*EPF309 12/20/00
Excerpts: National Institutes of Health Information on Influenza
(Agency offers tips on prevention, research) (3850)

The National Institute of Allergies and Infectious Diseases (NIAID), a component of the National Institutes of Health, has issued information for consumers about influenza -- suggesting methods of prevention and treatment, describing the biologic structure of the virus, and how researchers are attempting to learn more about it.

NIAID hosts a Web site focused exclusively on the flu. It can be found at
http://www.niaid.nih.gov/spotlight/flu00/default.htm

Following are excerpts from the NIAID information package on influenza:

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FOCUS ON THE FLU

FACTSHEET

Flu

Influenza, or the flu, is a respiratory infection caused by a variety of flu viruses. The most familiar aspect of the flu is the way it can "knock you off your feet" as it sweeps through entire communities.

The flu differs in several ways from the common cold, a respiratory infection also caused by viruses. For example, people with colds rarely get fevers or headaches or suffer from the extreme exhaustion that flu viruses cause.

The U.S. Centers for Disease Control and Prevention (CDC) estimates that 35 to 50 million Americans come down with the flu during each flu season, which typically lasts from November to March. Children are two to three times more likely than adults to get sick with the flu, and children frequently spread the virus to others. Although most people recover from the illness, CDC estimates that in the United States more than 100,000 people are hospitalized and more than 20,000 people die from the flu and its complications every year.

When and Where Do People Usually Get the Flu?

Flu outbreaks usually begin suddenly and occur mainly in the late fall and winter. The disease spreads through communities creating an epidemic. During the epidemic, the number of cases peaks in about three weeks and subsides after another three or four weeks. Half of the population of a community may be affected. Because schools are an excellent place for flu viruses to attack and spread, families with school-age children have more infections than other families, with an average of one-third of the family members infected each year.

Is the Flu an Important Disease?

Besides the rapid start of the outbreaks and the large numbers of people affected, the flu is an important disease because it can cause serious complications. Most people who get the flu get better within a week (although they may have a lingering cough and tire easily for a while longer). For elderly people, newborn babies, and people with certain chronic illnesses, however, the flu and its complications can be life-threatening.

How is the Flu Transmitted?

You can get the flu if someone around you who has the flu coughs or sneezes. You can get the flu simply by touching a surface like a telephone or door knob that has been contaminated by a touch from someone who has the flu. The viruses can pass through the air and can enter your body through your nose or mouth. If you've touched a contaminated surface, they can pass from your hand to your nose or mouth.

You are at greatest risk of getting infected in highly populated areas, such as in crowded living conditions and in schools.

What are Flu Symptoms?

If you get infected by the flu virus, you will usually feel symptoms one to four days later. You can spread the flu to others before your symptoms start and for another three to four days after your symptoms appear. The symptoms start very quickly and are

-- Headache
-- Chills
-- Dry cough
-- Body aches
-- Fever
-- Stuffy nose
-- Sore throat

Typically, the fever begins to decline on the second or third day of the illness. The flu almost never causes symptoms in the stomach and intestines. The illness that some people often call "stomach flu" is not influenza.

How Does a Doctor Diagnose the Flu?

Usually, doctors or other health care workers diagnose the flu on the basis of whether flu is epidemic in the community and whether the patient's complaints fit the current pattern of symptoms. Doctors rarely use laboratory tests to identify the virus during an epidemic. Health officials, however, monitor certain U.S. health clinics and do laboratory tests to determine which type of flu virus is responsible for the epidemic.

How Can I Keep from Getting the Flu?

Flu Vaccine

The main way to keep from getting the flu is to get a yearly flu vaccine. You can get the vaccine at your doctor's office or a local clinic, and in many communities at workplaces, supermarkets, and drugstores. You must get the vaccine every year because it changes.

Scientists make a different vaccine every year because the strains of flu viruses change from year to year. Nine to 10 months before the flu season begins, they prepare a new vaccine made from inactivated (killed) flu viruses. Because the viruses are killed, they cannot cause infections. The vaccine preparation is based on the strains of the flu viruses that are in circulation at the time. It includes those A and B viruses (see section below on types of flu viruses) expected to circulate the following winter.

Sometimes, an unpredicted new strain may appear after the vaccine has been made and distributed to doctors and clinics. Because of this, even if you do get the flu vaccine, you still may get infected. If you do get infected, however, the disease usually is milder because the vaccine still will give you some protection.

Your immune system takes time to respond to the flu vaccine. Therefore, you should get vaccinated six to eight weeks before flu season begins to prevent getting infected or reduce the severity of flu if you do get it. The vaccine itself cannot cause the flu, but you could become exposed to the virus by someone else and get infected soon after you are vaccinated.

Are there possible side effects from the flu vaccine?

