Influenza

Definition

Usually referred to as the flu or grippe, influenza is a highly infectious respiratory disease. Its name comes from the Italian word for "influence," because people in eighteenth-century Europe thought that the disease was caused by the influence of bad weather. We now know that flu is caused by a virus. When the influenza virus is inhaled, it attacks cells in the upper respiratory tract, causing such typical flu symptoms as fatigue, fever and chills , a hacking cough , and body aches. Although the stomach or intestinal "flu" is commonly blamed for stomach upsets and diarrhea , the influenza virus affects humans less often than is commonly believed.

Description

Influenza is considerably more debilitating than the common cold . Influenza outbreaks occur suddenly, and infection spreads rapidly. The annual death toll attributable to influenza and its complications averages 20,000 in the United States alone. In the 1918-1919 Spanish flu pandemic, the death toll reached a staggering 20–40 million worldwide. Approximately 500,000 of these fatalities occurred in North America.

Influenza outbreaks occur on a regular basis. The most serious outbreaks are pandemics, which affect millions of people worldwide and last for several months. The 1918-19 influenza outbreak serves as the primary example of an influenza pandemic. Pandemics also occurred in 1957 and 1968 with the Asian flu and Hong Kong flu, respectively.

Epidemics are widespread regional outbreaks that occur every two to three years and affect 5–10% of the population. A regional epidemic is shorter lived than a pandemic, lasting only several weeks. Finally, there are smaller outbreaks each winter that are confined to specific locales.

There are three types of influenza viruses, identified as A, B, and C. Influenza A can infect a range of animal species, including humans, pigs, horses, and birds, but only humans are infected by types B and C. Influenza A is responsible for most flu cases, while infection with types B and C virus are less common and cause a milder illness.

In the United States, 90% of all deaths from influenza occur among persons older than 65. Flu-related deaths have increased substantially in the United States since the 1970s, largely because of the aging of the American population. In addition, elderly persons are vulnerable because they are often reluctant to be vaccinated against flu.

A new concern regarding influenza is the possibility that hostile groups or governments could use the virus as an agent of bioterrorism. A report published in early 2003 noted that Type A influenza virus has a high potential for use as such an agent because of the virulence of the Type A strain that broke out in Hong Kong in 1997 and the development of laboratory methods for generating large quantities of the virus. The report recommended the stockpiling of present antiviral drugs and speeding up the development of new ones.

Causes & symptoms

Approximately one to four days after infection with the influenza virus, the victim develops an array of symptoms. Symptoms are usually sudden, although the sequence can be quite variable. They include the onset of headache, sore throat , dry cough, and chills, nasal congestion, fatigue, malaise, overall achiness and a fever that may run as high as 104°F (40°C). Flu victims feel extremely tired and weak, and may not return to their normal energy levels for several days or weeks.

Influenza complications usually arise from bacterial infections of the lower respiratory tract. Signs of a secondary respiratory infection often appear just as the patient seems to be recovering. These signs include high fever, intense chills, chest pains associated with breathing, and a productive cough or sinus discharge with thick yellowish-green sputum. If these symptoms appear, medical treatment is often necessary. Other secondary infections, such as sinus or ear infections, may also require medical intervention. Heart and lung problems and other chronic diseases, can be aggravated by influenza, which is a particular concern with elderly patients.

With children and teenagers, it is advisable to be alert for symptoms of Reye's syndrome, a rare but serious complication that occurs when children are given aspirin. Symptoms of Reye's syndrome are nausea and vomiting ,

and more seriously, such neurological problems as confusion or delirium. The syndrome is primarily associated with the use of aspirin to relieve flu symptoms in children.

Diagnosis

Although there are specific laboratory tests to identify the flu virus strain from respiratory samples, doctors typically rely on a set of symptoms and the presence of influenza in the community for diagnosis. Specific tests are useful to determine the type of flu in the community, but they do little for individual treatment. Doctors may administer such tests as throat or sinus cultures or blood tests to identify secondary infections.

Since 1999, however, seven rapid diagnostic tests for flu have become commercially available. These tests appear to be especially useful in diagnosing flu in children, allowing doctors to make more accurate treatment decisions in less time.

Treatment

The patient should drink plenty of fluids and eat nutritious foods. Chicken soup with ginger , scallions, and rice noodles is nutritious and has healing powers. Rest, to allow the body to fight infection, is very important. Gargling with salt water (half teaspoon salt in one cup of water) helps to soothe a sore throat. A vaporizer with eucalyptus or Vicks VapoRub will make the patient feel more comfortable by easing breathing and aiding sleep. Applying Vicks ointment over chest and back will assist and speed recovery. Returning to normal activities too quickly invites a possible relapse or complications.

Herbals

Herbal teas and other preparations can be taken to stimulate the immune system, for antiviral activity, and to relieve symptoms. The following herbs are used to treat influenza:

• Ginger (Zingiber officinalis ) reduces fever and pain , has a sedative effect, settles the stomach, and suppresses cough.
• Forsythia (Forsythia suspensa ) fruit can be taken as a tea for its anti-inflammatory, fever-reducing, and antimicrobial properties.
• Honeysuckle (Lonicera japonica ) flower can be taken as a tea for its anti-inflammatory, fever-reducing, and antimicrobial properties.
• Anise seed (Pimpinella anisum ) can be added to tea to expel phlegm, induce sweating, ease nausea, and ease stomach gas.
• Slippery elm (Ulmus rubra ) can be taken as a tea or slurry to soothe sore throat and ease cough.
• Echinacea (Echinacea purpurea or angustifolia ), in clinical studies, reduced flu symptoms including sore throat, chills, sweating, fatigue, weakness, body aches, and headaches. The usual dosage is 500 mg thrice on the first day, then 250 mg four times daily thereafter.
• Goldenseal (Hydrastis canadensis ) has fever reducing, antibacterial, anti-inflammatory, and antitussive properties. The usual dose is 125 mg three to four times daily. Goldenseal shouldn't be taken for more than one week.
• Astragalus (Astragalus membranaceus ) boosts the immune system and improves the body's response to stress . The common dose is 250 mg of extract four times daily.
• Cordyceps (Cordyceps sinensis ) modulates and boosts the immune system and improves respiration. The usual dose is 500 mg two to three times daily.
• Elder (Sambucus nigra ) has antiviral activity, increases sweating, decreases inflammation, and decreases nasal discharge. In a study, elderberry extract reduced flu symptoms within two days whereas placebo took six days. The usual dose is 500 mg of extract thrice daily. Also use 2 tsp of dried flowers in 1 cup of water as a tea.
• Schisandra (Schisandra chinensis ) helps the body fight disease and increases endurance.
• Grape (Vitis vinifera ) seed extract has antihistamine and anti-inflammatory properties. The usual dose is 50 mg three times daily.
• Eucalyptus (Eucalyptus globulus ) or peppermint (Mentha piperita ) essential oils added to a steam vaporizer may help clear chest and nasal congestion.
• Boneset infusion (Eupatorium perfoliatum ) relieves aches and fever.
• Yarrow (Achillea millefolium ) relieves chills.

Other remedies

Acupuncture and acupressure are said to stimulate natural resistance, relieve nasal congestion and headaches, fight fever, and calm coughs, depending on the points used.

A homeopathic remedy called Oscillococcinum may be taken at the first sign of flu symptoms and repeated for a day or two. This remedy is said to shorten the duration of flu by one or two days. Although oscillococcinum is a popular flu remedy in Europe, however, a research study published in 2003 found it to be ineffective.

Other homeopathic remedies recommended vary according to the specific flu symptoms present. Gelsemium (Gelsemium sempervirens ) is recommended to combat weakness accompanied by chills, a headache, and nasal congestion. Bryonia (Bryonia alba ) may be used to treat muscle aches, headaches, and a dry cough. For restlessness, chills, hoarseness, and achy joints, poison ivy (Rhus toxicodendron ) is recommended. Finally, for achiness and a dry cough or chills, Eupatorium perfoliatum is suggested.

Hydrotherapy can be utilized. A bath to induce a fever will speed recovery from the flu. While supervised, the patient should take a bath as hot as he/she can tolerate and remain in the bath for 20–30 minutes. While in the bath, the patient drinks a cup of yarrow or elder-flower tea to induce sweating. During the bath, a cold cloth is held on the forehead or at the nape of the neck to keep the temperature down. The patient is assisted when getting out of the bath (he/she may feel weak or dizzy) and then gets into bed and covers up with layers of blankets to induce more sweating.

Supplemental vitamins are recommended for treating influenza, and include 500–2000 mg vitamin C , 400 IU to 500 IU of vitamin E , 200 micrograms to 300 micrograms selenium , and 25,000 IU beta-carotene. Zinc lozenges are helpful, as is supplemental zinc at 25 mg per day for two weeks or more.

Traditional Chinese medicine (TCM) uses mixtures of herbs to prevent flu as well as to relieve symptoms once a person has fallen ill. There are several different recipes for these remedies, but most contain ginger and Japanese honeysuckle in addition to other ingredients.

Allopathic treatment

Because influenza is a viral infection, antibiotics are useless in treating it. However, antibiotics are frequently used to treat secondary infections.

