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CME

Confronting Influenza: Prevention Strategies That Work

  • Authors: Chairperson: Robert B. Belshe, MD; Faculty: Randy Bergen, MD, MPH; Stan L. Block, MD; Charles S. Bryan, MD; Richard D. Clover, MD; Pierce Gardner, MD; W. Paul Glezen, MD; Lisa A. Jackson, MD, MPH; Harry L. Keyserling, MD; Jay M. Lieberman, MD; Arnold S. Monto, MD; Maurice A. Mufson, MD, MACP; Pedro A. Piedra, MD; Keith S. Reisinger, MD, MPH; John J. Treanor, MD
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Target Audience and Goal Statement

This program is intended for office-based family practice physicians and pediatricians, general preventive medicine physicians, and other primary care physicians and healthcare professionals who treat patients with influenza.

Upon completion of this activity, participants will be able to:

  1. Convey the medical importance of influenza virus infection in children and adults.
  2. Review the practice priorities for influenza vaccination, including the guidelines of the Advisory Committee on Immunization Practices, and the prophylactic use of antiviral medications.
  3. Assess the safety, efficacy, and effectiveness of the trivalent inactivated and the trivalent live attenuated cold-adapted influenza vaccines.
  4. Discuss strategies to prevent influenza-related illnesses in individuals and the spread of influenza in communities.


Author(s)

  • Robert B. Belshe, MD

    Diane and J. Joseph Adorjan Endowed Professor of Infectious Diseases and Immunology; Professor of Medicine, Pediatrics, and Molecular Microbiology, Saint Louis University School of Medicine; Director, Division of Infectious Diseases and Immunology, Saint Louis University Hospital, Saint Louis, Missouri

    Disclosures

    Disclosure: Consultant: MedImmune.

    Dr Belshe has intellectual property licensed to Wyeth.

  • Randy Bergen, MD, MPH

    The Permanente Medical Group, Kaiser Walnut Creek Medical Center, Walnut Creek, California

    Disclosures

    Disclosure: Dr. Bergen has indicated no significant financial interests or affiliations

  • Stan L. Block, MD

    Professor of Pediatrics, University of Louisville Medical School, Louisville, Kentucky, University of Kentucky College of Medicine, Lexington, Kentucky; President, Kentucky Pediatric Research, Bardstown, Kentucky

    Disclosures

    Disclosure: Clinical Investigator: Wyeth. MedImmune; Research Consultant: Wyeth, MedImmune; Retained Consultant: Wyeth.

  • Charles S. Bryan, MD

    Professor of Medicine, University of South Carolina School of Medicine, Columbia, South Carolina

    Disclosures

    Disclosure: Dr. Bryan has indicated no significant financial interests or affiliations.

  • Richard D. Clover, MD

    Dean, School of Public Health and Information Sciences, University of Louisville, Louisville, Kentucky

    Disclosures

    Disclosure: Clinical Investigator: Aventis.

  • Pierce Gardner, MD

    Professor of Medicine, State University of New York at Stony Brook, Stony Brook, New York

    Disclosures

    Disclosure: Dr. Gardner has indicated no significant financial interests or affiliations.

  • W. Paul Glezen, MD

    Professor of Molecular Virology and Microbiology; Professor and Head, Preventive Medicine Section, Department of Pediatrics, Baylor College of Medicine, Houston, Texas

    Disclosures

    Disclosure: Clinical Investigator: MedImmune.

  • Lisa A. Jackson, MD, MPH

    Associate Professor, Department of Epidemiology, University of Washington; Associate Investigator, Center for Health Studies, Group Health Cooperative, Seattle, Washington

    Disclosures

    Disclosure: Clinical Investigator: Aventis Pasteur.

  • Harry L. Keyserling, MD

    Professor of Pediatrics, Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia; Chief, Pediatric Infectious Disease, Children's Healthcare of Atlanta at Egleston, Atlanta, Georgia.

    Disclosures

    Disclosure: Clinical Investigator: Aventis Pasteur, Aviron, Wyeth-Lederle Vaccines.

  • Jay M. Lieberman, MD

    Associate Professor of Clinical Pediatrics, University of California, Irvine; Chief, Pediatric Infectious Diseases, Miller Children's Hospital, Long Beach, California

    Disclosures

    Disclosure: Clinical investigator: MedImmune; Speaker bureau: Wyeth, Aventis Pasteur.

  • Arnold S. Monto, MD

    Professor of Epidemiology, University of Michigan, Ann Arbor, Michigan

    Disclosures

    Disclosure: Research consultant: Roche and Wyeth/MedImmune.

  • Maurice A. Mufson, MD, MACP

    Professor of Medicine; Chair Emeritus, Department of Medicine; Professor of Microbiology, Marshall University School of Medicine; Courtesy Staff, Cabell Huntington Hospital and Saint Mary's Hospital, Huntington, West Virginia

    Disclosures

    Disclosure: Dr. Mufson has indicated no significant financial interests or affiliations.

  • Pedro A. Piedra, MD

    Associate Professor, Baylor College of Medicine, Texas Children's Hospital, Ben Taub General Hospital, Houston, Texas

    Disclosures

    Disclosure: Clinical Investigator: Aventis, GlaxoSmithKline, NIH, ViroPharma, Wyeth; Research Consultant: GlaxoSmithKline.

  • Keith S. Reisinger, MD, MPH

    Medical Director, Primary Physicians Research, Pittsburgh, Pennsylvania

    Disclosures

    Disclosure: Clinical Investigator: Aviron, Wyeth-Lederle Vaccines.

  • John J. Treanor, MD

    Associate Professor of Medicine, University of Rochester, Attending Physician, Strong Memorial Hospital, Rochester, New York

    Disclosures

    Disclosure: Dr. Treanor has indicated no significant financial interests or affiliations.


Accreditation Statements

    For Physicians

  • Professional Postgraduate Services® is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

    Thomson Professional Postgraduate Services® designates this educational activity for a maximum of 1.5 category 1 credits toward the AMA Physician's Recognition Award. Each physician should claim only those credits that he/she actually spent in the educational activity.

    The American Medical Association has determined that non-US licensed physicians who participate in this CME activity are eligible for AMA PRA category 1 credit.