You should be aware that the flu vaccine can cause side effects. The most common side effect in children and adults is soreness at the site of the vaccination. Other side effects, especially in children who previously have not been exposed to the flu virus, include fever, tiredness, and sore muscles. These side effects may begin 6 to 12 hours after vaccination and may last for up to two days.

Viruses for producing the vaccine are grown in chicken eggs and then killed with a chemical so that they can no longer cause an infection. The flu vaccine may contain some egg protein, which can cause an allergic reaction. Therefore, if you are allergic to eggs or have ever had a serious allergic reaction to the flu vaccine, CDC recommends that you consult with your doctor before getting vaccinated. . .

What is the Treatment for the Flu?

Many people treat their flu infections by simply

-- Resting in bed
-- Drinking plenty of fluids
-- Taking over-the-counter medicine such as aspirin or acetaminophen.

You should not give aspirin to children and adolescents who have the flu.

You should not take antibiotics to treat the flu because they do not work on viruses. Antibiotics only work against some infections caused by bacteria.. . .

What are Possible Complications from the Flu?

You can have flu complications if you get a bacterial infection, which causes pneumonia in your weakened lungs. Pneumonia also can be caused by the flu virus itself.

Symptoms of complications will usually appear after you start feeling better. After a brief period of improvement, you may suddenly get

-- High fever
-- Shaking chills
-- Chest pain with each breath
-- Coughing that produces thick, yellow-greenish-colored mucus

Pneumonia can be a very serious and sometimes life-threatening condition. If you have any of these symptoms, you should contact your doctor immediately so that you can get the appropriate treatment.

Are There Other Flu Complications that Only Affect Children?

Reye's syndrome, a condition that affects the nerves, sometimes develops in children and adolescents who are recovering from the flu. Reye's syndrome begins with nausea and vomiting, but the progressive mental changes (such as confusion or delirium) cause the greatest concern.

The syndrome often begins in young people after they take aspirin to get rid of fever or pain. Although very few children develop Reye's syndrome, you should consult a doctor before giving aspirin or products that contain aspirin to children. Acetaminophen does not seem to be associated with Reye's syndrome.

Other complications of the flu that affect children are

-- Convulsions caused by fever
-- Croup
-- Ear infections, such as otitis media

Newborn babies recently out of intensive care units are particularly vulnerable to suffering from flu complications.

Are There Different Types of Flu Viruses?

The first flu virus was identified in the 1930's. Since then, scientists have classified flu viruses into types A, B, and C.

Type A is the most common and usually causes the most serious epidemics. Type B outbreaks also can cause epidemics, but the disease it produces generally is milder than that caused by type A. Type C viruses, on the other hand, never have been connected with a large epidemic.

Flu Pandemics in the 20th Century

If a flu virus emerges that is either new or that has not circulated in many years, and if it is able to spread easily from person to person, it could quickly travel around the world and cause serious illness and death for millions of people. This is called a flu pandemic.

The 1918 Spanish flu pandemic is the catastrophe against which all modern pandemics are measured. More than 20 million people were killed worldwide; 500,000 died in the United States alone. This virus was especially quick to kill. So far, the world has not seen a virus that severe again.

In 1957 and 1968, the Asian flu and Hong Kong flu, respectively, invaded the United States. Although hundreds of thousands of people in the United States died, the death toll for each pandemic was not as high as that for the Spanish flu .

In 1976, the United States experienced a swine flu scare. When a new flu virus was first identified at Fort Dix, New Jersey, it was labeled the "killer flu," and health experts were afraid that it would infect people around the world. In fact, swine flu never left the Fort Dix area. Research on the virus later showed that if it had spread, it would probably have been much less deadly than the Spanish flu.

In 1997, another "near miss" pandemic occurred when 18 people in Hong Kong became ill from a new flu virus. Six of the infected people subsequently died. Usually, flu viruses move first from chickens to pigs, and then from pigs to humans. This virus was different because it moved directly from chickens to people. The avian flu never became a pandemic, however, because it didn't easily spread from person to person. In addition, public health authorities ordered the slaughter of all live chickens in Hong Kong.

What Research is Going On?

Although flu epidemics pop up in the fall and winter seasons in communities throughout the world every year, including the United States, there has not been a pandemic since 1968. Scientists are worried that a new flu virus will emerge in the 21st century and cause a severe pandemic again. For this reason, research institutions and health departments around the world are cooperating to track flu outbreaks in humans and animals, and to determine what types and strains of flu viruses are the causes.

To prevent another flu pandemic and reduce the numbers of flu epidemics, the National Institute of Allergy and Infectious Diseases (NIAID) supports research to find out how influenza viruses work, and to develop better vaccines to prevent and treat influenza virus infections.

