Influenza, also known as flu, contagious infection primarily of the respiratory tract. Influenza is sometimes referred to as grippe. Influenza is caused by a virus transmitted from one person to another in droplets coughed or sneezed into the air. It is characterized by coldlike symptoms plus chills, fever, headaches, muscle aches, and fatigue. Most people recover completely in about a week. But some people are vulnerable to complications such as bronchitis and pneumonia. This group includes children with asthma, people with heart or lung disease, and the elderly. In the United States, people age 65 and older account for about 90 percent of influenza-associated deaths.
In addition to humans, influenza occurs in pigs, horses, and several other mammals as well as in certain wild and domesticated birds. At least some influenza viruses can jump from one species to another. For example, in late 1997 a strain of the influenza virus in chickens began to infect humans in Hong Kong, leading to a massive effort to eradicate the strain. See also Avian Flu.
Because influenza is highly contagious and spreads easily, it usually appears as epidemics—that is, outbreaks involving many people. If an outbreak spreads around the world—not uncommon in this age of rapid international travel—it is called a pandemic.
Many millions of people develop the flu each year. In most years less than 1 percent of those infected die. Nonetheless, this translates into large numbers. The United States Centers for Disease Control and Prevention (CDC) estimates that influenza causes more than 20,000 deaths in the United States each year; combined, influenza and pneumonia are among the nation’s ten leading causes of death. During epidemics and pandemics, death rates soar. The influenza pandemic that occurred from 1918 to 1919—the worst on record—killed about 500,000 people in the United States and from 20 million to 50 million people worldwide.
Viral StructureThe influenza virus has a relatively simple structure. A lipid (fatty) envelope surrounds the protein shell (capsid), which encloses coiled genetic material (RNA). Projecting from this envelope are two kinds of protein spikes, hemagglutinin and neuraminidase. These proteins act as antigens, eliciting an immune response in the organism that the virus invades. Influenza viruses exhibit the unique quality of periodically mutating these protein spikes. Because the viruses continually change, they can cause repeated waves of infection, even among people previously infected.© Microsoft Corporation. All Rights Reserved.
The word influenza is derived from the Latin word influentia. Italians in the early 16th century first applied the word influenza to outbreaks of any epidemic disease because they blamed such outbreaks on the influence of heavenly bodies. The first known use of the name specifically for the flu occurred in 1743 when an epidemic swept through Rome and its environs.
Today scientists know that members of the family Orthomyxoviridae, a group of viruses that infect vertebrate animals, cause influenza. The virus consists of an inner core of the genetic material ribonucleic acid (RNA) surrounded by a protein coat and an outer lipid (fatty) envelope. From this envelope, spikes of proteins called hemagglutinin and neuraminidase stick out. Hemagglutinin enables the virus to bind to and invade cells, and neuraminidase allows the virus to move among cells. But these proteins also act as antigens—that is, they are recognized as foreign matter by the human or other host organism, and this recognition triggers an immune response in the host.
There are three types of influenza viruses, known as A, B, and C. Type A, the most dangerous, infects a wide variety of mammals and birds. It causes the most cases of the disease in humans and is the type most likely to become epidemic. Type B infects humans and birds, producing a milder disease that can also cause epidemics. Type C apparently infects only humans. It typically produces either a very mild illness indistinguishable from a common cold or no symptoms at all. Type C does not cause epidemics.
Bird FluAvian influenza, more commonly known as bird flu, is a type of influenza that affects birds and can infect humans. Here, health authorities in China are vaccinating a chicken against the H5N1 avian influenza virus as part of a free vaccination program for backyard poultry.Alex Hofford/epa/Corbis
Influenza type A and B viruses continually change. Some changes involve a series of genetic mutations that, over a period of time, cause a gradual evolution of the virus. Called antigenic drift, this process accounts for most of the changes in influenza viruses that occur from one year to the next. Other changes, less common but more injurious, involve abrupt changes in the hemagglutinin or neuraminidase. This type of change is called antigenic shift and results in a new subtype of the virus. Type A viruses undergo both kinds of transformations; influenza type B viruses apparently change only by the process of antigenic drift.
Scientists further differentiate virus subtypes into strains, generally named for the geographic area where they were first detected. For example, the strains that caused the most infections during the 2001-2002 flu season in the Northern Hemisphere were type A New Caledonia and Moscow strains and Type B Sichuan strain.
Once a person has been infected by a specific strain of influenza, he or she has built up immunity to that strain in the form of antibodies. The person’s immune system then can recognize the strain’s hemagglutinin or neuraminidase and attack them if they reappear. The antibodies offer some protection against antigenic drifts, but not against antigenic shifts. Thus, because the viruses continually change, they can cause repeated waves of infection, even among people previously infected.