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For questions regarding the content of this activity, contact the accredited provider for this CME/CE activity noted above. For technical assistance, contact [email protected]


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CME

Confronting Influenza: Prevention Strategies That Work

Authors: Chairperson: Robert B. Belshe, MD; Faculty: Randy Bergen, MD, MPH; Stan L. Block, MD; Charles S. Bryan, MD; Richard D. Clover, MD; Pierce Gardner, MD; W. Paul Glezen, MD; Lisa A. Jackson, MD, MPH; Harry L. Keyserling, MD; Jay M. Lieberman, MD; Arnold S. Monto, MD; Maurice A. Mufson, MD, MACP; Pedro A. Piedra, MD; Keith S. Reisinger, MD, MPH; John J. Treanor, MDFaculty and Disclosures
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Confronting Influenza: Prevention Strategies That Work, Presented by John J. Treanor, MD

An Influenza Overview

  • This Dinner Dialogue talk is sponsored by the National Campaign for Influenza Prevention (NCIP), "Confronting Influenza: Prevention Strategies That Work." As the name implies, the National Campaign for Influenza Prevention is an organization whose goal is to help physicians implement practices that can effectively reduce or eliminate the impact of this important public health problem on patients.

  • Confronting Influenza: Prevention Strategies That Work

    Slide 1.

    Confronting Influenza: Prevention Strategies That Work

    (Enlarge Slide)
  • My objectives are, first of all, to stress the medical importance of influenza virus infection, to review the practice priorities for influenza vaccination, put out every year by the Advisory Committee on Immunization Practices (ACIP), and also to talk about using an adjunctive vaccination, an antiviral medication, to prevent influenza.

    Then we'll discuss the 2 available influenza virus vaccines. The first is the trivalent inactivated vaccine (TIV), which is given intramuscularly, and with which most people probably are familiar. The TIV has been in use off and on in the United States since the late 1940s. Second is a new vaccine, the trivalent cold-adapted live attenuated influenza virus vaccine (CAIV-T), which is given intranasally, and which has just recently been licensed for use in individuals between the ages of 5 and 49 years. Also, we'll discuss strategies for using those vaccines in conjunction with antiviral drugs to reduce or eliminate the impact of influenza on patients.

    First of all, let's review what we mean when we talk about influenza. Influenza is a clinical syndrome that is caused by the influenza virus. There are actually 3 types of influenza viruses: influenza A, B, and C. It turns out that influenza C viruses mostly cause relatively trivial infections, similar to those of the common cold. Those viruses seldom raise concern. Thus, I will focused on the 2 main disease-causing types of influenza: influenza A and B. Both of these have a very similar structure.

  • Confronting Influenza: Prevention Strategies That Work

    Slide 2.

    Confronting Influenza: Prevention Strategies That Work

    (Enlarge Slide)
  • This is influenza A, which is characterized by a few very important features.

    The influenza A virus has an envelope -- a lipid membrane derived from the cell membrane -- that encompasses the genetic material of the virus. You can think of these viruses almost as little beanbags full of viral genes with a sticky surface on the outside that helps them attach to susceptible cells.

    In this case, the sticky outside material is the hemagglutinin (HA) shown here as the red dot with the ball on the end of. This molecule plays an absolutely critical role in the replication of influenza viruses because it's responsible for attaching to susceptible cells and then allowing the virus to gain entry to the cell where the genetic material, the ribonucleic acid (RNA), can go to work and make new copies of the virus.

    The other very important protein on the outside of the virus is the neuraminidase (NA). Neuraminidase is an enzyme that actually eliminates the receptors for the virus from the surface of the infected cell, allowing the virus to be released and spread to other cells. So the HA has the important role of entering the cell, and NA has the important role of leaving the cell.

    The critical importance of these 2 substances is illustrated by the fact that if you have antibody directed at the HA or the NA of the influenza A virus, you will be protected against infection or illness caused by that virus. The goal of influenza vaccination as we use it today is to generate antibody against the specific HA and NA of the virus that we're vaccinating against to try and prevent influenza virus illness and disease.

    The other protein indicated on the outside here is a little green, barbell-shaped protein called the M2 ion channel. We'll discuss this protein a bit more when we talk about antiviral approaches, but this ion channel also plays an important role in viral infection and it's a target of the antiviral drugs amantadine and rimantadine. The NA is the target of the antiviral drugs zanamivir and oseltamivir. These are drugs that specifically inhibit the activity of the NA enzyme.

    Finally, the other important thing to know about influenza A and B viruses is that they have a segmented RNA genome. This means that the pieces of genetic element, the RNA, are little physically discrete particles. Each one of those segments encodes 1 or 2 of the viral proteins. Because they're physically discrete -- segmented -- if 2 individual influenza viruses get together in the same cell, the daughter progeny viruses can contain any combination of those 8 gene segments. So, theoretically, there could be 28 or 256 different combinations of genes resulting from an infected cell with 2 original parent viruses. This is an important mechanism that influenza viruses use to maintain their diversity in nature.

  • The Influenza Virus

    Slide 3.

    The Influenza Virus

    (Enlarge Slide)
  • Since there are many strains of influenza viruses, we've developed a somewhat complicated and sometimes confusing naming system for these viruses.

    This system is illustrated here. The convention for naming influenza viruses is to start with the influenza type, type A or type B, shown in green. Then we add the geographic location in which this virus was first isolated or identified. In this particular case, Panama is shown in blue. Then an isolate number, shown in white, then the year of isolation -- in this case, 1999 -- shown in beige here. Therefore, this virus is the A/Panama 2007 '99 virus.

    For influenza A viruses -- influenza B viruses have no subtypes -- we also designate the specific subtype of HA and subtype of NA. We designate these subtypes because influenza viruses, in the course of evolving in animal hosts, which are probably their more natural host, have evolved a very diverse set of HAs and NAs that are antigenically distinct from each other. Thus the subtypes are numbered by virologists -- H1 to H15, in the case of the HA and N1 to N9, in the case of the NA.

    In summary, we always designate the HA subtype and the NA subtype when we give the full name of an influenza A virus. This particular virus happens to be the H3 component of the 2003 inactivated influenza virus vaccine.

    We keep track of the HA and NA because the influenza viruses have developed a very complicated way of evading the immunity that's present in the population. The viruses use 2 mechanisms to accomplish this evasive action. Both of these mechanisms rely on the fact that these viruses have an RNA genome with a very high mutation rate. So mutations can occur quite rapidly, and under the right circumstances, can occur through natural selection.

  • World Health Organization (WHO) Influenza Nomenclature

    Slide 4.

    World Health Organization (WHO) Influenza Nomenclature

    (Enlarge Slide)
  • In the case of antibody, what is selected are variants in the HA. This selection process, shown here, allows the new variant viruses to escape from the previous antibody. On the left is an influenza virus whose HA, shown as the 3 green rods, are in the process of being blocked by antibody from attaching to the receptor. The receptor is denoted here as sialic acid.

    In response to this selection process, influenza viruses develop mutations in the gene from the HA, which is shown on the right. These mutations result in slight changes in the HA that prevent those antibodies from binding. The virus, then, is no longer inhibited by that antibody.

  • Antigenic Drift: A Modest Change in the Influenza Virus

    Slide 5.

