What is influenza?

Influenza, commonly called "the flu," is an illness caused by RNA viruses that infect the respiratory tract of
many animals, birds, and humans. In most people, the infection results in the person getting fever, cough,
headache, and malaise (tired, no energy); some people also may develop a sore throat, nausea, vomiting, and
diarrhea. The majority of individuals has symptoms for about one to two weeks and then recovers with no
problems. However, compared with most other viral respiratory infections, such as the common cold,
influenza (flu) infection can cause a more severe illness with a mortality rate (death rate) of about 0.1% of
people who are infected with the virus.
The above is the usual situation for the yearly occurring "conventional" or "seasonal" flu strains. However,
there are situations in which some flu outbreaks are severe. These severe outbreaks occur when the human
population is exposed to a flu strain against which the population has little or no immunity because the virus
has become altered in a significant way. Unusually severe worldwide outbreaks (pandemics) have occurred
several times in the last hundred years since influenza virus was identified in 1933. By an examination of
preserved tissue, the worst influenza pandemic (also termed the Spanish flu) occurred in 1918 when the virus
caused between 40-100 million deaths worldwide, with a mortality rate estimated to range from 2%-20%.
In April 2009, a new influenza strain against which the world population has little or no immunity was
isolated from humans in Mexico. It quickly spread throughout the world so fast that the WHO declared this
new flu strain (termed novel H1N1 influenza A swine flu, often shortened to H1N1 or swine flu) as the cause
of a pandemic on June 11, 2009. This was the first declared flu pandemic in 41 years.
Haemophilus influenzae is a bacterium that was incorrectly considered to cause the flu until the virus was
demonstrated to be the correct cause in 1933. This bacterium can cause lung infections in infants and
children, and it occasionally causes ear, eye, sinus, joint, and a few other infections, but it does not cause the
flu.

What are the causes of the flu?

Influenza viruses cause the flu and are divided into three types, designated A, B, and C. Influenza types A
and B are responsible for epidemics of respiratory illness that occur almost every winter and are often
associated with increased rates of hospitalization and death. Influenza type C differs from types A and B in
some important ways. Type C infection usually causes either a very mild respiratory illness or no symptoms
at all; it does not cause epidemics and does not have the severe public-health impact of influenza types A and
B. Efforts to control the impact of influenza are aimed at types A and B, and the remainder of this discussion
will be devoted only to these two types.
Influenza viruses continually change over time, usually by mutation (change in the viral RNA). This constant
changing often enables the virus to evade the immune system of the host (humans, birds, and other animals)
so that the host is susceptible to changing influenza virus infections throughout life. This process works as
follows: a host infected with influenza virus develops antibodies against that virus; as the virus changes, the
"first" antibody no longer recognizes the "newer" virus and infection can occur because the host does not
recognize the new flu virus as a problem until the infection is well under way. The first antibody developed
may, in some instances, provide partial protection against infection with a new influenza virus.
Unfortunately, almost all individuals have no antibodies that will recognize the novel H1N1 virus
immediately. Consequently, without vaccination, the majority of the human population is susceptible to
novel H1N1 flu.

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Type A viruses are divided into types based on differences in two viral surface proteins called the
hemagglutinin (H) and the neuraminidase (N). There are 16 known H subtypes and nine known N subtypes.
These surface proteins can occur in many combinations. When spread by droplets or direct contact, the virus,
if not killed by the host's immune system, replicates in the respiratory tract and damages host cells. In people
who are immune compromised (for example, pregnant individuals, infants, cancer patients, asthma patients,
people with pulmonary disease and many others), the virus can cause viral pneumonia or stress the
individual's system to make them more susceptible to bacterial infections, especially bacterial pneumonia.
Both pneumonia types, viral and bacterial, can cause severe disease and sometimes death.
Influenza type A viruses undergo two kinds of changes. One is a series of mutations that occurs over time
and causes a gradual evolution of the virus. This is called antigenic "drift." The other kind of change is an
abrupt change in the hemagglutinin and/or the neuraminidase proteins. This is called antigenic "shift." In this
case, a new subtype of the virus suddenly emerges. Type A viruses undergo both kinds of changes; influenza
type B viruses change only by the more gradual process of antigenic drift and therefore do not cause
pandemics.