Over-the-counter medications are used to treat flu symptoms. Any medication that is designed to relieve such symptoms as pain and coughing will provide some relief. The best medicine for symptoms is an analgesic, such as aspirin, acetaminophen, or naproxen. Without a doctor's approval, aspirin is generally not recommended for people under 18 owing to its association with Reye's syndrome, a rare aspirin-associated complication seen in children recovering from viral infections. Children should receive acetaminophen or ibuprofen to treat their symptoms.

There are four antiviral drugs marketed for treating influenza as of 2003. To be effective, treatment should begin no later than two days after symptoms appear. Antivirals may be useful in treating patients who have weakened immune systems or who are at risk for developing serious complications. They include amantadine (Symmetrel, Symadine) and rimantadine (Flumandine), which work against Type A influenza; and zanamavir (Relenza) and oseltamavir phosphate (Tamiflu), which work against both Types A and B influenza. Amantadine and rimantadine can cause such side effects as nervousness, anxiety , lightheadedness, and nausea. Severe side effects include seizures, delirium, and hallucination, but are rare and are nearly always limited to people who have kidney problems, seizure disorders, or psychiatric disorders. The new drugs zanamavir and oseltamavir phosphate have few side effects but can cause dizziness , jitters, and insomnia .

Expected results

Following proper treatment guidelines, healthy people under the age of 65 usually suffer no long-term consequences associated with flu infection. The elderly and the chronically ill are at greater risk for secondary infection and other complications, but they can also enjoy a complete recovery.

Most people recover fully from an influenza infection, but it should not be viewed complacently. Influenza is a serious disease, and approximately 1 in 1,000 cases proves fatal.

Prevention

The Centers for Disease Control and Prevention recommend that people get an influenza vaccine injection each year before flu season starts. In the United States, flu season typically runs from late December to early March. Vaccines should be received two to six weeks prior to the onset of flu season to allow the body enough time to establish immunity.

Each season's flu vaccine contains three virus strains that are the most likely to be encountered in the coming flu season. The virus strains used to make the vaccine are inactivated and will not cause illness. When there is a good match between the anticipated flu strains and the strains used in the vaccine, the vaccine is 70-90% effective in people under 65. Because immune response diminishes somewhat with age, people over 65 may not receive the same level of protection from the vaccine, but even if they do contract the flu, the vaccine diminishes the severity and helps prevent complications.

It should be noted that certain people should not receive an influenza vaccine. Infants six months and younger have immature immune systems and will not benefit from the vaccine. Because the vaccines are prepared using hen eggs, people who have severe allergies to eggs or other vaccine components should not receive the influenza vaccine. Some persons may receive a course of amantadine or rimantadine, which are 70-90% effective in preventing influenza.

Certain groups are strongly advised to be vaccinated because they are at greater risk for influenza-related complications:

• All people 65 years and older.
• Residents of nursing homes and chronic-care facilities.
• Adults and children who have chronic heart or lung problems.
• Adults and children who have chronic metabolic diseases, such as diabetes and renal dysfunction, as well as severe anemia or inherited hemoglobin disorders.
• Children and teenagers who are on long-term aspirin therapy.
• Anyone who is immunocompromised, including HIV-infected persons, cancer patients, organ transplant recipients, and patients receiving steroids, chemotherapy, or radiation therapy.
• Anyone in contact with the above groups, such as teachers, care givers, health-care personnel, and family members.
• Travelers to foreign countries.

As of early 2003, researchers are working on developing an intranasal flu vaccine in aerosol form. An aerosol vaccine using a weakened form of Type A influenza virus has been tested in pilot studies and awaits further clinical trials.

The following dietary supplements may be taken to help prevent influenza:

• Elderberry prevents influenza virus from infecting cells.
• Astragalus: 250–500 mg daily.
• Multivitamins with zinc.
• Vitamin C; 500 mg.
• Echinacea; at the first sign of malaise or infection, take 3–5 ml of tincture or 2 tablets three or four times daily for three to 10 days.

Resources

BOOKS

Pelletier, Kenneth R., MD. The Best Alternative Medicine, Part II, "CAM Therapies for Specific Conditions: Colds/Flu." New York: Simon & Schuster, 2002.

"Respiratory Viral Diseases: Influenza." Section 13, Chapter 162 in The Merck Manual of Diagnosis and Therapy, edited by Mark H. Beers, MD, and Robert Berkow, MD. Whitehouse Station, NJ: Merck Research Laboratories, 1999.

PERIODICALS

Elkins, Rita. "Combat Colds and Flu." Let's Live. 68 (January 2000): 81+.

Jonas, W. B., T. J. Kaptchuk, and K. Linde. "A Critical Overview of Homeopathy." Annals of Internal Medicine 138 (March 4, 2003): 393–399.

Krug, R. M. "The Potential Use of Influenza Virus as an Agent for Bioterrorism." Antiviral Research 57 (January 2003): 147–150.

La Valle, James B., and Ernie Hawkins. "Colds and Flu: A Natural Approach." Drug Store News. 20 (12/14/98): CP17+.

Oxford, J. S., S. Bossuyt, S. Balasingam, et al. "Treatment of Epidemic and Pandemic Influenza with Neuraminidase and M2 Proton Channel Inhibitors." Clinical Microbiology and Infection 9 (January 2003): 1–14.

Roth, Y., J. S. Chapnik, and P. Cole. "Feasibility of Aerosol Vaccination in Humans." Annals of Otology, Rhinology, and Laryngology 112 (March 2003): 264–270.

Shortridge, K. F., J. S. Peiris, and Y. Guan. "The Next Influenza Pandemic: Lessons from Hong Kong." Journal of Applied Microbiology 94 (2003 Supplement): 70S–79S.

Storch, G. A. "Rapid Diagnostic Tests for Influenza." Current Opinion in Pediatrics 15 (February 2003): 77–84.

Thompson, W. W., D. K. Shay, E. Weintraub, et al. "Mortality Associated with Influenza and Respiratory Syncytial Virus in the United States." Journal of the American Medical Association 289 (January 8, 2003): 179–186.

ORGANIZATIONS

Centers for Disease Control and Prevention. 1600 Clifton Road, NE, Atlanta, Georgia 30333. (888) CDC-FACTS (888-232-3228). <http://www.cdc.gov/>.

National Institute of Allergy and Infectious Diseases (NIAID). 31 Center Drive, MSC 2520, Bethesda, MD 20892-2520. <http://www.niaid.nih.gov>.

OTHER

NIAID Fact Sheet: Flu. Bethesda, MD: NIAID, January 2003. <http://www.niaid.nih.gov/factsheets/flu.htm>.

Belinda Rowland

Rebecca J. Frey, PhD

Influenza

Definition

Usually referred to as the flu or grippe, influenza is a highly infectious respiratory disease. The disease is caused by certain strains of the influenza virus. When the virus is inhaled, it attacks cells in the upper respiratory tract, causing typical flu symptoms such as fatigue, fever and chills, a hacking cough, and body aches. Influenza victims are also susceptible to potentially life-threatening secondary infections. Although the stomach or intestinal "flu" is commonly blamed for stomach upsets and diarrhea, the influenza virus rarely causes gastrointestinal symptoms. Such symptoms are most likely due to other organisms such as rotavirus, Salmonella, Shigella, or Escherichia coli.

Description

The flu is considerably more debilitating than the common cold. Influenza outbreaks occur suddenly, and infection spreads rapidly. The annual death toll attributable to influenza and its complications averages 20,000 in the United States alone. In the 1918–1919 Spanish flu pandemic, the death toll reached a staggering 20-40 million worldwide. Approximately 500,000 of these fatalities occurred in America.

Influenza outbreaks occur on a regular basis. The most serious outbreaks are pandemics, which affect millions of people worldwide and last for several months. The 1918–1919 influenza outbreak serves as the primary example of an influenza pandemic. Pandemics also occurred in 1957 and 1968 with the Asian flu and Hong Kong flu, respectively. The Asian flu was responsible for 70,000 deaths in the United States, while the Hong Kong flu killed 34,000.

Epidemics are widespread regional outbreaks that occur every two to three years and affect 5-10% of the population. The Russian flu in the winter of 1977 is an example of an epidemic. A regional epidemic is shorter lived than a pandemic, lasting only several weeks. Finally, there are smaller outbreaks each winter that are confined to specific locales.

The earliest existing descriptions of influenza were written nearly 2500 years ago by the ancient Greek physician Hippocrates. Historically, influenza was ascribed to a number of different agents, including "bad air" and several different bacteria. In fact, its name comes from the Italian word for "influence," because people in eighteenth-century Europe thought that the disease was caused by the influence of bad weather. It was not until 1933 that the causative agent was identified as a virus.

There are three types of influenza viruses, identified as A, B, and C. Influenza A can infect a range of animal species, including humans, pigs, horses, and birds, but only humans are infected by types B and C. Influenza A is responsible for most flu cases, while infection with types B and C virus are less common and cause a milder illness.

In the United States, 90% of all deaths from influenza occur among persons older than 65. Flu-related deaths have increased substantially in the United States since the 1970s, largely because of the aging of the American population. In addition, elderly persons are vulnerable because they are often reluctant to be vaccinated against flu.