Scientists do not understand exactly what causes antigenic shifts. One leading theory suggests that a human strain and an animal strain recombine to create a new strain. This strain has the ability to infect humans but has antigens on its surface that are unfamiliar to the human immune system.
Influenza viruses pass from person to person mainly in droplets expelled during sneezes and coughs. When a person breathes in virus-laden droplets, the hemagglutinin on the surface of the virus binds to enzymes in the mucous membranes that line the respiratory tract. The enzymes, known as proteases, cut the hemagglutinin in two, which enables the virus to gain entry into cells and begin to multiply. These proteases are common in the respiratory and digestive tracts but not elsewhere, which is why the flu causes primarily a respiratory illness with occasional gastrointestinal symptoms. In the 1990s scientists discovered that some flu strains also can use the enzyme plasmin to cut hemagglutinin. Plasmin is common throughout the body, enabling the flu strains to infect a variety of tissues.
Although an influenza epidemic can occur at any time of year, flu season in temperate regions typically begins with the approach of winter—November in the Northern Hemisphere, April in the Southern Hemisphere. Flu viruses spread more easily during cold weather. An influenza epidemic may be restricted to a town or city or may quickly spread geographically as infected people travel.
Scientists long thought that the flu season occurred in winter because that is when people tend to spend more time crowded together in homes and schools, as well as in buses, subways, and other places with poor ventilation. A study on guinea pigs, reported in 2007, found that transmission of the virus depends upon temperature and humidity. Transmission among the guinea pigs declined as the temperature rose above 5°C (41°F) and stopped completely at 30°C (86°F). Low humidity favors transmission of the virus. The scientists who conducted the study believe the flu virus is most stable at low temperatures and in dry air, conditions prevalent in winter.
IV SYMPTOMS AND DIAGNOSIS
Influenza is an acute disease with a rapid onset and pronounced symptoms. After the influenza virus invades a person’s body, an incubation period of one to two days passes before symptoms appear. Classic symptoms include sore throat, dry cough, stuffed or runny nose, chills, fever with temperatures as high as 39ºC (103ºF), aching muscles and joints, headache, loss of appetite, occasional nausea and vomiting, and fatigue. For most people flu symptoms begin to subside after two to three days and disappear in seven to ten days. However, coughing and fatigue may persist for two or more weeks.
Death from influenza itself is rare. But influenza can aggravate underlying medical conditions, such as heart or lung disease. Invading influenza viruses produce inflammation in the lining of the respiratory tract, damage that increases the risk that secondary infections will develop. Common complications include bronchitis, sinusitis, and bacterial pneumonia, occurring most frequently in older people, people on chemotherapy, and people with acquired immunodeficiency syndrome (AIDS) or other diseases that compromise the immune system. If properly treated, these complications seldom are fatal.
Because influenza is so common and exhibits standard symptoms, doctors often diagnose the illness based on the season and whether flu cases have recently been reported in the area. To prove a diagnosis of influenza in a patient, the virus must be isolated from the person’s nasal or cough secretions or blood and identified under a microscope.
V TREATMENT AND PREVENTION
There is no specific cure for influenza. Recommended treatment usually consists of bed rest and increased intake of nonalcoholic fluids until fever and other symptoms lessen in severity. Certain drugs have been found effective in lessening flu symptoms, but medical efforts against the disease focus chiefly on prevention by means of vaccines that create immunity.
A Drugs That Ease Symptoms
No drugs can cure influenza, but certain antiviral medicines can relieve flu symptoms. Available by prescription, these drugs provide modest relief, but only if taken on the first or second day of symptoms. The drugs amantadine (sold under the brand name Symmetrel) and rimantadine (Flumadine), both in pill form, work against hemagglutinin and are effective in treating type A influenza. Two other drugs inhibit neuraminidase and are effective against both type A and type B strains: oseltamivir (Tamiflu) is in pill form and zanamivir (Relenza) is an inhalant.
A flu vaccine consists of greatly weakened or killed flu viruses, or fragments of dead viruses. Antigens in the vaccine stimulate a person’s immune system to produce antibodies against the viruses. If the flu viruses invade a vaccinated person at a later time, the sensitized immune system recognizes the antigens and quickly responds to help destroy the viruses.
About 5 to 10 percent of people who receive a flu vaccine experience mild, temporary side effects, typically soreness at the injection site. Young children who have not previously been exposed to the influenza virus are most likely to have side effects.
