Flu
Content
What is influenza?
Influenza, commonly called "the flu," is an illness caused by RNA viruses that infect the respiratory tract of many animals, birds, and humans. In most people, the infection results in the person getting fever, cough, headache, and malaise (tired, no energy); some people also may develop a sore throat, nausea, vomiting, and diarrhea. The majority of individuals has symptoms for about one to two weeks and then recovers with no problems. However, compared with most other viral respiratory infections, such as the common cold, influenza (flu) infection can cause a more severe illness with a mortality rate (death rate) of about 0.1% of people who are infected with the virus. The above is the usual situation for the yearly occurring "conventional" or "seasonal" flu strains. However, there are situations in which some flu outbreaks are severe. These severe outbreaks occur when the human population is exposed to a flu strain against which the population has little or no immunity because the virus has become altered in a significant way. Unusually severe worldwide outbreaks (pandemics) have occurred several times in the last hundred years since influenza virus was identified in 1933. By an examination of preserved tissue, the worst influenza pandemic (also termed the Spanish flu) occurred in 1918 when the virus caused between 40-100 million deaths worldwide, with a mortality rate estimated to range from 2%-20%. In April 2009, a new influenza strain against which the world population has little or no immunity was isolated from humans in Mexico. It quickly spread throughout the world so fast that the WHO declared this new flu strain (termed novel H1N1 influenza A swine flu, often shortened to H1N1 or swine flu) as the cause of a pandemic on June 11, 2009. This was the first declared flu pandemic in 41 years. Haemophilus influenzae is a bacterium that was incorrectly considered to cause the flu until the virus was demonstrated to be the correct cause in 1933. This bacterium can cause lung infections in infants and children, and it occasionally causes ear, eye, sinus, joint, and a few other infections, but it does not cause the flu.
What are the causes of the flu?
Influenza viruses cause the flu and are divided into three types, designated A, B, and C. Influenza types A and B are responsible for epidemics of respiratory illness that occur almost every winter and are often associated with increased rates of hospitalization and death. Influenza type C differs from types A and B in some important ways. Type C infection usually causes either a very mild respiratory illness or no symptoms at all; it does not cause epidemics and does not have the severe public-health impact of influenza types A and B. Efforts to control the impact of influenza are aimed at types A and B, and the remainder of this discussion will be devoted only to these two types. Influenza viruses continually change over time, usually by mutation (change in the viral RNA). This constant changing often enables the virus to evade the immune system of the host (humans, birds, and other animals) so that the host is susceptible to changing influenza virus infections throughout life. This process works as follows: a host infected with influenza virus develops antibodies against that virus; as the virus changes, the "first" antibody no longer recognizes the "newer" virus and infection can occur because the host does not recognize the new flu virus as a problem until the infection is well under way. The first antibody developed may, in some instances, provide partial protection against infection with a new influenza virus. Unfortunately, almost all individuals have no antibodies that will recognize the novel H1N1 virus immediately. Consequently, without vaccination, the majority of the human population is susceptible to novel H1N1 flu. Type A viruses are divided into types based on differences in two viral surface proteins called the hemagglutinin (H) and the neuraminidase (N). There are 16 known H subtypes and nine known N subtypes. 1
These surface proteins can occur in many combinations. When spread by droplets or direct contact, the virus, if not killed by the host's immune system, replicates in the respiratory tract and damages host cells. In people who are immune compromised (for example, pregnant individuals, infants, cancer patients, asthma patients, people with pulmonary disease and many others), the virus can cause viral pneumonia or stress the individual's system to make them more susceptible to bacterial infections, especially bacterial pneumonia. Both pneumonia types, viral and bacterial, can cause severe disease and sometimes death. Influenza type A viruses undergo two kinds of changes. One is a series of mutations that occurs over time and causes a gradual evolution of the virus. This is called antigenic "drift." The other kind of change is an abrupt change in the hemagglutinin and/or the neuraminidase proteins. This is called antigenic "shift." In this case, a new subtype of the virus suddenly emerges. Type A viruses undergo both kinds of changes; influenza type B viruses change only by the more gradual process of antigenic drift and therefore do not cause pandemics.
What are flu symptoms?
Typical clinical features of influenza include y y y y y fever (usually 100 F-103 F in adults and often even higher in children), respiratory symptoms such as cough, sore throat, runny or stuffy nose, headache, muscle aches, and fatigue, sometimes extreme.
Although nausea, vomiting, and diarrhea can sometimes accompany influenza infection, especially in children, gastrointestinal symptoms are rarely prominent. The term "stomach flu" is a misnomer that is sometimes used to describe gastrointestinal illnesses caused by other microorganisms. Novel H1N1 infections cause more nausea, vomiting, and diarrhea than the conventional (seasonal) flu viruses. Most people who get the flu recover completely in one to two weeks, but some people develop serious and potentially life-threatening medical complications, such as pneumonia. In an average year, influenza is associated with about 36,000 deaths nationwide and many more hospitalizations. Flu-related complications can occur at any age; however, the elderly and people with chronic health problems are much more likely to develop serious complications after the conventional influenza infections than are younger, healthier people. However, the novel H1N1 virus has initially developed a different pattern of infection. Unfortunately, the pattern of infection is similar to that of the 1918 "Spanish flu" pandemic in which young people (pregnant individuals, infants, teens, and adults through age 49) are the most susceptible populations worldwide.
What is the key to flu prevention?
Much of the illness and death caused by influenza can be prevented by annual influenza vaccination. Flu vaccine (influenza vaccine made from inactivated and sometimes attenuated [non-infective] virus) is specifically recommended for those who are at high risk for developing serious complications as a result of influenza infection. These high-risk groups for conventional flu include all people aged 65 years or older and people of any age with chronic diseases of the heart, lung, or kidneys; diabetes; immunosuppression; or severe forms of anemia. However, with the novel H1N1 flu, the CDC has listed these groups listed below as being at high risk and should obtain the novel H1N1 vaccine as soon as it is available to them: y y pregnant women, people who live with or care for children younger than 6 months of age, 2
y y y
health-care and emergency-services personnel, people between the ages of 6 months through 24 years of age and children 5-18 years of age who have chronic medical problems, and people from 25-64 years of age who are at higher risk for novel H1N1 because of chronic health disorders or compromised immune systems.