    Antigenic Drift: A Modest Change in the Influenza Virus

    (Enlarge Slide)

Following the Antigenic Drift

  • This process is shown in a bit more detail here. An influenza virus attached to a HA is prevented from proceeding into the population by the presence of antibody that recognizes that HA, shown as the red bars.

    Under those circumstances, once it builds up in the population, the antibody begins to prevent further transmission of that virus, and the strain begins to die out. Because of the mutation rate of influenza viruses, however, a new virus may emerge -- one with a mutation in one of the 4 antigenic sites on the HA. That new virus is now able to escape from the antibody in the population and is selected by that antibody pressure to become the dominant virus. When this process occurs, we have what is referred to as antigenic drift -- slight changes in the virus over time that allow it to escape from antibody in the population.

    In response to epidemics involving that virus, the population eventually develops antibody that blocks the new variant, shown in blue. The same process is repeated as a new variant arises with the new mutation, shown in purple. The population develops purple antibody. The virus develops a green mutation. Throughout this process, there's a constant battle waged between the virus and the population. The population is exposed to the old virus, develops antibody, and the new virus emerges.

  • Antigenic Drift -- Minor Changes in the HA and/or NA

    Slide 6.

    Antigenic Drift -- Minor Changes in the HA and/or NA

    (Enlarge Slide)
  • This is a list of the H3N2 viruses that have been with us since about 1968 -- the first isolates, A/Hong Kong/68. Then every few years a new antigenic variant developed as the virus slowly evolved from Hong Kong to England to Port Chalmers, all the way to the current virus, A/Panama. Thus, vaccines must be updated every year or so to keep pace with this constant evolution of the HA and, to a lesser extent, the NA.

    A much more serious problem with influenza virus that arises from time to time, however, is referred to as antigenic shift. Antigenic shift refers to situations where the HA or the NA is completely replaced by a new HA. For example, an H1 might be replaced by an H2, or an H2 replaced by an H3. When these new radically different HAs enter the population, it is as though no one has any immunity at all to influenza virus, because they don't. Antibody to H1 does not protect against H2. So when a population that's only been exposed to H1 viruses is exposed to H2, a very large worldwide epidemic results, referred to as a pandemic. Pandemics may be associated with very high levels of mortality, even in young people. Pandemics cause tremendous morbidity, hospitalizations, and wreak economic havoc.

  • Antigenic Variants of Influenza A (H3N2)

    Slide 7.

    Antigenic Variants of Influenza A (H3N2)

    (Enlarge Slide)
  • Shown here is our history of exposure to antigenically shifted influenza viruses from the late 19th century, when we think we had mostly H2N2 viruses, to the recognized pandemic of approximately 1900. We didn't know what influenza viruses were at that time, but serologically it looks like that pandemic may have been due to H3N8 viruses.

    Then in 1918 we had the really big one, the Spanish pandemic of influenza. We now know -- based on polymerase chain reaction techniques -- that this pandemic was due to H1N1 viruses. We continued to have H1N1 disease as almost the exclusive influenza A virus until 1957. At that time the H2N2 virus, referred to as the Asian flu, emerged. This virus, which had a new HA, resulted in a very significant pandemic of influenza.

    We proceeded with antigenic variation of the H2N2 viruses until 1968, when the H3N2 viruses appeared. Since 1968, we've had H3N2 viruses. These viruses are illustrated diagrammatically here -- the H1N1 viruses with their yellow H1 HA and yellow N1 NA. The 1957 virus, both the HA and the NA were different. The 1968 virus had only a change in the HA. The NA stayed the same. Then in 1977 there was a reemergence of H1N1 viruses, which looked genetically identical to the H1N1 viruses that had been circulating in 1950. The origins of this virus and how it arose after all that time remains a mystery to this day.

    But what we do know by genetic sequence analysis is that the H1N1 Spanish flu probably was a direct introduction from some animal species into humans of this new antigenic variant, replacing the H3 viruses that preceded it.

  • History of Antigenic Shift

    Slide 8.

    History of Antigenic Shift

    (Enlarge Slide)
  • The other pandemic viruses in recent memory all were the result of a reassortment of events in which the HA and NA genes were donated by some animal virus. Other internal genes, however, which probably promoted replication in humans, were inherited from previously circulating H1N1 viruses.

    The same event occurred in 1968. The pandemic virus was actually a reassortment of viruses that circulated in nature. We now know that the prime source of these new variants is probably waterfowl, which are considered to be the natural host for influenza A viruses.

    Pandemics don't occur with influenza B viruses because there is only one HA and one NA for flu B viruses. That's probably because flu B viruses, unlike A, are exclusively pathogens of humans. This characteristic has probably limited the antigenic diversity of these viruses and is the reason why we may have severe epidemics, but we never really have pandemics of flu B.

    One of the unique features about influenza viruses is that they are responsible for increased hospitalizations and deaths in adults in a regular yearly fashion.

  • Antigenic Shift = Pandemic Potential

    Slide 9.

    Antigenic Shift = Pandemic Potential

    (Enlarge Slide)

Influenza's Cascade of Complications

  • The reason why influenza viruses have this impact is that, in addition to causing a severe illness, they also predispose individuals to a number of complications. Some of these complications can be quite common, including otitis media in children, sinusitis, and pneumonia. We now recognize that these viruses often cause exacerbations of underlying diseases of both the pulmonary system and the cardiovascular system. They also can be causes of dehydration in infants. There are other more rare complications as well, such as encephalopathy, which seems to be emerging as a more common problem in recent years. Other complications include Reye's syndrome, seen predominantly in children taking aspirin products, as well as myositis, myocarditis, and febrile seizures.

    These complications can drive people with influenza into the hospital and are responsible for increased death rates during influenza virus epidemics.

  • Influenza Virus Infections Cause a Spectrum of Complications

    Slide 10.

    Influenza Virus Infections Cause a Spectrum of Complications

    (Enlarge Slide)
  • We typically try to quantify the impact of influenza viruses by comparing rates of deaths due to pneumonia and influenza or due to all causes during epidemics. The death rates are compared with a baseline that is calculated by looking at 5-year rolling averages of deaths in the winter and the summer. The green line represents the observed number of deaths; the red line indicates the upper limit of the expected number; and the area bounded by those 2 lines shows the impact of influenza on excess deaths or hospitalizations.

    The impact of influenza-related illnesses can vary from year to year; 1998, 1999, and 2000 were particularly severe years. In 2001, however, we had relatively mild disease, and the observed numbers of deaths never exceeded the baseline. The year 2002 was slightly more severe, but these 2 years have been relatively mild from the point of view of influenza virus hospitalizations.

  • Pneumonia and Influenza Mortality

    Slide 11.