A new concern regarding influenza is the possibility that hostile groups or governments could use the virus as an agent of bioterrorism. A report published in early 2003 noted that Type A influenza virus has a high potential for use as such an agent because of the virulence of the Type A strain that broke out in Hong Kong in 1997 and the development of laboratory methods for generating large quantities of the virus. The report recommended the stockpiling of present antiviral drugs and speeding up the development of new ones.

Causes and symptoms

Approximately one to four days after infection with the influenza virus, the victim is hit with an array of symptoms. "Hit" is an appropriate term, because symptoms are sudden, harsh, and unmistakable. Typical influenza symptoms include the abrupt onset of a headache, dry cough, and chills, rapidly followed by overall achiness and a fever that may run as high as 104°F (40°C). As the fever subsides, nasal congestion and a sore throat become noticeable. Flu victims feel extremely tired and weak and may not return to their normal energy levels for several days or even a couple of weeks.

Influenza complications usually arise from bacterial infections of the lower respiratory tract. Signs of a secondary respiratory infection often appear just as the victim seems to be recovering. These signs include high fever, intense chills, chest pains associated with breathing, and a productive cough with thick yellowish green sputum. If these symptoms appear, medical treatment is necessary. Other secondary infections, such as sinus or ear infections, may also require medical intervention. Heart and lung problems, and other chronic diseases, can be aggravated by influenza, which is a particular concern with elderly patients.

With children and teenagers, it is advisable to be alert for symptoms of Reye's syndrome, a rare, but serious complication. Symptoms of Reye's syndrome are nausea and vomiting, and more seriously, neurological problems such as confusion or delirium. The syndrome has been associated with the use of aspirin to relieve flu symptoms.

Diagnosis

Although there are specific tests to identify the flu virus strain from respiratory samples, doctors typically rely on a set of symptoms and the presence of influenza in the community for diagnosis. Specific tests are useful to determine the type of flu in the community, but they do little for individual treatment. Doctors may administer tests, such as throat cultures, to identify secondary infections.

Since 1999, however, seven rapid diagnostic tests for flu have become commercially available. These tests appear to be especially useful in diagnosing flu in children, allowing doctors to make more accurate treatment decisions in less time.

Treatment

Essentially, a bout of influenza must be allowed to run its course. Symptoms can be relieved with bed rest and by keeping well hydrated. A steam vaporizer may make breathing easier, and pain relievers will take care of the aches and pain. Food may not seem very appetizing, but an effort should be made to consume nourishing food. Recovery should not be pushed too rapidly. Returning to normal activities too quickly invites a possible relapse or complications.

Drugs

Since influenza is a viral infection, antibiotics are useless in treating it. However, antibiotics are frequently used to treat secondary infections.

Over-the-counter medications are used to treat flu symptoms, but it is not necessary to purchase a medication marketed specifically for flu symptoms. Any medication that is designed to relieve symptoms, such as pain and coughing, will provide some relief. Medications containing alcohol, however, should be avoided because of the dehydrating effects of alcohol. The best medicine for symptoms is simply an analgesic, such as aspirin, acetaminophen, or naproxen. Without a doctor's approval, aspirin is generally not recommended for people under 18 owing to its association with Reye's syndrome, a rare aspirin-associated complication seen in children recovering from the flu. To be on the safe side, children should receive acetaminophen or ibuprofen to treat their symptoms.

There are four antiviral drugs marketed for treating influenza as of 2003. To be effective, treatment should begin no later than two days after symptoms appear. Antivirals may be useful in treating patients who have weakened immune systems or who are at risk for developing serious complications. They include amantadine (Symmetrel, Symadine) and rimantadine (Flumandine), which work against Type A influenza, and zanamavir (Relenza) and oseltamavir phosphate (Tamiflu), which work against both Types A and B influenza. Amantadine and rimantadine can cause side effects such as nervousness, anxiety, lightheadedness, and nausea. Severe side effects include seizures, delirium, and hallucination, but are rare and are nearly always limited to people who have kidney problems, seizure disorders, or psychiatric disorders. The new drugs zanamavir and oseltamavir phosphate have few side effects but can cause dizziness, jitters, and insomnia.

Alternative treatments

There are several alternative treatments that may help in fighting off the virus and recovering from the flu, in addition to easing flu symptoms.

• Acupuncture and acupressure. Both are said to stimulate natural resistance, relieve nasal congestion and headaches, fight fever, and calm coughs, depending on the acupuncture and acupressure points used.
• Aromatherapy. Aromatherapists recommend gargling daily with one drop each of the essential oils of tea tree (Melaleuca spp.) and lemon mixed in a glass of warm water. If already suffering from the flu, two drops of tea tree oil in a hot bath may help ease the symptoms. Essential oils of eucalyptus (Eucalyptus globulus ) or peppermint (Mentha piperita ) added to a steam vaporizer may help clear chest and nasal congestion.
• Herbal remedies. Herbal remedies can be used stimulate the immune system (echinacea ), as antivirals (Hydrastis canadensis ) goldenseal and garlic (Allium sativum ), or directed at whatever symptoms arise as a result of the flu. For example, an infusion of boneset (Eupatroium perfoliatum ) may counteract aches and fever, and yarrow (Achillea millefolium ) or elderflower tinctures may combat chills.
• Homeopathy. To prevent flu, a homeopathic remedy called Oscillococcinum may be taken at the first sign of flu symptoms and repeated for a day or two. Although oscillococcinum is a popular flu remedy in Europe, however, a research study published in 2003 found it to be ineffective. Other homeopathic remedies recommended vary according to the specific flu symptoms present. Gelsemium (Gelsemium sempervirens) is recommended to combat weakness accompanied by chills, a headache, and nasal congestion. Bryonia (Bryonia alba) may be used to treat muscle aches, headaches, and a dry cough. For restlessness, chills, hoarseness, and achy joints, poison ivy (Rhus toxicodendron ) is recommended. Finally, for achiness and a dry cough or chills, Eupatorium perfoliatum is suggested.
• Hydrotherapy. A bath to induce a fever will speed recovery from the flu by creating an environment in the body where the flu virus cannot survive. The patient should take a bath as hot as he/she can tolerate and remain in the bath for 20-30 minutes. While in the bath, the patient drinks a cup of yarrow or elderflower tea to induce sweating. During the bath, a cold cloth is held on the forehead or at the nape of the neck to keep the temperature down in the brain. The patient is assisted when getting out of the bath (he/she may feel weak or dizzy) and then gets into bed and covers up with layers of blankets to induce more sweating.
• Traditional Chinese medicine (TCM). Practitioners of TCM recommend mixtures of herbs to prevent flu as well as to relieve symptoms once a person has fallen ill. There are several different recipes for these remedies, but most contain ginger and Japanese honeysuckle in addition to other ingredients.
• Vitamins. For adults, 2-3 grams of vitamin C daily may help prevent the flu. Increasing the dose to 5-7 grams per day during the flu can felp fight the infection. (The dose should be reduced if diarrhea develops.)

Prognosis

Following proper treatment guidelines, healthy people under the age of 65 usually suffer no long-term consequences associated with flu infection. The elderly and the chronically ill are at greater risk for secondary infection and other complications, but they can also enjoy a complete recovery.

Most people recover fully from an influenza infection, but it should not be viewed complacently. Influenza is a serious disease, and approximately 1 in 1,000 cases proves fatal.

Prevention

The Centers for Disease Control and Prevention recommend that people get an influenza vaccine injection each year before flu season starts. In the United States, flu season typically runs from late December to early March. Vaccines should be received two to six weeks prior to the onset of flu season to allow the body enough time to establish immunity. Adults only need one dose of the yearly vaccine, but children under nine years of age who have not previously been immunized should receive two doses with a month between each dose.

Each season's flu vaccine contains three virus strains that are the most likely to be encountered in the coming flu season. When there is a good match between the anticipated flu strains and the strains used in the vaccine, the vaccine is 70-90% effective in people under 65. Because immune response diminishes somewhat with age, people over 65 may not receive the same level of protection from the vaccine, but even if they do contract the flu, the vaccine diminishes the severity and helps prevent complications.

The virus strains used to make the vaccine are inactivated and will not cause the flu. In the past, flu symptoms were associated with vaccine preparations that were not as highly purified as modern vaccines, not to the virus itself. In 1976, there was a slightly increased risk of developing Guillain-Barré syndrome, a very rare disorder, associated with the swine flu vaccine. This association occurred only with the 1976 swine flu vaccine preparation and has never recurred.

Serious side effects with modern vaccines are extremely unusual. Some people experience a slight soreness at the point of injection, which resolves within a day or two. People who have never been exposed to influenza, particularly children, may experience one to two days of a slight fever, tiredness, and muscle aches. These symptoms start within 6-12 hours after the vaccination.

It should be noted that certain people should not receive an influenza vaccine. Infants six months and younger have immature immune systems and will not benefit from the vaccine. Since the vaccines are prepared using hen eggs, people who have severe allergies to eggs or other vaccine components should not receive the influenza vaccine. As an alternative, they may receive a course of amantadine or rimantadine, which are also used as a protective measure against influenza. Other people who might receive these drugs are those that have been immunized after the flu season has started or who are immunocompromised, such as people with advanced HIV disease. Amantadine and rimantadine are 70-90% effective in preventing influenza.

