 Welcome to the 2009 edition of Epidemiology and Prevention of Vaccine Preventable Diseases. I'm William Atkinson. The Centers for Disease Control and Prevention has presented this immunization training series at least once a year since 1995. We update it annually because immunization recommendations change frequently. In the past, we recorded all 12 hours of this program every year. Beginning in 2009, our 15th anniversary, we're taking a different approach to the annual revision of the program. While there have been changes in vaccine recommendations in the past year, not everything has changed. So this year we did new recordings of only the sections of the program that changed significantly, about 3 hours of the 12 hours of the program. We used the same facility, the CDC television studio, to record the new sections. But you might notice minor differences in the set and different presenters. We also made many other revisions throughout the program with updated graphics and voiceover inserts. For each vaccine preventable disease, we will discuss briefly the microbiology, clinical features and the epidemiology of the disease. We will not go into the diagnosis or treatment of the diseases. This information is available in many other courses and in medical textbooks. We will primarily concentrate on the vaccines and their use in your practice. The immunization recommendations we will discuss are those of the Advisory Committee on Immunization Practices or ACIP. Please note that all 2008 data are provisional and reflect reporting from the 50 states unless we indicate otherwise. Thank you for joining us for this program. We look forward to hearing from you about our new strategy for keeping it up to date. We will provide you with our contact information at the end of the session. Immunization practice is complicated and getting more complicated every year. New vaccines such as rotavirus and human papillomavirus are introduced and need to be integrated into the schedule. Recommendations are changed for existing vaccines as recently occurred for mumps vaccine. It is easy to get confused. We have found that a discussion of the general principles of vaccination and broad recommendations for the use of vaccines can help reduce confusion. So we will spend most of this session discussing these general principles and recommendations. We will then apply the general principles to specific vaccines in subsequent sessions. Any discussion of immunization should begin with a discussion of immunology. We do not intend to go into much detail, but we will give you enough to get the general idea. Let's start off with a consideration of immunity. What is it exactly? In the broadest sense, immunity is our ability to recognize self from non-self. That is, the immune system is able to recognize and eliminate foreign or non-self material from the body and leave everything that belongs there alone. But for the purposes of this program, we will use a narrower concept of immunity. You can think of immunity as protection from infectious disease, the ability to recognize and eliminate infectious agents such as viruses and bacteria, and to prevent infection with these agents in the future. There are two basic types of immunity, active and passive. It is possible for both types to be present simultaneously. We will discuss both types of immunity starting with active immunity. Active immunity is the best type because it is protection provided by a person's own immune system. Active immunity is usually permanent and provides long-lasting protection against reinfection with that virus or bacterium. A good model for active immunity is that which occurs after an infectious disease. In most cases, lifelong immunity results if a person survives an infectious disease. Second infections, at least symptomatic infections, are not common in an immune person. Here is a short animation to illustrate the process of active immunity from infection. The first event leading to immunity is exposure of a susceptible person to an infectious agent. In this case, a virus. Because the person is not immune, the virus is able to replicate and spreads throughout the body. As the virus is spread, some are captured by special antigen presenting cells such as B cells. The B cell engulfs the virus, disassembles it into smaller parts, and presents some of the viral parts on its surface. The viral antigens presented by the B cell attract another key cell of the immune system, a T cell, shown here in yellow. The T cell controls many functions of the immune system. It sends chemical signals to activate the B cell. Each activated B cell then begins to divide. This process is known as clonal expansion because each daughter B cell is a clone identical to the original activated cell. Many of these millions of activated B cells will transform into plasma cells and begin to produce protein molecules called antibodies. Antibodies attached to the invading virus interfere with its ability to produce more viruses and facilitate destruction of the virus by other cells of the immune system. The combined forces of the antibodies and other components of the immune system eliminate the invading virus from the body and confer active immunity. The antibodies and some of the activated B cells, called memory cells, remain after the virus has been eliminated, making the person immune to that virus. Active immunity can result either from infection with the disease causing form of the organism or through vaccination and will persist for years, probably for the life of the person. The entire process from infection to elimination of virus usually takes one to two weeks, but it can take longer depending on the organism. Months or years later another exposure to the virus may occur. The circulating antibodies will recognize the virus and memory cells will rapidly produce more antibody. Because of the antibody and other components of the immune system, the virus will be unable to replicate enough to cause disease. The exposed person is usually unaware that the exposure even occurred. What was illustrated in that animation is generically known as an immune response. There are two central elements in this immune response to infection, antigen and antibody. Antigen is alive or inactivated substance such as a protein or polysaccharide which is capable of producing an immune response. The antigen in the animation was the invading virus. Antibodies are the muscle of the immune response. Antibodies are protein molecules known as immunoglobulins produced by B lymphocytes in response to the antigen. Antibodies assist other components of the immune system in the elimination of an antigen. Antibodies are very specific and only recognize the antigen which produced them or very closely related antigens. The immune system is complex. There are other components which help control invasion by infectious agents. There is another important arm of the immune system known as cell mediated immunity which involves activated T lymphocytes or killer cells. But for simplicity we will equate the presence of antibody with the person being immune or protected from that disease. There are exceptions to this such as pertussis which we will discuss later in the second session of the series. So antibodies are great things to have around. It is preferable to actively produce the antibodies yourself but it is not the only way to get them. It is possible to get them ready made from another person or animal. The transfer of antibody from one person to another is known as passive immunity. The antibodies still do what they are supposed to do, recognize and help eliminate antigen. This type of immunity is usually effective at least for a while. The problem is that passive immunity is not permanent and wanes with time. Here is a short animation that illustrates the process of passive immunity. One type of immunity is passive immunity. With passive immunity a person receives antibodies from another person rather than producing them. The most common type of passive immunity occurs when a fetus receives its mother's antibodies across the placenta. A full term infant is born with antibodies against the same diseases to which the mother is immune. As the infant grows the maternally acquired antibodies circulate throughout the body. Since the infant did not actively produce the antibodies the level declines with time. If the infant is exposed to a disease for which it has maternally acquired antibodies the antibodies will recognize and help to eliminate the invading organism just as it would if the infant were immune from infection. One potential problem with passive immunity is that the maternally acquired antibodies cannot tell the difference between disease causing virus and live vaccine virus. So if the infant receives a live virus vaccine while maternal antibodies are still circulating the antibodies will recognize the vaccine virus and help eliminate it from the body preventing active immunity from occurring. By the time the infant is about a year old all maternal antibodies will have disappeared. Now the infant is susceptible to infection with either the disease causing or