What are flu symptoms?

Typical clinical features of influenza include

 fever (usually 100 F-103 F in adults and often even higher in children),
 respiratory symptoms such as cough, sore throat, runny or stuffy nose,
 headache,
 muscle aches, and
 fatigue, sometimes extreme.
Although nausea, vomiting, and diarrhea can sometimes accompany influenza infection, especially in
children, gastrointestinal symptoms are rarely prominent. The term "stomach flu" is a misnomer that is
sometimes used to describe gastrointestinal illnesses caused by other microorganisms. Novel H1N1
infections cause more nausea, vomiting, and diarrhea than the conventional (seasonal) flu viruses.
Most people who get the flu recover completely in one to two weeks, but some people develop serious and
potentially life-threatening medical complications, such as pneumonia. In an average year, influenza is
associated with about 36,000 deaths nationwide and many more hospitalizations. Flu-related complications
can occur at any age; however, the elderly and people with chronic health problems are much more likely to
develop serious complications after the conventional influenza infections than are younger, healthier people.
However, the novel H1N1 virus has initially developed a different pattern of infection. Unfortunately, the
pattern of infection is similar to that of the 1918 "Spanish flu" pandemic in which young people (pregnant
individuals, infants, teens, and adults through age 49) are the most susceptible populations worldwide.

What is the key to flu prevention?

Much of the illness and death caused by influenza can be prevented by annual influenza vaccination. Flu
vaccine (influenza vaccine made from inactivated and sometimes attenuated [non-infective] virus) is
specifically recommended for those who are at high risk for developing serious complications as a result of
influenza infection. These high-risk groups for conventional flu include all people aged 65 years or older and
people of any age with chronic diseases of the heart, lung, or kidneys; diabetes; immunosuppression; or
severe forms of anemia. However, with the novel H1N1 flu, the CDC has listed these groups listed below as
being at high risk and should obtain the novel H1N1 vaccine as soon as it is available to them:

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  pregnant women,
 people who live with or care for children younger than 6 months of age,
 health-care and emergency-services personnel,
 people between the ages of 6 months through 24 years of age and children 5-18 years of age who
have chronic medical problems, and
 people from 25-64 years of age who are at higher risk for novel H1N1 because of chronic health
disorders or compromised immune systems.
Other groups for whom conventional flu vaccine is specifically recommended are residents of nursing homes
and other chronic care facilities housing patients of any age with chronic medical conditions and children and
teenagers who are receiving long-term aspirin therapy and who may therefore be at risk for developing Reye
syndrome after an influenza virus infection. Influenza vaccine is also recommended for people who are in
close or frequent contact with anyone in the high-risk groups defined above. These people include health-
care personnel and volunteers who work with high-risk patients and people who live in a household with a
high-risk person.
Because the flu is easily spread among children and because many children require hospitalization with the
flu, the CDC now advises that all children 6-59 months of age receive a yearly conventional flu vaccination.

Are any side effects associated with the influenza vaccine?