For the first time, NIAID-supported researchers have built a flu virus from scratch. They made copies of a live influenza A virus by starting with its individual nucleic acid building blocks. Nucleic acids contain the virus's genetic blueprint. By allowing researchers to manipulate influenza viruses and produce mutations at will, the virus can be engineered to match exactly the strains that may be circulating in the coming season. This research has far-ranging implications for preventing flu and other infectious diseases, for gene therapy, and for understanding the ways flu strains mutate, spread, and cause widespread sickness and death.

Researchers supported by NIAID discovered why some influenza viruses are more deadly than others. They found an unusual molecular mechanism that amplifies the disease-causing power of influenza A virus. This mechanism could be a new marker for scientists to examine when attempting to predict the potential for a newly emergent influenza A virus to cause a pandemic.

In another research study, scientists supported by NIAID found that an investigational flu vaccine sprayed as a fine mist into children's nostrils is highly effective in preventing both the flu and otitis media, a common flu-related ear infection. If doctors give this vaccine to children routinely, the number of flu cases in children could decrease substantially. In addition, if the cases of ear infection with fever are reduced, children would have to take antibiotics less often.

A new NIAID program encourages private companies to get involved in influenza research. Through its Challenge Grants Program, NIAID gave matching funds to companies who were willing to commit their own dollars and resources toward developing new vaccines against several infectious diseases, including the flu.

In one of these studies, Aviron will try to develop a weakened live influenza virus vaccine and will study new ways to produce vaccines against future worldwide outbreaks (pandemics) of the flu. They will also work on a vaccine that can be given as a nasal mist instead of a shot, making it a promising option for widespread use.

Scientists at Aventis Pasteur hope to produce four new vaccines that will shorten the response time needed to produce vaccines against pandemic influenza viruses.

Currently, influenza vaccines are produced by growing the virus in chicken eggs. Egg proteins, however, cause allergic reactions in some people. Moreover, eggs may be in short supply during a pandemic. For these reasons, Novavax is studying ways to produce several influenza vaccines without growing them in eggs.

Where Can I Get More Information About the Flu?

-- National Institute on Aging Information Center 1-800-222-2225 http://www.nih.gov/nia

-- Centers for Disease Control and Prevention (CDC) National Immunization Information Program 1-800-232-2522 http://www.cdc.gov/nip

-- Food and Drug Administration (FDA) HFI-40 Rockville, MD 20857 1-888-INFO-FDA (1-888-463-6332) http://www.fda.gov

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FOCUS ON THE FLU

Flu Fighters: NIAID Research on the Frontier

Many people consider a bout with the flu to be merely uncomfortable or inconvenient, but this winter 20,000 to 40,000 people in the United States will likely die from the flu or its complications. The victims will be mostly children, the elderly, and those with compromised immune systems. Investigators supported by the National Institute of Allergy and Infectious Diseases (NIAID) have recently made important progress in flu research. These "flu fighters," working on the front lines of the battle against this disease, hope to design more effective vaccines and treatments, and to eventually predict and prevent flu outbreaks. . . .

Some background: The influenza virus, which causes the flu, keeps coming back each year because it continually changes; subtle genetic mutations allow new strains of the virus to infect people who would otherwise be immune because of prior infection or vaccination. New influenza strains can even slip past the vaccines painstakingly redesigned each year to combat them. The U.S. economy loses an estimated $1 to $3 billion annually to this illness. Occasionally, the influenza virus undergoes a more dramatic genetic change that causes it to become even more infectious, triggering a global pandemic. Should another major influenza pandemic like the one of 1918 hit the United States, the estimated death toll would be 89,000 to 207,000 people, and the predicted cost to the economy could be as high as $166.5 billion.

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FOCUS ON THE FLU

NIAID Research Highlights: Surveillance

Pandemic Preparedness

Two of the past three major influenza pandemics -- the Asian flu of 1957 and the Hong Kong flu of 1968 -- were caused by new viral strains spreading from birds to humans. That is why Robert Webster, Ph.D., of St. Jude Children's Research Hospital, in conjunction with Kennedy F. Shortridge, Ph.D., at the University of Hong Kong, keep a careful watch on the birds in Hong Kong's poultry market, testing to see how many birds are infected and which viral strains are lurking there. Recent findings are cause for concern, Dr. Webster says.

The researchers found that two potentially dangerous viral lineages are circulating in Hong Kong poultry, infecting 3 to 5 percent of chickens and about 16 percent of quail. Although these strains are not closely related to those that caused past pandemics, they are closely related to strains that have recently infected humans. Both are similar to the H9N2 influenza virus that infected two children (non-fatally) in 1999, and one of the lineages contains several gene segments very similar to those of the H5N1 virus that caused six deaths and spurred the slaughter of 1.3 million chickens in Hong Kong in 1997. Infected chickens rarely show any symptoms when infected with H9N2.