Other groups for whom conventional flu vaccine is specifically recommended are residents of nursing homes and other chronic care facilities housing patients of any age with chronic medical conditions and children and teenagers who are receiving long-term aspirin therapy and who may therefore be at risk for developing Reye syndrome after an influenza virus infection. Influenza vaccine is also recommended for people who are in close or frequent contact with anyone in the high-risk groups defined above. These people include healthcare personnel and volunteers who work with high-risk patients and people who live in a household with a high-risk person. Because the flu is easily spread among children and because many children require hospitalization with the flu, the CDC now advises that all children 6-59 months of age receive a yearly conventional flu vaccination.
Are any side effects associated with the influenza vaccine?
Although annual influenza (injectable) vaccination has long been recommended for people in the high-risk groups, many still do not receive the vaccine, often because of their concern about side effects. They mistakenly perceive influenza as merely a nuisance and believe that the vaccine causes unpleasant side effects or that it may even cause the flu. The truth is that influenza vaccine causes no side effects in most people. The most serious side effect that can occur after influenza vaccination is an allergic reaction in people who have a severe allergy to eggs, since the viruses used in the vaccine are grown in hens' eggs. For this reason, people who have an allergy to eggs should not receive the influenza vaccine. Also, the vaccine is not recommended while individuals have active infections or active diseases of the nervous system. Less than one-third of those who receive the vaccine have some soreness at the vaccination site, and about 5%-10% experience mild side effects, such as headache, low-grade fever, or muscle cramps, for about a day after vaccination. These side effects are most likely to occur in children who have not been exposed to influenza virus in the past. Nevertheless, some older people remember earlier influenza vaccines that did, in fact, produce more unpleasant side effects. Vaccines produced from the 1940s to the mid-1960s were not as highly purified as modern influenza vaccines, and it was these impurities that caused most of the side effects. Since the side effects associated with these early vaccines, such as fever, headache, muscle aches, and fatigue, were similar to some of the symptoms of influenza, people believed that the vaccine had caused them to get the flu. However, injectable influenza vaccine produced in the United States has never been capable of causing influenza because it consists of killed virus. Another type of influenza vaccine (nasal spray) is made with live attenuated (altered) influenza viruses. This vaccine is made with live viruses that can stimulate the immune response enough to confer immunity but do not cause classic influenza symptoms (in most instances). The nasal spray vaccine (FluMist) is only approved for healthy individuals ages 2-49 years of age. This nasal spray vaccine contains live attenuated virus (less able to cause flu symptoms due to a designed inability to replicate at normal body temperatures). This live vaccine could possibly cause the disease in infants and immunocompromised people and does not produce a strong immune response in many older people. Side effects of the nasal mist include nasal congestion, sore throat, and fever. Headaches, muscle aches irritability, and malaise have also been noted. In most instances, if side effects occur, they only last a day or two. This nasal spray has been produced for both conventional and the novel H1N1 flu viruses and should not be given to pregnant individuals or anyone who has a medical 3
condition that may compromise the immune system because in some instances the flu is the side effect. Caregivers should read the vaccine precaution insert before giving any vaccine, injectable or nasal, as these inserts are occasionally updated. Some people do not receive influenza vaccine because they believe it is not very effective. There are several different reasons for this belief. People who have received influenza vaccine may subsequently have an illness that is mistaken for influenza, and they believe that the vaccine failed to protect them. In other cases, people who have received the vaccine may indeed have an influenza infection. Overall vaccine effectiveness varies from year to year, depending upon the degree of similarity between the influenza virus strains included in the vaccine and the strain or strains that circulate during the influenza season. Because the vaccine strains must be chosen nine to 10 months before the influenza season, and because influenza viruses mutate over time, sometimes mutations occur in the circulating virus strains between the time the vaccine strains are chosen and the next influenza season ends. These mutations sometimes reduce the ability of the vaccineinduced antibody to inhibit the newly mutated virus, thereby reducing vaccine efficacy. This commonly occurs with the conventional flu vaccines as the specific virus types chosen for vaccine inclusion are based on reasoned projections for the upcoming flu season. Occasionally, the vaccine does not match the actual predominating virus strain and is not very effective in generating a specific immune response to the predominant infecting flu strain. Vaccine efficacy also varies from one person to another. Studies of healthy young adults have shown influenza vaccine to be 70%-90% effective in preventing illness. In the elderly and those with certain chronic medical conditions such as HIV, the vaccine is often less effective in preventing illness. Studies show the vaccine reduces hospitalization by about 70% and death by about 85% among the elderly who are not in nursing homes. Among nursing-home residents, vaccine can reduce the risk of hospitalization by about 50%, the risk of pneumonia by about 60%, and the risk of death by 75%-80%. If antigenic drift results in changing the circulating virus from the strains used in the vaccine, vaccine efficacy may be reduced. However, the vaccine is still likely to lessen the severity of the illness and to prevent complications and death. The vaccine produced against the novel H1N1 swine flu was just initiated in the summer of 2009 and then rapidly tested for safety and effectiveness, in contrast to the longer time cycle used for production of conventional flu vaccine. However, the injectable (and nasal) vaccines used the same methods developed for conventional flu vaccines over many years. The expedited clinical trials for the novel H1N1 vaccines, according to the CDC, have shown the injected vaccine to be safe and very effective with immunologic protection developing in healthy people. In the 18-64 age group, 98% were protected while those over 65 were 93% protected. Other groups are being studied, but protection with the injected vaccine in preliminary and ongoing trials seems good, according to the CDC. To date, about 39,000 Chinese people have been given the vaccine with very few (four) developing only mild side effects such as muscle cramps and headache, according to WHO officials. Recently, data presented on the effectiveness of the nasal mist vaccine in adults were published; the data indicated that for conventional flu protection, the nasal mist was less effective than the injected vaccine in adults for the conventional flu. Other studies have shown that the nasal mist vaccine was slightly more effective in healthy children than the injectable vaccine. The following is a list of the CDC-approved H1N1 vaccines and the companies that name and manufacture them as of 10/29/09: y y y y Influenza A (H1N1) 2009 Monovalent Vaccine by Sanofi Pasteur Influenza A (H1N1) 2009 Monovalent Vaccine by Novartis Influenza A (H1N1) 2009 Monovalent Vaccine Live, Intranasal by MedImmune, LLC Influenza A (H1N1) 2009 Monovalent Vaccine by CSL Limited
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Why should the flu vaccine be taken every year?