Although annual influenza (injectable) vaccination has long been recommended for people in the high-risk
groups, many still do not receive the vaccine, often because of their concern about side effects. They
mistakenly perceive influenza as merely a nuisance and believe that the vaccine causes unpleasant side
effects or that it may even cause the flu. The truth is that influenza vaccine causes no side effects in most
people. The most serious side effect that can occur after influenza vaccination is an allergic reaction in
people who have a severe allergy to eggs, since the viruses used in the vaccine are grown in hens' eggs. For
this reason, people who have an allergy to eggs should not receive the influenza vaccine. Also, the vaccine is
not recommended while individuals have active infections or active diseases of the nervous system. Less than
one-third of those who receive the vaccine have some soreness at the vaccination site, and about 5%-10%
experience mild side effects, such as headache, low-grade fever, or muscle cramps, for about a day after
vaccination. These side effects are most likely to occur in children who have not been exposed to influenza
virus in the past.
Nevertheless, some older people remember earlier influenza vaccines that did, in fact, produce more
unpleasant side effects. Vaccines produced from the 1940s to the mid-1960s were not as highly purified as
modern influenza vaccines, and it was these impurities that caused most of the side effects. Since the side
effects associated with these early vaccines, such as fever, headache, muscle aches, and fatigue, were similar
to some of the symptoms of influenza, people believed that the vaccine had caused them to get the flu.
However, injectable influenza vaccine produced in the United States has never been capable of causing
influenza because it consists of killed virus.
Another type of influenza vaccine (nasal spray) is made with live attenuated (altered) influenza viruses. This
vaccine is made with live viruses that can stimulate the immune response enough to confer immunity but do
not cause classic influenza symptoms (in most instances). The nasal spray vaccine (FluMist) is only approved
for healthy individuals ages 2-49 years of age. This nasal spray vaccine contains live attenuated virus (less
able to cause flu symptoms due to a designed inability to replicate at normal body temperatures). This live
vaccine could possibly cause the disease in infants and immunocompromised people and does not produce a
strong immune response in many older people. Side effects of the nasal mist include nasal congestion, sore
throat, and fever. Headaches, muscle aches irritability, and malaise have also been noted. In most instances,
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if side effects occur, they only last a day or two. This nasal spray has been produced for both conventional
and the novel H1N1 flu viruses and should not be given to pregnant individuals or anyone who has a medical
condition that may compromise the immune system because in some instances the flu is the side effect.
Caregivers should read the vaccine precaution insert before giving any vaccine, injectable or nasal, as these
inserts are occasionally updated.
Some people do not receive influenza vaccine because they believe it is not very effective. There are several
different reasons for this belief. People who have received influenza vaccine may subsequently have an
illness that is mistaken for influenza, and they believe that the vaccine failed to protect them. In other cases,
people who have received the vaccine may indeed have an influenza infection. Overall vaccine effectiveness
varies from year to year, depending upon the degree of similarity between the influenza virus strains included
in the vaccine and the strain or strains that circulate during the influenza season. Because the vaccine strains
must be chosen nine to 10 months before the influenza season, and because influenza viruses mutate over
time, sometimes mutations occur in the circulating virus strains between the time the vaccine strains are
chosen and the next influenza season ends. These mutations sometimes reduce the ability of the vaccine-
induced antibody to inhibit the newly mutated virus, thereby reducing vaccine efficacy. This commonly
occurs with the conventional flu vaccines as the specific virus types chosen for vaccine inclusion are based
on reasoned projections for the upcoming flu season. Occasionally, the vaccine does not match the actual
predominating virus strain and is not very effective in generating a specific immune response to the
predominant infecting flu strain.
Vaccine efficacy also varies from one person to another. Studies of healthy young adults have shown
influenza vaccine to be 70%-90% effective in preventing illness. In the elderly and those with certain chronic
medical conditions such as HIV, the vaccine is often less effective in preventing illness. Studies show the
vaccine reduces hospitalization by about 70% and death by about 85% among the elderly who are not in
nursing homes. Among nursing-home residents, vaccine can reduce the risk of hospitalization by about 50%,
the risk of pneumonia by about 60%, and the risk of death by 75%-80%. If antigenic drift results in changing
the circulating virus from the strains used in the vaccine, vaccine efficacy may be reduced. However, the
vaccine is still likely to lessen the severity of the illness and to prevent complications and death.
The vaccine produced against the novel H1N1 swine flu was just initiated in the summer of 2009 and then
rapidly tested for safety and effectiveness, in contrast to the longer time cycle used for production of
conventional flu vaccine. However, the injectable (and nasal) vaccines used the same methods developed for
conventional flu vaccines over many years. The expedited clinical trials for the novel H1N1 vaccines,
according to the CDC, have shown the injected vaccine to be safe and very effective with immunologic
protection developing in healthy people. In the 18-64 age group, 98% were protected while those over 65
were 93% protected. Other groups are being studied, but protection with the injected vaccine in preliminary
and ongoing trials seems good, according to the CDC. To date, about 39,000 Chinese people have been given
the vaccine with very few (four) developing only mild side effects such as muscle cramps and headache,
according to WHO officials. Recently, data presented on the effectiveness of the nasal mist vaccine in adults
were published; the data indicated that for conventional flu protection, the nasal mist was less effective than
the injected vaccine in adults for the conventional flu. Other studies have shown that the nasal mist vaccine
was slightly more effective in healthy children than the injectable vaccine. The following is a list of the
CDC-approved H1N1 vaccines and the companies that name and manufacture them as of 10/29/09:

