Prevention and Treatment of Influenza
Like many of the other children in their preschool, four-year-old Jessica Stein and her brother, Eric, developed a fever and cold symptoms in January 2002. A few days later, the children’s parents, Gary and Doris, felt that both Jessica and Eric had recovered so the children returned to school. Jessica, however, continued to exhibit signs of decreased energy and soon thereafter appeared to suffer a relapse. Her parents were concerned enough to call the doctor’s office. The nurse advised them not to bring her into the office since she likely had the same virus that remained widespread in their community, and the presence of her appetite indicated that she likely had a mild case. The nurse also instructed Gary and Doris to give Jessica plenty of fluids. However, Jessica’s condition did not improve. On Friday, February 1, 2002 Jessica’s breathing grew uneasy as she slept and her hands and feet felt slightly cool. Gary and Doris called their pediatrician again that night who advised them to take Jessica to the emergency room for what appeared to be dehydration. Sadly, Jessica died the next morning at the hospital from myocarditis (swelling of the heart), a complication that can occur due to influenza virus infection.
Annual deaths in the U.S. due to influenza far exceed the total of all other vaccine preventable diseases combined, with an average of 36,000 influenza-associated respiratory and circulatory deaths annually. Influenza-associated complications are also substantial with greater than 200,000 annual hospitalizations. Age-specific rates of death are greatest in those >65 years old, while children less than two years of age have the highest hospitalization rates. Furthermore, influenza virus infects about 10 percent of the population on a yearly basis resulting in millions of people seeking medical attention each year (see Chapter One for additional information about the impact of influenza on the U.S. and worldwide).
Influenza Vaccines: Use in Prevention of Influenza Disease
Getting an annual influenza vaccination is the best means available to help prevent the flu. Although drugs are available to treat the flu if given within 48 hours of onset of the illness, preventing the flu is clearly preferable to treating the disease. Methods of prevention include avoiding exposure to the virus, good hygiene and most importantly annual vaccination. While avoiding exposure to someone who is ill with any infectious disease is a great idea in theory, from a practical standpoint this is often difficult to achieve. This is particularly true for children who play a central role in the spread of influenza virus in a community. The rate of infection is particularly high in child care and school settings because children shed virus from their nose and throat in larger amounts and for approximately twice as long as adults, and in addition, children are less likely to use good hygiene practices such as hand washing.
Individuals remain susceptible to influenza disease even if they have previously been infected or been given the vaccine in years past. This is due to changes that occur in the surface proteins (hemagglutinin and neuraminidase) of the virus (see Chapter One for more information). The effectiveness of the vaccine is highest in years where the strains of the virus circulating in the community are well matched to the strains contained in the vaccine used that year. Three different types of influenza virus (A/H1N1, A/H3N2 and B) currently cause most of the influenza disease. On a yearly basis the specific strains of virus that are spreading throughout the world can undergo genetic changes in these external proteins so that the previous year’s vaccine may not be as effective. For this reason in February of each year the Centers for Disease Control and Prevention (CDC) and World Health Organization (WHO) meet to determine the specific strain of each type of influenza virus H1N1, H3N2 and B that will go into the influenza vaccine for the upcoming season. They base their decision in large part on the strains of influenza virus that are present in Asia at that time. For example, during the 2008–2009 influenza season the H1N1 and B strains caused a great majority of disease in the U.S. The H1N1 strain circulating in the community was a very good match with the one in the vaccine, but the B strain circulating in the U.S. was not as good a match. This resulted in the vaccine being more effective against the H1N1 strain than the B strain during that influenza season.
Yearly immunization with influenza vaccine is routinely recommended by the CDC for children six months through 18 years of age. During most epidemic years, disease due to influenza virus peaks between December and March. However, in some years the peaks occur as early as October or November or as late as April. While it is optimal to get the vaccine early in the fall, vaccination as late as March can be protective. Although the number of people getting the vaccine has increased in recent years (Table 4), a much greater percentage of the population needs to be vaccinated before influenza will stop being the leading cause of vaccine-preventable deaths in the U.S.
Because the risk of hospitalization among pregnant women who develop influenza is three-fold higher than in non-pregnant women, the CDC recommends that all women receive the inactivated vaccine if they will be pregnant anytime during the influenza season. Immunization is also recommended for other adults who are at high risk for complications due to influenza virus (e.g., those with underlying heart and lung disease). Vaccinating adults who are in the same household or otherwise have close contact with children can offer further protection both for the adult as well as the child.
Types of Vaccines & Adverse Effects
There are currently two kinds of influenza vaccine available in the U.S. – a killed virus vaccine, also known as an inactivated virus vaccine that contains inactivated H1N1, H3N2 and B virus strains, and a live virus vaccine containing the same three virus strains. In the live virus vaccine the virus has been genetically altered so that the virus can grow at temperatures found in human nasal cavities (32-33 degrees C), but not at temperatures found in internal organs such as the lung (>37 degrees C), thereby eliminating the chance that the vaccine can cause the flu. The inactivated vaccine is given as a shot into a muscle, while the live vaccine is administered by spraying the vaccine into the nose. The inactivated vaccine is approved for children six months and older, and the live vaccine is approved for children two years and older. The inactivated vaccine is approved for use in healthy children and those with chronic illnesses such as asthma. Currently, the live vaccine is recommended only for healthy people between two to 49 years of age.
A large number of studies involving many thousands of children and adults indicate that these influenza vaccines are effective in preventing illness. Overall, the effectiveness of the vaccine averages 75 percent with a range of 50 to 95 percent in any given year. Studies suggest that the live vaccine is more effective than the killed vaccine in children five years of age or younger. In older children and adults the inactivated vaccine appears to be more effective.