vaccine form of the organism. Because there are no circulating antibodies to interfere live vaccines given to the infant will confer active immunity. Maternally acquired immunity is only one type of passive immunity. Injection with immune globulin or disease specific globulin or transfusion of blood products are other ways of conferring passive immunity. But passive immunity no matter how acquired is always temporary. Active immunity either from infection with the disease causing form of the organism or through vaccination is the only way to become permanently immune to disease. Passive immunity is defined as protection in the form of antibody transferred from an exogenous source usually another person. Transplacental antibody is a very important source of passive immunity. Maternal antibody is actively transported across the placenta in the last six to eight weeks of pregnancy. So a full term infant is born with the same antibodies that the mother has. The problem is that if the mother is not immune to a disease the infant will not be immune and is susceptible to infection from the moment of birth. Passive antibody transfer happens in other ways. Some antibody is passively transferred with blood transfusions for example. There are three chief medical sources of passive antibody. The first is homologous meaning same species pooled human antibody commonly known as immune globulin. Those little vials of immune globulin contain antibody from the blood of hundreds of American adult donors. Immune globulin is used for hepatitis A and measles post-exposure prophylaxis among other indications. Immune globulin derived from American donors will contain antibodies to these viruses. In contrast immune globulin from the U.S. would have little or no antibody to yellow fever since relatively few North Americans are exposed to this disease or vaccinated against it. A second antibody product is homologous human hyperimmune globulin. These products have a high concentration of antibody to a specific disease. For instance hepatitis B immune globulin H-Big which is used for post-exposure prophylaxis is taken from donors with high levels of hepatitis B antibody. H-Big will contain a large amount of hepatitis B antibody but also smaller amounts of antibodies to other antigens like measles and hepatitis A. Hyperimmune globulin products are also available for post-exposure prophylaxis of tetanus, varicella and rabies. Vaccinia immune globulin is used to treat certain adverse reactions following smallpox vaccine. There's also an antibody product available for the prevention of infection with respiratory syncytial virus or RSV in infants. There's been a lot of confusion about this product. Although it is used to prevent RSV infection and administered by intramuscular injection, it contains only antibody. It is not a vaccine. The product is palavisumab or synegis. Synegis is unique because it's monoclonal. It's produced in a special way so that it contains only RSV antibody. It does not contain antibody to any other antigen. We'll discuss the implications of this a little later when we talk about antibody vaccine interactions. A third antibody product is heterologous, meaning different species, hyperimmune serum, also known as antitoxin. Antitoxin is different because it's produced in horses, not humans. Equine antitoxin is used in the United States for treatment of diphtheria, botulism and some snake bites. The problem with equine antitoxin is that the immune system may identify the horse protein as not self and develop an immune response to it. This could result in a condition known as serum sickness. We'll come back to passive immunity a little later in this program because the presence of passively acquired antibody may reduce the effectiveness of some injected live virus vaccines. Let's talk now about how vaccines produce active immunity. Now you'll recall that active immunity is induced by infection with the disease causing form of the virus or bacteria. With vaccines, we attempt to simulate that process but without actually producing the disease and without producing the complications that may accompany the disease. At present, there are two basic types of vaccines. Live attenuated vaccines which must replicate inside the body in order to be effective and inactivated vaccines which cannot replicate. There are subtypes of both. Among live attenuated vaccines, live viral vaccines predominate. There are two live bacterial vaccines but these are not commonly used in the U.S. There are two main groups of inactivated vaccines. Those that contain inactivated whole viruses or bacteria and a second large group which we will refer to as fractional vaccines. These vaccines contain only immunogenic pieces or fragments of the organism of interest. Among the fractional vaccines, most are protein based such as subunit vaccines and toxoids. Some fractional vaccines are polysaccharide based and may be either pure polysaccharide or conjugate polysaccharide. In order to simplify some of the principles of vaccination, we have developed a few general rules. Here's the first general rule. The more similar a vaccine is to the disease causing form of the organism, the better the immune response to the vaccine. This makes sense since disease induced immunity is generally long lasting and the closer we can approximate that with vaccine, the better the protection from the vaccine. From this rule, you might expect that live vaccines would have some advantages since infectious diseases are caused by live organisms. To illustrate how live vaccines work, here's our third animation. The events that produce immunity with a live attenuated vaccine are almost identical to those which lead to immunity following infection with the disease causing form of the organism. The two main differences are that exposure is intentional, usually through injection of the virus and that the virus is attenuated or weakened so it does not cause illness. Since the person is not immune, the vaccine virus is able to replicate and spreads throughout the body. The vaccine virus is very similar to natural disease virus so the immune system cannot tell them apart. B cells and other antigen presenting cells engulf and disassemble the virus and present viral antigens on their surface. The viral antigens are recognized by a T cell shown here in yellow. The T cell signals the B cell to activate. The activated B cells begin to divide, producing millions of identical daughter B cells. Many of these B cells transform into plasma cells and produce antibodies directed against the vaccine virus. As with infection with the disease causing form of the virus, the antibody attaches to the vaccine virus and facilitates its destruction by other components of the immune system. This leads to elimination of the virus from the body. The antibody and memory B cells produced in response to the vaccine virus infection will persist for many years after the vaccine virus has been eliminated. Because the antibodies cannot distinguish between vaccine virus and disease virus, the person is now immune, probably for life, to infection with the disease causing form of the organism. So if months or years later an exposure to disease virus occurs, the antibodies will recognize the virus and facilitate its elimination by other components of the immune system. No disease will result from the exposure. As you can see, the immune response to a live vaccine is very similar to active immunity that results from infection with the disease causing form of the organism. In both situations, the infectious organism replicates until an immune response is generated, which eliminates the invading pathogen. We will be mostly talking about live virus vaccines, since we rarely use live bacterial vaccines in the United States. There are several characteristics of live vaccines of which you should be aware. Live vaccines are an attenuated or weakened form of the wild viruses or bacteria. Wild is a jargon term for the form of the virus or bacterium which causes the disease. For example, the measles vaccine that is used today originally caused measles disease in a child in 1954. It took nine years to transform the wild measles virus into the vaccine virus that is used now. Live vaccines must replicate to be effective and to produce an immune response. That is how they work. Anything that interferes with replication can decrease or eliminate the vaccine's ability to produce immunity. The immune response to a live vaccine is very similar to the immune response that occurs following natural illness or infection with the disease causing form of the organism. The mechanism is the same in both cases. The viruses or bacteria replicate until an immune response stops the organisms from replicating and eliminates it from the body. As a result, live vaccines produce immunity in most recipients with one dose. However, a small percentage of recipients do not respond to the first dose of an injected live vaccine such as MMR or varicella. So a second dose is recommended to provide a very high level of immunity in the population. Typically, live oral vaccines require more doses than injected