    Pneumonia and Influenza Mortality

    (Enlarge Slide)
  • Illustrated here are influenza-related pneumonia and excess hospitalizations, calculated in the way I just described, in the United States in the last 25 years or so. As I mentioned, you can see the numbers are fairly variable, going up and down. In some years, there may be many hospitalizations -- up to 250,000 or more -- and in other years fewer people may require hospitalization.

  • P&I Excess Hospitalizations for United States Influenza Epidemics, 1970-1995

    Slide 12.

    P&I Excess Hospitalizations for United States Influenza Epidemics, 1970-1995

    (Enlarge Slide)
  • Typically, we think of these hospitalizations as occurring in individuals who are elderly, and this is true in a large number of cases. But in some years, a significant amount of the impact of influenza actually occurs in people under the age of 65. These numbers are also quite variable from year to year.

  • P&I Excess Hospitalizations for United States Influenza Epidemics, 1970-1995

    Slide 13.

    P&I Excess Hospitalizations for United States Influenza Epidemics, 1970-1995

    (Enlarge Slide)
  • Potentially, there are differences in virulence between the different types of influenza. In general, it is true that in years when H3N2 viruses are predominant, we tend to see greater impact in terms of pneumonia and influenza-related hospitalizations.

    We think that 2003 will be a predominantly H3N2 year. There's already been significant activity in certain parts of the country, particularly Texas. Such activity often heralds a relatively more severe year. The isolates in Texas have all been H3N2 viruses. So 2003 may be a fairly severe influenza virus season. That concern should propel people into getting vaccinated.

    Here we've divided the years up in terms of which virus predominated. The years in which H3N2 was predominate were the years in which influenza caused the most severe impact.

  • P&I Excess Hospitalizations for United States Influenza Epidemics, 1970-1995

    Slide 14.

    P&I Excess Hospitalizations for United States Influenza Epidemics, 1970-1995

    (Enlarge Slide)

The Heavy Toll in Hospitalizations and Deaths

  • In years in which H1N1 predominates, there is less impact in terms of hospitalizations, with the bulk of those hospitalizations occurring in younger people.

  • P&I Excess Hospitalizations for United States Influenza Epidemics, 1970-1995

    Slide 15.

    P&I Excess Hospitalizations for United States Influenza Epidemics, 1970-1995

    (Enlarge Slide)
  • Influenza B viruses tend to occur somewhere in the middle; these viruses generally are responsible for more hospitalizations than H1N1 but less than H3N2.

  • P&I Excess Hospitalizations for United States Influenza Epidemics, 1970-1995

    Slide 16.

    P&I Excess Hospitalizations for United States Influenza Epidemics, 1970-1995

    (Enlarge Slide)
  • These are much the same data, but if you look now at all-cause deaths rather than those specifically where pneumonia or influenza were listed on the death certificate, the impact is quite enormous. An average of 51,000 deaths each year in the United States during that period of time -- the 1990s -- could be attributed to influenza virus. We now have 2 highly effective vaccines to prevent influenza, which is the leading cause of vaccine-preventable death in the United States by quite a large margin. The statistics tell us that we need to be paying more attention to trying to prevent influenza.

    In terms of pneumonia hospitalizations and deaths, the elderly population is certainly hit hard by influenza.

  • Estimated Annual Influenza-Associated Deaths, 1990-1999

    Slide 17.

    Estimated Annual Influenza-Associated Deaths, 1990-1999

    (Enlarge Slide)
  • But healthy children, especially children under the age of about 3 years, also suffer a significant toll from influenza virus infection. Very young children tend to be the most susceptible people in the population to influenza virus infection. As is true of other respiratory viruses, these children haven't had these illnesses before, so they have no immunity. In these youngsters, the rates of excess hospitalization can be as high as in older people with chronic high-risk conditions. For these reasons, we now think of very young children as a potentially important target for influenza virus immunization.

  • Excess Hospitalizations in Healthy Children Older Than 6 Months and Adults 65 Years or Older

    Slide 18.

    Excess Hospitalizations in Healthy Children Older Than 6 Months and Adults 65 Years or Older

    (Enlarge Slide)
  • When we concentrate on deaths or hospitalizations, we really are looking at the tip of the iceberg in terms of the impact of influenza on public health. Remember that for every one of those hospitalizations or deaths, there are dozens and dozens of illnesses.

    The impact of illnesses in the United States is estimated during a typical flu outbreak to be as many as 40 million illnesses, leading to about $4 billion in direct medical care costs, and as much as $8 billion in economic loss due to lost time from work or school. So in addition to driving people into the hospital and causing deaths, influenza epidemics wreak tremendous havoc on economics and lifestyle in our patients. Since these illnesses are so preventable, we should be paying a lot of attention to these statistics.

  • Current Estimates of the Disease Burden of Influenza

    Slide 19.

    Current Estimates of the Disease Burden of Influenza

    (Enlarge Slide)

Highlighting the High-Risk Groups

  • Neuzil examined the impact of influenza on children and their families. Of course, kids themselves are not going to work, they are missing school and staying home. They're causing parents to miss work, and so there is an economic impact on their families and on society when they get sick.

    Currently, our strategy for influenza vaccination is mostly designed to target those who are identified as being at the highest risk for suffering complications. So our strategy is to use vaccine to prevent complications.

  • Impact of Influenza on Children and Their Families

    Slide 20.

    Impact of Influenza on Children and Their Families

    (Enlarge Slide)
  • Thus the current ACIP recommendations are that we should be giving these vaccines especially, although not exclusively, to persons at the highest risk for influenza complications. That group includes those over 65 years of age or those residing in chronic care facilities regardless of age. Chronic care facilities tend to have many people who are at high risk in a crowded environment that facilitates transmission. Many chronic conditions are known to increase the risk of influenza complications. These conditions include pulmonary and cardiovascular disorders and metabolic disorders -- diabetes in particular. Also at high risk are individuals with renal dysfunction or hemoglobinopathies, such as sickle cell disease, which can certainly be triggered into crisis by influenza virus infection; and those who are immunosuppressed, including individuals with HIV. The recommendation to immunize is very strong because there are much data now showing that individuals with HIV have very increased risk of hospitalization during flu epidemics. It's quite clear that the vaccine effectively prevents influenza in that group and is well tolerated without significant impact on HIV viral load. All expert groups now recommend that individuals with HIV be vaccinated yearly against influenza.

    Pregnant women who are going to be in the second or third trimester during the flu season clearly have an increased risk of hospitalization during the flu. Although the reasons are not clear, the speculation is that the increased cardiopulmonary demands, particularly late in pregnancy, in women who get the flu, may be enough to tip them over into some respiratory distress. But whatever the mechanism, it's clear that there's about a 2- to 5-times increased risk of hospitalization if you're pregnant during the flu season. Thus, pregnant women have been identified as a target group for vaccination.