Although only a few different influenza virus strains circulate at any given time, people may continue to become ill with the flu throughout their lives. The reason for this continuing susceptibility is that influenza viruses are continually mutating, through the mechanisms of antigenic shift and drift described above. Each year, the vaccine is updated to include the most current influenza virus strains that are infecting people worldwide. The fact that influenza viral genes continually change is one of the reasons vaccine must be taken every year. Another reason is that antibody produced by the host in response to the vaccine declines over time, and antibody levels are often low one year after vaccination.
What are some treatments an individual can do at home for the flu?
First, individuals should be sure they are not members of a high-risk group that is more susceptible to getting severe flu symptoms. Check with your physician if you are unsure if you are a higher risk person. Home care is recommended by the CDC if a person is normally healthy with no underlying diseases or conditions (for example, asthma, lung disease, pregnant, or immunosuppressed). Increasing liquid intake, warm showers, and warm compresses, especially in the nasal area, can reduce the body aches and reduce nasal congestion. Nasal strips and humidifiers may help reduce congestion, especially while trying to sleep. Some physicians recommend nasal irrigation with saline to further reduces congestion; some recommend nonprescription decongestants. Fever can be treated with over-the counter acetaminophen (Tylenol) or ibuprofen (Motrin and others) (read labels for safe dosage). Cough can be suppressed by cough drops and over-the-counter cough syrup. If an individual's symptoms at home get worse, their doctor should be notified.
When should a person go to the emergency department for the flu?
The CDC has recently published guidelines on who should go to the emergency department for flu symptoms and who should not go. The CDC published these guidelines to avoid a crush of people going to the emergency department during the H1N1 flu pandemic and utilizing limited resources needed for true emergency patients such as cardiac or trauma patients and to avoid transmitting the virus to high-risk patients. The CDC guidelines are as follows for children and adults. The CDC urges normally healthy people that get either the conventional or novel H1N1 swine flu to stay home as the large majority of infected individuals will recover without antiviral medications or other treatments. The CDC urges people to seek emergency medical care for a sick child with any of these symptoms: 1. 2. 3. 4. 5. 6. 7. Fast breathing or trouble breathing Bluish or gray skin color Not drinking enough fluids Severe or persistent vomiting Not waking up or not interacting Being so irritable that the child does not want to be held Flu-like symptoms improve but then return with fever and cough
The following is the CDC's list of symptoms that should trigger emergency medical care for adults: 1. Difficulty breathing or shortness of breath 2. Pain or pressure in the chest or abdomen 3. Sudden dizziness 5
4. 5. 6. 7.
Confusion Severe or persistent vomiting Flu-like symptoms improve but then return with fever and worse cough Having a high fever for more than three days is another danger sign, according to the WHO, so the CDC has also included this as another serious symptom.
Who should receive the flu vaccine? When should someone get the flu shot?
In the United States, the flu season usually occurs from about November until April. Officials have decided each new flu season will start on Oct. 4. Typically, activity is very low until December, and peak activity most often occurs between January and March. Ideally, the conventional flu vaccine should be administered between September and mid-November. It takes about one to two weeks after vaccination for antibodies against influenza to develop and provide protection. Groups at increased risk of conventional influenza complications include: y y y y people aged 65 years or older; residents of nursing homes and other chronic-care facilities housing patients of any age who have chronic medical conditions; adults and children with chronic disorders of the pulmonary, cardiovascular, or immune systems, including children with asthma; adults and children who have required regular medical follow-up or hospitalization during the preceding year because of chronic metabolic diseases (including diabetes mellitus), renal dysfunction, hemoglobinopathies, or immunosuppression (including immunosuppression caused by medications); children and teenagers (6 months to 18 years of age) who are receiving long-term aspirin therapy and therefore may be at risk for developing Reye syndrome after influenza; and women in the third trimester of pregnancy or in the early postpartum period. There is some evidence to suggest that women who are in the third trimester of pregnancy or in the early postpartum period may be at increased risk for serious medical complications after influenza infection. Pregnant women who will be in the third trimester of pregnancy between December and April should consult their health-care provider about receiving influenza vaccine during the period from September to midNovember.
y y
Unfortunately, because the novel H1N1 flu virus is not following the conventional flu pattern for time of disease appearance (appeared in April and increased over the summer and fall of 2009) or susceptible populations, the CDC has had to alter somewhat the recommendations this year. Consequently, the CDC has listed these groups as being at high risk for novel H1N1 flu and should obtain the novel H1N1 vaccine as soon as it is available to them: y y y y y pregnant women, people who live with or care for children younger than 6 months of age, health-care and emergency-services personnel, people between the ages of 6 months through 24 years of age and children 5-18 years of age who have chronic medical problems, and people from 25-64 years of age who are at higher risk for novel H1N1 because of chronic health disorders or compromised immune systems.