live vaccines. Because they replicate, severe reactions are possible if the immune system cannot eliminate the vaccine organism. Fortunately, these severe reactions are rare and occur mainly when live vaccines are erroneously administered to immunosuppressed persons. An important limitation of some live vaccines, particularly measles vaccine, is interference from circulating antibody. Antibody against the vaccine virus can reduce or eliminate the ability of the live vaccine agent to replicate. And if live vaccines do not replicate, they do not work. Interference by circulating antibody appears to be a problem mainly with injected live virus vaccines. Finally, live vaccines are relatively fragile. They must be stored and handled very carefully or risk reducing or destroying their potency. The virus in that little vial has to be kept viable. If the live agent is dead when you give it, it cannot replicate and it will not be effective. We use several live attenuated vaccines in the United States. Here is a list of them. The live viral vaccines are measles, mumps, and rubella, which are usually given as combined MMR vaccine, varicella and zoster, which contain the same vaccine virus but in different amounts, yellow fever, live attenuated influenza, rotavirus, and vaccinia or smallpox vaccine. Oral polio is a live virus vaccine but is not currently available in the United States. There are two live bacterial vaccines, BCG and oral typhoid. BCG is used for the prevention of tuberculosis. It is one of the most commonly used vaccines in the world. Most of you will never administer a dose of BCG vaccine since it is not available in the United States. But most of you have seen the results of BCG vaccination on the arms of children and adults from other countries. This image shows two circular BCG scars on the arm of a woman from El Salvador. These scars are sometimes confused with those caused by smallpox vaccine. Most of you will not use oral typhoid vaccine either since it is used almost exclusively among international travelers and the military. So that is the story with live vaccines. The second major vaccine category is inactivated vaccine. The antigen in inactivated vaccine is not alive but it interacts with the immune system in a way similar to live vaccines. To illustrate how inactivated vaccines work, we would like to show you our last animation. The events which produce immunity to inactivated vaccine are similar to those leading to immunity following infection with the disease causing form of the organism or vaccination with live attenuated vaccine. The person is injected with inactivated antigen which can be a whole inactivated virus or fragments of a killed virus or bacterium. Since the antigen is dead, it cannot reproduce. So larger quantities of inactivated vaccine antigen must be injected to stimulate an immune response. As with infection or vaccination with live vaccines, the inactivated antigen is captured and ingested by B-cells and other antigen presenting cells. The B-cell processes the antigen and presents it on its surface. These antigens are recognized by a T-cell. The T-cell signals the B-cell to activate. The B-cells divide just as they do after infection with the disease causing form of the organism or after receipt of live attenuated vaccine. Many will transform into plasma cells and then produce antibody directed against the vaccine antigen. Antibodies attach to the vaccine antigen leading to its elimination from the body. Unlike infection with the disease causing form of the organism or vaccination with live vaccines, a single dose of inactivated vaccine may not confirm immunity. Only a small amount of antibody is produced and it may disappear quickly. Additional doses may be needed to boost the immune response. A second dose of antigen usually given within a few months of the first causes a similar response. More antibody is produced which attaches to the vaccine antigen and facilitates its elimination by other components of the immune system. This time more antibodies remain but long-lasting immunity still may not be conferred. One or more additional doses may be required to increase the antibodies to a protective level. But even this protection can gradually decline over time. An additional booster dose may be needed years after the primary series to ensure that the antibody level remains protective. While antibodies remain, the person is immune to the disease causing form of the virus or bacterium. If an exposure to the disease organism occurs, the antibodies will recognize and help to eliminate it. Usually there is no illness from the exposure. Illness may occur but it is usually less severe than in an unvaccinated person. The basic immune response process is similar with both live and inactivated vaccines. The main difference is that live antigens replicate until the immune system stops them. Inactivated agents cannot replicate so the immune system must usually be exposed to the antigen several times in order to produce immunity. Here are some other characteristics of inactivated vaccines. Inactivated vaccines are not alive so they cannot replicate and are non-infectious. Because they are non-infectious they can be administered to an immunosuppressed person. In general inactivated vaccines are not as effective as live attenuated vaccines meaning that estimates of vaccine efficacy are usually lower than with live vaccines. One way that circulating antibody helps to eliminate infectious agents is to interfere with their replication. Since inactivated vaccines do not replicate there is less interference from circulating antibody than for live vaccines. This means you can give inactivated vaccines in the presence of passive antibody such as maternal antibody so you can give them earlier in life. In fact it is common to give inactivated vaccine and antibody at the same time. For instance an infant born to a woman with acute or chronic hepatitis B virus infection receives hepatitis B immune globulin in one leg and hepatitis B vaccine in the other leg. The same thing happens for post-exposure rabies prophylaxis. Another difference between live and inactivated vaccines is that live vaccines produce immunity in most recipients with a single dose. Inactivated vaccines generally require three to five doses. The first dose usually does not provide much protection. It is a primer for the immune system. The subsequent two or three doses provide protection by increasing antibody levels. The immune response to an inactivated vaccine is mostly humoral unlike live vaccines which produce both humoral and cellular immunity. Unlike live vaccines in which immunity is generally long-lasting the antibody titer following an inactivated vaccine may diminish with time and may in some cases fall below a protective level. It is not known why live vaccines produce such good long-term immunologic memory and some inactivated vaccines do not. When antibody wanes to a non-protective level it may be necessary to give the immune system a little reminder in the form of a booster dose of vaccine. At present tetanus and diphtheria toxoids are the only routine vaccines that require booster doses to maintain protection in healthy people. Inactivated whole virus vaccines available in the U.S. include inactivated polio, rabies and hepatitis A vaccines, inactivated whole cell bacteria vaccines such as cholera and whole cell pertussis vaccine are available in some countries but none are available in the United States. Here is a list of fractional vaccines which contain only parts of a virus or bacterium. Subunit vaccines include hepatitis B, influenza, acellular pertussis, human papillomavirus and anthrax. There are two toxoids which are inactivated toxins of diphtheria and tetanus. Acellular pertussis vaccines could be classified as toxoids as well. We will talk about pertussis vaccines in the second session of the course. Another type of fractional vaccine is composed of polysaccharide either alone or conjugated to a protein carrier. Polysaccharides are complex sugars that make up the outer coat of certain bacteria, most notably the streptococcus, NY, and hemophilus families. The polysaccharide code is important in the development of disease and immunity, so vaccine production should be fairly straightforward. Just purify the polysaccharide and put it in a vial. Well that is one way to make a polysaccharide vaccine, but there is a catch. Most polysaccharides are T-independent antigens. You will recall from the animations that the T cell is very important in the development of immunity. Polysaccharides are capable of stimulating the B cell directly without the help of a T cell. This may seem like a good thing, but it is not. Polysaccharides are not very potent antigens. Most importantly, polysaccharide vaccines are not consistently immunogenic in children younger than two years of age. This is a serious shortcoming if the disease you want to prevent occurs commonly in infants like Hib and pneumococcal disease. In addition to this lack of effect in infants, polysaccharide vaccines do not reliably produce a booster response. That means that the amount of antibody