Flu viruses constantly change so different virus strains must be incorporated in vaccines from one year to the next. Scientists try to provide a good match between the vaccine and the most serious virus strains circulating at the time. But because it takes months to manufacture and distribute vaccines, decisions on their composition must be made well before the start of each flu season. Each February experts at the World Health Organization (WHO) recommend the composition of the vaccine for the forthcoming winter in the Northern Hemisphere; a second recommendation is made in September for vaccines to be used in the Southern Hemisphere. Typically vaccines contain antigens from three virus strains, usually two type A and one type B.
According to the CDC, the success of flu vaccines varies from one person to another. In healthy young adults, the vaccines are 70 to 90 percent effective in preventing the disease. In the elderly and people with certain chronic medical conditions, the vaccines are less effective in preventing illness but help reduce the severity of an infection and the risk of major complications or death. Studies show that flu vaccines reduce hospitalization by about 70 percent and death by about 85 percent among elderly people.
C Recommendations for Flu Shots
The CDC recommends annual flu shots for people who are at high risk for developing serious complications as a result of an influenza infection. This group includes all people age 65 and older; people in nursing homes and other facilities that house people with chronic medical conditions; people with chronic heart, lung or kidney disease, diabetes, an impaired immune system, or severe forms of anemia; children and adolescents with conditions treated for long periods of time with aspirin (which makes them vulnerable to Reye’s syndrome); and women who will be in the second or third trimester of pregnancy during the influenza season.
To help stop the disease’s spread, the CDC also recommends vaccination for health-care workers, employees of nursing homes and chronic-care facilities, and household members of people in high-risk groups. Doctors encourage individuals who travel to areas of the world where influenza viruses circulate to receive the most current vaccine, particularly if they are at higher risk of complications.
It takes the human immune system one to two weeks after vaccination to develop antibodies to the flu antigens. According to the CDC, the best time to get flu shots in the United States is between October 1 and mid-November—sufficiently in advance of the peak of influenza activity, which in the United States generally lasts from late December until early March.
Flu shots must be given annually for two reasons. First, antibody protection provided by the vaccine decreases during the year following vaccination. Second, vaccines created for pre-existing viral strains may not work against new strains; nor does an infection with one flu strain confer immunity to infection by another strain.
VI HISTORIC OUTBREAKS AND PANDEMICS
The 1918 Flu PandemicAn influenza pandemic that began in 1918 affected tens of millions of people worldwide. To deal with the crisis, health officials created emergency facilities, such as this outdoor field hospital, to house patients. Fresh air also was thought to cure the disease.Archive Photos
Evidence suggests that all influenza viruses in mammals, including humans, derived from viruses in wild ducks and other waterfowl. Some of these viruses could have been acquired by humans thousands of years ago. But medical historians know of no clearly identifiable influenza epidemics until large-scale outbreaks occurred in Europe in 1510, 1557, and 1580. The 1580 outbreak also spread into Africa and Asia, making it the first known pandemic. Pandemics have occurred periodically ever since. Major pandemics took place in 1729-1730, 1732-1733, 1781-1782, 1830-1831, 1833, and 1889-1890. The last of these, called the Russian flu because it reached Europe from the east, was the first pandemic for which detailed records are available.
In the 20th century, major pandemics occurred in 1918-1919, 1957-1958, and 1968-1969. The 1918-1919 pandemic was the most destructive in recorded history. It started as World War I (1914-1918) was ending and caused from 20 million to 50 million deaths—two to five times as many deaths as the war itself. When and where the pandemic began is uncertain, but because Spain experienced the first major outbreak, the disease came to be called the Spanish flu. The virus was exceptionally lethal; many of the deaths were among young adults age 20 to 40, a group usually not severely affected by influenza.
Scientists succeeded in reconstructing the 1918 influenza virus in 2005 after finding samples of the virus in the preserved tissues of three people killed by the Spanish flu. The scientists concluded that it was an avian flu virus that spread directly to humans. The virus penetrated deep into human lung tissue, causing a type of pneumonia that was capable of killing the young and healthy.
The 1918 Influenza Pandemic in the United StatesBeginning in September 1918, an unusually deadly influenza pandemic swept across the United States. Twenty percent of those infected died and, unlike influenza infections in the past, this influenza strain targeted healthy adults aged 20 to 40 years. At a time when viruses were still unknown, public health officials stood by helplessly as deadly influenza swept across the country in less than two months, causing terror and panic as the death toll mounted. By the time the disease had run its course in the United States, more than 600,000 Americans had died. Worldwide the 1918-1919 influenza pandemic caused over 20 million deaths in one year, more than twice the number of deaths that occurred in World War I (1914-1918). This interactive illustration shows the swift progression as influenza spread across the United States in 1918. © Microsoft Corporation. All Rights Reserved.
