Script for Influenza Update 2003

December 19, 2003

DR. JULIE GERBERDING

Hi, I’m Dr. Julie Gerberding, Director of the Centers for Disease Control and Prevention. Thank you for joining this program. We hope to give you the latest update on managing patients during this 2003/2004 influenza season.

This is a year where flu started early and is already very widespread in many states across the country. This has caused some shortages of flu vaccine, so it’s more challenging to manage flu this year than in some of the recent years we’ve experienced. We know that this year’s flu virus so far is predominantly the H3N2 Fujian strain. H3N2 strains are often associated with outbreaks that are a little more serious and result in more hospitalizations and sometimes more deaths than some of the other flu strains, so that’s what got us worried in the first place. We also know that this strain is not in the vaccine although a close cousin of the strain, the H3N2 Panama strain is in the vaccine.

We have not enough information yet to say whether or not the vaccine will cross protect against the Fujian strain but our past experience leads us to believe this is likely and we’ll be sure and provide you additional information as the evaluation of this becomes available.

What we hope to do in this video is provide you with some information on what we’re doing to deal with the vaccine shortages, how we can prioritize vaccine, the steps that the state and local health departments are taking to try to get vaccines to the highest risk people as quickly as possible. We’ll also provide a perspective on how to use the anti-viral agents for chemoprophylaxis or treatment of influenza, and we’ll give you the latest recommendations for infection control in hospitals and other settings. We hope this information is useful and as always, as new information becomes available, we’ll be sure to get it to you as quickly as we can. Thank you.

ATKINSON:

Welcome to Influenza Update 2003. We're coming to you live from the Centers for Disease Control and Prevention in Atlanta, Georgia. 

I’m William Atkinson and I'll be your host for this program.

In the United States, the 2003-2004 influenza season began unusually early, and most states are now reporting widespread influenza activity. There has been much media attention to influenza and influenza vaccine this year, and the vaccine is in short supply in some places. This program is intended to update you on the status of influenza now, and update you on the vaccine supply and other important influenza-related issues.

We have three presenters for this program. Dr. Keiji Fukuda is chief of the Epidemiology Section of the influenza branch in the CDC National Center for Infectious Diseases.

Dr. Raymond Strikas is a medical epidemiologist in the CDC National Immunization Program, and has been involved in influenza related activities for more than 10 years.

Dr. Clifford McDonald is a medical epidemiologist in the Division of Healthcare Quality Promotion in the CDC National Center for Infectious Diseases.

During this program we will provide you updates on several influenza-related issues.

We will begin with a discussion of current influenza activity in the United States, including information on influenza associated deaths. We will then update you on the status of the influenza vaccine supply, and recommendations for vaccination.

Following our discussion of influenza vaccine, we will talk about laboratory diagnosis of influenza, in particular the use of rapid diagnostic tests. This will be followed by information about the use of influenza antiviral drugs, and recommendations for influenza infection control.

ATKINSON:

Before we begin our discussion, we need to take care of a few operational details.

We would like to thank all the states who are participating today, especially the state coordinators and local site facilitators who arranged for this program on very short notice.

If you are having technical trouble receiving our signal, you can call us here at CDC at 800-728-8232. If you are viewing the program from outside the United States, the technical number is 404-639-1289.

Continuing education credit is not available for this program. However, a certificate of attendance will be awarded to participants who register and complete the course evaluation. We will give you more details about the registration process and the online system at the end of the broadcast.

We know that many of you joining us today will have questions during and after our broadcast, and we want to answer those questions for you. But due to the nature of this broadcasts, and the large amount of material we need to present, we will not be able to answer your questions on the air. We will address many of the most common questions we have received concerning influenza and influenza vaccine during our presentations. We will also provide you with contact information you can use get answers to your questions. We will provide the contact information at the end of the program.

We would like to begin this program with a discussion of current influenza activity in the United States. Dr. Keiji Fukuda will present this information. Keiji?

FUKUDA:

Thanks Bill. Influenza activity clearly began early this year in the U.S. Community outbreaks were first reported from Texas in early October and soon was followed by increasing activity each week in other states. During October and November, activity levels generally were higher west of the Mississippi but more recently, influenza is in all areas of the country.

National activity levels have not peaked yet, and we do not know how long activity will continue. One bit of good news, however, is that influenza activity levels in two states with early activity, Texas and Colorado, appears to be on the downturn.

I would like to summarize for you our most current influenza surveillance data for week 50, the week ending December 13, 2003.

Let me first briefly describe the influenza surveillance system in the United States. CDC uses four systems to monitor national influenza activity in the United States and these reports typically are put out between October and May of each year. The first system is a group of about 120 WHO and National Respiratory and Enteric Virus Surveillance Laboratories scattered throughout the country. These laboratories, many of which belong to state health departments, help monitor influenza virus activity and the emergence of new influenza strains in the country. These laboratories send information on virus detections and a subset of the isolates to CDC to be characterized further. The second system consists of reports from the state and territorial epidemiologists who report their levels of influenza activity in their local area each week to CDC. These epidemiologists report the activity levels as either sporadic, local, regional, or widespread. The third system consists of about 1,000 sentinel providers located throughout the United States. These physicians report the percentage of all patient visits that are being made to them for influenza-like illness. The fourth system consists of 122 cities that report the percentage of all deaths in their cities attributable to pneumonia or influenza. During severe seasons the percentage of such deaths will exceed the expected baseline or so-called epidemic threshold for several weeks.