produced does not increase substantially following subsequent doses. This is the reason the recommendations for revaccination with pneumococcal and meningococcal polysaccharide vaccines are a bit vague. Repeated doses result in little or no additional protection. Another limitation of polysaccharide vaccines is that they produce antibody with less functional activity. Much of the antibody produced is IgM instead of IgG. The good news is that the limitations of pure polysaccharide vaccines can be remedied. The immunogenicity of these vaccines is improved by conjugation, literally a joining of polysaccharide with protein. The resulting conjugated material is a T-dependent antigen and does not have the limitations of a T-independent antigen. Most importantly, conjugates are effective in infants. We now have six polysaccharide-based vaccines. Pure polysaccharide vaccines, which are only administered to persons two years and older, include pneumococcal, meningococcal, and typhoid VI vaccines. Conjugate polysaccharide vaccines include hemophilus influenzae type B, pneumococcal, and meningococcal conjugate vaccines. Unlike Hib and pneumococcal conjugate, meningococcal conjugate vaccine is not routinely recommended for infants in the United States. So in summary, there are two basic types of immunity. Active immunity is produced by a person's own immune system and is often lifelong. This type of immunity is produced by vaccination. Passive immunity is effective but is always temporary. There are also two basic types of vaccine. Those that contain live, attenuated organisms that produce immunity by replication in the recipient, and those that contain inactivated organisms are only parts of an organism. The age of vaccination and schedule for most vaccines varies depending on type. We will discuss specific information for each vaccine and subsequent sessions of this program. Immunization schedules for the United States are revised and published in Morbidity and Mortality Weekly Report or MMWR every year. The schedule for children and adolescents through age 18 years are published together in January. In previous years, the schedule for adults 19 years and older was published in the fall. Beginning in 2009, the annual adult immunization schedule will also be published in the MMWR in January. Immunization schedules are an integral part of immunization practice, so we want to present an overview of them. We will discuss specific vaccines and their recommendations in subsequent sessions of this series. The development of immunization schedules is a collaborative effort. The schedule for children and adolescents birth through 18 years are developed by the three principal groups that make pediatric immunization recommendations in the United States. These groups are the Advisory Committee on Immunization Practices, or ACIP, the American Academy of Pediatrics, and the American Academy of Family Physicians. The schedule represents the concurrence of all three groups for vaccination of children and adolescents. The ACIP is a group of 15 non-governmental experts in public health, infectious diseases, and clinical medicine. They are appointed to ACIP by the Secretary of the Department of Health and Human Services and serve four-year terms. The ACIP advises the Centers for Disease Control and Prevention and the Department of Health and Human Services on immunization policy. It is these recommendations that we'll mainly discuss during this program. Creation of immunization schedules is a complicated, year-long process that requires input from ACIP as well as members of the Academies of Pediatrics and Family Physicians and others. The childhood and adolescent schedules must be revised and approved no later than October of each year in order to be published in January. There are several important changes in the 2009 schedule. These changes include new age recommendations for the first dose and any dose of Rotovirus vaccine, expansion of routine, annual, childhood influenza vaccination through 18 years of age, and clarification of the minimum interval between adult TD and TDAP vaccination. Other changes include information about the use of HIP vaccine among persons five years of age and older, and clarification of the catch-up schedule for HPV vaccine. We will discuss each of these new recommendations in the respective segment of this series. Here is the 2009 schedule for children birth through six years of age. This schedule was published in Morbidity and Mortality Weekly Report on January 2, 2009. The basic layout of the schedule is similar to schedules for other age groups. Vaccines are listed down the left side, and ages are indicated across the top. In the table, vaccine names are listed under the recommended age for each dose. Yellow bars that span ages indicate a range in the recommended age for that dose. The purple bars indicate vaccines that are not routinely indicated for all children, but are recommended for children at increased risk for certain diseases. The child and adolescent schedule is intended to serve as a summary of routine immunization recommendations for children through 18 years of age. It does not replace the ACIP statements that provide much more detail than can be included on the schedule. The schedule also illustrates many of the basic principles of vaccination that were discussed earlier in this session. Notice that the inactivated vaccines, hepatitis B, DTAP, Hib, pneumococcal conjugate, and inactivated polio vaccines can be started as early as two months of age and required three to five doses. The first dose of hepatitis B vaccine is recommended to be given at birth before the infant goes home from the hospital. Influenza vaccine can be given as early as six months of age and requires two doses, the first year child receives it. Although rotavirus vaccine is a live virus vaccine, it should also be started at two months of age and requires three doses. The injected live vaccines, MMR and varicella are not given until after the first birthday due to the presence of maternal antibody, which could interfere with vaccine virus replication. If you look down any age column and follow the vaccine rows to the left, you can see what vaccines a child will need to be adequately immunized by that age. For instance, at four months of age, a child should have received two doses of rotavirus, two doses of DTAP, two doses of Hib, two doses of pneumococcal conjugate, and two doses of IPV. A child should also have received at least two doses of hepatitis B vaccine if it was given as a single antigen formulation. The child may have received three doses of hepatitis B vaccine at this age if he or she received a combination vaccine that contains hepatitis B vaccine at two and four months of age. Looking down the column marked 18 months and counting to the left, you can see that by that age a child should have received at least three doses of hepatitis B and rotavirus vaccines. Four doses of DTAP, three of four doses of Hib, four doses of pneumococcal conjugate, three doses of IPV, at least one dose of influenza vaccine, one dose each of MMR and varicella vaccines, and at least one dose of hepatitis A vaccine. That is what is referred to as series complete, that these 24 to 28 doses of vaccine have been given by 18 to 24 months of age. For many years, the recommended immunizations for all children through 18 years of age were included on a single schedule. But those were simpler times when there were fewer vaccines recommended for older children. There just was not enough space on a single schedule to include recommendations for TDAP, meningococcal conjugate, and HPV vaccines at 11 or 12 years of age. As a result, since 2007, children 7 through 18 years of age have had their own schedule. Here it is. It is laid out like the schedule for younger children with ages across the top and vaccines in the rows. It also has yellow bars that indicate the age range for routinely recommended vaccines and purple bars for vaccination of persons in this age group with certain high risk conditions. This schedule also has blue bars to indicate catch-up vaccination. That is, vaccines that should be administered at this age if they were not administered earlier. The lower half of both schedules contain footnotes. The footnotes provide important details about the schedule, such as minimal intervals and ages. You should always read the footnotes carefully. And you should read the footnotes on each new edition of the schedules because footnote content changes often. Another helpful feature of the child and adolescent schedule is the catch-up immunization schedules. The catch-up schedule will help you accelerate the schedule for children who start late or who are more than one month behind. These schedules utilize minimum intervals between doses. We will talk more about minimum intervals and catch-up schedules later in the program. Childhood vaccination schedules have existed for decades, although they have been revised annually only since 1995. Adults have always needed vaccines as well, but the first immunization schedule for adults 19 years and older was not developed until 