Dr. Webster is concerned because past experience suggests that influenza strains such as these start out infecting aquatic birds, often ducks, and then jump to chickens as an intermediate step on their way to infecting humans. The fact that a significant number of chickens are infected means humans could be next.

Constant viral variations allow certain strains to make the leap to new species. The researchers cannot predict where or when such new strains of influenza might strike, but they hope their work will add to a body of knowledge that may one day help scientists make such predictions and even forestall future outbreaks. They are also working to understand why influenza outbreaks frequently originate in Asia.

Predicting Influenza Virus Evolution

Scientists are constantly striving to stay one step ahead of the influenza virus. Each year the World Health Organization makes predictions about which new strains will be the most virulent, and health officials redesign vaccines accordingly. A new evolution study will help scientists keep their edge over influenza by showing how to predict which viral lineages are likely to give rise to the next successful strains.

University of California at Irvine grantees Walter M. Fitch, Ph.D., Robin M. Bush, Ph.D., and their colleagues at the Centers for Disease Prevention and Control in Atlanta, Georgia, identified a small set of rapidly mutating locations on the virus' hemagglutinin (HA) gene. The researchers determined that the tiny mutations often helped the virus adapt to environmental changes. The HA molecule is a prominent target for antibodies, and Dr. Fitch speculates that the mutations hinder antibodies from recognizing the slightly new versions of hemagglutinin.

By looking back at an 11-year history of flu virus evolution, the researchers established that viral strains undergoing the most mutations to this small set of positions on the HA gene were more likely to foster successful new viral lineages. This information allows them to make predictions about future viral evolution. Their method cannot foretell what the actual genetic makeup of successful new strains will be, and it cannot predict epidemics, but it does allow scientists to make more-informed guesses about likely new strains. "Our model appears to provide a general indication of the way the evolutionary wind is blowing," says Dr. Bush.

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FOCUS ON THE FLU

More Background on the Influenza Virus

Virus Types

There are three types of influenza viruses: A, B, and C. Type A, which includes several subtypes, causes widespread epidemics and global pandemics such as those that occurred in 1918, 1957, and 1968. Type B causes regional epidemics. Type C causes sporadic cases and minor, local outbreaks. These virus types are based on differences in two structural proteins, the nucleoprotein, found in the center of the virus, and the matrix protein, which forms the viral shell.

Virus Structure

A flu virus is roughly spherical, but it can also be elongated or irregularly shaped. Inside the virus, eight segments of single-stranded RNA contain the genetic instructions for making the virus. The most striking feature of the virus is a layer of spikes projecting outward over its surface. There are two different types of spikes: one is composed of the molecule hemagglutinin (HA), the other of neuraminidase (NA). The HA molecule allows the virus to "stick" to a cell, initiating infection. The NA molecule allows newly formed viruses to exit their host cell without sticking to the cell surface or to each other. Because antibodies against HA and NA have traditionally proved the most effective in fighting infection, much research has focused on the structure, function, and genetic variation of those molecules. Researchers are also interested in a second matrix protein, M2, and in a nonstructural protein called NS1; both molecules play important roles in viral infection.

Naming Viral Strains

Type A subtypes are described by a nomenclature system that includes the geographic site of discovery, a lab identification number, the year of discovery, and in parentheses the type of HA and NA it possesses, for example, A/Hong Kong/156/97 (H5N1). If the virus infects non-humans, the host species is included before the geographical site, as in A/Chicken/Hong Kong/G9/97 (H9N2). There are no type B or C subtypes.

Where Influenza Comes From

In nature, the flu virus can often be found in wild aquatic birds such as ducks and shore birds. The virus has persisted in these birds for millions of years, scientists believe, and does them no harm. But because the virus is always mutating in ways that allow it to infect the cells of a different species, it can jump from wild aquatic birds to other birds. Usually, the virus spreads to domestic ducks, and from there moves on to either pigs or chickens before infecting humans. Pigs facilitate transition of the virus from ducks to humans because pig cells have both the receptor molecules on their surfaces used by viruses that infect birds and also the receptors used by viruses that infect humans. So a pig could pick up the influenza virus from a bird, and that virus could mutate in the pig into a form infectious to humans. Recently, the virus has jumped from chickens to humans, and scientists speculate that chickens may also have the receptor used by human-type viruses. When a brand new viral strain reaches humans, individuals don't have immunity and the virus can spread quickly around the globe. This is called a flu pandemic. Pandemics can also be triggered by the reemergence of a viral strain that has not circulated for many years. Epidemics are more localized outbreaks, usually occurring yearly, caused by variants of already circulating strains.

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(Distributed by the Office of International Information Programs, U.S. Department of State. Web site: http://usinfo.state.gov)
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