Now in this graph here we see a summary of the influenza virus information collected in the U.S. so far. The stack bars represent the number of viruses which have been isolated so far, and the black line represents the percentage of clinical specimens which are testing positive for influenza in the surveillance laboratories. Overall we can see that the 2003-04 season has been dominated by influenza A viruses as shown by the stacked yellow bars which represent influenza A viruses that have not yet been subtyped, and the red bars which represent influenza A (H3N2) viruses. Now through the week ending 50 or the week ending December 13^th, national surveillance laboratories have reported detecting 9,395 influenza A viruses and 69 B viruses. 2,113 of the A viruses were subtyped and all of them have been influenza A (H3N2) viruses except one H1 virus. Now although this graph looks like there’s peaking of activity, I do want to put out a caveat that this probably represents a lag in reporting. It won’t be clear until a few weeks later. Now influenza viruses have been reported from all 50 states. 29% of the viruses have come from the southwest central region which represents Arkansas, Louisiana, Oklahoma and Texas, and 28% of the viruses have come from the mountain region which represents Arizona, Colorado, Idaho, and Montana. Now so far over 99% of all influenza viruses have been A viruses in the country, and of the A viruses that have been subtyped which is 2,113, over 99% of them have been influenza A (H3N2) viruses. Of the 265 H3N2 viruses that have been further characterized for strain typing, 23% have been Panama-strain viruses and 77% have been Fujian-strain viruses.

So at this point let me say a few things about the vaccine since it fits in with the viruses being detected in the country. Influenza vaccine normally contains three viruses: an influenza A (H3N2) virus, an influenza A (H1N1) virus and the B virus. The H3N2 strain contained in the 2003 vaccine is a Panama virus and not an A/Fujian virus. Now there’s several important reasons for this situation that I want to explain. The strains used in the U.S. vaccine are usually selected each year between February and March at a meeting held by the Food and Drug Administration. Now these strains must be chosen by this time each year to provide manufacturers with enough time to produce and distribute vaccine and the Food and Drug Administration with enough time to test lots before they’re released. Now this year global surveillance detected A/Fujian-like viruses late in January. Due to the late detection there was not enough time to find a suitable Fujian-like virus that had been passaged and grown completely in eggs. Most surveillance laboratories worldwide now use cell cultures to isolate influenza viruses. However, by law only viruses grown solely in embryonated eggs can be used for vaccines. This year because the virus emerged so late, there was not enough time to locate such a virus so the decision was made to retain Panama as the H3N2 virus in the vaccine.

Let me say a few words about the vaccine effectiveness. The A/Fujian-like viruses represent drift variance or mutated viruses that evolved from the A/Panama viruses. Antibodies to A/Panama viruses will cross react with A/Fujian-like viruses but at lower levels. Now because antibodies to A/Panama cross react with Fujian viruses it is expected that this year’s vaccine will provide some degree of protection against A/Fujian viruses. However, the degree of protection is unknown and cannot be estimated by laboratory test results. The vaccine effectiveness can only be estimated by clinical vaccine effectiveness studies. Such studies are underway in the U.S. right now but we do not have results yet.

Now in this map here we see state activity levels as reported by the state and territorial epidemiologists. In week 50 we can see that 36 states shown here in red are reporting widespread activity. Twelve states shown in blue and New York City are reporting regional activity. New Hampshire, which is represented in green which sticks out nicely, is reporting sporadic activity levels. Now in this graph here, we see the percentage of patient visits being made to sentinel providers for influenza-like illness. The 2003 season is represented by the red line which clearly shows that activity began early this year. Two other seasons, the 1999-2000 season in green, and the 2002 and 2003 season in purple are shown for purposes of comparison. In week 50, 7.4% of patient visits to U.S. sentinel providers were due to influenza-like illness which is about the national baseline of 2.5%. In the most recent surveillance results patients for influenza-like illness are increasing in 7 of the 9 surveillance regions. However, these visits are beginning to decline in two regions, the west-south central region where Texas is located, and the mountain region where Colorado is located.

Now in this graph here we see the pneumonia and influenza mortality reported by 122 cities in the United States. Now the sinusoidal baseline represents the expected pneumonia and influenza deaths throughout the year. The jagged line shows the actual deaths which occurred and which are measured. You can see from this graph that there’s a great deal of variability from year to year in terms of measured deaths. For example, if you look to the left you can see that for the 1999-2000 season there was a high peak in deaths occurring, whereas in the years between 2001 and 2003 there really were very small or minimal peaks. Now this year is represented at the far right of the graph and you can see that so far the P&I or pneumonia and influenza deaths have not yet gone above the baseline. However, increases in deaths typically lag other markers by about a few weeks, so we’ll have to watch this line carefully.