2002. Like the childhood schedule, the adult schedule is revised annually. It is now published each January. The adult immunization schedule is a collaborative effort of the ACIP, the American Academy of Family Physicians, the American College of Obstetricians and Gynecologists, and the American College of Physicians. The schedule is officially endorsed by each organization. Here is the adult schedule for 2009. It is laid out similarly to the childhood schedule with age groups in the columns and vaccines listed on the left. The color coding is also similar to the childhood schedule with yellow bars indicating vaccines recommended for all persons in that age group who do not have evidence of immunity. Purple bars indicate vaccines indicated for persons with increased risk for that disease. The adult schedule includes the second table that you will find very useful. Most adult vaccine recommendations are driven by a risk condition rather than age. This table lists a variety of conditions or indications in the columns such as pregnancy, immunosuppression, HIV infection, asplenia, and others. Vaccines are listed on the left. Yellow bars indicate vaccines the person should receive if the condition or indication is present. Unique to this table, red bars indicate a condition when a particular vaccine is contraindicated and should not be given, such as MMR and varicella vaccine during pregnancy. We will discuss the schedule for specific vaccines in subsequent sessions of this program. Please get a copy of the schedules and have them handy as you view this program. And be sure to read all the footnotes. In this segment of the program, we will discuss the general recommendations on immunization. The title refers to immunization recommendations that apply to more than one vaccine or group of vaccines. But the title also refers to a specific publication of the Advisory Committee on Immunization Practices, or ACIP. Most ACIP statements address a single vaccine or vaccination issue. The general recommendations on immunization is unique among ACIP statements because it provides guidance on vaccination issues common to more than one vaccine. The general recommendations on immunization is revised every three to five years. The current version was published in December 2006 and is the most comprehensive version to date. The general recommendations includes information on the timing and spacing of vaccines, contraindications and precautions, vaccine administration, storage and handling, altered immunocompetence, and preventing and reporting adverse reactions. There are also sections discussing special vaccination situations including persons with allergy to vaccine components, vaccination of preterm infants, pregnant and breastfeeding women, internationally adopted children, stem cell transplant recipients, and much more. We would like to discuss three issues from the general recommendations that relate to the spacing and timing of vaccines. The three interval issues we are going to discuss are the timing of antibody-containing blood products and live vaccines, simultaneous and non-simultaneous administration of different vaccines, and the interval between subsequent doses of the same vaccine. These issues come up frequently in vaccination practice and we get many questions about them. Let's begin with a general rule. Inactivated vaccines are generally not affected by circulating antibody to the antigen. As a result, inactivated vaccines can be given anytime before or after antibody has been given or in infancy when maternal antibody is still present. Live attenuated vaccines, primarily injected live attenuated vaccines, may be affected by circulating antibody to the antigen. The presence of circulating antibody may affect the age at which a vaccine is given because of persistent maternal antibody. It may also influence the length of the interval between administration of an antibody-containing product, such as a blood transfusion and a vaccine dose. The interval between antibody and vaccine is most important for measles and probably varicella. Mumps, rubella and rotavirus vaccines seem to be less sensitive to circulating antibody. Yellow fever and oral typhoid are not affected because most blood products in the United States do not contain a substantial amount of yellow fever or typhoid antibody. Live attenuated influenza vaccine and zoster vaccine do not appear to be affected by circulating antibody. If a measles or varicella-containing vaccine is administered before the antibody-containing product, an interval of at least two weeks should separate them. This interval allows the vaccine virus time to replicate and produce an immune response before encountering the antibody. If the antibody-containing product is given first, the interval between it and measles or varicella-containing vaccine should be three months or longer, depending on the antibody product and dose that was administered. On the occasions when you encounter this situation, it would be useful to have a table that indicates the recommended interval between the antibody product and the vaccine. There is a table of these intervals on page 8 of the general recommendations. This is an image of it. The table is also available on the Updates and Resources webpage and in the course text. It will be helpful if you get a copy of the table from one of these sources and follow along this next part of the discussion. You can see the table has three columns. The first column lists most of the antibody products available in the United States. The second column is the recommended dose for that particular product and indication. The third column lists the interval between receipt of that product and measles or varicella-vaccine administration. Let's look at three examples. The third line is labeled Hepatitis A-I-G. The second column gives the dose of immune globulin recommended for contact prophylaxis and for international travel. The third column shows the suggested interval before vaccination with measles or varicella-containing vaccine is three months for either a contact prophylaxis dose or a dose used before international travel. This means that in three months the dose of antibody should have waned enough to allow replication of measles and varicella-vaccine virus. Near the middle of the page below blood transfusion is the listing for whole blood. The recommended interval between a transfusion of whole blood and measles or varicella-vaccine is six months. At the bottom of the table are five rows for intravenous immune globulin or I-G-I-V for various indications such as the treatment of immune thrombocytopenic purpura and Kawasaki disease. Because of the amount of antibody present in I-G-I-V, eight to eleven month intervals are recommended between its administration and live virus vaccination. You should be aware that some children with HIV infection are on routine I-G-I-V schedules so you may need to check this table for intervals before administration of MMR or varicella-vaccine. The table also includes an entry for an antibody product for the prevention of RSV. The product is synegous located on the top row of the table. Synegous, whose generic name is Palovisumab, contains monoclonal antibody only to RSV and does not contain any other antibody. So, synegous does not interfere with live virus vaccination because it does not contain measles, mumps, rubella, or varicella antibody. The interval between synegous and live virus vaccines is zero. Live virus vaccines can be administered any time before or after administration of synegous. We strongly suggest that you use the intervals in this table if your client has received some type of blood product and needs MMR or varicella-vaccine. If MMR or varicella-vaccine is given at an interval shorter than those in the table, you should either repeat the vaccine dose at a later time or use a laboratory test to verify that there has been a response to the vaccine. Administering a second dose is probably the easiest and cheapest course of action. Do not memorize the antibody table. When you get back to your office, copy it, laminate it, post it, and explain it to other members of your staff. Whatever it takes so everyone knows how to use it and where to find it. Please note that the intervals on table four do not apply to Zoster vaccine. Rotavirus is a live virus vaccine. However, as of 2009, the ACIP no longer recommends deferral of rotavirus vaccine after receipt of an antibody containing blood product. We will discuss both these issues in the respective segments in subsequent sessions of this course. Donna? We will now discuss the simultaneous and non-simultaneous administration of vaccines. The next general rule of vaccination is one that we will mention often during this program. All vaccines can be administered at the same visit as all other vaccines. Now let me repeat that all vaccines used in the United States can be administered at the same visit as all other vaccines. The simultaneous administration of vaccines is absolutely critical to raising and maintaining high immunization levels. Simultaneous administration neither decreases vaccine efficacy nor