    In addition, in order to forestall the development of Reye's syndrome, children who are 6 to 18 months of age and who must receive long-term aspirin therapy should certainly be vaccinated every year.

  • Persons at Highest Risk for Influenza Complications

    Slide 21.

    Persons at Highest Risk for Influenza Complications

    (Enlarge Slide)
  • Because we're recognizing that even in healthy children influenza has a significant impact, particularly in very young kids, ACIP is now encouraging vaccination to protect children under the age of 2 years. Currently we're vaccinating household contacts and caretakers of those children as well as children between the ages of 6 and 23 months.

    Now I would like to point out 2 things. Neither the inactivated vaccine nor the cold-adapted vaccine is licensed for use in children under the age of 6 months. So the only ways to protect those little ones are either to immunize family members or to vaccinate their mothers when they're pregnant. Immunizing pregnant women will result in some transfer of passive immunity to the infant. This immunity typically lasts about 4 to 6 months.

  • ACIP Encourages Vaccination to Protect Children Under 2 Years of Age

    Slide 22.

    ACIP Encourages Vaccination to Protect Children Under 2 Years of Age

    (Enlarge Slide)
  • Another very important group to vaccinate is healthcare providers in order to reduce the chance of transmitting influenza to a high-risk patient. We recommend that the medical community be vaccinated, including hospital, outpatient, and emergency-response personnel, employees of chronic care facilities, employees of assisted living facilities, and other types of residencies, and individuals who provide healthcare in the home.

    How about you? Have you been vaccinated? If you haven't, think of vaccination as a way to reduce the impact of influenza virus on your patients as well as to protect yourself from a serious illness that is going to disrupt your ability to provide patient care.

  • Healthcare Providers Transmit Influenza to Those at High Risk

    Slide 23.

    Healthcare Providers Transmit Influenza to Those at High Risk

    (Enlarge Slide)
  • Nowadays we use a trivalent vaccine because although we can make predictions about the specific strains that might circulate every year, we can't always predict which specific type -- H1N1, H3N2, or B -- is going to predominate. Some years, all 3 may circulate. Thus, we use a trivalent vaccine containing the most likely candidate for an H1N1 virus for that year, the most likely candidate for an H3N2, and the most likely B virus candidate.

    The ingredients for the 2003 vaccine include an A/New Caledonia/20/99-like virus. It may not actually be that exact virus, but it will resemble that virus or be identical to that virus as far as its immunogenicity or antigenicity it concerned. Another ingredient is an A/Moscow/10/99-like virus, which is antigenically identical to the Panama virus previously discussed. The third component is the B/Hong Kong/330/2001-like virus. Together we have a trivalent defense against influenza.

  • Influenza Vaccine: A Trivalent Defense

    Slide 24.

    Influenza Vaccine: A Trivalent Defense

    (Enlarge Slide)
  • There are now 2 different types of vaccine, as I mentioned earlier. One is the TIV, delivered by intramuscular injection -- the flu shot. These vaccines were originally licensed in 1944, but we've made a lot of changes in the way we make these vaccines. We now have much more purified and well-tolerated examples of inactivated vaccines, but the basic strategy is the same as it was 50 or 60 years ago. More recently, the CIAV-T has been introduced. This vaccine represents a change in the way we administer the vaccine, giving it intranasally rather than by injection.

  • Two Influenza Vaccines Are Available

    Slide 25.

    Two Influenza Vaccines Are Available

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Comparing Vaccine Strategies

  • Now I just want to compare these 2 different vaccine strategies. The TIV is shown on the left; the cold-adapted vaccine is shown on the right. First of all, how are they similar? They're similar in that they're both designed to generate immunity against the HA and NA. In that regard, they work in the same way. It's the way they get to that point that varies a bit. As previously mentioned, the TIV is administered intramuscularly; cold-adapted vaccine is administered intranasally.

    Because of the way they're administered, the focus of the inactivated vaccine is to generate antibodies in the blood -- so-called serum antibody; whereas the cold-adapted vaccine, which is a live virus that replicates in the upper respiratory tract, is designed mostly to produce antibody at that mucosal surface -- so-called mucosal immunity.

    The inactivated vaccine is inactivated, which means there's no living virus in TIV. But the cold-adapted vaccine is a live viral vaccine. The virus has been altered so that its replication is attenuated, and it cannot cause illness. The cold-adapted vaccine is similar to the measles vaccine or polio vaccine -- all attenuated live viruses.

    The main side effect of the TIV is sore arm. Cold-adapted vaccine may be associated with runny nose. Both vaccines are extremely well tolerated. They're both grown in chick embryos or eggs, so neither vaccine can be administered to individuals who have egg allergy. Currently, the indication for use of TIV is any person over 6 months of age. Cold-adapted vaccine is currently limited to use in people between the ages of 5 and 49 years.

    The efficacy of these vaccines appears to be similar.

  • Comparing TIV and CAIV-T

    Slide 26.

    Comparing TIV and CAIV-T

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  • In children, efficacy rates of 30% to 70% have been documented for TIV; and live attenuated vaccines have been shown to have somewhat greater levels of efficacy, but these vaccines have not been compared directly. The efficacy rate in healthy working adults is between 70% to 90% if it's a good antigenic match between the vaccine and the circulating epidemic strength. In the elderly, the vaccine is somewhat less effective in preventing confirmed influenza, but it's quite effective in preventing death, with protection rates of about 80%.

  • TIV Prevents Influenza Illness

    Slide 27.

    TIV Prevents Influenza Illness

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  • In studies of the elderly living in the community, we've seen 30% to 70% protection against hospitalization. In healthy adults, we've seen 30% to 45% protection against influenza-related work loss, reductions in antibiotic use and physician office visits. In children, we've seen reductions in pediatric household contacts, reductions in the rate of respiratory illness or febrile respiratory illness, and reductions in terms of missed school days.

  • TIV Prevents Complications of Influenza

    Slide 28.

    Comparing TIV and CAIV-T

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  • A number of years ago, Nichol conducted studies examining the ability of influenza vaccines to prevent nonspecific outcomes like illnesses, work days lost or reduced work effectiveness in individuals who were otherwise healthy and employed in the community. There were significant reductions in the numbers of work days lost, or numbers of days with reduced work effectiveness -- people going to work but not being able to get as much done -- and reductions in the numbers of physician visits and hospitalizations in this healthy population.

  • In Adults 18-64 Years, TIV Reduces Number of Illnesses, Physician Visits, and Hospitalizations

    Slide 29.

    In Adults 18-64 Years, TIV Reduces Number of Illnesses, Physician Visits, and Hospitalizations

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  • More recently, Nichol has also shown that influenza vaccine can reduce the rates of cardiac disease and cerebrovascular disease in older people. We've long recognized that individuals benefit by reducing the rates of pneumonia. By looking at a large managed care organization, Nichols compared those who received the vaccine with those who did not. She found significant reductions -- 15% to 20% -- in the rates of cardiac disease in those who were vaccinated. Cardiac disease included heart attacks, stroke, and other forms of cerebrovascular disease.