Certain groups are strongly advised to be vaccinated because they are at increased risk for influenza-related complications:

• All people 65 years and older
• Residents of nursing homes and chronic-care facilities, regardless of age
• Adults and children who have chronic heart or lung problems, such as asthma
• Adults and children who have chronic metabolic diseases, such as diabetes and renal dysfunction, as well as severe anemia or inherited hemoglobin disorders
• Children and teenagers who are on long-term aspirin therapy

• Women who will be in their second or third trimester during flu season or women who are nursing
• Anyone who is immunocompromised, including HIV-infected persons, cancer patients, organ transplant recipients, and patients receiving steroids, chemotherapy, or radiation therapy
• Anyone in contact with the above groups, such as teachers, care givers, health-care personnel, and family members
• Travelers to foreign countries.

A person need not be in one of the at-risk categories listed above, however, to receive a flu vaccination. Anyone who wants to forego the discomfort and inconvenience of an influenza attack may receive the vaccine.

As of early 2003, researchers are working on developing an intranasal flu vaccine in aerosol form. An aerosol vaccine using a weakened form of Type A influenza virus has been tested in pilot studies and awaits further clinical trials.

Resources

BOOKS

Beers, Mark H., MD, and Robert Berkow, MD, editors. "Respiratory Viral Diseases: Influenza." Section 13, Chapter 162. In The Merck Manual of Diagnosis and Therapy. Whitehouse Station, NJ: Merck Research Laboratories, 2004.

Pelletier, Kenneth R., MD. The Best Alternative Medicine, Part II. "CAM Therapies for Specific Conditions: Colds/Flu." New York: Simon & Schuster, 2002.

PERIODICALS

Elkins, Rita. "Combat Colds and Flu." Let's Live. 68 (January 2000): 81+.

Jonas, W. B., T. J. Kaptchuk, and K. Linde. "A Critical Overview of Homeopathy." Annals of Internal Medicine 138 (March 4, 2003): 393-399.

Krug, R. M. "The Potential Use of Influenza Virus as an Agent for Bioterrorism." Antiviral Research 57 (January 2003): 147-150.

Oxford, J. S., S. Bossuyt, S. Balasingam, et al. "Treatment of Epidemic and Pandemic Influenza with Neuraminidase and M2 Proton Channel Inhibitors." Clinical Microbiology and Infection 9 (January 2003): 1-14.

Roth, Y., J. S. Chapnik, and P. Cole. "Feasibility of Aerosol Vaccination in Humans." Annals of Otology, Rhinology, and Laryngology 112 (March 2003): 264-270.

Shortridge, K. F., J. S. Peiris, and Y. Guan. "The Next Influenza Pandemic: Lessons from Hong Kong." Journal of Applied Microbiology 94, Supplement (2003): 70S-79S.

Storch, G. A. "Rapid Diagnostic Tests for Influenza." Current Opinion in Pediatrics 15 (February 2003): 77-84.

Thompson, W. W., D. K. Shay, E. Weintraub, et al. "Mortality Associated with Influenza and Respiratory Syncytial Virus in the United States." Journal of the American Medical Association 289 (January 8, 2003): 179-186.

ORGANIZATIONS

Centers for Disease Control and Prevention. 1600 Clifton Rd., NE, Atlanta, GA 30333. (800) 311-3435, (404) 639-3311. 〈http://www.cdc.gov〉.

National Institute of Allergy and Infectious Diseases (NIAID). 31 Center Drive, MSC 2520, Bethesda, MD 20892-2520. 〈http://www.niaid.nih.gov〉.

OTHER

NIAID Fact Sheet: Flu. Bethesda, MD: NIAID, January 2003. 〈http://www.niaid.nih.gov/factsheets/flu.htm〉.

KEY TERMS

Bioterrorism— The intentional use of disease-causing microbes or other biologic agents to intimidate or terrorize a civilian population for political or military reasons. Type A influenza virus could be used as an agent of bioterrorism.

Common cold— A mild illness caused by a upper respiratory viruses. Usual symptoms include nasal congestion, coughing, sneezing, throat irritation, and a low-grade fever.

Epidemic— A widespread regional disease outbreak.

Guillain-Barré syndrome— Also called acute idiopathic polyneuritis, this condition is a neurologic syndrome that can cause numbness in the limbs and muscle weakness following certain viral infections.

Pandemic— Worldwide outbreak of an infection, afflicting millions of victims.

INFLUENZA

Influenza is a potentially severe acute respiratory illness caused by various strains of the influenza virus. The different strains all produce characteristic symptoms, and because major outbreaks are associated with increased mortality, occurrences can be identified in history. Outbreaks consistent with influenza can be traced back at least to the court of Elizabeth I. Some have speculated that the Plague of Athens described by Thucydides was influenza complicated by bacterial superinfection. The influenza syndrome, commonly known as the flu, with its fever, cough, rapid onset and body aches, is not only typical enough to be recognized in the past, but it also allows physicians to recognize it, especially when it is known that the virus is circulating. Unfortunately, death is the other consistent phenomena associated with influenza. Mortality statistics are the principal way the intensity of an influenza outbreak is quantified, and are so characteristic that viral identification of etiology is not required.

THE VIRUS AND ITS ANTIGENS

The influenza viruses contain RNA (ribonucleic acid) and are somewhat unusual in that they have a segmented genome, which means that there are eight distinct segments to the single-stranded RNA. Influenza types A and B are the only strains with epidemic potential; type C viruses are difficult to work with in the laboratory and are one of the multiple agents able to cause the common cold. While the viruses are classified into type A and B on the basis of their internal components, it is the surface antigens that are important in eliciting antibodies that will protect against future infection. These surface antigens and their changes make influenza challenging to control. Two types of changes are recognized.

One change occurs in both type A and B viruses and is a result of point mutations in the segments of the genome coding for two specific surface antigens (the neuraminidase [N] and the hemagglutinin [H] segments). These mutations are the reason that both type A and B viruses change regularly from year to year, though type A changes somewhat more rapidly than type B. Such changes are referred to as "antigen drift." Another change is more dramatic, only occurring with type A viruses, and is an example of "antigen shift." It takes place when one or two gene segments are replaced in a circulating virus. The same two antigens, or proteins, are involved in both types of change. The various influenza A viruses are categorized into subtypes by the differences in those two antigens, such as A (H₁N₁) or A (H₃N₂).

The most widely accepted theory explaining this antigen shift is that the segments come from animal influenza viruses. Type B influenza is confined to humans, while type A exists in numerous species of birds and domestic animals. There are fifteen types of hemagglutinin in the influenza virus of birds, but only three in human viruses, which gives an ample opportunity for the segment coding for the hemagglutinin to move from avian viruses to human. This has apparently happened in the past, and is likely to occur in the future, either directly or through pigs. In 1997, in Hong Kong, an avian virus infected humans directly, but did not become adapted to humans by exchange of gene segments. If it had, a pandemic undoubtedly would have resulted.

PANDEMICS: HISTORY AND IMPACT

While some trace influenza pandemics back to ancient Greece, the first documented occurrence was in 1889 (see Table 1). In that and subsequent years, outbreaks of influenza were reported in many areas of the world, and in the United States, deaths reported in the state of Massachusetts for the first time demonstrated the U- or J-shaped mortality curve—an elevated mortality in young children, low mortality until age forty-five, followed by gradually increasing mortality with a relatively sharp inflection upward at age sixty-five (see Figure 1). By testing blood specimens of persons who lived through this period, researchers have been able to hypothesize about the strain of virus that caused this pandemic. In 1899, there was an apparent antigen shift, but this was determined serologically, not on the basis of an observed pandemic.

It is now certain that a virus resembling one isolated from pigs in the 1930s caused the devastating 1918 pandemic. No influenza viruses were isolated until the 1930s, so that any identification of viruses responsible for events occurring before that time has traditionally been done by testing the blood of people living through the period of an outbreak. Confirmation of this approach has recently taken place using modern molecular technique involving tissue of individuals who died during the 1918 pandemic. The virus is now termed A(H₁N₁). The estimated death toll from this pandemic has been revised upwards from 20 million to 40 million, since large segments of the world— mainly the current developing countries—were originally omitted from the counts. The lethality of this pandemic was related in large part to the death of an unexpectedly large number of healthy

Table 1

young adults. This resulted in a W-shaped agespecific mortality curve (see Figure 1). It is hoped that genetic research with lung tissue, either stored or recovered from bodies, will enable epidemiologists to predict the potential behavior of future pandemic strains of influenza when they are identified. However, this has not as yet been possible, so it is only by observing the epidemiology of infection that the age-specific pattern of illness can be determined.

The first influenza viruses were isolated from humans in the early 1930s. However, the next pandemic did not occur until 1957, when the A(H₂N₂) virus appeared in South China (see Figure 1). The pandemic that resulted was the most severe since 1918, but again exhibited the more typical U-shaped mortality curve, concentrated in very young children and older individuals. A little more than ten years later, in 1968, the hemagglutinin changed and the resulting pandemic was similar to 1957 in age distribution, but more moderate in overall impact.