increases the risk of adverse reactions. It does not overload the immune system, which is very capable of coping with many antigens every day. Simultaneous administration is also preferred by most parents who would rather make one trip to your office than two. Finally, simultaneous administration of all needed vaccines helps assure that children are protected, so it is the right thing to do. So what about vaccines that are not given simultaneously? For instance, a child got his one-year vaccines from his primary care provider, but that practice did not have an inventory control plan and has run out of varicella vaccine, so the child must be rescheduled for the varicella vaccine. When should he come back? The only time that a specific interval should separate two vaccines not given on the same day is when both of them are live and both are either injected or administered by nasal spray, in the case of live attenuated influenza vaccine. If two live injected or intranasal vaccines are not given simultaneously, they should be separated by at least four weeks. All other combinations, including live oral vaccines, may be administered at any time before or after each other without waiting. The recommendation to separate live virus vaccines by at least four weeks results from concern that the vaccine given first could interfere with response to the vaccine given second. These concerns were initially based on two 1965 studies that indicated that recent measles vaccination reduced the response to smallpox vaccine. In 2001, the CDC conducted a study using the Vaccine Safety Datalink system to investigate risk factors for varicella vaccine failure. That's children who got chickenpox even though they had been vaccinated. This study found that children who received varicella vaccine less than 30 days after MMR vaccination had a significantly increased risk of breakthrough varicella compared to those who received varicella vaccine before, simultaneous with, or more than 30 days after MMR. This study provided additional evidence that interference can occur between two live vaccines given less than 28 days apart. ACIP recommends that when two injected or intranasal live vaccines are not given on the same day but are separated by less than 28 days, the live vaccine given second should be repeated unless serologic testing indicates that a response to the vaccine has occurred. For example, if a dose of MMR were given two weeks after a dose of varicella vaccine, the MMR should be repeated. The repeat dose should be spaced at least four weeks after the invalid dose. I would like to emphasize that live vaccines not given simultaneously need to be separated by at least four weeks only if they are injected or intranasal. The four-week separation rule does not apply to rotavirus or oral typhoid vaccine, which can be administered at any time before or after any other vaccine. Remember, you can and should give all routine vaccines simultaneously. That is the gold standard. The alternatives we have discussed here are only for situations when there has been a problem and simultaneous administration did not occur. Andrew. You should always try to keep the child on the routine schedule and make sure the parents know the importance of keeping on schedule. But sometimes things just do not go according to plan. Children sometimes are brought in early, or more commonly, a child is behind in the schedule and needs to be caught up. Also, spacing becomes an issue when assessing a record of vaccines given outside the United States since non-U.S. schedules may differ from those used here. Here is the general rule that applies to this situation. Increasing or lengthening the interval between doses of a multi-dose vaccine does not diminish the ultimate effectiveness of the vaccine after the series has been completed. While an increased interval between doses does not ultimately reduce antibody titers or protection, it may compromise protection in the short run because the series is incomplete. However, decreasing the interval between doses of a multi-dose vaccine may interfere with antibody response and protection. Doses of vaccine given too close together may not provide the full benefit of the vaccine. So, if the minimum intervals are so important, it would seem reasonable that there should be a table listing them somewhere, and there is. This is table one of the general recommendations on immunization. This table contains a listing of every dose of every commonly used vaccine. It is also available on the Updates and Resources webpage and in the course text. Here is a closer view of table one. The table has five columns. The first column on the left lists the vaccines by dose. The second column indicates the recommended age for that dose. This is the age listed for that dose on the childhood schedule. The third column lists the minimum age for that dose. Vaccine doses should not be given at an age younger than the minimum age. The fourth column indicates the recommended interval to the next dose, like the recommended age, this is information derived from the routine childhood schedule. The fifth column indicates the minimum interval to the next dose. Doses of vaccine should not be spaced closer than the minimum interval. Table one provides all the information you need for scheduling vaccine doses. Be sure to have a close look at it, and be sure to read all the footnotes. The ACIP recommends that providers schedule vaccines as close to the recommended age and intervals as possible. The recommended schedule, age for specific doses, and spacing of doses is supported by data from clinical trials of the vaccine. There are times when it is necessary to give vaccines earlier or closer together than recommended in the routine schedule. Minimum ages and intervals can be used in these circumstances. For instance, when a person is behind on the schedule and it is necessary to catch them up. Minimum ages and intervals could also be used in other situations, when the vaccination series may need to be accelerated, such as when international travel is impending. While there are less scientific data supporting the use of minimum intervals and ages, ACIP believes that the response to doses given at minimum intervals and ages will be acceptable. Donna? In practice, vaccine doses are sometimes administered earlier than the minimum age or minimum interval. In the past, ACIP has recommended that a dose of vaccine separated from the previous dose by less than the recommended minimum interval, even one day less, should not be considered a valid dose. ACIP continues to recommend that vaccine doses should not be given at less than the minimum interval or earlier than the minimum age. But in an effort to increase the flexibility of the complicated childhood immunization schedule, the ACIP now recommends that vaccine doses administered up to four days before the minimum interval or age can be counted as valid. This four-day period before the minimum age or interval is sometimes referred to as the grace period. The ACIP believes that administering a dose a few days earlier than the minimum interval or age is unlikely to have a significant negative effect on the immune response to that dose. This four-day grace period can be applied to all ages and intervals listed in Table 1. However, the grace period does not apply to minimum intervals between different live vaccines. For example, if MMR and varicella vaccine are not given on the same day, do not use the four-day grace period to shorten the 28-day minimum interval between these two vaccines. The grace period should not be used when scheduling future vaccination visits. It should be used primarily when reviewing vaccination records such as for child care or school entry. The four-day grace period may also be useful in situations where a child visits a provider a few days earlier than a scheduled vaccination appointment. For example, if a child comes to the office or clinic for an ear check 27 days after his or her second DTAP dose, the provider could administer the third DTAP at that visit rather than having the child return for vaccination the next day. The four-day grace period recommendation by ACIP may cause a conflict with some state school entry requirements. For instance, most state school requirements mandate the first dose of MMR to be given on or after the first birthday. As a result, not all states will accept the grace period for some or all vaccine doses. Providers should determine the position of their state immunization program on this issue before using the grace period. The reason that some states are not accepting the grace period is because to do so would mean changing the school requirement or law, which often requires an act of the state legislature. So be sure to check with your state immunization program before using the grace period. Remember to stay on the routine schedule whenever possible, but sometimes children fall behind. If this happens, you need to do several things. Talk to the parent about the importance of staying on schedule, flag the chart for special attention, and speed up or accelerate the vaccination schedule. This means