    It's interesting to speculate on the reasons for this outcome. There's much reason to believe that many of these cardiovascular events are the result of inflammatory responses. So, in people who already have some existing disease, the inflammation as a result of an influenza virus infection may be enough to trigger some of these events. By preventing influenza, therefore, you may prevent cardiovascular and cerebrovascular disease.

  • Influenza Vaccine Reduces Pneumonia, Cardiac, and Cerebrovascular Disease in Older Patients

    Slide 30.

    Influenza Vaccine Reduces Pneumonia, Cardiac, and Cerebrovascular Disease in Older Patients

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A New Vaccine in Our Midst

  • The new vaccine is FluMist (influenza virus vaccine live, intranasal). This is just a picture of the device that's used to administer the live attenuated vaccine. The mist is not actually sprayed in the air. This illustration just shows what the spray looks like. The device is actually placed in the nares and a fine mist is squirted that settles in the upper respiratory tract and allows the virus to get to work inducing immunity.

    These viruses are live and attenuated; they take advantage of the unique feature of influenza to work against flu by using that same strategy to make attenuated vaccine viruses.

  • A New Vaccine: Trivalent Live Attenuated Cold-Adapted Influenza Vaccine (CAIV-T)

    Slide 31.

    A New Vaccine: Trivalent Live Attenuated Cold-Adapted Influenza Vaccine (CAIV-T)

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  • Illustrated here is an attenuated donor virus. This is the so-called cold-adapted virus generated in cell culture by passing the virus at progressively lower temperatures until a virus is derived that can induce immunity but not cause disease. The virus also has restricted replication and is limited only to the upper respiratory tract.

    Obviously, the problem with a live vaccine is that there's a lot to go through every time you want to make a new virus and we have to update these vaccines every year.

    We take advantage of the segmented genome to create a reassortment virus in which those genes responsible for attenuation are derived from the attenuated donor virus. The genes that are responsible for the 2 proteins we're interested in -- HA and NA -- come from the new antigenic variant. Thus we are able to very rapidly generate a new attenuated vaccine virus each year. The new virus is exactly the same as last year's vaccine except for a new HA and NA.

    These vaccine viruses are very reproducible, so there's no change from year to year in the degree of attenuation, the lack of symptoms, and the immunogenicity generated by these viruses. The genetic component that's responsible for that lack of change is always the same and always comes from that same attenuated donor virus. There's an attenuated donor influenza A and an attenuated donor influenza B virus that are used to make their respective vaccines.

    These vaccines are administered intranasally. The idea is to induce the special immunity in the upper respiratory tract.

  • Rapid Attenuation of New Antigenic Variants by Genetic Reassortment

    Slide 32.

    Rapid Attenuation of New Antigenic Variants by Genetic Reassortment

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  • That special immunity is largely due to immunoglobulin A (IgA), as illustrated here. We know that immunoglobulin G (IgG) in the lungs can be derived either from immunization in the upper respiratory tract or from parenteral immunization, as in a flu shot. To get antibody in the upper respiratory tract, we generally have to induce the antibody by vaccinating the upper respiratory tract, and that is the basic goal of giving a live virus in the nose -- trying to generate that local immunity.

    These vaccines are very, very effective in young children.

  • Mucosal and Humoral Immunity to Influenza

    Slide 33.

    Mucosal and Humoral Immunity to Influenza

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  • This is a randomized, controlled study that was done by Belshe and colleagues. The investigators gave healthy young children between the ages of about 2 years and 6 years a dose of either the cold-adapted flu vaccine or placebo, and then followed them over 2 years. In the first year, there was a 95% reduction in the rate of influenza A of the H3N2 type in the children who were vaccinated compared with the placebo recipients, and a 91% protection against influenza B.

    In year 2 there was a revaccination. The children were assigned to the same group they were in originally, and those who'd been vaccinated in the first year got another dose of vaccine. The placebo recipients got placebo in the second year, and that was a year when an antigenic variant circulated that did not match well with the vaccine. Even so, there was an 86% reduction in influenza A of the H3N2 type in year 2 compared with placebo. There was no influenza B in that study in the second year. We also did a small study to investigate protection against H1N1 by simply examining the rates of reduction in replication of the vaccine virus. This is a bit complicated, but basically there was about a 90% reduction in the rates of H1N1 as well.

  • Protective Efficacy of CAIV-T Is High in Healthy Young Children

    Slide 34.

    Protective Efficacy of CAIV-T Is High in Healthy Young Children

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  • There were a variety of other outcomes examined that are shown here. These outcomes were also reduced in the vaccine group, as you might expect, because they're all flu-associated outcomes. Things like febrile otitis media and febrile illnesses requiring antibiotics all were significantly reduced in the vaccinated children.

  • CAIV-T Is Effective at Reducing Illness and Complications in Children Aged 15 to 71 Months

    Slide 35.

    CAIV-T Is Effective at Reducing Illness and Complications in Children Aged 15 to 71 Months

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  • Nichol and her group also did a study with the cold-adapted flu vaccine that was similar to studies that had been done earlier with inactivated vaccine. She also showed significant reductions in outcomes -- such as days of illness, days of work lost, and physician visits -- in healthy adults who received the live intranasal influenza virus vaccine.

    In a much smaller study of the ability of the vaccine to protect against artificial influenza -- intentionally induced by challenging subjects with wild-type influenza viruses -- we showed an 85% reduction in the rates of influenza illness with the live intranasal influenza virus vaccine.

  • Efficacy and Effectiveness of CAIV-T in Adults

    Slide 36.

    Efficacy and Effectiveness of CAIV-T in Adults

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A Look at Vaccination Programs

  • Currently this cold-adapted vaccine is approved for use in healthy persons aged 5 to 49 years. Children between the ages of 5 and 8 years and who are receiving a vaccination with any vaccine for the first time require 2 doses. Individuals over age 9 or those who have been previously vaccinated only need one dose. Currently, cold-adapted vaccine is not approved for use in persons with underlying chronic disease.

    One of the interesting things about flu vaccine that's emerged more recently is the possibility that we might be able to control epidemics not only by vaccinating those individuals who are at high risk for complications but also by trying to vaccinate those individuals who are felt to play the biggest role in transmitting influenza viruses throughout the community -- schoolchildren.

    In schools there are large populations of individuals who are relatively susceptible to infection, who tend to have high attack rates and shed lots of virus, and who are crowded together. And there are epidemiologic data to suggest that schoolchildren play a very important role in transmitting influenza viruses throughout the community.

    People have often wondered whether it would be possible to interrupt virus transmission in communities by giving vaccines to children.