In addition, the following groups should be vaccinated because they may transmit influenza to people who are at high risk for complications if they become infected with either the conventional or novel H1N1 flu. 1. Physicians, nurses, and other health-care personnel in both hospital and outpatient-care settings 6
2. Employees in nursing homes and chronic-care facilities who have contact with patients or residents 3. Providers of home care to people at high risk (for example, visiting nurses and volunteer workers) 4. Household members (including children) of high-risk people Furthermore, the CDC advises that all children 6-59 months of age get a yearly conventional flu vaccination since each year there are over 20,000 children who require hospitalization because of the flu and flu is easily passed from child to child. Finally, the flu vaccine, both the conventional and H1N1, may be administered to any person who wishes to reduce his or her chances of acquiring influenza infection. People who provide essential community services should be considered for vaccination to minimize disruption of essential activities during influenza outbreaks. Students or other people in institutional settings, such as those who reside in dormitories, should be encouraged to receive the vaccine to minimize the disruption of routine activities during epidemics. Such outbreaks have been reported for H1N1 in 2009. People needing further information regarding the use and availability of the influenza vaccine should consult with their health-care provider or their local health department or the CDC at the flu.gov Web site.
What is the bird (avian) flu?
The bird flu, also known as avian influenza, is an infection caused by avian influenza A. Bird flu can infect many bird species, including domesticated birds such as chickens. In most cases, the disease is mild; however, some subtypes can be pathogenic and rapidly kill birds within 48 hours. Rarely, humans can be infected by these bird viruses. People who get infected with bird flu usually have direct contact with the infected birds or their waste products. Depending on the viral type, the infections can range from mild influenza to severe respiratory problems or death. When this virus (H5N1) infects human, it is highly pathogenic and although only about 700 people worldwide have been infected, about 10% died. Fortunately, this virus does not seem to be easily passed from person to person. The major concern among scientists and physicians about bird flu is that it will change (mutate) its viral RNA enough to be easily transferred among people and produce a pandemic similar to the one of 1918.
Do antiviral agents protect people from the flu?
Vaccination is the primary method for control of influenza; however, antiviral agents have a role in the prevention and treatment of mainly influenza type A infection. Regardless, antiviral agents should not be considered as a substitute or alternative for vaccination. Currently, there are four antiviral agents available in the United States. They are amantadine (Symmetrel), rimantadine (Flumadine), zanamivir (Relenza), and oseltamivir (Tamiflu). In 2006, the CDC recommended that neither amantadine nor rimantadine be used for prevention of influenza A as resistance to these drugs had developed. This resistance problem and additional adverse reactions to the drugs (behavioral changes, seizures) have limited their subsequent use. Oseltamivir has had a similar FDA label warning about behavioral changes. The 2007-2008 Advisory Committee on Immunization Practices (ACIP) recommends that only zanamivir and oseltamivir be used in the U.S. for treatment or prevention until influenza A susceptibility to the other drugs is reestablished. In general, infected people need to begin taking the antiviral medications within two days of developing the initial symptoms of influenza. This may reduce the symptoms and shorten the illness by one or two days. However, in high-risk people, these drugs may either prevent the flu disease symptoms (both conventional and novel H1N1) or, once established, prevent the flu from becoming severe. There is a 7
high potential for overuse of these drugs so the CDC has put out the following guidelines to be used with clinical judgment: y y y Uncomplicated febrile illness typically does not require antiviral treatment unless individuals are at higher risk for influenza complications. Treatment is recommended for all hospitalized patients with confirmed, probable, or suspected novel influenza (H1N1). Clinical judgment should be used when evaluating children; caregivers should be aware that the risk for severe complications from seasonal influenza among children younger than 5 years of age is highest among children younger than 2 years of age and may require antiviral medication.
In early September 2009, CDC officials further modified the antiviral guidelines for the interim guidelines for use of Tamiflu and Relenza as follows: 1. People with high risk factors should discuss flu symptoms and when to use antivirals; doctors should provide a prescription for the antiviral for the patient to use if the patient is exposed or develops flulike symptoms without having to go in to see the doctor. 2. "Watchful waiting" was added as a response to taking antiviral drugs with the emphasis on those people who develop fever and have a preexisting health condition should then begin the antiviral medication. 3. The antivirals are the first-line medicines for treatment of novel H1N1 swine flu, and most current cases of flu are novel H1N1 and are, to date, susceptible to Tamiflu and Relenza. Prevention of influenza (both A and B) is possible with both zanamivir and oseltamivir. While zanamivir was approved for people 7 years of age or older and oseltamivir was approved for people 1 year of age and older for the conventional flu, the CDC has published guidelines for antiviral use against novel H1N1 in late September 2009 that includes children under 2 years of age and pregnant women: y y People with more severe illness, such as those hospitalized with suspected or confirmed influenza People with suspected or confirmed influenza who are at higher risk for complications o Children younger than 2 years of age o Adults 65 years of age and older o Pregnant women o People with certain chronic medical or immunosuppressive conditions People younger than 19 years of age who are receiving long-term aspirin therapy
y
Prevention rates vary from about 68%-89% when these antiviral medications were given to individuals before they developed symptoms of the conventional flu or were exposed to infected people; data are not yet available for novel H1N1. Treatment usually consists of a five-day schedule of antiviral medication, while prevention usually requires 10 days of medication. For example, duration of antiviral chemoprophylaxis (prevention) post-exposure is 10 days after the last known exposure. However, recommended treatment and prevention schedules vary according to age, weight, drug formulation, and if the individual is hospitalized. Details about dosing in adults, pregnant women, children, and infants are available and updated on both the CDC and FDA web sites: http://www.cdc.gov/H1N1flu/antiviral.htm and http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm18387 0.htm. Gastrointestinal symptoms (nausea, vomiting) are some of the most common side effects of these drugs. Influenza viruses are known to develop resistance to both drugs but at a much lower rate than to the other antiviral drugs. These drugs and others that are in development (such as peramivir, favipiravir, and ligand epitopes) are being studied to determine if they can be used to prevent or treat new influenza strains such as novel H1N1 and bird flu. 8
Influenza, commonly called "the flu," is an illness caused by RNA viruses that infect the respiratory tract of many animals, birds, and humans. In most people, the infection results in the person getting fever, cough, headache, and malaise (tired, no energy); some people also may develop a sore throat, nausea, vomiting, and diarrhea. The majority of individuals has symptoms for about one to two weeks and then recovers with no problems. However, compared with most other viral respiratory infections, such as the common cold, influenza (flu) infection can cause a more severe illness with a mortality rate (death rate) of about 0.1% of people who are infected with the virus. The above is the usual situation for the yearly occurring "conventional" or "seasonal" flu strains. However, there are situations in which some flu outbreaks are severe. These severe outbreaks occur when the human population is exposed to a flu strain against which the population has little or no immunity because the virus has become altered in a significant way. Unusually severe worldwide outbreaks (pandemics) have occurred several times in the last hundred years since influenza virus was identified in 1933. By an examination of preserved tissue, the worst influenza pandemic (also termed the Spanish flu) occurred in 1918 when the virus caused between 40-100 million deaths worldwide, with a mortality rate estimated to range from 2%-20%. In April 2009, a new influenza strain against which the world population has little or no immunity was isolated from humans in Mexico. It quickly spread throughout the world so fast that the WHO declared this new flu strain (termed novel H1N1 influenza A swine flu, often shortened to H1N1 or swine flu) as the cause of a pandemic on June 11, 2009. This was the first declared flu pandemic in 41 years. Haemophilus influenzae is a bacterium that was incorrectly considered to cause the flu until the virus was demonstrated to be the correct cause in 1933. This bacterium can cause lung infections in infants and children, and it occasionally causes ear, eye, sinus, joint, and a few other infections, but it does not cause the flu.