 Influenza A (H1N1) 2009 Monovalent Vaccine by Sanofi Pasteur

 Influenza A (H1N1) 2009 Monovalent Vaccine by Novartis
 Influenza A (H1N1) 2009 Monovalent Vaccine Live, Intranasal by MedImmune, LLC
 Influenza A (H1N1) 2009 Monovalent Vaccine by CSL Limited

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Why should the flu vaccine be taken every year?

Although only a few different influenza virus strains circulate at any given time, people may continue to
become ill with the flu throughout their lives. The reason for this continuing susceptibility is that influenza
viruses are continually mutating, through the mechanisms of antigenic shift and drift described above. Each
year, the vaccine is updated to include the most current influenza virus strains that are infecting people
worldwide. The fact that influenza viral genes continually change is one of the reasons vaccine must be taken
every year. Another reason is that antibody produced by the host in response to the vaccine declines over
time, and antibody levels are often low one year after vaccination.

What are some treatments an individual can do at home for the flu?

First, individuals should be sure they are not members of a high-risk group that is more susceptible to getting
severe flu symptoms. Check with your physician if you are unsure if you are a higher risk person. Home care
is recommended by the CDC if a person is normally healthy with no underlying diseases or conditions (for
example, asthma, lung disease, pregnant, or immunosuppressed).
Increasing liquid intake, warm showers, and warm compresses, especially in the nasal area, can reduce the
body aches and reduce nasal congestion. Nasal strips and humidifiers may help reduce congestion, especially
while trying to sleep. Some physicians recommend nasal irrigation with saline to further reduces congestion;
some recommend nonprescription decongestants. Fever can be treated with over-the counter acetaminophen
(Tylenol) or ibuprofen (Motrin and others) (read labels for safe dosage). Cough can be suppressed by cough
drops and over-the-counter cough syrup. If an individual's symptoms at home get worse, their doctor should
be notified.

When should a person go to the emergency department for the flu?

The CDC has recently published guidelines on who should go to the emergency department for flu symptoms
and who should not go. The CDC published these guidelines to avoid a crush of people going to the
emergency department during the H1N1 flu pandemic and utilizing limited resources needed for true
emergency patients such as cardiac or trauma patients and to avoid transmitting the virus to high-risk
patients. The CDC guidelines are as follows for children and adults. The CDC urges normally healthy people
that get either the conventional or novel H1N1 swine flu to stay home as the large majority of infected
individuals will recover without antiviral medications or other treatments.
The CDC urges people to seek emergency medical care for a sick child with any of these symptoms:
1. Fast breathing or trouble breathing
2. Bluish or gray skin color
3. Not drinking enough fluids
4. Severe or persistent vomiting
5. Not waking up or not interacting
6. Being so irritable that the child does not want to be held
7. Flu-like symptoms improve but then return with fever and cough
The following is the CDC's list of symptoms that should trigger emergency medical care for adults:
1. Difficulty breathing or shortness of breath
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 2. Pain or pressure in the chest or abdomen
3. Sudden dizziness
4. Confusion
5. Severe or persistent vomiting
6. Flu-like symptoms improve but then return with fever and worse cough
7. Having a high fever for more than three days is another danger sign, according to the WHO, so the
CDC has also included this as another serious symptom.

Who should receive the flu vaccine? When should someone get the flu shot?