Inactivated and live influenza vaccines can be given at the same time as other routinely recommended vaccines. Children less than nine years of age receiving influenza vaccine for the first time require two doses administered one month apart to produce a satisfactory immune response. However, older children and adults only need one dose of the vaccine to exhibit a good immune response to help protect them from developing the flu.
Influenza vaccines are associated with few adverse effects (side effects). With the inactivated vaccine low grade fever is most common in children younger than two years of age (10 to 35 percent of recipients), and occurs primarily six to 24 hours after vaccination. Local reactions are infrequent in children younger than 13 years of age, while they occur in approximately 10 percent of adolescents and adults. Those with severe allergic reactions to egg protein can experience, on rare occasion, a similar type of reaction to influenza vaccines. Although influenza vaccines have been administered safely to such children after skin testing and desensitization (a method used where a physician specializing in allergic diseases gives small, but increasing amounts of the egg protein over a short period of time followed by the influenza vaccine, which prevents the allergic reaction from occurring), children and adults with this allergy generally should not receive influenza vaccines because of their risk of a serious reaction. Instead, there are drugs available that can be used as an alternative way to try and prevent influenza infection in this population. The inactivated vaccine contains gelatin and should generally not be used in those who are allergic to this protein. People who have a history of Guillain-Barre syndrome (a disease that results in weakness of muscles that starts in the legs and ascends upwards) should also not receive influenza vaccines.
The most common side effect of the live vaccine is nasal congestion. Many people make the assumption that the live virus vaccine can cause the flu, but the virus in the vaccine can only grow in the nose and not at body temperature. Furthermore, studies show that flu-like symptoms are no more common in those who received the vaccine versus those who did not.
Antiviral Medication: Treatment of Influenza Disease
There are two types of influenza antiviral drugs currently licensed in the U.S.: adamantanes (amantadine and rimantadine) and neuraminidase inhibitors (zanamivir [Relenza®] and oseltamivir [Tamiflu®]). These drugs can reduce the severity and shorten the length of influenza illness by approximately one day if treatment is started within 48 hours of onset of the person’s symptoms. These drugs also decrease the amount of influenza virus in the nose thereby reducing the chance that they will pass the virus to others. Treatment with antiviral therapy (i.e., medicines that kill the virus) should be considered for any child or adult at high risk for complications from influenza or for anyone with influenza in whom it may be useful to reduce the length of symptoms (Table 5). While the use of influenza vaccine is clearly the preferred method for preventing influenza, these drugs can also be used to prevent illness in an unvaccinated person who is exposed to someone with the flu (Table 6).
Amantadine and rimantadine are effective against some strains of influenza type A. These drugs are given by mouth and work by blocking the ability of the virus to reproduce. Some disadvantages of amantadine and rimantadine include: 1) emergence of resistance (i.e., the virus undergoes changes that results in the drug no longer being able to kill the virus), which is now seen in most strains of influenza A H3N2; 2) the inability of these drugs to kill any strains of influenza type B; and 3) the occurrence of reversible central nervous system (CNS) side effects, including nervousness, lightheadedness, difficulty with concentration and rarely, tremors or seizures.
The neuraminidase inhibitors, oseltamivir and zanamivir, work by interfering with the release of viral particles from the surface of infected respiratory tract cells. Oseltamivir is taken by mouth and is approved for use only in those who are one year of age or older. Zanamivir is a powder taken by inhaling it through a breath-activated device and is approved for use only in those who are seven years of age or older. Oseltamivir has been shown to reduce the frequency of serious complications such as bacterial pneumonia. Until recently these drugs were effective for the treatment of influenza type A or type B if given within 48 hours of the start of symptoms. However, the H1N1 strain of influenza A has become resistant to oseltamivir, but zanamivir still remains able to kill the virus. The safety and efficacy of zanamivir in patients with chronic lung disease have not been established; some patients with a history of asthma have experienced wheezing, so zanamivir is generally not recommended for patients with underlying airway disease. Oseltamivir is associated with nausea and vomiting in approximately 10 percent of recipients.
These drugs can also be helpful in preventing influenza. When determining who should get these antiviral medications for prevention of the flu, factors related to cost, compliance and potential side events should be considered. To be maximally effective as preventive agents, the drugs must be taken each day for the duration of influenza activity in the community. Using these drugs to help prevent influenza should not be considered a substitute for annual vaccination.
The recent occurrence of oseltamivir resistance among influenza A H1N1 virus strains presents challenges for selecting antiviral medications to treat and prevent influenza. It also provides additional reasons for clinicians to do rapid testing on patients for influenza virus infection. Due to this recent issue with resistance of H1N1 to oseltamivir interim guidelines have been provided by the CDC to health care workers for treatment or prevention of influenza in the U.S. If available, confirmatory testing with a rapid diagnostic test capable of distinguishing influenza disease caused by influenza H1N1 from H3N2 or influenza B virus can be used to guide treatment. In some circumstances treatment with both a neuraminidase inhibitor and an adamantane should be considered.
Educating About Flu
Prior to Jessica’s illness her parents did not think that the flu was serious enough to get their children or themselves vaccinated even though they had always made sure their children had received all their other immunizations. They thought at worst their children might develop a “bad cold” and that nothing could occur that modern science could not resolve. Since Jessica’s death, Gary and Doris not only make sure that everyone in their family gets an annual flu vaccine, but as board members of Families Fighting Flu they work tirelessly to help ensure that all parents are aware that influenza virus is a serious disease that can result in hospitalization and even death. Gary and Doris, along with the other members of the organization, spend a great deal of time educating the public about the importance of vaccinating children and other family members every year against this vaccine-preventable illness. As a result, their advocacy has been instrumental in getting the CDC to expand the influenza vaccination recommendations to include routine immunization of all children six months through 18 years of age, as well as all adults living in the same household.
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