What are the causes of the flu?
Influenza viruses cause the flu and are divided into three types, designated A, B, and C. Influenza types A and B are responsible for epidemics of respiratory illness that occur almost every winter and are often associated with increased rates of hospitalization and death. Influenza type C differs from types A and B in some important ways. Type C infection usually causes either a very mild respiratory illness or no symptoms at all; it does not cause epidemics and does not have the severe public-health impact of influenza types A and B. Efforts to control the impact of influenza are aimed at types A and B, and the remainder of this discussion will be devoted only to these two types. Influenza viruses continually change over time, usually by mutation (change in the viral RNA). This constant changing often enables the virus to evade the immune system of the host (humans, birds, and other animals) so that the host is susceptible to changing influenza virus infections throughout life. This process works as follows: a host infected with influenza virus develops antibodies against that virus; as the virus changes, the "first" antibody no longer recognizes the "newer" virus and infection can occur because the host does not recognize the new flu virus as a problem until the infection is well under way. The first antibody developed may, in some instances, provide partial protection against infection with a new influenza virus. Unfortunately, almost all individuals have no antibodies that will recognize the novel H1N1 virus immediately. Consequently, without vaccination, the majority of the human population is susceptible to novel H1N1 flu. Type A viruses are divided into types based on differences in two viral surface proteins called the hemagglutinin (H) and the neuraminidase (N). There are 16 known H subtypes and nine known N subtypes. 1
These surface proteins can occur in many combinations. When spread by droplets or direct contact, the virus, if not killed by the host's immune system, replicates in the respiratory tract and damages host cells. In people who are immune compromised (for example, pregnant individuals, infants, cancer patients, asthma patients, people with pulmonary disease and many others), the virus can cause viral pneumonia or stress the individual's system to make them more susceptible to bacterial infections, especially bacterial pneumonia. Both pneumonia types, viral and bacterial, can cause severe disease and sometimes death. Influenza type A viruses undergo two kinds of changes. One is a series of mutations that occurs over time and causes a gradual evolution of the virus. This is called antigenic "drift." The other kind of change is an abrupt change in the hemagglutinin and/or the neuraminidase proteins. This is called antigenic "shift." In this case, a new subtype of the virus suddenly emerges. Type A viruses undergo both kinds of changes; influenza type B viruses change only by the more gradual process of antigenic drift and therefore do not cause pandemics.
What are flu symptoms?
Typical clinical features of influenza include y y y y y fever (usually 100 F-103 F in adults and often even higher in children), respiratory symptoms such as cough, sore throat, runny or stuffy nose, headache, muscle aches, and fatigue, sometimes extreme.
Although nausea, vomiting, and diarrhea can sometimes accompany influenza infection, especially in children, gastrointestinal symptoms are rarely prominent. The term "stomach flu" is a misnomer that is sometimes used to describe gastrointestinal illnesses caused by other microorganisms. Novel H1N1 infections cause more nausea, vomiting, and diarrhea than the conventional (seasonal) flu viruses. Most people who get the flu recover completely in one to two weeks, but some people develop serious and potentially life-threatening medical complications, such as pneumonia. In an average year, influenza is associated with about 36,000 deaths nationwide and many more hospitalizations. Flu-related complications can occur at any age; however, the elderly and people with chronic health problems are much more likely to develop serious complications after the conventional influenza infections than are younger, healthier people. However, the novel H1N1 virus has initially developed a different pattern of infection. Unfortunately, the pattern of infection is similar to that of the 1918 "Spanish flu" pandemic in which young people (pregnant individuals, infants, teens, and adults through age 49) are the most susceptible populations worldwide.
What is the key to flu prevention?
Much of the illness and death caused by influenza can be prevented by annual influenza vaccination. Flu vaccine (influenza vaccine made from inactivated and sometimes attenuated [non-infective] virus) is specifically recommended for those who are at high risk for developing serious complications as a result of influenza infection. These high-risk groups for conventional flu include all people aged 65 years or older and people of any age with chronic diseases of the heart, lung, or kidneys; diabetes; immunosuppression; or severe forms of anemia. However, with the novel H1N1 flu, the CDC has listed these groups listed below as being at high risk and should obtain the novel H1N1 vaccine as soon as it is available to them: y y pregnant women, people who live with or care for children younger than 6 months of age, 2
y y y
health-care and emergency-services personnel, people between the ages of 6 months through 24 years of age and children 5-18 years of age who have chronic medical problems, and people from 25-64 years of age who are at higher risk for novel H1N1 because of chronic health disorders or compromised immune systems.