Now I also want to comment upon some of the reports of influenza-associated deaths in children which have occurred this year. There has been a lot of media coverage about these deaths in children particularly in places such as Colorado. From October through December 17^th, CDC has received reports of 42 deaths in children age younger than 18 years reported from multiple states. The mean age of these children is six years and the median age is four years. About half of them are males and about half of them are occurring in females. These deaths are located, or have been reported from several different states. Now all of the deaths reported to CDC have been laboratory or rapid test confirmed influenza-associated deaths. That is, infection has been confirmed in all of those children. Among these children about 40% of them have underlying medical conditions and 50% of them have no known underlying medical conditions. The medical status of 10% is unknown. I also want to add that the vaccination status of most of these children is still not known. Among six children, four who are healthy and two who had chronic medical conditions, there were several bacterial super infections which were identified. These included methicillin resistant Staphylococcus aureus infections, Streptococcus pneumoniae infections, group A Streptococcus infections, and Neisseria Meningitidis.

Today we should be having an MMWR dispatch coming out describing these cases in somewhat more detail. The MMWR report also contains a request for states to report all such influenza-associated deaths to CDC. Now the number of deaths being reported to CDC this year is striking. However, this is not a reportable condition and so right now we do not have a baseline of such deaths and it is uncertain whether this is an unusual number of cases to occur in an H3N2 year. Mathematical models have estimated that on average about 92 deaths each year occur from influenza in children younger than five years. CDC will be investigating whether the deaths being reported this year are unusual and whether this is a more severe year for influenza than usual.

The national Influenza surveillance reports are updated each week during influenza season. Previously, these reports were available on the CDC influenza website on Friday but now reports will be posted a day earlier on Thursday.

ATKINSON:

Keiji, there seems to be a perception that the A Fujian virus is more virulent than other recent influenza viruses. Is there any evidence this?

FUKUDA:

This season began earlier than usual. Also, most of the influenza has been type A (H3N2). Historically, A (H3N2) viruses have been associated with more severe seasons, with higher numbers of influenza related hospitalizations and deaths. However, we also have heard about many hospitals being overwhelmed by many patients. I do want to point out, however, that this occurs in all severe influenza seasons. We have no solid evidence that A/Fujian is more virulent than other H3N2 viruses. It is also possible that we will see other flu viruses such as B viruses predominate later in the season. Bottom line, we probably won’t know the answer to this question until the season ends.

ATKINSON:

Thanks, Keiji. Our next presentation will address the current influenza vaccine supply and vaccination recommendations. Dr. Ray Strikas will discuss this. Ray?

STRIKAS:

Thanks Bill. There has been a marked increase in demand for influenza vaccine this year. Some health care providers have used - or may use - all of their supply of influenza vaccine.

It's difficult to predict - months in advance- how many people will want an influenza vaccination. In past years, supply has generally been sufficient to meet demand, but this year, a strong demand has continued for longer than usual into the month of December. At a time when influenza vaccination clinics are typically winding down, people are still seeking flu shots.

Three companies produce influenza vaccine for the United States. Two of these companies, Evans/Chiron and Aventis Pasteur, produce only inactivated vaccine. The three companies together made about 87 million doses of vaccine, which ordinarily would be enough to exceed U.S. demand. The third company - actually a pair of companies, Wyeth and Medimune- makes a live attenuated influenza vaccine which is given as a nasal spray.

The two manufacturers of inactivated influenza vaccine have shipped almost all of their inventory. There will be no more vaccine produced this year, because by the time it would be ready, influenza season will have ended.

The Department of Health and Human Services and CDC have been looking at all of our options as to possibly acquiring additional supplies of influenza vaccine.

The Department has purchased 100 thousand doses of adult vaccine from Aventis Pasteur. This vaccine was shipped to state health departments last week. Each state’s supply was based upon its population. We have also purchased from Aventis Pasteur an additional 150,000 doses of pediatric vaccine and expect to have it ready for shipment to the states by January of next year.

CDC has also arranged a contract with Chiron/Evans for 375 thousand doses of their injectable vaccine, which will be available for states to order in mid-January. States have been asked to work with their local health departments, federally qualified health centers, rural health centers, and Indian Health Service and tribal facilities to determine their needs.

Finally, CDC has signed a contract with Wyeth/Medimmune to purchase the live attenuated vaccine. We have also negotiated the ability for public entities, such as local health departments, in addition to Federal immunization grantees, to purchase vaccine through this contract.

We are working with the states to distribute the vaccine based on population in the states. At the state level, decisions about who should receive these extra doses will be based on what is the overall availability and need in that particular jurisdiction.

Because demand for vaccine exceeds supply in some areas, it is necessary to establish priorities for the vaccine that is available. The priority should be to vaccinate persons at highest risk of complications of influenza.

First priority should be placed on targeting trivalent inactivated vaccine to persons at high risk for complications from influenza: all children aged 6 to 23 months; adults aged 65 years and older; pregnant women in their second or third trimester during influenza season; and persons aged 2 years and older with underlying chronic conditions. Persons at high risk should be encouraged to search locally for vaccine if their usual healthcare provider no longer has vaccine available.