In the United States, the flu season usually occurs from about November until April. Officials have decided
each new flu season will start on Oct. 4. Typically, activity is very low until December, and peak activity
most often occurs between January and March. Ideally, the conventional flu vaccine should be administered
between September and mid-November. It takes about one to two weeks after vaccination for antibodies
against influenza to develop and provide protection. Groups at increased risk of conventional influenza
complications include:

 people aged 65 years or older;

 residents of nursing homes and other chronic-care facilities housing patients of any age who have
chronic medical conditions;
 adults and children with chronic disorders of the pulmonary, cardiovascular, or immune systems,
including children with asthma;
 adults and children who have required regular medical follow-up or hospitalization during the
preceding year because of chronic metabolic diseases (including diabetes mellitus), renal dysfunction,
hemoglobinopathies, or immunosuppression (including immunosuppression caused by medications);
 children and teenagers (6 months to 18 years of age) who are receiving long-term aspirin therapy and
therefore may be at risk for developing Reye syndrome after influenza; and
 women in the third trimester of pregnancy or in the early postpartum period. There is some evidence
to suggest that women who are in the third trimester of pregnancy or in the early postpartum period
may be at increased risk for serious medical complications after influenza infection. Pregnant women
who will be in the third trimester of pregnancy between December and April should consult their
health-care provider about receiving influenza vaccine during the period from September to mid-
November.
Unfortunately, because the novel H1N1 flu virus is not following the conventional flu pattern for time of
disease appearance (appeared in April and increased over the summer and fall of 2009) or susceptible
populations, the CDC has had to alter somewhat the recommendations this year. Consequently, the CDC has
listed these groups as being at high risk for novel H1N1 flu and should obtain the novel H1N1 vaccine as
soon as it is available to them:

 pregnant women,
 people who live with or care for children younger than 6 months of age,
 health-care and emergency-services personnel,
 people between the ages of 6 months through 24 years of age and children 5-18 years of age who
have chronic medical problems, and
 people from 25-64 years of age who are at higher risk for novel H1N1 because of chronic health
disorders or compromised immune systems.

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In addition, the following groups should be vaccinated because they may transmit influenza to people who
are at high risk for complications if they become infected with either the conventional or novel H1N1 flu.
1. Physicians, nurses, and other health-care personnel in both hospital and outpatient-care settings
2. Employees in nursing homes and chronic-care facilities who have contact with patients or residents
3. Providers of home care to people at high risk (for example, visiting nurses and volunteer workers)
4. Household members (including children) of high-risk people
Furthermore, the CDC advises that all children 6-59 months of age get a yearly conventional flu vaccination
since each year there are over 20,000 children who require hospitalization because of the flu and flu is easily
passed from child to child.
Finally, the flu vaccine, both the conventional and H1N1, may be administered to any person who wishes to
reduce his or her chances of acquiring influenza infection. People who provide essential community services
should be considered for vaccination to minimize disruption of essential activities during influenza
outbreaks. Students or other people in institutional settings, such as those who reside in dormitories, should
be encouraged to receive the vaccine to minimize the disruption of routine activities during epidemics. Such
outbreaks have been reported for H1N1 in 2009. People needing further information regarding the use and
availability of the influenza vaccine should consult with their health-care provider or their local health
department or the CDC at the flu.gov Web site.

What is the bird (avian) flu?

The bird flu, also known as avian influenza, is an infection caused by avian influenza A. Bird flu can infect
many bird species, including domesticated birds such as chickens. In most cases, the disease is mild;
however, some subtypes can be pathogenic and rapidly kill birds within 48 hours. Rarely, humans can be
infected by these bird viruses. People who get infected with bird flu usually have direct contact with the
infected birds or their waste products. Depending on the viral type, the infections can range from mild
influenza to severe respiratory problems or death. When this virus (H5N1) infects human, it is highly
pathogenic and although only about 700 people worldwide have been infected, about 10% died. Fortunately,
this virus does not seem to be easily passed from person to person. The major concern among scientists and
physicians about bird flu is that it will change (mutate) its viral RNA enough to be easily transferred among
people and produce a pandemic similar to the one of 1918.

Do antiviral agents protect people from the flu?

