Clinical Features of Influenza
Influenza, commonly called “the flu,” is an infection of the respiratory tract caused by the influenza virus. Compared with most other viral respiratory infections, such as the common cold, influenza infection often causes a more severe illness. Typical influenza illness includes fever (usually 100ºF to 103ºF 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, these symptoms are rarely the primary symptoms. The term “stomach flu” is a misnomer that is sometimes used to describe gastrointestinal illnesses caused by organisms other than influenza viruses.
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 more than 20,000 deaths nationwide and more than 100,000 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 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 A(H1N1), A(H3N2), and influenza B strains are included in each year’s influenza vaccine.
Influenza type A viruses undergo two kinds of changes. One is a series of mutations that occur over time and cause a gradual change in the virus. This is called antigenic “drift.” 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.
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
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. If the new virus is capable of being spread easily from person to person, a worldwide epidemic, called a pandemic, can occur. 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 fewer deaths than that caused by the two previous pandemic viruses. There are several possible reasons for this. First, only the hemagglutinin changed from the “Asian” strain [type A(H2N2)]; the neuraminidase (N2) stayed the same, and therefore, people previously infected with H2N2 viruses may have had some protection against the H3N2 virus. A second possibility is 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.
Many things about influenza viruses still are not understood. Although the newly emerged type A(H3N2) virus caused many fewer deaths in 1968 compared with other pandemic viruses, it has continued to cause many deaths during annual epidemics. 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 people age 65 and older. 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 had protective antibody, 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.