Other groups for whom conventional flu vaccine is specifically recommended are residents of nursing homes and other chronic care facilities housing patients of any age with chronic medical conditions and children and teenagers who are receiving long-term aspirin therapy and who may therefore be at risk for developing Reye syndrome after an influenza virus infection. Influenza vaccine is also recommended for people who are in close or frequent contact with anyone in the high-risk groups defined above. These people include healthcare personnel and volunteers who work with high-risk patients and people who live in a household with a high-risk person. Because the flu is easily spread among children and because many children require hospitalization with the flu, the CDC now advises that all children 6-59 months of age receive a yearly conventional flu vaccination.
Are any side effects associated with the influenza vaccine?
Although annual influenza (injectable) vaccination has long been recommended for people in the high-risk groups, many still do not receive the vaccine, often because of their concern about side effects. They mistakenly perceive influenza as merely a nuisance and believe that the vaccine causes unpleasant side effects or that it may even cause the flu. The truth is that influenza vaccine causes no side effects in most people. The most serious side effect that can occur after influenza vaccination is an allergic reaction in people who have a severe allergy to eggs, since the viruses used in the vaccine are grown in hens' eggs. For this reason, people who have an allergy to eggs should not receive the influenza vaccine. Also, the vaccine is not recommended while individuals have active infections or active diseases of the nervous system. Less than one-third of those who receive the vaccine have some soreness at the vaccination site, and about 5%-10% experience mild side effects, such as headache, low-grade fever, or muscle cramps, for about a day after vaccination. These side effects are most likely to occur in children who have not been exposed to influenza virus in the past. Nevertheless, some older people remember earlier influenza vaccines that did, in fact, produce more unpleasant side effects. Vaccines produced from the 1940s to the mid-1960s were not as highly purified as modern influenza vaccines, and it was these impurities that caused most of the side effects. Since the side effects associated with these early vaccines, such as fever, headache, muscle aches, and fatigue, were similar to some of the symptoms of influenza, people believed that the vaccine had caused them to get the flu. However, injectable influenza vaccine produced in the United States has never been capable of causing influenza because it consists of killed virus. Another type of influenza vaccine (nasal spray) is made with live attenuated (altered) influenza viruses. This vaccine is made with live viruses that can stimulate the immune response enough to confer immunity but do not cause classic influenza symptoms (in most instances). The nasal spray vaccine (FluMist) is only approved for healthy individuals ages 2-49 years of age. This nasal spray vaccine contains live attenuated virus (less able to cause flu symptoms due to a designed inability to replicate at normal body temperatures). This live vaccine could possibly cause the disease in infants and immunocompromised people and does not produce a strong immune response in many older people. Side effects of the nasal mist include nasal congestion, sore throat, and fever. Headaches, muscle aches irritability, and malaise have also been noted. In most instances, if side effects occur, they only last a day or two. This nasal spray has been produced for both conventional and the novel H1N1 flu viruses and should not be given to pregnant individuals or anyone who has a medical 3
condition that may compromise the immune system because in some instances the flu is the side effect. Caregivers should read the vaccine precaution insert before giving any vaccine, injectable or nasal, as these inserts are occasionally updated. Some people do not receive influenza vaccine because they believe it is not very effective. There are several different reasons for this belief. People who have received influenza vaccine may subsequently have an illness that is mistaken for influenza, and they believe that the vaccine failed to protect them. In other cases, people who have received the vaccine may indeed have an influenza infection. Overall vaccine effectiveness varies from year to year, depending upon the degree of similarity between the influenza virus strains included in the vaccine and the strain or strains that circulate during the influenza season. Because the vaccine strains must be chosen nine to 10 months before the influenza season, and because influenza viruses mutate over time, sometimes mutations occur in the circulating virus strains between the time the vaccine strains are chosen and the next influenza season ends. These mutations sometimes reduce the ability of the vaccineinduced antibody to inhibit the newly mutated virus, thereby reducing vaccine efficacy. This commonly occurs with the conventional flu vaccines as the specific virus types chosen for vaccine inclusion are based on reasoned projections for the upcoming flu season. Occasionally, the vaccine does not match the actual predominating virus strain and is not very effective in generating a specific immune response to the predominant infecting flu strain. Vaccine efficacy also varies from one person to another. Studies of healthy young adults have shown influenza vaccine to be 70%-90% effective in preventing illness. In the elderly and those with certain chronic medical conditions such as HIV, the vaccine is often less effective in preventing illness. Studies show the vaccine reduces hospitalization by about 70% and death by about 85% among the elderly who are not in nursing homes. Among nursing-home residents, vaccine can reduce the risk of hospitalization by about 50%, the risk of pneumonia by about 60%, and the risk of death by 75%-80%. If antigenic drift results in changing the circulating virus from the strains used in the vaccine, vaccine efficacy may be reduced. However, the vaccine is still likely to lessen the severity of the illness and to prevent complications and death. The vaccine produced against the novel H1N1 swine flu was just initiated in the summer of 2009 and then rapidly tested for safety and effectiveness, in contrast to the longer time cycle used for production of conventional flu vaccine. However, the injectable (and nasal) vaccines used the same methods developed for conventional flu vaccines over many years. The expedited clinical trials for the novel H1N1 vaccines, according to the CDC, have shown the injected vaccine to be safe and very effective with immunologic protection developing in healthy people. In the 18-64 age group, 98% were protected while those over 65 were 93% protected. Other groups are being studied, but protection with the injected vaccine in preliminary and ongoing trials seems good, according to the CDC. To date, about 39,000 Chinese people have been given the vaccine with very few (four) developing only mild side effects such as muscle cramps and headache, according to WHO officials. Recently, data presented on the effectiveness of the nasal mist vaccine in adults were published; the data indicated that for conventional flu protection, the nasal mist was less effective than the injected vaccine in adults for the conventional flu. Other studies have shown that the nasal mist vaccine was slightly more effective in healthy children than the injectable vaccine. The following is a list of the CDC-approved H1N1 vaccines and the companies that name and manufacture them as of 10/29/09: y y y y Influenza A (H1N1) 2009 Monovalent Vaccine by Sanofi Pasteur Influenza A (H1N1) 2009 Monovalent Vaccine by Novartis Influenza A (H1N1) 2009 Monovalent Vaccine Live, Intranasal by MedImmune, LLC Influenza A (H1N1) 2009 Monovalent Vaccine by CSL Limited
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Why should the flu vaccine be taken every year?