All children at high risk, including those aged 6 to 23 months, who report for vaccination should be vaccinated with a first or second dose, depending on vaccination status. Doses should NOT be held in reserve to ensure that two doses will be available.

Next priority should be given to vaccinating those persons at greatest risk for transmission of disease to persons at high risk, including household contacts and health-care workers.

Decisions about vaccinating healthy persons, including adults aged 50 to 64 years, with inactivated influenza vaccine should be made on a case-by-case basis, depending on local disease activity and vaccine supply.

The new live attenuated influenza vaccine – FluMist- can play an important role in our influenza vaccination efforts. Live attenuated influenza vaccine is approved by the Food and Drug Administration ONLY for use among healthy persons 5 through 49 years of age. Healthy persons aged 5 to 49 years should be encouraged to be vaccinated with this vaccine if possible.

This table shows the vaccination schedule for LAIV based on age and prior influenza vaccination history. A dose of LAIV is 0.5 milliliter, regardless of age, divided equally between nostrils. Children 5 to 8 years of age who have received NO previous influenza vaccine- either LAIV or inactivated influenza vaccine- should receive two doses of LAIV separated by 6 to 10 weeks. Note that this is longer than the 4 weeks recommended between the first two doses of inactivated influenza vaccine. ACIP recommends that children 5 to 8 years of age previously vaccinated at any time with either LAIV or inactivated influenza vaccine receive one dose of LAIV. They do not require a second dose. This is different than the manufacturer’s labeling, which recommends that children who have not previously received LAIV should receive two doses, regardless of whether they may have previously received inactivated influenza vaccine. Persons 9 through 49 years of age should receive one dose of LAIV.

LAIV is approved for use ONLY in healthy persons 5 through 49 years of age. Consequently, LAIV is NOT approved, and is not recommended for administration to most people for whom inactivated influenza vaccine has been recommended for many years.

Persons who should NOT receive LAIV include children less than 5 years of age; persons 50 years of age and older; persons with asthma, reactive airways disease or other chronic pulmonary or cardiovascular conditions. These persons should receive inactivated influenza vaccine.

Persons with other underlying medical conditions should not receive LAIV. These conditions include metabolic disease such as diabetes, renal disease, or hemoglobinopathy, such as sickle cell disease; and children or adolescents receiving chronic therapy with aspirin or other salicylates, because of the association of Reye syndrome with wild-type influenza infection. Persons in these groups should receive inactivated influenza vaccine.

As with all live virus vaccines, persons who are immunosuppressed because of disease, including HIV, or who are receiving immunosuppressive therapy, should not receive LAIV. Pregnant women should not receive LAIV. Immunosuppressed persons and pregnant women should receive inactivated influenza vaccine. Since LAIV contains residual egg protein, it should not be administered to persons with a history of severe allergy to egg or any other vaccine component. Finally, the vaccine should not be administered to a person with a history of Guillain-Barré syndrome.

Close contacts of persons at high risk for complications from influenza should receive influenza vaccine. This reduces the risk of transmission of wild-type influenza viruses to high risk individuals. There are no data assessing the risk of transmission of LAIV from vaccine recipients to immunosuppressed contacts.

In the absence of such data, use of inactivated influenza vaccine is preferred for vaccinating household members, healthcare workers, and others who have close contact with immunosuppressed individuals. This preference is because of the theoretical risk that a live attenuated vaccine virus could be transmitted to the immunosuppressed individual and cause disease. ACIP states no preference between inactivated vaccine and LAIV for vaccination of healthy persons aged 5 to 49 years in close contact with all other high-risk groups.

The influenza vaccine situation will continue to evolve during the next one to two months. Health departments and healthcare providers should work together to reallocate influenza vaccine to health-care providers in need when possible. We will post vaccine supply and recommendation information on the CDC influenza website as it becomes available.

ATKINSON:

Ray, as you know we have received many questions from providers about the use of their available vaccine supply. One of the most common questions is the amount of protection we expect for a child who is receiving influenza vaccine for the first time, but receives only one dose. Can you comment on this?

STRIKAS:

That’s a good question. The first dose of vaccine provides some protection, and is better than no vaccination. But it is the second vaccination that provides the bulk of the protective antibodies. A few antibody studies in the 1970s suggested that children without prior exposure to the influenza virus produce lower titer of antibody after one dose of influenza vaccine than after two doses, and two doses are needed to reach optimal protective antibody levels in most such children. So one dose of influenza vaccine might provide some protection for many children. Because the child’s immune system has been “primed” by the first dose of vaccine, it is possible that influenza disease could be less severe in a child younger than 9 years of age who has received only one dose compared to an unvaccinated child. However, here are no vaccine efficacy studies to tell us how MUCH protection is provided by one versus two influenza vaccinations.

ATKINSON:

We have also received a lot of questions about combining pediatric doses or splitting adult doses of inactivated vaccine. What about this practice?