Vaccination is the primary method for control of influenza; however, antiviral agents have a role in the
prevention and treatment of mainly influenza type A infection. Regardless, antiviral agents should not be
considered as a substitute or alternative for vaccination.
Currently, there are four antiviral agents available in the United States. They are amantadine (Symmetrel),
rimantadine (Flumadine), zanamivir (Relenza), and oseltamivir (Tamiflu). In 2006, the CDC recommended
that neither amantadine nor rimantadine be used for prevention of influenza A as resistance to these drugs
had developed. This resistance problem and additional adverse reactions to the drugs (behavioral changes,
seizures) have limited their subsequent use. Oseltamivir has had a similar FDA label warning about
behavioral changes.
The 2007-2008 Advisory Committee on Immunization Practices (ACIP) recommends that only zanamivir
and oseltamivir be used in the U.S. for treatment or prevention until influenza A susceptibility to the other
drugs is reestablished. In general, infected people need to begin taking the antiviral medications within two

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days of developing the initial symptoms of influenza. This may reduce the symptoms and shorten the illness
by one or two days. However, in high-risk people, these drugs may either prevent the flu disease symptoms
(both conventional and novel H1N1) or, once established, prevent the flu from becoming severe. There is a
high potential for overuse of these drugs so the CDC has put out the following guidelines to be used with
clinical judgment:

 Uncomplicated febrile illness typically does not require antiviral treatment unless individuals are at
higher risk for influenza complications.
 Treatment is recommended for all hospitalized patients with confirmed, probable, or suspected novel
influenza (H1N1).
 Clinical judgment should be used when evaluating children; caregivers should be aware that the risk
for severe complications from seasonal influenza among children younger than 5 years of age is
highest among children younger than 2 years of age and may require antiviral medication.
In early September 2009, CDC officials further modified the antiviral guidelines for the interim guidelines
for use of Tamiflu and Relenza as follows:
1. People with high risk factors should discuss flu symptoms and when to use antivirals; doctors should
provide a prescription for the antiviral for the patient to use if the patient is exposed or develops flu-
like symptoms without having to go in to see the doctor.
2. "Watchful waiting" was added as a response to taking antiviral drugs with the emphasis on those
people who develop fever and have a preexisting health condition should then begin the antiviral
medication.
3. The antivirals are the first-line medicines for treatment of novel H1N1 swine flu, and most current
cases of flu are novel H1N1 and are, to date, susceptible to Tamiflu and Relenza.
Prevention of influenza (both A and B) is possible with both zanamivir and oseltamivir. While zanamivir was
approved for people 7 years of age or older and oseltamivir was approved for people 1 year of age and older
for the conventional flu, the CDC has published guidelines for antiviral use against novel H1N1 in late
September 2009 that includes children under 2 years of age and pregnant women:

 People with more severe illness, such as those hospitalized with suspected or confirmed influenza
 People with suspected or confirmed influenza who are at higher risk for complications
o Children younger than 2 years of age
o Adults 65 years of age and older
o Pregnant women
o People with certain chronic medical or immunosuppressive conditions
 People younger than 19 years of age who are receiving long-term aspirin therapy
Prevention rates vary from about 68%-89% when these antiviral medications were given to individuals
before they developed symptoms of the conventional flu or were exposed to infected people; data are not yet
available for novel H1N1. Treatment usually consists of a five-day schedule of antiviral medication, while
prevention usually requires 10 days of medication. For example, duration of antiviral chemoprophylaxis
(prevention) post-exposure is 10 days after the last known exposure. However, recommended treatment and
prevention schedules vary according to age, weight, drug formulation, and if the individual is hospitalized.
Details about dosing in adults, pregnant women, children, and infants are available and updated on both the
CDC and FDA web sites: http://www.cdc.gov/H1N1flu/antiviral.htm and
http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm18387
0.htm. Gastrointestinal symptoms (nausea, vomiting) are some of the most common side effects of these
drugs. Influenza viruses are known to develop resistance to both drugs but at a much lower rate than to the
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other antiviral drugs. These drugs and others that are in development (such as peramivir, favipiravir, and
ligand epitopes) are being studied to determine if they can be used to prevent or treat new influenza strains
such as novel H1N1 and bird flu.