Although only a few different influenza virus strains circulate at any given time, people may continue to become ill with the flu throughout their lives. The reason for this continuing susceptibility is that influenza viruses are continually mutating, through the mechanisms of antigenic shift and drift described above. Each year, the vaccine is updated to include the most current influenza virus strains that are infecting people worldwide. The fact that influenza viral genes continually change is one of the reasons vaccine must be taken every year. Another reason is that antibody produced by the host in response to the vaccine declines over time, and antibody levels are often low one year after vaccination.
What are some treatments an individual can do at home for the flu?
First, individuals should be sure they are not members of a high-risk group that is more susceptible to getting severe flu symptoms. Check with your physician if you are unsure if you are a higher risk person. Home care is recommended by the CDC if a person is normally healthy with no underlying diseases or conditions (for example, asthma, lung disease, pregnant, or immunosuppressed). Increasing liquid intake, warm showers, and warm compresses, especially in the nasal area, can reduce the body aches and reduce nasal congestion. Nasal strips and humidifiers may help reduce congestion, especially while trying to sleep. Some physicians recommend nasal irrigation with saline to further reduces congestion; some recommend nonprescription decongestants. Fever can be treated with over-the counter acetaminophen (Tylenol) or ibuprofen (Motrin and others) (read labels for safe dosage). Cough can be suppressed by cough drops and over-the-counter cough syrup. If an individual's symptoms at home get worse, their doctor should be notified.
When should a person go to the emergency department for the flu?
The CDC has recently published guidelines on who should go to the emergency department for flu symptoms and who should not go. The CDC published these guidelines to avoid a crush of people going to the emergency department during the H1N1 flu pandemic and utilizing limited resources needed for true emergency patients such as cardiac or trauma patients and to avoid transmitting the virus to high-risk patients. The CDC guidelines are as follows for children and adults. The CDC urges normally healthy people that get either the conventional or novel H1N1 swine flu to stay home as the large majority of infected individuals will recover without antiviral medications or other treatments. The CDC urges people to seek emergency medical care for a sick child with any of these symptoms: 1. 2. 3. 4. 5. 6. 7. Fast breathing or trouble breathing Bluish or gray skin color Not drinking enough fluids Severe or persistent vomiting Not waking up or not interacting Being so irritable that the child does not want to be held Flu-like symptoms improve but then return with fever and cough
The following is the CDC's list of symptoms that should trigger emergency medical care for adults: 1. Difficulty breathing or shortness of breath 2. Pain or pressure in the chest or abdomen 3. Sudden dizziness 5
4. 5. 6. 7.
Confusion Severe or persistent vomiting Flu-like symptoms improve but then return with fever and worse cough Having a high fever for more than three days is another danger sign, according to the WHO, so the CDC has also included this as another serious symptom.
Who should receive the flu vaccine? When should someone get the flu shot?
In the United States, the flu season usually occurs from about November until April. Officials have decided each new flu season will start on Oct. 4. Typically, activity is very low until December, and peak activity most often occurs between January and March. Ideally, the conventional flu vaccine should be administered between September and mid-November. It takes about one to two weeks after vaccination for antibodies against influenza to develop and provide protection. Groups at increased risk of conventional influenza complications include: y y y y people aged 65 years or older; residents of nursing homes and other chronic-care facilities housing patients of any age who have chronic medical conditions; adults and children with chronic disorders of the pulmonary, cardiovascular, or immune systems, including children with asthma; adults and children who have required regular medical follow-up or hospitalization during the preceding year because of chronic metabolic diseases (including diabetes mellitus), renal dysfunction, hemoglobinopathies, or immunosuppression (including immunosuppression caused by medications); children and teenagers (6 months to 18 years of age) who are receiving long-term aspirin therapy and therefore may be at risk for developing Reye syndrome after influenza; and women in the third trimester of pregnancy or in the early postpartum period. There is some evidence to suggest that women who are in the third trimester of pregnancy or in the early postpartum period may be at increased risk for serious medical complications after influenza infection. Pregnant women who will be in the third trimester of pregnancy between December and April should consult their health-care provider about receiving influenza vaccine during the period from September to midNovember.
y y
Unfortunately, because the novel H1N1 flu virus is not following the conventional flu pattern for time of disease appearance (appeared in April and increased over the summer and fall of 2009) or susceptible populations, the CDC has had to alter somewhat the recommendations this year. Consequently, the CDC has listed these groups as being at high risk for novel H1N1 flu and should obtain the novel H1N1 vaccine as soon as it is available to them: y y y y y pregnant women, people who live with or care for children younger than 6 months of age, health-care and emergency-services personnel, people between the ages of 6 months through 24 years of age and children 5-18 years of age who have chronic medical problems, and people from 25-64 years of age who are at higher risk for novel H1N1 because of chronic health disorders or compromised immune systems.