STRIKAS:

Bill, the first point to make here is about the age limit for use of the Evans/Chiron vaccine, Fluvirin.

Fluvirin is not licensed for children younger than 4 years of age because data to demonstrate the efficacy of this vaccine in younger children have not been provided to FDA. We do NOT recommend that Fluvirin be administered to children 6 to 47 months of age. Only Aventis vaccine should be used for this age group.

Two pediatric doses of Aventis vaccine can be used for a person 3 years of age or older. Two 0.25 mL doses can be administered at the same visit and can be counted as a single valid 0.5 mL dose. However, there are no data as to the effectiveness or safety of this practice. Providers who use two pediatric doses to vaccinate persons aged 3 years and older should do so using two separate injections at two different sites during the same visit. Under no circumstances should vaccine be transferred from one syringe into another syringe to administer two 0.25 mL doses with a single injection. Transfer of vaccine in this manner greatly increases the chance for contamination.

Adult doses cannot be divided into two pediatric doses. Single dose 0.5 mL syringes filled by the manufacturer cannot be split. Under no circumstances should vaccine be transferred from one syringe into another syringe to administer two 0.25 mL doses from a 0.5 mL pre-filled syringe. Transfer of vaccine in this manner greatly increases the chance for contamination and the distribution of the active components of the vaccine may not be equal within the syringe, even after shaking. Therefore, splitting the 0.5 mL volume may result in unequal amounts of active vaccine ingredients in the two halves.

Similarly, a single dose 0.5 mL syringe filled by the manufacturer should not be used to give a single 0.25 mL dose, either by discarding half the volume prior to administration or by injecting only half the volume.

The only exception to the use of adult vaccine for children is for vaccine supplied in a 10 dose vial. In this case it is acceptable to remove a 0.25 mL dose from a 10 dose vial.

ATKINSON:

Ray, one more question we have received several times has to do with providers who administer live attenuated influenza vaccine - FluMist. Should providers who have a contraindication to LAIV administer LAIV? For instance, should a nurse who has asthma or is immunosuppressed administer the vaccine?

STRIKAS:

Environmental contamination with live attenuated influenza vaccine virus is probably unavoidable. There are no data on the risk of infection with vaccine virus for the person administering the vaccine. Until such data are available, it seems prudent that providers who have a contraindication to LAIV avoid administering the vaccine.

ATKINSON:

Thanks Ray. Our next topic is influenza diagnostics, particularly the use of rapid diagnostic kits. Dr. Fukuda has this. Keiji?

FUKUDA:

Thanks Bill. There are a number of tests can help in the diagnosis of influenza. Before discussing these tests, one thing I want to emphasize is that a test does not need to be done on each individual patient to decide about therapy, including whether or not to use influenza antiviral drugs.

During a respiratory illness outbreak, testing for influenza is extremely helpful. If influenza has been established as the cause of an outbreak, testing of all ill persons is usually unnecessary.

Available tests to identify the presence of virus or virus antigens include viral culture, which is the gold standard, PCR, and immunofluorescence antibody tests such as DFA or IFA. In addition, several rapid antigen detection kits now are commercially available that are very useful in clinical and outbreak settings.

Appropriate samples for influenza virus testing include nasopharyngeal or throat swabs, nasal wash, or nasal aspirates. The type of specimen which is collected depends in part on what type of test is used. Samples should be collected as early as possible in the course of illness, because virus shedding are highest early in the illness, and within the first 4 days of illness.

Rapid influenza tests can provide results within half an hour. Viral culture generally takes 3-10 days.

Most of the commercially available rapid antigen detection tests can be done in a physician's office. As a group, they are approximately 70 percent sensitive for detecting influenza and approximately 90 percent specific compared to viral culture. This means that in general these tests will detect fewer true infections than viral culture and that some positive results will be false positive results.

The rapid tests are least reliable when there the prevalence of circulating influenza viruses is low, for example at the start of a season. By contrast, the test results are most reliable when influenza infections are relatively common. A table listing currently available rapid diagnostic tests is available on the CDC influenza website.

Serum samples also can be tested for influenza antibody to diagnose recent infections. Serologic tests are more often used in epidemiological studies than in clinical settings because an acute and convalescent serum sample is required. An acute influenza infection cannot be diagnosed on the basis of a single blood sample.

An acute or early sample should be collected within the first week of illness and a convalescent or late sample collected about 2-3 weeks later. Influenza infection is diagnosed if antibody levels in the late sample are at least 4 times higher than antibody levels in the first sample.

Based on these considerations, we can make some recommendations about testing. First, let’s discuss outbreak situations. If influenza is suspected to be the cause of a respiratory illness outbreak, then respiratory specimens should be collected from several ill persons and tested both by rapid tests and by viral culture. The rapid tests will provide preliminary results that can be acted upon.

If they are positive, then influenza specific control measures should be started as soon as possible. The viral culture results will provide definitive confirmation of the rapid test results and also will provide viral isolates that can be typed and subtyped. Further strain characterization of such isolates also may provide information needed to help select new strains for the next year's influenza vaccine. Viral culture will also help identify other viruses as the cause of the outbreak.