Two more episodes have occurred since 1968 that had the potential to be full pandemics. In 1977, the A(H₁N₁) virus returned, with outbreaks occurring first in China and then in the former Soviet Union. Since the virus had circulated twenty or more years before, when worldwide outbreaks occurred, these epidemics were confined to younger individuals. This virus has continued to circulate, along with the A(H₃N₂) and B viruses. Finally, in 1997, A(H₅N₁) moved from chickens to humans in Hong Kong. There were eighteen confirmed cases, with six deaths that were not restricted to older individuals. Fortunately, this avian virus did not

Figure 1

become fully adapted to humans. No human-to-human transmission was observed, but this episode showed how a catastrophic pandemic might have occurred had such adaptation taken place.

PREVENTION AND CONTROL OF INFLUENZA

A vaccine for the prevention of influenza was developed during World War II in order to maintain military readiness. This was done in recognition of the high morbidity that could result among troops exposed to the virus. A similar inactivated vaccine is still in use, improved in both potency and lack of side effects. It is known to be 70 to 90 percent efficacious in healthy young adults as long as the vaccine viruses resemble those circulating. This necessitates updating the viruses in the vaccine each year. For this and other reasons, the vaccine must be given annually. Since vaccination programs must be sustained, the goal in most countries has been to reduce influenza mortality by vaccinating older individuals and those with chronic underlying diseases. An exception to this has been Japan, where, for a time, school-age children were vaccinated in an effort to control influenza morbidity. It has been repeatedly demonstrated that the inactivated vaccine is effective in preventing hospitalization and death in older individuals and, as such, is also cost effective. The inactivated vaccine is cost effective in healthy adults only when the attack rates are above 12 percent. A live attenuated influenza vaccine has been used in the former Soviet Union for many years, and another is in development in the United States. Because of its delivery—intranasally rather than by injection—it may prove to be particularly useful in children and younger adults.

Antiviral drugs have been available both for treatment and prophylaxis. Two of these are active only against type A viruses. A new group of drugs, acting as neuraminidase inhibitors, is active against both type A and B viruses. These drugs have been shown to have a prevention efficacy similar to vaccines. They start protecting more quickly than the vaccine, but have to be taken daily to continue protection. Therefore, vaccination will continue to be the usual means of prophylaxis. The neuraminidase inhibitors also significantly shorten the duration of illness, reducing severity and preventing complications. Influenza can be debilitating, even in the absence of complications, so that the drugs will be used for treatment during defined influenza outbreaks. They are likely also to be useful prophylactically, especially for outbreak control in nursing homes.

Arnold Monto

Bibliography

Belshe, R. B.; Mendelman, P. M.; Treanor, J. et al. (1998). "The Efficacy of Live Attenuated, Cold-adapted, Trivalent, Intranasal Influenza Virus Vaccine in Children." New England Journal of Medicine 149:1113–1117.

Dolin, R.; Reichman, R. C.; Madore, H. P.; Maynard, R.; Linton, P. N.; and Webber-Jones, J. (1982). "A Controlled Trial of Amantadine and Rimantadine in the Prophylaxis of Influenza A Infection." New England Journal of Medicine 307:580–584.

Douglas, R. B., Jr. (1990). "Drug Therapy: Prophylaxis and Treatment of Influenza." New England Journal of Medicine 322:443–450.

Eickhoff, T. C.; Sherman, I. L.; and Serfling, R. E. (1961). "Observations on Excess Mortality Associated with Epidemic Influenza." Journal of the American Medical Association 176:776–782.

Gubareva, L. B.; Kaiser, L.; and Hayde, F. G. (2000). "Influenza Virus Neuraminidase Inhibitors." New England Journal of Medicine 355:827–835.

Lui, K. J., and Kendal, A. P. (1987). "Impact of Influenza Epidemics on Mortality in the United States from October 1972 to May 1985." American Journal of Public Health 77:712–716.

Monto, A. S., and Arden, N. H. (1992). "Implications of Viral Resistance to Amantadine in Control of Influenza A." Clinical Infectious Diseases 15:362–367.

Monto, A. S., and Kioumehr, F. (1975). "The Tecumseh Study of Respiratory Illness. IX. Occurrence of Influenza in the Community, 1966–1971." American Journal of Epidemiology 102:553–563.

Patriarca, P. A.; Weber, J. A.; Parker, R. A. et al. (1985). "Efficacy of Influenza Vaccine in Nursing Homes: Reduction in Illness and Complications During an Influenza A (H₃N₂) Epidemic." Journal of the American Medical Association 253:1136–1139.

Sullivan, F. M.; Monto, A. S.; and Longini, I. M., Jr. (1993). "Estimates of the U.S. Health Impact of Influenza." American Journal of Public Health 83: 1712–1716.

Wilde, J. A.; McMillan, J. A.; Serwint, J.; Butta, J; O'Riordan, M. A.; and Steinhoff, M. C. (1999). "Effectiveness of Influenza Vaccine in Health Care Professionals: A Randomized Trial." Journal of the American Medical Association 281:908–913.

Influenza

Introduction

Disease History, Characteristics, and Transmission

Treatment and Prevention

Scope and Distribution

Impacts and Issues

Primary Source Connection

BIBLIOGRAPHY

Introduction

Influenza is a viral disease that has plagued humans since the time of learning to walk upright. The medical writings of antiquity contain evidence that implicates influenza in causing epidemics of death and disease. A form of the influenza virus exists in nearly all animals, including domesticated birds and pigs, and these animal viruses bear a close genetic relationship to human influenza viruses.

A typical attack of influenza starts with high fever, chills, muscle aches, a dry cough, and feeling distinctly ill. Soon a sore throat with nasal congestion and a runny nose develops. The cough worsens and misery results. In healthy adults and children, a case of influenza lasts about a week and recovery is complete. Many think the illness is nothing more than a particularly severe “cold.” However, influenza can be unpredictable, and can kill healthy adults and children.

Disease History, Characteristics, and Transmission

Most often, influenza primarily attacks the nose, throat, and lungs, but any part of the body can be infected. Sometimes influenza will cause abdominal pain, nausea, and diarrhea. Rarely, the muscles will be infected and can be severely damaged. Infants may develop a severe form of viral pneumonia with the heart and lungs struggling to sustain life. Influenza can infect the brain as well, resulting in seizures and coma. Influenza is predictably unpredictable in how severe the disease may be in any one person.

Other diseases can take advantage of the weakened state of the body after a case of influenza and cause a secondary infection. Bacteria such as group A streptococcus, Staph aureus, and strep pneumonia are particularly efficient at causing a lethal pneumonia after influenza damages the lungs. About 10% of children will develop a secondary infection while recovering from influenza, and ear infections frequently afflict infants and young children just as they are trying to recover from influenza. The secondary infections often cause another visit to the doctor when parents discover their child, who seemed to be recovering, is ill again.

Influenza is highly contagious and primarily spreads person to person in virus-laden droplets produced by sneezing or coughing. Alternatively, the droplets land on a surface and contaminate the hands that, if not washed, carry the virus to the mouth or nose. Schoolaged children are the main culprits in spreading influenza. Usually 10–40% of school-aged children will get influenza in any one season. They swap virus at school and bring it home to infect family members. Children are contagious before they even appear or feel ill, and the virus is present in nasal mucous and cough droplets for over a week after apparent recovery from influenza.

The microbiology of the influenza virus is quite complex. Influenza viruses consist of three different major types known as A, B, and C. Of the three types, only A and B cause significant disease in humans. Both A and B types cause the seasonal epidemics around the world, but at any one time there may be hundreds of different variations of each type circulating the globe. This multitude of subtly different varieties presents a challenge to the human immune system.

Both influenza A and B virus change their structure often enough such that the immune system can never develop long-lasting immunity. Influenza B virus changes much more slowly than influenza A and usually causes milder illness compared to influenza A. However, influenza B can cause severe disease in the elderly, those with impaired immunity, or those with chronic lung or heart disease.

Influenza A generally causes more severe disease and is the most unpredictable. The yearly season epidemics of the “flu” are primarily the result of influenza A. The virus has two specific proteins on its surface, which are important for infecting humans. These proteins, known as antigens, bear the names hemagglutinin (HA) and neuraminidase (NA). The HA and NA proteins vary in their chemical structure from year to year. This process, termed antigenic drift, results in virus particle proteins with subtle variations in structure. Fifteen different HA subtypes are known to exist while there are nine NA subtypes. These slightly different proteins get different number designations, and the various influenza strains are named by the specific HA and NA proteins on the virus. The H3N1 virus contains HA protein 3 and NA protein 1.

Influenza A employs an additional means of evading the immune system. When two different viral strains infect someone at the same time, the two viral variants will swap component genes and create yet another slightly different form of influenza. The new virus will contain some proteins of one variety of influenza A and some proteins of the other variety. This sloppy way of making new virus particles extends to swapping genetic material with animal or bird influenza viruses. This process, termed antigenic shift, will sometimes create an influenza virus for which humans have no immunity at all. A novel virus produced this way has the potential to spread worldwide, resulting in a pandemic.

Three influenza pandemics have occurred in the twentieth century. The influenza pandemic in 1918 killed at least twenty million people, and some experts think there were fifty million deaths within a period of 24 weeks. Nearly as many United States soldiers died of influenza in 1918 as died in battle in all of World War I. In the United States, the 1957 pandemic resulted in 70,000 deaths while in 1968 about 30,000 died. During influenza pandemics, a larger proportion of healthy adults die than during the yearly “flu season” outbreaks.