giving doses with the minimum acceptable intervals until the child is caught up. The ACIP and the Academies of Pediatrics and Family Physicians publish a harmonized catch-up schedule every year with the recommended schedule. The one you see here is for children four months through six years of age. There is also a version for children seven through 18 years of age. The information in the catch-up schedule is basically the minimum interval information from table one in a condensed and reconfigured form. You need to be familiar with the catch-up schedules. Be sure to take some time to look at them carefully, and of course, read all the footnotes. The catch-up schedules are also available on the CDC Vaccines and Immunization website. Table one of the general recommendations and the catch-up schedules address the minimum acceptable interval between doses. But what if the interval is too long? It is not necessary to restart the series of any vaccine due to an extended interval between doses. The one possible exception to this is oral typhoid vaccine, which you are not likely to use unless you deal with travelers. Extended intervals between doses happen all the time. Healthcare personnel sometimes decide to take one or two or ten years off between doses of hepatitis B vaccine. Adolescents may only make it into their doctor's office once a year. Sometimes parents just forget or do not understand the importance of staying on schedule. If the interval between doses is longer than the recommended interval, you do not have to restart the series or add doses. Just pick up where you left off and try to get the rest of the doses in on time. So the main issues on spacing and timing of vaccines are the timing of antibody-containing products and MMR and varicella vaccines, spacing of doses of different vaccines, and spacing of doses of the same vaccine. These issues arise frequently in practice, so you need to be clear on them. These issues and more are discussed in the general recommendations. We strongly suggest that you get a copy if you do not already have one and take some time to read it. We would now like to present a case study that addresses issues that we've discussed on the program today. The case studies are available on the Updates and Resources webpage for this program. Case number one is Anna. Anna is a 15-month-old who's been in your practice since birth. She's brought to your office for routine vaccinations in early June. At 11 months of age, Anna was diagnosed as having immune thrombocytopenic perpura, or ITP. She was treated with intravenous immune globulin. The ITP symptoms have now resolved and she has no other medical problems. Here's Anna's vaccination history. She received pediatrics. You recall that's the DTAP, IPV, Hepatitis B combination vaccine at 8, 12, and 20 weeks of age. At the same visits, she also received Hib and pneumococcal conjugate vaccines. Here are three questions about Anna. What vaccines, if any, does Anna need today? When should she return for her next vaccinations? And what vaccines will be needed when she returns? If you're viewing this program with a group, we suggest you pause the program now and discuss it among yourselves. We'll return in just a moment to discuss it with you. There are several issues with Anna. This is actually a fairly complicated situation, but not one that is rare in clinical practice. The issues that you have to deal with first are whether the vaccine she's gotten so far are considered valid. And for that, you would mainly want to consider the ages and intervals between them. And then there is the issue of the ITP, whether that's an issue for vaccines or not, and the treatment of the ITP, which in this case was intravenous immune globulin. So you need to consider all those things and you will probably need your general recommendations, at least a couple of tables from them, to answer some of the questions about Anna. So here is the first question about Anna. And it of course is, she's in your office. What vaccines, if any, does Anna need today? Well, today, Anna needs her third Hepatitis B vaccine, her fourth DTAP, HIB number four, PCV number four, and her first dose of Hepatitis A vaccine. Why does she need Hepatitis B vaccine? Well, you of course, check those intervals and you know that in table one, which has all the intervals and ages in it, that the minimum age for the third dose of Hepatitis B vaccine is 24 weeks. She got her third dose at 20 weeks of age, which was four weeks early. So while the DTAP and IPV components of the pediatrics can be counted as valid, because there were four weeks between them, the Hepatitis B vaccine dose is not considered valid and because it was too early, and so that needs to be repeated. Again, her DTAP and IPV intervals were fine, so those are all right, she can continue. And the PCV intervals are four weeks, so those are also acceptable. Hepatitis A vaccine, you recall, was first recommended for all children in their second year of life, between 12 and 23 months in 2006. So you have the opportunity, you should give her her first dose today. Now, what about that HIB booster dose? Well, Kerry, you would give her her fourth dose and final dose of HIB vaccine today while she's there. The problem is, at the moment, you may not have any HIB vaccine, and currently, given the HIB vaccine supply situation, we actually recommend that the HIB booster, after a year of age, not be administered to children who do not have a high-risk condition. Well, Anna doesn't really have a high-risk condition. She had ITP, but she's healthy now, and so Anna, really, given the current situation, although eligible, would not receive her fourth dose of HIB vaccine today, you would defer that to later. She is, of course, age-eligible for MMR and varicella vaccines, but the ITP and the IVIGIV kind of throw a flag up about that, and so we're probably not going to deal with that because it may be too short. So, the next question about Anna is, when should she return for her next set of vaccinations? The answer is that Anna should return for her next vaccinations in three months. That would make it eight months after the intravenous immune globulin. Now, to deal with this and answer the question of when should she come back, you will need the other important table from the general recommendations. That's table four, which lists the recommended interval between various antibody products and live vaccines, MMR and varicella. You'll notice she got IGIV about eight months ago, and so if you look at table four, the ITP, the interval between IGIV and MMR is actually anywhere from eight to ten months, so we don't really know exactly what dose Anna got, so the soonest she could come back would be three months, which would be the minimum eight months after the ITP dose of intravenous immune globulin, but it may actually end up being longer because you're going to need to find out what dose she got, and so that would help drive when she returns and when she can get her MMR and varicella. She will need her MMR and varicella when she comes back. If you have it available, you could give MMRV the combination vaccine at that visit. Now she's seeing you in June, she's going to come back earliest in September, so of course she's going to need influenza vaccine, and it will be September, and so you're probably going to be looking, she'll be nineteen months old at that time, and you're probably going to be looking at influenza vaccine. So what about the last question about Anna, which is really which vaccines, what all are the vaccines that she's going to need when she comes back? She will need, assuming that enough time has passed since her IGIV, when you should have looked that up in the table, she'll need her first MMR, her first varicella, and her first dose of influenza vaccine. Again, you can use your MMRV when she comes back if you have it available to you. She will be nineteen months old, assuming it's going to be three months when she comes back, so she will need either her first or second dose of influenza vaccine. She will not yet be old enough to receive the live attenuated influenza vaccine, the minimum age for that is two years, so she will need a dose of inactivated influenza vaccine as her first or second dose, depending on if she received a dose in the previous year. Now, there's one other issue about Anna, and that is the whole issue of using measles vaccine, giving measles vaccine to a person who had thrombocytopenia. As you may know, and we will discuss later in a subsequent section, that history of thrombocytopenia, low platelet count, is a precaution to the use of measles vaccine. We know that, in fact, it's possible that a person with this history could be at increased risk of having another episode of low platelet count should they be exposed to measles vaccine. This is a classic risk and benefit situation, because we know that, in fact, if you leave her unvaccinated, the risk if she would get measles of thrombocytopenia would be much higher than from the vaccine, and so the clinician would need to consider these things very carefully. In our opinion, in almost every case, the