Centers for Disease Control and Prevention INFLUENZA
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Clinical Features
of Influenza | The Influenza Viruses |
DNA or RNA? Why is the flu a
bummer?
Natural History of
Human Influenza
Clinical Features
of Influenza
Influenza, commonly called "the
flu," is caused by viruses that infect the respiratory tract. Compared
with most other viral respiratory infections, such as the common cold,
influenza infection often causes a more severe illness. Typical clinical
features of influenza include fever (usually 100F to 103F in adults and often
even higher in children) and respiratory symptoms, such as cough, sore throat,
runny or stuffy nose, as well as headache, muscle aches, and often extreme
fatigue. 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.
Most people who get
the flu recover completely in 1 to 2 weeks, but some people develop serious and
potentially life-threatening medical complications, such as pneumonia. In an
average year, influenza is associated with about 20,000 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 influenza infection than are
younger, healthier people.
The Influenza
Viruses
Influenza viruses
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 for 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 that influenza types A and B do. 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. This constant changing
enables the virus to evade the immune system of its host, so that people are
susceptible to influenza virus infection throughout life.
This process works
as follows: a person infected with influenza virus develops antibody against
that virus; as the virus changes, the "older" antibody no longer
recognizes the "newer" virus, and reinfection can occur.
The older antibody
can, however, provide partial protection against
reinfection.
Currently, three different influenza strains circulate worldwide: two type A
viruses and one type B. Type A viruses are divided into subtypes based on
differences in two viral proteins called the hemagglutinin (H) and the
neuraminidase (N). The current subtypes of influenza A are designated
A(H1N1) and
A(H3N2).
Influenza type A
viruses undergo two kinds of changes. One is a series of mutations that occur
over time and cause 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.
Natural History of
Human Influenza
Influenza A and B
viruses continually undergo antigenic drift. This process accounts for most of
the changes that occur in the viruses from one influenza season to another.
Antigenic shift occurs only occasionally. When it does occur, large numbers of
people, and sometimes the entire population, have no antibody protection
against the virus. This may result in a worldwide epidemic, called a pandemic.
During this century, pandemics occurred in 1918, 1957, and 1968, each of which
resulted in large numbers of deaths, as noted below.
Mortality
associated with pandemics:

1918-19 "Spanish flu" A(H1N1) -- Caused the highest known
influenza-related mortality: approximately 500,000 deaths occurred in the
United States, 20
million worldwide.

1957-58 "Asian flu" A(H2N2) -- 70,000 deaths in the United States.

1968-69 "Hong-Kong flu" A(H3N2) -- 34,000 deaths in the United
States.
The emergence of
the "Hong Kong flu" in 1968-69 marked the beginning of the type
A(H3N2) era. When this virus first emerged, it was associated with lower
mortality than that caused by the two previous pandemic viruses.
Several possible
reasons for this lower mortality have been hypothesized.
First, only the
hemagglutinin changed from the "Asian" strain [type A(H2N2)]; the
neuraminidase (N2) stayed the same, and therefore existing antibody could be
expected to offer some protection. A second possibility is suggested by
evidence that a virus with a similar hemagglutinin may have circulated from the
late 1890s to the early 1900s. If this were the case, people who were in their
sixties and older in 1968 may have had some protection from antibody acquired
in their youth.
There are still
many things about influenza viruses that are not understood.
Although the newly
emerged type A(H3N2) virus caused only moderate mortality in 1968 compared with
other pandemic viruses, this virus has continued to cause substantial mortality
as it has continued to circulate and evolve. In the years since its emergence,
type A(H3N2) epidemics have caused more than
400,000 deaths in
the United States alone, and more than 90% of these deaths have occurred among
elderly people. Of the influenza viruses currently in worldwide circulation,
A(H3N2) still has the most severe overall impact.
The other influenza
A subtype currently in circulation, type A(H1N1), also has an interesting
history. After the devastating pandemic of 1918-19, this subtype continued to
circulate and undergo antigenic drift. It periodically caused large epidemics,
but never on the scale of the 1918-19 pandemic. When the "Asian"
strain [(A(H2N2)] emerged in 1957, the A(H1N1) viruses disappeared (as did the
A(H2N2) viruses when the "Hong Kong" virus emerged in 1968). In 1977,
the A(H1N1) viruses reappeared and have cocirculated with A(H3N2) viruses ever
since. However, the impact of A(H1N1) has been different during its most recent
appearance. The virus that reappeared in 1977 was virtually identical to an
A(H1N1) virus that circulated in 1950.
Therefore, most
people born before 1950 were immune, and epidemics caused by
A(H1N1) viruses
since 1977 have primarily affected younger people. The fact that the elderly
appear to have natural protection against current A(H1N1) viruses probably
explains the low mortality associated with recent epidemics in which this
subtype was the predominant strain. However, as A(H1N1) viruses continue to
evolve, they could begin to have a more severe impact on the elderly.