  • CAIV-T Indications

    Slide 37.

    CAIV-T Indications

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  • In this study conducted by Monto a number of years ago, investigators examined 2 comparison communities in Michigan, Adrian and Tecumseh, and decided to take the schoolchildren in Tecumseh and uniformly vaccinate them against influenza in that community. There also was a control community, Adrian, that was otherwise very well matched in terms of geographic location and size. Control children were not vaccinated against influenza.

    The rates of respiratory illness in those 2 populations during the subsequent flu season are shown. As you might expect, there were reductions in the rates of respiratory illness in school children ages 5 to 9, 10 to 14, and 15 to 19, in Tecumseh compared with Adrian.

    What was somewhat comforting and interesting to know is that other researchers demonstrated significant reductions in the rates of respiratory illness in adults even though their vaccination rate was not different. Their exposure to unvaccinated children was different; this exposure difference seems to have played a role in reducing transmission to adults.

  • Tecumseh, Michigan: Modification of Influenza Outbreak

    Slide 38.

    Tecumseh, Michigan: Modification of Influenza Outbreak

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  • This has been studied in Japan as well. In the 1960s, Japan adopted a program of uniformly vaccinating schoolchildren and did not use vaccine in the elderly to any great extent. When that program began, shown here in 1962 in blue, researchers observed significant reductions in the rates of both pneumonia- and influenza-related mortality, and all-cause mortality in individuals over the age of 65. This trend continued until 1987 when the program to vaccinate schoolchildren was eliminated.

    When that program stopped and vaccination rates declined to about 5% of schoolchildren, there was a corresponding significant increase in the rates of both all-cause mortality as well as pneumonia- and influenza-related mortality in the elderly. This increase occurred without any significant changes in the rates of influenza vaccine use in the elderly themselves. These findings suggested that vaccination programs in schoolchildren could have this tantalizing effect in their elderly contacts.

    These findings also are recognized as potentially true in the healthcare setting.

  • A Mass Vaccination Program in Japan

    Slide 39.

    A Mass Vaccination Program in Japan

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  • This is a study looking at all-cause mortality in nursing homes. In some of the homes, shown in yellow, influenza vaccine was used routinely in healthcare workers; in other homes, shown in red, the vaccine was not administered. Those nursing homes in which the vaccine was used routinely had significantly lower mortality rates in the elderly subjects, independent of vaccine use in the elderly residents themselves.

    Despite all of this evidence that influenza vaccine is a great intervention to prevent disease and deaths and hospitalizations, we don't vaccinate as much as we should. Currently, the Healthy People 2010 goals for the United States are that by 2010 we'd like to see 90% or more of those over age 65 and those in nursing homes receiving annual influenza vaccination.

  • Vaccinating Healthcare Workers May Reduce Mortality in Residents of Nursing Homes

    Slide 40.

    Vaccinating Healthcare Workers May Reduce Mortality in Residents of Nursing Homes

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  • We're doing a very good job with the nursing home patients, and an okay, but not terrific job in influenza vaccination rates in those over the age of 65. Although the immunization issue has been compounded recently by problems with vaccine shortages, we still have a way to go to get to that 90% data by 2010.

    We'd also like to be able to do a much better job at immunizing those individuals between ages 18 and 64 who have high-risk conditions. Our goal is to achieve at least 60% rates by 2010. Currently we're at an abysmal 29% rate. We're also doing a very poor job of immunizing asthmatic children. Shockingly, there is only a 36% rate of immunization of healthcare workers, and a 14% rate of immunization of pregnant women. We need to do more to get those rates up, particularly among healthcare workers. As shown here, among even those over age 65, there are significant disparities in vaccine use by socioeconomic and ethnic status. We need to do a much better job of reaching those underrepresented minorities and getting them vaccinated.

  • Influenza Vaccination Rates by Population Group

    Slide 41.

    Influenza Vaccination Rates by Population Group

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Breaking the Barriers to Immunization

  • So what are the barriers, what are the hurdles that are preventing these vaccinations from occurring? These barriers have been identified by the Centers for Disease Control and Prevention (CDC) and others, and clearly there are quite a number of clear impediments.

    First of all, many people have inadequate access to vaccination. Either they don't have regular healthcare or they're not able to get to an area where vaccines are being administered. We've already seen that race and socioeconomic status have been clearly identified as factors that predict vaccination rates.

    Another often-cited problem is inadequate reimbursement. Everyone recognizes that giving vaccines is not a good way to make a lot of money, and this economic issue is clearly an impediment to getting these programs going. In addition, in terms of children, vaccination is not mandated for influenza, unlike many other childhood diseases.

    There are a lot of misconceptions, both among physicians as well as among patients, about the actual severity of influenza. Often, patients do not realize how severe influenza is and that it carries a risk of death. There are many concerns about vaccine safety. Most of these concerns are unfounded, although vaccination is contraindicated in a small number of individuals. We recognize that for various reasons, people come into hospitals and physicians' offices needing to be vaccinated, and are on a list to be vaccinated, but for whatever reason don't get vaccinated. There are many missed opportunities for vaccination in both the hospital and physicians' offices.

  • Influenza: Barriers to Immunization

    Slide 42.

    Influenza: Barriers to Immunization

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  • This is a summary of a recent meta-analysis of about 81 controlled trials looking at ways to improve preventative healthcare, including vaccination. For delivery of influenza vaccine, there were several things that were identified as effective in helping to increase those rates. The most effective strategies tended to be those referred to as "organizational change," things that are done by the organization that change the way that you do business.

    One of the things that was identified as increasing vaccination rates by factors of 3 or 6 was establishing separate clinics. In vaccine clinics, people can come in, get vaccinated, and leave; the process is over with quickly. Using a planned physician visit just for vaccination is a variation on that same theme.

    It can be enormously helpful to have a program in the office that employs continuous quality improvement and keeps track of your vaccination rates. It's often useful to assign the task to a nonphysician -- someone who can focus exclusively on making sure everybody gets vaccinated.

    Other effective measures included provider reminders, trying to reduce the financial burden on patients to be vaccinated, education for both providers as well as patients, and patient reminders. In particular, what was seen in this study was that strategies that combined more than one effective method could be particularly effective in increasing vaccination rates.

  • Organizational Change Is Most Effective Method for Increasing Influenza Vaccination Rates

    Slide 43.

    Organizational Change Is Most Effective Method for Increasing Influenza Vaccination Rates

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  • Other effective methods that have been suggested by pediatricians who are in the trenches include telephone reminder systems -- sending out reminders or postcards with the monthly billing. In particular, it's a good idea to discuss the risks and benefits of vaccine with patients when they're seen for an office visit. It's also important to remember, particularly in children but also in adults, that a mild illness is really not a contraindication to vaccination. A child with a mild respiratory illness or who is otherwise afebrile, an adult who's feeling a little under the weather but is afebrile and otherwise well, can certainly be vaccinated safely.