In addition, the following groups should be vaccinated because they may transmit influenza to people who are at high risk for complications if they become infected with either the conventional or novel H1N1 flu. 1. Physicians, nurses, and other health-care personnel in both hospital and outpatient-care settings 6
2. Employees in nursing homes and chronic-care facilities who have contact with patients or residents 3. Providers of home care to people at high risk (for example, visiting nurses and volunteer workers) 4. Household members (including children) of high-risk people Furthermore, the CDC advises that all children 6-59 months of age get a yearly conventional flu vaccination since each year there are over 20,000 children who require hospitalization because of the flu and flu is easily passed from child to child. Finally, the flu vaccine, both the conventional and H1N1, may be administered to any person who wishes to reduce his or her chances of acquiring influenza infection. People who provide essential community services should be considered for vaccination to minimize disruption of essential activities during influenza outbreaks. Students or other people in institutional settings, such as those who reside in dormitories, should be encouraged to receive the vaccine to minimize the disruption of routine activities during epidemics. Such outbreaks have been reported for H1N1 in 2009. People needing further information regarding the use and availability of the influenza vaccine should consult with their health-care provider or their local health department or the CDC at the flu.gov Web site.
What is the bird (avian) flu?
The bird flu, also known as avian influenza, is an infection caused by avian influenza A. Bird flu can infect many bird species, including domesticated birds such as chickens. In most cases, the disease is mild; however, some subtypes can be pathogenic and rapidly kill birds within 48 hours. Rarely, humans can be infected by these bird viruses. People who get infected with bird flu usually have direct contact with the infected birds or their waste products. Depending on the viral type, the infections can range from mild influenza to severe respiratory problems or death. When this virus (H5N1) infects human, it is highly pathogenic and although only about 700 people worldwide have been infected, about 10% died. Fortunately, this virus does not seem to be easily passed from person to person. The major concern among scientists and physicians about bird flu is that it will change (mutate) its viral RNA enough to be easily transferred among people and produce a pandemic similar to the one of 1918.
Do antiviral agents protect people from the flu?
Vaccination is the primary method for control of influenza; however, antiviral agents have a role in the prevention and treatment of mainly influenza type A infection. Regardless, antiviral agents should not be considered as a substitute or alternative for vaccination. Currently, there are four antiviral agents available in the United States. They are amantadine (Symmetrel), rimantadine (Flumadine), zanamivir (Relenza), and oseltamivir (Tamiflu). In 2006, the CDC recommended that neither amantadine nor rimantadine be used for prevention of influenza A as resistance to these drugs had developed. This resistance problem and additional adverse reactions to the drugs (behavioral changes, seizures) have limited their subsequent use. Oseltamivir has had a similar FDA label warning about behavioral changes. The 2007-2008 Advisory Committee on Immunization Practices (ACIP) recommends that only zanamivir and oseltamivir be used in the U.S. for treatment or prevention until influenza A susceptibility to the other drugs is reestablished. In general, infected people need to begin taking the antiviral medications within two days of developing the initial symptoms of influenza. This may reduce the symptoms and shorten the illness by one or two days. However, in high-risk people, these drugs may either prevent the flu disease symptoms (both conventional and novel H1N1) or, once established, prevent the flu from becoming severe. There is a 7
high potential for overuse of these drugs so the CDC has put out the following guidelines to be used with clinical judgment: y y y Uncomplicated febrile illness typically does not require antiviral treatment unless individuals are at higher risk for influenza complications. Treatment is recommended for all hospitalized patients with confirmed, probable, or suspected novel influenza (H1N1). Clinical judgment should be used when evaluating children; caregivers should be aware that the risk for severe complications from seasonal influenza among children younger than 5 years of age is highest among children younger than 2 years of age and may require antiviral medication.
In early September 2009, CDC officials further modified the antiviral guidelines for the interim guidelines for use of Tamiflu and Relenza as follows: 1. People with high risk factors should discuss flu symptoms and when to use antivirals; doctors should provide a prescription for the antiviral for the patient to use if the patient is exposed or develops flulike symptoms without having to go in to see the doctor. 2. "Watchful waiting" was added as a response to taking antiviral drugs with the emphasis on those people who develop fever and have a preexisting health condition should then begin the antiviral medication. 3. The antivirals are the first-line medicines for treatment of novel H1N1 swine flu, and most current cases of flu are novel H1N1 and are, to date, susceptible to Tamiflu and Relenza. Prevention of influenza (both A and B) is possible with both zanamivir and oseltamivir. While zanamivir was approved for people 7 years of age or older and oseltamivir was approved for people 1 year of age and older for the conventional flu, the CDC has published guidelines for antiviral use against novel H1N1 in late September 2009 that includes children under 2 years of age and pregnant women: y y People with more severe illness, such as those hospitalized with suspected or confirmed influenza People with suspected or confirmed influenza who are at higher risk for complications o Children younger than 2 years of age o Adults 65 years of age and older o Pregnant women o People with certain chronic medical or immunosuppressive conditions People younger than 19 years of age who are receiving long-term aspirin therapy
y
Prevention rates vary from about 68%-89% when these antiviral medications were given to individuals before they developed symptoms of the conventional flu or were exposed to infected people; data are not yet available for novel H1N1. Treatment usually consists of a five-day schedule of antiviral medication, while prevention usually requires 10 days of medication. For example, duration of antiviral chemoprophylaxis (prevention) post-exposure is 10 days after the last known exposure. However, recommended treatment and prevention schedules vary according to age, weight, drug formulation, and if the individual is hospitalized. Details about dosing in adults, pregnant women, children, and infants are available and updated on both the CDC and FDA web sites: http://www.cdc.gov/H1N1flu/antiviral.htm and http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm18387 0.htm. Gastrointestinal symptoms (nausea, vomiting) are some of the most common side effects of these drugs. Influenza viruses are known to develop resistance to both drugs but at a much lower rate than to the other antiviral drugs. These drugs and others that are in development (such as peramivir, favipiravir, and ligand epitopes) are being studied to determine if they can be used to prevent or treat new influenza strains such as novel H1N1 and bird flu. 8