WORDS TO KNOW

ANTIGEN: Antigens, which are usually proteins or polysaccharides, stimulate the immune system to produce antibodies. The antibodies inactivate the antigen and help to remove it from the body. While antigens can be the source of infections from pathogenic bacteria and viruses, organic molecules detrimental to the body from internal or environmental sources also act as antigens. Genetic engineering and the use of various mutational mechanisms allow the construction of a vast array of anti-bodies (each with a unique genetic sequence).

ANTIGENIC SHIFT: Antigenic shift describes an abrupt and major genetic change (e.g. in genes coding for surface proteins of a virus).

DROPLET TRANSMISSION: Droplet transmission is the spread of microorganisms from one space to another (including from person to person) via droplets that are larger than 5 microns in diameter. Droplets are typically expelled into the air by coughing and sneezing.

PANDEMIC: Pandemic, which means all the people, describes an epidemic that occurs in more than one country or population simultaneously.

STRAIN: A subclass or a specific genetic variation of an organism.

Treatment and Prevention

Medicine has developed weapons with which to combat influenza, specifically the adamantanes and the neuraminidase inhibitor drugs. The adamantanes treat only influenza A while the neuraminidase inhibitors will treat both influenza A and B. Both of these classes of medicines interfere with the ability of the influenza virus to make more virus particles. They either stop production of the viral genetic material or prevent the viral particles from escaping from infected cells to infect other cells. In order to help relieve symptoms or shorten the course of influenza, one must take these drugs early in the course of influenza. Once the illness is established and new influenza virus particles have replicated, the medications are largely ineffective. Many of the symptoms of influenza are due to the damage the virus does to the body during the making of new virus particles so stopping the virus early provides the greatest relief in symptoms.

Until effective medications became available to treat influenza, determining who has influenza rather than one of a similar multitude of viral respiratory illnesses was of little use. Treatment involved decreasing the fever, resting, and drinking plenty of fluids. This treatment is appropriate for most viral illnesses, but now with medications available, there is a difference whether the illness is a “cold” or the “flu” and testing for influenza is often done.

Several rapid tests are available to detect the influenza virus. These tests, often run in a doctor's office, use a sample of mucus taken from the nose or from the back of the throat. The tests are rapid usually taking only five minutes and will detect influenza virus accurately about 75-85% of the time if properly done.

Contrary to popular belief, antibiotics are not effective treatment for influenza. Antibiotics are useful in the treatment of bacterial infections and have no benefit during viral illnesses. Antibiotics may be helpful if secondary bacterial infections develop during the course of influenza.

Drugs provide a treatment option unavailable in past decades, but they do not provide the best option for control of influenza. Many will not realize their illness is influenza until it is too late for medications to be effective. Additionally they have usually already spread influenza to family members and co-workers.

Influenza vaccination provides the most effective treatment by preventing the disease, but the influenza virus poses a challenge for vaccine development. Since the virus changess lightly year to year and changes dramatically at unpredictable intervals, vaccines also need altering from year to year. Each year, public health officials make an educated guess as to what will be the prevalent strains circulating in the next season, and vaccine preparation commences targeting those strains.

Influenza vaccines provide excellent protection when administered at least two weeks before exposure to the influenza virus, and vaccination is needed each year. The vaccine itself does not cause influenza, but depending on the exact form of vaccine administered, side effects may include soreness at the injection site, muscle aches, runny nose, or sore throat. Young children often need two doses of vaccine for full protection. In the United States, the current vaccine recommendations include everyone older than 65 years, those between six months and five years, and everyone with chronic health problems involving the lungs or heart.

Scope and Distribution

Every year about 35,000 deaths occur in the United States due to influenza. Most of these deaths are those older than 65 years, but more children die of influenza or its complications each year than all the deaths due to whooping cough and measles combined. The World Health Organization credits influenza with causing between 250,000 and 500,000 deaths yearly throughout the world. For example, in 2002, an influenza outbreak started in Madagascar. Over a period of three months, 27,000 people developed influenza, and despite rapid medical intervention, 800 deaths occurred.

Impacts and Issues

Unless a family member or close friend dies of influenza, many people do not really give much thought to the impact influenza has on their health and pocketbook. Influenza ranks far behind heart disease and cancer as a worldwide cause of death, yet its economic impact is considerable. Public health experts have estimated a cost of $60-$4,000 for every case of influenza in a healthy adult in the United States. These costs include direct medical expenses, lost wages, and lost productivity at work. For parents, the cost often includes lost work while caring for the sick child, and afterwards, lost work from the case of influenza caught from the child.

A pandemic raises great concern for public health officials worldwide. Influenza pandemics occur several times a century but are unpredictable as to the exact timing. Each of the past three influenza pandemics (in 1918, 1957, and 1968) resulted from human influenza virus sharing genetic material with a bird influenza virus. Human immune systems had never encountered the new virus, and everyone was susceptible to the new form of influenza. As a result, the new virus swept through countries throughout the globe.

The pandemic of 1918 deserves further explanation as medical history warns that a similar event at some point in the future is highly likely. In the 1918 pandemic, about one third of the world's population suffered a severe case of influenza, and nearly 3% of those infected with the virus died. An unusually high percentage of the young and healthy died during this pandemic. All current strains of influenza A virus are descended from the 1918 virus, but the current strains have weakened considerably. Now less than 0.1% of people die when infected by today's forms of influenza.

Given that the medical system has advanced since 1918, what would be the impact of a new, more lethal influenza virus today? The answer is that the impact could be devastating. Public health experts predict an estimated 90,000–200,000 deaths, over 700,000 hospital admissions, and about forty million visits to doctors in the United States alone. The estimated economic impact exceeds $160 billion, not including the disruptions due to illness in the police, transportation workers, and the health workers themselves.

Over the past several years, a particularly vicious strain (type) of avian (bird) flu, known as H5N1 influenza, has caused many cases of disease and death in humans. Presently, transmission of this virus from human to human does not readily occur. Close contact with infected birds is required to catch this form of influenza. If this bird virus ever acquires the ability to infect humans from one person to another, a new pandemic could occur. The Center for Disease Control and the World Health organization recognize this possibility, and planning for the potential pandemic continues.

Primary Source Connection

Scientists at the Centers for Disease Control and Prevention play a key role in accessing influenza viruses and formulating vaccines for them. In order to prepare for a future pandemic influenza, CDC scientists studied the characteristics of the 1918 pandemic flu virus. The CDC press release below, released in February 2007, relates that by manipulating the 1918 virus, CDC scientists have found a way to render it less capable of spreading among animals that were in close contact with each other. This type of research could prove beneficial in reducing the ability of future influenza viruses to spread rapidly across heavily populated regions and cause a pandemic.

Small Changes in 1918 Pandemic Virus Knocks Out Transmission: Research Provides Clues for Assessing Pandemic Potential of New Influenza Viruses

Press Release

Embargoed Until 2 p.m. EST: February 1, 2007

Contact:

CDC Media Relations

(404) 639-3286

Experts at the Centers for Disease Control and Prevention have shown that a molecular change in the 1918 pandemic influenza virus stops its transmission in ferrets that were in close proximity, shedding light on the properties that allowed the 1918 pandemic virus to spread so quickly and potentially providing important clues that could help scientists assess emerging influenza viruses, such as H5N1.

The study, which is published in the Feb. 5 issue of Science, showed that a modest change of two amino acids in the main protein found on the surface of the 1918 virus did not change the virus's ability to cause disease, but stopped respiratory droplet transmission of the virus between ferrets placed in close proximity. The experiments were conducted with ferrets because their reaction to influenza viruses closely mimics how the disease affects humans.

“With this vital research, we are learning more about what may have contributed to the spread and deadliness of the 1918 pandemic,” said CDC Director Dr. Julie Gerberding. “By better understanding how this virus spreads, we can be better positioned to slow down or stop the spread of the pandemic virus and hence be better prepared for the next pandemic.”

To spread and cause illness, the influenza virus must first bind to host cells found in humans and animals. The Science study suggests that the hemagglutinin (HA), a type of protein found on the surface of influenza viruses, plays an important role in the 1918 virus's ability to transmit from one host to another efficiently. This research suggests that, for an influenza virus to spread efficiently, the virus's HA must prefer attaching to cells that are found predominately in the human upper airway instead of cells found predominately in the gastrointestinal tracts of birds. Other changes may be necessary as well. Current H5N1 viruses prefer attaching to avian cells, suggesting the virus would need to make genetic changes before it could pass easily between humans.

“Work on the 1918 virus is providing clues that are helping us evaluate other influenza viruses with pandemic potential, such as H5N1, that may emerge,” said Dr. Terrence Tumpey, lead author of the paper and a CDC senior microbiologist. “Though we still don't know what changes might be necessary for H5N1 to transmit easily among people, it's likely that changes in more than one virus protein would be required for the H5N1 virus to be transmitted among humans.”

Influenza pandemics occur when a new strain emerges to which people have little or no immunity. Most experts argue another pandemic will occur, but it is impossible to predict which strain will emerge as the next pandemic strain, when it will occur or how severe it will be.