  • Specific Mechanisms for Increasing In-Office Vaccination Rates

    Slide 44.

    Specific Mechanisms for Increasing In-Office Vaccination Rates

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  • Another strategy that is very effective where it's been employed is a so-called standing order. That is, an order is written to vaccinate without requiring a specific order for each individual patient. Standing orders have been shown to be very effective at increasing vaccination rates.

    These are data from the Minneapolis VA Medical Center. However, similar data showing a progressive increase in vaccination rates when standing orders are used could be generated in almost any setting.

  • Standing Orders Increase Inpatient Influenza Immunization Rates

    Slide 45.

    Standing Orders Increase Inpatient Influenza Immunization Rates

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  • In the emergency department, a standing order to vaccinate anyone who doesn't have a contraindication can be very effective in increasing vaccination rates in that setting. We recognize that for many underserved populations, the emergency department may be the only source of regular medical care. Thus, administering vaccines in the emergency department setting can be an important component of a strategy to increase vaccination rates in certain populations.

  • Success of Standing Orders in an Emergency Department Setting

    Slide 46.

    Success of Standing Orders in an Emergency Department Setting

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  • This is a list of all the different interventions that increase adult immunizations, including reminders, financial incentives, and the targets of these methods. Some of the strategies are directed at the patient; some are directed at the provider; some are organizational; some are community-wide. Also, these strategies can be used in combination in an effort to increase vaccination rates.

  • Interventions That Increase Adult Immunizations

    Slide 47.

    Interventions That Increase Adult Immunizations

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New Options in Prophylaxis and Treatment

  • It is important to try and set aside some time for these clinics, and to use a few techniques for improving pediatric vaccination rates. For example, if possible, try and waive the office visit charge for a kid or an adult who's just coming in to get a shot and otherwise isn't being evaluated. That technique also may encourage some people to come in.

    If people don't get vaccinated, or if they get the flu despite being vaccinated, there are antiviral options, which I'm just going to discuss very briefly.

  • Improving Pediatric Vaccination Rates: An Office-Based Model

    Slide 48.

    Improving Pediatric Vaccination Rates: An Office-Based Model

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  • There are 2 classes of anti-influenza virus drugs that are currently approved for either prophylaxis or treatment. These include drugs of the M2 class -- amantadine and rimantadine. These drugs inhibit the M2 protein. It's important to realize that the M2 protein is only present in influenza A viruses, so amantadine and rimantadine are restricted in their activity to influenza A. Amantadine is approved for both prophylaxis and treatment. Rimantadine is approved for treatment in adults and for prophylaxis in children and adults.

    The newer drugs -- the NA inhibitors -- are active against both influenza A and B and include the inhaled drug Relenza (zanamivir). Currently, zanamivir is only approved for treatment in individuals over the age of 7. And Tamiflu (oseltamivir), which is given orally, currently is approved for both treatment and prophylaxis -- treatment in individuals age 1 and older, and prophylaxis in those over age 13.

    Treatment is effective in reducing the duration of illness in individuals who have acute influenza if administered within the first 48 hours.

  • Antiviral Drugs for Influenza Prophylaxis and Treatment

    Slide 49.

    Antiviral Drugs for Influenza Prophylaxis and Treatment

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  • This is a study examining the rates of recovery in 3 groups -- the yellow group represents placebo recipients; the blue and green groups represent recipients of oseltamivir. If you look at the amount of time it took for 50% of the individuals to feel better, you can see a significant difference between the oseltamivir-treated groups and those who received placebo. Ultimately, there was about a 30% reduction in the duration of illness in those who received therapy.

  • Effect of Oseltamivir Phosphate on Duration of Illness in Uncomplicated Influenza

    Slide 50.

    Effect of Oseltamivir Phosphate on Duration of Illness in Uncomplicated Influenza

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  • This result was accompanied by a much more rapid return to what was judged to be normal health by these patients, and return to normal activities -- impact on activities of daily living or quality-of-life indicators also benefit from an effective treatment for a severe illness.

    Neuraminidase inhibitors and M2 inhibitors can be used effectively for prophylaxis.

  • Effects of Oseltamivir Treatment on Return to Normal Activities

    Slide 51.

    Effects of Oseltamivir Treatment on Return to Normal Activities

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  • This is a study that looks at oseltamivir prophylaxis of influenza. The drug was given throughout the flu season. There were reductions in the cumulative incidence of influenza over the 6 weeks of prophylaxis in those who received oseltamivir -- the gray and blue bars -- compared with placebo recipients.

  • Effect of 6-Week Seasonal Prophylaxis on Incidence of Clinical Influenza

    Slide 52.

    Effect of 6-Week Seasonal Prophylaxis on Incidence of Microbiologically Documented Clinical Influenza

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  • This finding also is true in the elderly. This is a study that examined seasonal prophylaxis with oseltamivir during the flu season in nursing homes. There was about a 90% reduction in the incidence of influenza, both in unvaccinated as well as vaccinated individuals, when seasonal prophylaxis with oseltamivir was administered.

  • Oseltamivir Seasonal Prophylaxis in Vaccinated Elderly

    Slide 53.

    Oseltamivir Seasonal Prophylaxis in Vaccinated Elderly

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  • Currently, prophylaxis is indicated in individuals who need an adjunct to vaccination, in unvaccinated persons who are caring for high-risk persons, in those who are immunodeficient and who are expected to have a poor response to vaccine, in individuals who have contraindications to influenza vaccine, and in others, if desired to prevent illness.

    Prophylaxis is a very effective strategy but, unfortunately, it requires people to take medicine every single day for 6 or possibly 8 or more weeks during the period of potential exposure. So it's a very unwieldy strategy to prevent influenza compared with vaccination, which is a one-time situation that provides protection throughout the season. But under certain circumstances, the use of prophylactic antivirals may be considered.

  • Influenza Prophylaxis: Indications

    Slide 54.

    Influenza Prophylaxis: Indications

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The Take-Home Messages

  • Here are some take-home messages. I hope I've left you with the message that influenza is a major medical problem. There are currently 2 vaccines available for prevention of influenza -- a trivalent vaccine that is inactivated, and a trivalent vaccine that is live and administered intranasally.

    There are also 4 antiviral drugs available for treatment, and 3 for prophylaxis. These drugs are the M2 and NA inhibitors. Overall, we think that increased use of vaccine and antiviral medications can improve the control of influenza. Influenza vaccination is the critical first line of defense in the strategy, and I think that there are effective strategies that can improve immunization rates.

    And don't forget to be vaccinated yourself.

  • Take Home Messages

    Slide 55.

    Take Home Messages

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