Now let’s discuss outpatient and hospital clinic settings. In these settings, influenza tests also are very useful for establishing the presence of influenza as a cause of respiratory illnesses occurring among the patient population. Once influenza has been established for the patient population, testing of each individual patient before deciding on appropriate therapy, including use of antiviral medications, is not necessary.

ATKINSON:

Keiji, a common question we have received is whether recent influenza vaccination will cause a false positive rapid diagnostic test. Could you comment on this?

FUKUDA:

A recent vaccination with inactivated influenza vaccine will not cause a false positive result with any of the virus or antigen detection methods. Therefore, rapid antigen detection kits will not be affected. However, inactivated vaccine will induce antibody production and therefore could affect serology tests.

A recent vaccination with live attenuated influenza vaccine, say within a week, could cause a false positive result with the virus and antigen detection tests, such as rapid antigen detection tests, immunofluorescene antibody tests, or culture.

ATKINSON:

Keiji, with the shortage of influenza vaccine has come increased interest in the use of antiviral agents for influenza. Could you give us an overview of this?

FUKUDA:

I’d be happy to. There are four prescription medications with antiviral activity against influenza viruses in the United States. They are amantadine and rimantadine, which are the adamantane derivatives – and oseltamivir and zanamivir, which are the neuraminidase inhibitors. Controlled clinical trials have shown that when used for treatment, all four antiviral medications can reduce symptoms if started within 48 hours of the start of illness. Three of the antiviral drugs -- amantadine, rimantadine, and oseltamivir – also have been approved for use as chemoprophylaxis.

Amantadine and rimantadine, are chemically related drugs that are taken by mouth. They both are approved for treatment and chemoprophylaxis of influenza A. These two drugs are effective against influenza A viruses, but not influenza B viruses.

Amantadine is approved for the treatment of influenza A in persons 1 year and older. Rimantadine is approved for treatment of influenza A in persons 13 years of age and older. Both drugs are approved for chemoprophylaxis of influenza A in people aged 1 year and older.

When administered within 48 hours of illness, both drugs decrease viral shedding and can reduce influenza A illness by approximately 1 day. The usual recommended duration of treatment is 5 days.

When used for chemoprophylaxis, amantadine and rimantadine are approximately 70 to 90 percent effective in preventing symptoms of influenza A illness. It is unknown whether amantadine and rimantadine can prevent secondary complications of influenza A. Both drugs have long been used as both treatment and chemoprophylaxis to control outbreaks of influenza A in institutional settings such as nursing homes.

The neuraminidase inhibitors, zanamivir and oseltamivir, are chemically related drugs that are active against both influenza A and B viruses.

Zanamivir – is a powdered drug that is administered by an oral inhaler. It is approved for treatment of influenza in persons aged 7 years and older. Zanamivir is not approved for chemoprophylaxis of influenza.

Oseltamivir – is an orally administered drug that comes in the form of capsules or, for children, a liquid suspension. Oseltamivir is approved for treatment of influenza in persons aged 1 year and older and for chemoprophylaxis of persons aged 13 years and older.

When used within 48 hours of illness onset, both drugs decrease shedding and reduce the duration of influenza symptoms by approximately 1 day compared to a placebo. One randomized, placebo-controlled double-blinded studies of oseltamivir showed that this drug significantly reduced influenza related pneumonia and bronchitis associated with antibiotic use, and hospitalizations. These findings occurred in both healthy and high risk adolescents and adults. No studies have assessed whether antiviral drug therapy can reduce mortality. For both drugs, the recommended duration of treatment is 5 days.

The decision of whether to use these antiviral drugs and how to use them must be made on an individual basis since several considerations and extenuating circumstances may reasonably be taken into account. For example, pharmacologic and approval differences among the drugs, the local availability of the drugs, and the population under consideration. Recognizing that there can many consideration, let me provide some general recommendations based on interim guidelines recently developed by CDC in response to this influenza season.

First, certain groups of people are at increased risk of serious complications from influenza and therefore it is likely that these groups will benefit most from antiviral drugs. So, in general, these groups should be given priority for use of influenza antiviral drugs if available supplies of antiviral drugs are limited. However, if the supplies are not limited, then use of these drugs certainly should also be considered for healthy persons as well.

Second, influenza antiviral drugs should be used for treatment and prophylaxis of residents or patients and staff to control outbreaks of influenza occurring within institutions or in other semi-enclosed settings housing many high risk individuals. Examples of such settings include nursing homes, long term care facilities, residential communities of high risk persons, hospitals, and some ship cruises. Otherwise, there are several situations in which use of the antiviral drugs should be considered. One situation is the treatment of persons 1 year and older at high risk of complications from influenza who have been ill with influenza for less than 48 hours.

Another situation is the chemoprophylaxis of unvaccinated high risk persons aged 1 year and older during community influenza outbreaks. In this situation, chemoprophylaxis could continue for several weeks but there is limited information about long term use of these drugs. Influenza antiviral drugs should also be considered for the chemoprophylaxis of unvaccinated health care workers who have close contact influenza-infected patients.