The 1918 pandemic caused an estimated 675,000 deaths in the United States and up to 50 million worldwide, in the worst pandemic of the past century.

The research was done in collaboration with Mount Sinai School of Medicine and the Southeast Poultry Research Laboratory. All laboratory work with 1918 virus was conducted at CDC in a high containment Biosafety Level 3 laboratory with enhancements, using stringent biosecurity precautions to protect both laboratory workers and the public from exposure to the virus. Currently available antiviral drugs have been shown to be effective against the 1918 influenza virus and similar viruses.

Centers for Disease Control and Prevention (CDC)

CENTERS FOR DISEASE CONTROL AND PREVENTION (CDC). “SMALL CHANGES IN 1918 PANDEMIC VIRUS KNOCKS OUT TRANSMISSION.” PRESS RELEASE. FEBRUARY 1, 2007. <HTTP://WWW.CDC.GOV/OD/OC/MEDIA/PRESSREL/2007/R070201.HTM> (ACCESSED JUNE 4, 2007).

See AlsoDroplet Precautions; H5N1 Virus; Influenza Pandemic of 1918; Influenza Pandemic of 1957; Influenza, Tracking Seasonal Influences and Virus Mutation; Pandemic Preparedness; Vaccines and Vaccine Development; Viral Disease.

BIBLIOGRAPHY

Books

Barry, John M. The Great Influenza: The Story of the Deadliest Pandemic in History. New York: Penguin Books, 2004.

Goldsmith, Connie. Influenza: The Next Pandemic? Brookfield, CT: Twenty-first Century Books, 2006.

Web Sites

Centers for Disease Control and Prevention. “Influenza (Flu).” <http://www.cdc.gov/flu> (accessed June 4, 2007).

World Health Organization. “Influenza.” <http://www.who.int/topics/influenza/en> (accessed June 4, 2007).

Lloyd Scott Clements

Influenza

Definition

Usually referred to as the flu or grippe, influenza is a highly infectious respiratory disease caused by certain strains of influenza virus. When the virus is inhaled it attacks cells in the upper respiratory tract causing typical flu symptoms such as fatigue, fever and chills, hacking cough, and body aches. Influenza victims are also susceptible to potentially life-threatening secondary infections. Although the stomach or intestinal upsets and diarrhea are commonly called "flu," the influenza virus rarely causes gastrointestinal symptoms. Such symptoms are most likely due to other organisms such as rotavirus, Salmonella, Shigella, or Escherichia coli.

Description

Influenza is considerably more debilitating than the common cold . Influenza outbreaks occur suddenly and infection rapidly spreads. The annual death toll attributable to influenza and its complications averages 20,000 in the United States alone.

Influenza outbreaks occur on a regular basis. Pandemics, the most serious outbreaks, affect millions of people worldwide and last for several months. The 1918–1919 influenza outbreak serves as the primary example of an influenza pandemic. In that Spanish flu pandemic, the death toll reached a staggering 20–40 million people worldwide. Approximately 500,000 of these fatalities occurred in the United States. Pandemics also occurred in 1957 and 1968 with the Asian flu and Hong Kong flu, respectively. The Asian flu was responsible for 70,000 deaths in the United States, while the Hong Kong flu killed 34,000 people.

Epidemics are widespread regional outbreaks that occur every two to three years and affect 5–10% of the population. The Russian flu in the winter of 1977 is an example of an epidemic. A regional epidemic is shorter lived than a pandemic, lasting only several weeks. Finally, there are smaller outbreaks each winter that are confined to specific locales.

The earliest existing descriptions of influenza were written nearly 2,500 years ago by the ancient Greek physician, Hippocrates. Historically, influenza was ascribed to a number of different agents, including "bad air" and several different bacteria . It was not until 1933 that the causative agent was identified as a virus.

There are three types of influenza viruses , identified as A, B, and C. Influenza A can infect a range of species, including humans, pigs, horses, and birds, but only humans are infected by types B and C. Influenza A is responsible for most flu cases, while infection with types B and C viruses are less common and cause a milder illness.

Causes and symptoms

Approximately one to four days after infection with the influenza virus, a person is hit with an array of symptoms. "Hit" is an appropriate term, because symptoms are sudden, harsh, and followed by overall bodily aches and a fever that may run as high as 104°F (40°C). As the fever subsides, nasal congestion and a sore throat become noticeable. Persons with the flu feel extremely tired and generally miserable. Typical influenza symptoms include the abrupt onset of a headache, dry cough, and chills, and a rapid onset of physical weakness. Normal energy levels typically do not return for several days, but this can extend up to two weeks.

Influenza complications usually arise from secondary bacterial infections of the lower respiratory tract. Signs of a secondary respiratory infection often appear just as a person seems to be recovering. These signs include high fever, intense chills, chest pains associated with breathing, and a productive cough with thick, yellowish-green sputum. If these symptoms appear, medical treatment is necessary. Other secondary infections, such as sinus or ear infections, may also require medical intervention. Heart and lung problems and other chronic diseases can be aggravated by influenza. This is a particular concern among elderly people.

With children and teenagers, it is advisable to be alert for symptoms of Reye's syndrome, a rare but serious complication of the flu. Symptoms of Reye's syndrome are nausea and vomiting, and—more seriously— neurological problems such as confusion or delirium. Among children Reye's syndrome can be fatal. The syndrome has been associated with the use of aspirin to relieve flu symptoms.

Diagnosis

Although specific laboratory tests can be performed on respiratory samples to identify a flu virus strain, doctors typically rely on a set of symptoms and the presence of influenza in the community for diagnosis. Specific tests are useful to determine the type of flu in the community, but they do little to influence individual treatment. Doctors may administer tests, such as throat cultures, to identify and treat secondary bacterial infections.

Treatment

Essentially, little can be done for a case of influenza an it must simply run its course. Symptoms can be relieved with bed rest and by keeping well hydrated. A steam vaporizer may make breathing easier, and pain relievers such as ibuprofen and acetaminophen will relieve most aches and pains. Food may not seem appetizing, but an effort should be made to consume nourishing food. Returning to normal activities too quickly invites a possible relapse or complications.

Drugs

Since influenza is a viral infection, antibiotics are not an effective treatment. However, antibiotics are frequently used to treat secondary infections. Over-thecounter medications are used to treat symptoms, but it is not necessary to purchase a product marketed specifically for flu symptoms. Any medication designed to relieve pain and coughing will provide some relief. Products containing alcohol, however, should be avoided because of the dehydrating effects of alcohol. The best medicine for symptoms is simply an analgesic, such as acetaminophen or ibuprofen. Without a doctor's approval, aspirin is generally not recommended for people under the age of 18 years owing to its association with Reye's syndrome. As a precaution against the syndrome, children should receive acetaminophen or ibuprofen to treat their symptoms.

There are two antiviral drugs marketed for use in the United States against the influenza virus. These may be useful in treating individuals who have weakened immune systems or who are at risk for developing serious complications of influenza but may be allergic to the flu vaccine. The first is amantadine hydrochloride, which is marketed under the names Symmetrel (syrup), Symadine (capsule), and Amantadine-hydrochloride (capsule and syrup). The second antiviral is rimantadine hydrochloride, marketed under the trade name Flumandine (tablet and syrup). These two drugs are chemically related and are only effective against type A influenza viruses. Both drugs can cause side effects such as nervousness, anxiety , lightheadedness, and nausea. Side effects are more likely to occur with amantadine. Severe side effects include seizures, delirium, and hallucinations. These are rare and are nearly always limited to people who have kidney problems, seizure disorders, or psychiatric disorders.

Alternative treatment

There are several alternative treatments that may help in fighting off the virus, easing symptoms, and promoting recovery:

• • Acupuncture and acupressure . Both are said to stimulate natural resistance, relieve nasal congestion and headaches, fight fever, and calm coughs, depending on the acupuncture and acupressure points used.
• • Aromatherapy. Aromatherapists recommend gargling daily with one drop each of the essential oils of tea tree (Melaleuca spp.) and lemon mixed in a glass of warm water. If the patient is already suffering from the flu, two drops of tea tree oil in a hot bath may help ease the symptoms. Essential oils of eucalyptus (Eucalyptus globulus) or peppermint (Mentha piperita) added to a steam vaporizer may help clear chest and nasal congestion.
• • Herbal remedies. Herbal remedies such as echinacea can be used to stimulate the immune system ; as antivirals, goldenseal (Hydrastis canadensis) and garlic (Allium sativum) can be used. They can also be used to alleviate whatever symptoms arise as a result of the flu. For example, an infusion of boneset (Eupatroium perfoliatum) may counteract aches and fever, and yarrow (Achillea millefolium) or elderflower tinctures may combat chills.
• • Homeopathy. To prevent flu a homeopathic remedy called Oscillococcinum may be taken at the first sign of flu symptoms and repeated for a day or two. Other recommended homeopathic remedies vary according to the specific flu symptoms present. Gelsemium (Gelsemium sempervirens) is recommended to combat weakness accompanied by chills, headache, and nasal congestion. Bryonia (Bryonia alba) may be used to treat muscle aches, headaches, and a dry cough. For restlessness, chills, hoarseness, and achy joints, poison ivy (Rhus toxicodendron) is recommended. Finally, for bodily aches and a dry cough or chills, Eupatorium perfoliatum is suggested.
• • Hydrotherapy. A hot bath to induce a fever will speed recovery from the flu by creating an environment in the body where the flu virus cannot survive. Taking a bath in water as hot as can be tolerated, and remain in the bath for 20–30 minutes, is recommended. While in the bath, drinking a cup of yarrow or elderflower tea helps induce sweating. However, a cold cloth should be held on the forehead or the nape of the neck to keep down the temperature of the brain . In case dizziness or weakness occurs, the patient should be assisted when getting out of the bath. The individual should then go to bed and cover up with layers of blankets to induce more sweating.
• • Vitamins. For adults, 2–3 grams of vitamin C daily may help prevent the flu. Increasing the dose to 5–7 grams per day if infected by the flu can help overcome the infection. The dose of vitamin C should be reduced if diarrhea develops.