In 1957 a flu outbreak occurred in Guizhou, a province in southwestern China. Within six months, most areas of the world were battling what became known as Asian flu. Before the 1957-1958 pandemic subsided, an estimated 10 to 35 percent of the world’s population had been affected. The overall mortality rate, however, was comparatively low.
About a decade later, a variant of the virus that caused the 1957-1958 pandemic originated in either Guizhou or Yunnan province in southern China. The variant was first isolated and identified in Hong Kong in July 1968. Within a few months, cases of this Hong Kong flu appeared around the world. Hardest hit by the pandemic were children under age 5 and adults aged 45 to 64. In the United States, an estimated 30 million people were infected and there were some 33,000 influenza-related deaths.
No additional pandemics occurred during the 20th century or at the beginning of the 21st century, but public health experts expect that there will be more pandemics in coming years. While scientists do not yet know how to accurately predict flu outbreaks, they have established an international network to track and monitor outbreaks so that health officials can take immediate preventive measures to avoid pandemics. The international network, called FluNet, consists of about 110 influenza centers in more than 80 countries and several World Health Organization (WHO) centers, all linked electronically.
VII INFLUENZA RESEARCH
By the late 1890s and early 1900s, scientists understood that microorganisms caused disease. Most disease research focused on bacteria, which are large enough to be visible under a light microscope and can be isolated using filters (see Filtration). But technology at the time prevented scientists from identifying a disease-causing agent as small as a virus.
In the 1890s German bacteriologist Richard F. J. Pfeiffer reported that he had identified the bacterium Haemophilus influenzae as the cause of influenza. Further investigation indicated, however, that this bacterium was not always present in people with influenza. Scientists concluded that the Haemophilus influenzae bacterium probably played a role in secondary infections.
Meanwhile, the long-held belief that influenza only occurred in humans was overturned. Around 1930 American bacteriologist Richard E. Shope showed that it was possible to transfer an influenza-like disease from one pig to another. Thereafter scientists chiefly used animals in their research on influenza.
In 1933 English physicians Wilson Smith, Christopher H. Andrewes, and Patrick P. Laidlaw removed secretions from the throat of a human flu victim, filtered out a suspect infectious agent, and injected the material into ferrets. The ferrets then developed influenza, thereby demonstrating that the infectious agent caused influenza. Research performed by other researchers eventually proved that the infectious agent was the influenza A virus. The influenza B virus was isolated in 1940, and the influenza C virus in 1950.
In 1941 scientists demonstrated that a vaccine could control influenza. The first vaccine was developed to protect soldiers during World War II (1939-1945). Early influenza vaccines produced from the 1940s to the mid-1960s were all made from killed viruses, which cannot cause infection. But these early vaccines contained impurities that produced fever, headaches, and other severe side effects. Improved pharmaceutical procedures have made today’s vaccines almost free from impurities, greatly reducing the chance that the vaccines will cause side effects.
In 2005 scientists demonstrated for the first time that they could reconstruct a virus from a historic pandemic. Two teams of U.S. government and university scientists, aided by medical researcher Jeffery Taubenberger of the U.S. Armed Forces Institute of Pathology, succeeded in sequencing the entire genetic code of the 1918 influenza virus after obtaining segments of the virus from tissue samples of three of its victims, including an Alaskan woman buried in permafrost.
The scientists injected the reconstructed virus into fertilized bird eggs and found that the eggs died, as would be expected if the virus originated as an avian flu virus rather than a human-based virus. By making the virus’s genetic code publicly available to researchers, the scientists hoped to determine exactly what made the 1918 virus so deadly and so infectious. They also hoped to understand what changes could be made to avian flu viruses to make them less deadly. For example, by replacing one gene in the reconstructed virus, the researchers were able to render it harmless.
Despite these advances, developing influenza vaccines remains a challenge. Current vaccines do not provide 100 percent protection against influenza, and they can be quickly rendered ineffective by changes in the viruses themselves. Some scientists, believing that vaccines will never be able to completely control influenza, work to expand the number and variety of drugs available to treat the disease once symptoms appear. Until a cure for influenza is discovered, public health officials hope that identifying and reporting new viral strains quickly will result in timely actions that prevent the recurrence of deadly pandemics. Even in best-case scenarios, however, influenza is expected to remain a formidable opponent of human health.