Ideally, high risk persons and health care workers should be vaccinated before the influenza season starts. However, many such persons remain unvaccinated after an outbreak begins and in this situation, they should be vaccinated and given chemoprophylaxis for two weeks after vaccination. If vaccination is not possible, either because vaccine is not available or is refused, or if the person is unlikely to mount an adequate antibody response to vaccination because of an immunocompromising condition, then chemoprophylaxis for the duration of influenza activity should be considered.

Finally, treatment or chemoprophylaxis of high risk or healthy individuals in a variety of other settings can be considered. For example, treatment of influenza-infected patients in critical condition, or chemoprophylaxis of family members of high risk individuals.

In each of these instances, the use of the antiviral agents should be guided by clear objectives for the use of these drugs, predefined limits on the duration of treatment or chemoprophylaxis, and an awareness of the locally available supply of the drugs.

Several documents on the CDC influenza website provide more information on side effects and dosing of all four drugs. This information is also summarized in the 2003 influenza ACIP statement.

ATKINSON:

Keiji, is it recommended to confirm the influenza infection with a rapid diagnostic kit prior to treating a person with one of these antiviral drugs?

FUKUDA:

[RESPONDS]

ATKINSON:

Thanks, Keiji. Our final presentation will be by Dr. Cliff McDonald, who will address influenza infection control issues. Cliff?

MCDONALD:

Thanks Bill. With widespread influenza in many states, hospitals and other health care facilities will have many infected people in their environments. Our goal is to minimize transmission of influenza to other people and staff in the facility.

Influenza transmission is thought to occur predominantly through large respiratory droplets. These are particles that are greater than 5 microns in diameter and are expelled from the respiratory tract during coughing, sneezing, and talking. These particles do not remain suspended in the air and therefore require close contact for spread between persons, usually within 3 feet. It is likely that influenza can also be transmitted through direct contact with visible secretions.

There are limited data, mostly from animal models but a few also in humans, to suggest an airborne route for transmission.

In contrast to large respiratory droplet transmission, airborne transmission is caused by smaller sized particles that can travel over larger distances. The very limited data from humans that could suggest airborne transmission of influenza would indicate that if airborne transmission does occur it does so under unusual circumstances. Therefore, the recommended isolation of influenza patients includes Standard and Droplet precautions.

Aspects of Standard Precautions that are especially important in the control of influenza include careful attention to hand hygiene and the use of gloves for contact with respiratory secretions. A gown should be worn if clothing is likely to come in contact with respiratory secretions, such as when picking up a small child. Gloves and gowns should be changed between patients.

Droplet precautions involve placing patients infected with influenza in private rooms with standard ventilation systems, or placing multiple influenza patients in the same room. In addition, all healthcare workers should wear a surgical mask whenever coming within 3 feet of the influenza patient. These masks should be removed when leaving the patient’s room.

Other key prevention strategies to prevent influenza transmission are listed on this graphic. Because infected healthcare workers often play an important role in the transmission of influenza in healthcare facilities, it is important to vaccinate healthcare workers. Policies should be implemented to limit visitors with symptoms of respiratory infection, especially when influenza activity has increased in the surrounding community. Likewise policies should be enforced to restrict ill healthcare workers from caring for patients during periods when they are likely to be contagious. Finally, if possible, healthcare facilities should develop a respiratory hygiene and cough etiquette policy to prevent transmission of respiratory pathogens, including influenza.

Respiratory hygiene and cough etiquette includes measures for patients as well as healthcare providers. Patients should be instructed via visual alerts and verbal instructions to inform staff if they have symptoms of a respiratory infection; cover the nose and mouth with a tissue or a surgical mask when coughing or sneezing; and to perform hand hygiene frequently, especially after handling tissues.

There are also precautions that providers can take to reduce the risk of respiratory transmission. Healthcare providers should offer masks to coughing persons; encourage coughing persons to sit apart from others, for example at least three feet, in common waiting areas; ensure adequate supplies of tissues, masks (if applicable), hand hygiene products, and no-touch waste receptacles; and use Droplet Precautions - in other words wear a surgical mask - when interacting with patients who have symptoms of respiratory infection.

Despite our best efforts, influenza outbreaks will occur in healthcare facilities. There are several important action steps that should be rapidly implemented if this should occur.

The first of these is to cohort patients with confirmed or suspected influenza; all patients potentially involved in the outbreak should be quickly assessed and those who are potential or confirmed influenza cases should be separated from those who are asymptomatic. Again, Droplet Precautions should be implemented for the care of all patients with confirmed or suspected influenza. In addition, depending upon availability, one should offer vaccine to unvaccinated staff and patients. To prevent potentially infected healthcare workers from spreading influenza throughout the facility, authorities should restrict staff movement between units. Finally, antiviral prophylaxis and treatment of symptomatic patients and staff can play an important role in helping to control outbreaks of influenza in healthcare facilities.

It is critical that healthcare facilities have policies and procedures in place to prevent transmission of influenza virus. A vaccinated workforce, and attention to appropriate isolation and hand hygiene can help protect both staff and patients from influenza and other respiratory pathogens. Bill?