Prognosis

Following proper treatment guidelines, healthy people under the age of 65 years of age usually suffer no long-term consequences associated with influenza infections. While the elderly and the chronically ill are at greater risk for secondary infection and other complications, they can also recover completely. While most people fully recover from an influenza infection, the flu should not be viewed with complacency. Influenza is a serious disease. Approximately one in every 1,000 cases proves fatal.

Health care team roles

Family physicians, internists, and pediatricians most often diagnose influenza in people who seek medical attention. Nurse practitioners and physician assistants may also make such diagnoses. A physician usually prescribes over-the-counter products for symptomatic relief. Occasionally, antiviral products are prescribed for people at particular risk. Nurses administer vaccines to prevent influenza, providing education and information to those contemplating or receiving the vaccine.

Prevention

The Centers for Disease Control and Prevention recommend that people—particularly the at-risk population such as children, individuals with other diseases or disorders or a compromised immune system, and the elderly—get an influenza vaccine injection each year before the flu season starts. In the United States the flu season typically runs from late December to early March. Vaccines should be received two to six weeks prior to the beginning of the flu season to allow people's bodies enough time to establish immunity. Adults need only one dose of the yearly vaccine, but children under nine years of age who have not previously been immunized should receive two doses with a month between each dose.

Each season's flu vaccine contains three virus strains that are the most likely to be encountered in the coming flu season. When there is a good match between the anticipated flu strains and the strains used in the vaccine, the vaccine is 70–90% effective in people younger than 65 years of age. Because immune response diminishes somewhat with age, people older than 65 years may not receive the same level of protection from the vaccine as do younger people. Even if they do contract the flu, the elderly benefit from vaccines, which diminish severity and help prevent complications.

The virus strains used to make the vaccine are inactivated and will not cause a case of influenza. In the past, flu symptoms following vaccination were associated with vaccine preparations that were not as highly purified as modern vaccines, not to the virus itself. In 1976 there was a slightly increased risk of developing Guillain-Barré syndrome, a very rare disorder associated with the swine flu vaccine. This association occurred only with the 1976 swine flu vaccine preparation and has never recurred.

Serious side effects with modern vaccines are extremely unusual. Some people experience a slight soreness at the point of injection, which resolves within a day or two. People who have never been exposed to influenza, particularly children, may experience one to two days of a slight fever, tiredness, and muscle aches. These symptoms start within 6 to 12 hours after vaccination.

It should be noted that certain people should not receive an influenza vaccine. Infants six months and younger have immature immune systems and will not benefit from the vaccine. Since the vaccines are prepared using hen eggs, people who have severe allergies to eggs or other vaccine components should not receive the influenza vaccine. As an alternative, they may receive a course of amantadine or rimantadine, which are also used as protective measures against influenza. Other people who might receive these drugs are those who have been immunized after the flu season has started or who are immunocompromised, such as people with advanced HIV disease. Amantadine and rimantadine are 70–90% effective in preventing influenza.

Members of certain groups are strongly advised to be vaccinated because they are at-risk for influenza-related complications:

• • all people 65 years and older
• • residents of nursing homes and chronic-care facilities, regardless of age
• • adults and children who have chronic heart or lung problems, such as asthma
• • adults and children who have chronic metabolic diseases, such as diabetes and renal dysfunction, as well as severe anemia or inherited hemoglobin disorders
• • children and teenagers receiving long-term aspirin therapy
• • pregnant women who will be in the second or third trimester during flu season, or women who are nursing
• • anyone who is immunocompromised, including HIV-infected people with CD4 count over 200; people with cancer ; organ transplant recipients; and people receiving steroids, chemotherapy , or radiation therapy
• • anyone in contact with people in these groups, such as teachers, care givers, health-care personnel, and family members
• • travelers to foreign countries

An individual need not be in one of the at-risk categories listed above, however, to receive a flu vaccination. Anyone who wants to avoid the discomfort and inconvenience of a case of influenza should receive the vaccine.

KEY TERMS

Common cold —A mild illness caused by an upper respiratory virus. Usual symptoms include nasal congestion, coughing, sneezing, throat irritation, and a low-grade fever.

Epidemic —A widespread regional disease out-break.

Guillain-Barré syndrome —Also called acute idiopathic polyneuritis, this condition is a neurologic syndrome that can cause numbness in the limbs and muscle weakness following certain viral infections.

Pandemic —Worldwide or multiregional outbreak of an infection afflicting millions of people.

Reye's syndrome —A syndrome of nausea, vomiting, and neurological problems such as confusion or delirium. It can be fatal in children.

Resources

BOOKS

Craighead, John E. Pathology and Pathogenesis of Human Viral Disease. New York: Academic Press, 2000.

Dolin, Raphael. "Influenza." In Harrison's Principles of Internal Medicine, 14^th ed. Ed. Anthony S. Fauci et al., New York: McGraw-Hill, 1998, 1096-1098.

Hayden, Frederick G. "Influenza." In Cecil Textbook of Medicine, 21^st ed. Ed. Lee Goldman and J. Claude Bennett. Philadelphia: W.B. Saunders, 2000, 1797-1800.

Kolata, Gina B. Flu: The Story of the Great Influenza Pandemic of 1918 and the Search for the Virus That Caused It. Carmichael, CA: Touchstone Books, 2001.

Ramen, Fred. Influenza. New York: Rosen Publishing Group, 2001.

Wright, Peter. "Influenza Viruses." In Nelson Textbook of Pediatrics, 16^th ed. Ed. Richard E. Behrman et al., Philadelphia: Saunders, 2000, 987-990.

PERIODICALS

Berry, B B, D.A. Ehlert, R.J. Battiola, and G. Sedmak. "Influenza Vaccination Is Safe and Immunogenic when Administered to Hospitalized Patients." Vaccine 19, nos. 25–26 (2001): 3493-3498.

Chisholm, J.C., T. Devine, A. Charlett, C.R. Pinkerton, and M. Zambon. "Response to Influenza Immunization During Treatment for Cancer." Archives of Diseases of Children 84, no. 6 (2001): 496-500.

Fleming, D.M., and M. Zambon. "Update on Influenza and Other Viral Pneumonias." Current Opinions on Infectious Diseases 14, no. 2 (2001): 199-204.

Fleming, D.M. "Managing Influenza: Amantadine, Rimantadine and Beyond." International Journal of Clinical Practice 55, no. 3 (2001): 189-195.

Green, M.S. "Compliance with Influenza Vaccination and the Health Belief Model." Israel Medical Association Journal 2, no. 12 (2001): 912-913.

Hak, E., T.J. Verheij, G.A. van Essen, A. B. Lafeber, D.E. a Grobbee, and A.W. Hoes. "Prognostic Factors for Influenza-Associated Hospitalization and Death During an Epidemic." Epidemiology of Infections 126, no. 2: 261-268.

James, J.S. "Flu Epidemic: Shots, New Treatments Available." AIDS Treatment News no 335 (21 Jan. 2000): 2-4.

Michaeli, D. "Influenza Vaccination." Israel Medical Association Journal 2, no. 12 (2000): 914-915.

Wareing, M.D., and G.A. Tannock. "Live Attenuated Vaccines Against Influenza; An Historical Review." Vaccine 19, nos. 25, 26 (2001): 3320-3330.

ORGANIZATIONS

American Academy of Emergency Medicine. 611 East Wells

Street, Milwaukee, WI 53202. (800) 884-2236. <http://www.aaem.org>.

American Academy of Pediatrics. 141 Northwest Point Boulevard, Elk Grove Village, IL 60007-1098. (847) 434-4000. <http://www.aap.org/default.htm>.

OTHER

Centers for Disease Control and Prevention. <http://www.cdc.gov/ncidod/diseases/flu/fluvirus.htm>.

Food and Drug Administration. <http://www.fda.gov/cder/drug/advisory/influenza.htm>.

National Coalition for Adult Immunization. <http://www.nfid.org/factsheets/influadult.html>.

National Foundation for Infectious Diseases. <http://www.nfid.org/library/influenza>.

National Institute of Allergy and Infectious Diseases. <http://www.niaid.nih.gov/publications/flu.htm>.

National Library of Medicine. <http://www.nlm.nih.gov/ medlineplus/influenza.html>.

World Health Organization. <http://www.who.int/emc/ diseases/flu/>.

L. Fleming Fallon, Jr., M.D., Dr.P.H.