf).
Fluzone	6 thru 35 months	0.25 ml, prefilled syringe1	1 or 22
	36 months and older	0.5 ml, prefilled syringe or 0.5 ml, single-dose vial
	6 months and older	Dose per age, multidose vial
Fluvirin	4 years and older	0.5 ml, multidose vial or 0.5 ml, prefilled syringe	1 or 22
FluLaval	18 years and older	0.5 ml, multidose vial	1
Fluarix	18 years and older	0.5 ml, prefilled syringe	1
Afluria	18 years and older	0.5 ml, prefilled syringe or 0.5 ml, multidose vial	1
Live Attenuated Influenza Vaccine (LAIV) Nasal Spray
FluMist	2 thru 49 years if healthy and non-pregnant	0.2 ml, spray 1/2 of dose into each nostril as indicated	1 or 23
1 Children age 6 through 35 months should receive 0.25 ml vaccine per dose. Children age 36 months through adults should receive 0.5 ml vaccine per dose. See footnote 2 to determine number of doses.
2 Children 6 months through 8 years who are receiving injectable influenza vaccine for the first time should receive two doses of vaccine separated by 4 weeks. Children who received influenza vaccine for the first time during the previous influenza season, and got only one dose, should receive two doses this season. However, children who were given influenza vaccine during any prior influenza season should receive only one dose.
3 Healthy children 2 through 8 years of age who are receiving live attenuated influenza vaccine (LAIV) for their first influenza vaccine should receive two doses separated by 4 weeks. Children who received influenza vaccine for the first time during the previous influenza season, and got only one dose, should receive two doses this season. However, children who were given influenza vaccine during any prior influenza season should receive only one dose.

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