ATKINSON:

Cliff, you mentioned the benefit of Standard and Droplet precautions in reducing transmission of influenza. What about the use of airborne precautions?

MCDONALD:

We get that question frequently. Although we know a lot about how to prevent and control influenza transmission in healthcare facilities, an unresolved issue is the use of airborne isolation precautions. The use of airborne infection isolation or negative pressure rooms may not add benefit to droplet precautions. Currently available evidence is insufficient to make a recommendation either for or against the use of such precautions. However, it appears that the measures I mentioned earlier, such as hand hygiene and droplet precautions, are likely of much greater importance in preventing transmission.

ATKINSON:

Another question we have received often concerns the use of live attenuated influenza vaccine among healthcare workers. Could you comment on this?

MCDONALD:

The concern about the use of live attenuated influenza vaccine among healthcare workers is due to shedding of the vaccine virus in respiratory secretions, and the possibility of infecting immuno-compromised patients with the vaccine strain. As a result, inactivated vaccine is the preferred vaccine for healthcare workers. Questions have arisen regarding what should be done with the healthcare worker who is inadvertently administered the live attenuated vaccine, and whether live attenuated vaccine may be safely used in healthcare workers in the setting of a shortage of inactivated vaccine.

At the root of these questions is whether vaccinated healthcare workers can reasonably avoid contact with immunocompromised patients. This might depend upon the healthcare setting, and the types of immuno-compromising conditions that could be encountered in that setting. However, for now, this remains an area in which we have no recommendations.

ATKINSON:

Thanks, Cliff. Before we close, I would like to mention several special influenza studies that are in progress. These studies will help us understand more about the influenza viruses that are circulating this year, and the ability of the vaccine to prevent it. Vaccine efficacy studies among both children and adults are in progress in multiple locations in two states. State health departments and CDC are investigating severe illnesses and deaths from influenza among children 18 years of age and younger. If you are aware of influenza-related deaths in this age group, please notify your local and state health department, who will in turn notify CDC. Surveys of hospitals and infectious disease practices are planned to determine the impact of influenza on medical practices and children. Finally, efforts are underway to assess vaccine supplies, antiviral drugs, and rapid diagnostic kits. We will provide you with the results of these and other studies through the influenza website, Morbidity and Mortality Weekly Report, and future satellite broadcasts.

As we mentioned earlier, we regret that we are not able to offer continuing education credit for this program. However, a certificate of attendance will be awarded to participants who register and complete the course evaluation. Course evaluations are very important to us in planning future programs like this, so we would appreciate your feedback.

To evaluate this program and receive your certificate of attendance you need to know the course number.

The course number for this satellite broadcast is SB0149. The course number for today’s webcast is WC0049. The course number for the web on demand, otherwise known as web archive, is WD0036. You will need one of these course numbers to identify the correct evaluation in the CDC ATSDR online system, so please write it down now. [PAUSE 5 SECONDS)

Participants will have until January 23, 2004, to register and evaluate the live broadcast or webcast. The web on demand evaluation and registration will begin on January 25, 2004.

Let’s talk for a moment about using the CDC ATSDR online registration and evaluation system. Many of you are already familiar with our online system. If you have not used it before, you can receive instructions through our FAX BACK system.

Call our toll free number using a touch tone telephone. The number is 888-CDC-FAXX. When prompted for a document number, request document number 130012. Then enter your fax number. The document will be faxed to you in just a few minutes.

Here is the address for the CDC ATSDR training and continuing education online system: www dot phppo dot cdc dot gov slash phtn online. When you get to the website, an extensive help function can also assist you in the registration process.

Rather than go through all the details of using the online system, you should use the instructions on the website, or order the instructions from our fax back system.

In addition to the online help function, you can receive assistance by telephone. If you have any problems with the online system, you can call us toll free at 800-41-TRAIN. You can also call us at 404-639-1292. CE unit personnel are available Monday through Friday from 8 am until 4:30 pm Eastern Time.

You can also receive assistance by Email. Our address is CE at cdc DOT gov. The continuing education staff will be happy to assist you with the login and registration process

This brings us to the close of this broadcast of Influenza Update 2003. We hope the information we have provided was useful to you.

Throughout this program we have mentioned several influenza related resources. The best source for this information is the CDC influenza website at www dot cdc dot gov slash flu. Here you will find updated recommendations on the use of influenza vaccine, influenza antiviral drugs, infection control, and much more.

If you have questions about influenza or influenza vaccine you can call the National Immunization Information Hotline. You can reach the Hotline toll free at 800-232-2522. The Hotline is staffed from 8 AM until 11 PM eastern time Monday through Friday.

You can also use the Internet to E-mail questions, comments, or requests to the National Immunization Program. Our Email address is nip info at cdc dot gov.

Finally, if you would like to find out more about upcoming Public Health Training Network courses, visit the PHTN website at www dot phppo dot cdc dot gov slash phtn.

It’s been our pleasure bringing you this program today. Thank you for joining us. Goodbye.