benefit of measles immunity outweighs the risk of a recurrence of her thrombocytopenia, and we would suggest that she receive MMR on schedule. Thank you, Bill, for discussing that case. While we have some time, why don't we take a few questions? We receive questions frequently by email, and why don't we discuss a few of them? One question we get often is if MMR and varicella vaccine are given and then a person returns the following week for flu vaccination, can LAIV be given? Donna, do you want to take that one? Yeah. Actually, the answer to that would be no, because MMR and varicella are live injectable vaccines and then LAIV is live intranasal. So if you'll remember the rule for that is that they would need to be separated by at least four weeks if not given on the same day. Now, just one other thing I would argue, if you've got the child there, you're trying to get the mom to get the TIV, the injectable influenza, so that you don't miss an opportunity to vaccinate and go ahead and get the, because inactivated, you don't have to worry about the time, the interval there. Thank you. Here's another question we receive. How long after vaccination can a person donate blood? We get that one a lot. Bill, why don't you take that one? We do get that a surprising amount. It's actually kind of a two-part answer. One of the things we do, of course, is would you really want to have virus in a person's blood if they were going to donate it to somebody who might be acutely ill? We don't really, CDC doesn't really have very specific guidance on this issue, but the American Red Cross does. As a general rule, the American Red Cross recommends that if a person's gotten a dose of live virus vaccine, MMR, varicella, yellow fever, that in fact an interval of four weeks should pass before the person shows up to donate blood, and make sure that off chance they might actually still have some live virus in their blood as a result of the vaccination. Smallpox vaccine is an exception to this. Actually, not using much smallpox vaccine these days, but actually it's recommended to wait eight weeks after a dose of smallpox vaccine. The other issue is hepatitis B vaccine, interestingly enough. There have been cases where a person has, persons have had a false positive hepatitis B surface antigen test as a result of having had hepatitis B vaccine. So the American Red Cross recommends that an interval of seven days be between a dose of hepatitis B vaccine and donating blood just to reduce the chance of having a false positive hepatitis B surface antigen. Actually, CDC, we don't have really this on officially, but we suggest that it might be a good idea to put a little more time and consider a 30 day interval between hepatitis B vaccination and donating blood just to be sure that we don't have a problem with a false positive surface antigen that might show up in the blood after hepatitis B vaccination. More information on this is available on the American Red Cross website. Okay. Here's another question, something we follow up to, something we mentioned during the talk. You stated that live virus vaccines usually work with one dose. Why then is a second dose routinely recommended for both MMR and varicella vaccines? Donna? Well, that's a common question and I think the key there is what Andrew said is usually works with just one dose. So you have around 5 to 10% of people that may not respond to the first dose. So the second dose of MMR and varicella actually are not booster doses. The intent of those vaccine doses is to catch those people who did not respond to the first dose. The measles, mumps, rubella and varicella are highly contagious diseases. So we need really high immunization coverage rates to protect against them. So we want to try to get that rate up above 90, 95% in terms of people who've responded. Great. Here's another question we receive often. Why is it okay to give rotavirus vaccine a live virus vaccine in the first year of life? Bill? A little odd, doesn't it? Well, rotavirus, of course, is a live virus vaccine and consequently you would expect, like other live virus vaccines, that it might have some interference from maternal antibody and since most women, in fact, are immune and have had rotavirus infection, you would expect the infant to have some transpositional rotavirus antibody. Some, maybe not as much as some of the other diseases. Probably the difference here is that there is evidence that rotavirus vaccine is affected by the age which is given, presumably that being a surrogate for maternal antibody. But it turns out since the virus is replicating in the GI tract that and like OPV was like this too, that in fact it's sort of protected from antibody so consequently it isn't affected as greatly by circulating antibody as is a vaccine you would inject right into the tissue. So consequently it is recommended that in fact you wait six weeks if you can, but it's not absolutely required and we'll discuss this in much more detail when we discuss rotavirus in the subsequent section. Thank you, Bill. Thank you, Donna. All providers who administer vaccine must have a thorough understanding of contraindications and precautions to vaccination. We include fairly detailed information about contraindications to vaccination because this is a common topic of questions we receive. From a practical standpoint you know that when a contraindication or precaution to a vaccine is present you usually do not give a dose of that vaccine but let's define these terms a little more precisely. A contraindication is a condition in a recipient that increases the likelihood of a serious adverse reaction to the vaccine. A contraindication is a condition in the recipient not with the vaccine itself. If the vaccine were given in the presence of that condition the resulting adverse reaction could seriously harm the recipient. The risk of an adverse reaction outweighs the benefit so you will rarely if ever give a vaccine when one of these conditions is present. A precaution is similar but not identical to a contraindication. A precaution is a condition in a recipient that might increase the chance or severity of an adverse reaction or a condition that may compromise the ability of the vaccine to produce immunity. Injury from the vaccine could result but the chance of this happening is less than with a contraindication. Generally you will not give the vaccine if a precaution is present but there may be situations when the benefit of the vaccine outweighs the risk of an adverse reaction such as during an outbreak of the disease. In these situations you may decide to give the vaccine. There are very few true contraindications and precautions so let's go through them briefly. There are only two permanent contraindications to the use of routine vaccines. The first which applies to all vaccines is a severe allergic reaction to a vaccine component or following a prior dose of vaccine. The second applies to pertussis containing vaccines only. It is encephalopathy within seven days of a prior dose of pertussis vaccine. There are other permanent contraindications for vaccines not routinely recommended. For example, for smallpox vaccine a history of eczema or a topic dermatitis in the person or a household contact is a permanent contraindication to pre-event vaccination. What do we mean by severe allergic reaction? This is an allergic reaction that is immediate and life-threatening also called anaphylaxis. Severe IgE mediated allergy usually presents as hypotension, respiratory difficulty such as wheezing or generalized urticaria or hives. Fortunately these types of reactions are extremely rare following vaccination. There are several other conditions that are temporary contraindications or precautions and whether the condition is a contraindication or precaution depends on the type of vaccine being used live or inactivated. Here's a table that lists the conditions. The C indicates a contraindication P indicates precaution and V means vaccinate if indicated. A severe allergic reaction to a vaccine component or a prior dose of vaccine is a contraindication to both live and inactivated vaccines. And cephalopathy following a prior dose of pertussis vaccine is a permanent contraindication that applies to pertussis containing vaccines in all age groups. Pregnancy is a contraindication to live vaccines because of the theoretical possibility of infection of and damage to a fetus. No vaccine except smallpox vaccine has ever been shown to actually damage a fetus. Since inactivated vaccines do not replicate they may be used if indicated. There are exceptions to this. Pregnancy is considered to be a precaution for human papillomavirus vaccine and Tdap vaccine. We will discuss this in more detail in the HPV and pertussis segments of the course. Pregnancy in a household contact is not a contraindication to any vaccine except smallpox vaccine. Immunosuppression is a contraindication to most live vaccines. Immunosuppression is considered to be a precaution to rotavirus vaccine. Inactivated vaccines may be administered to an immunosuppressed person if indicated. We will discuss immunosuppression in more detail in a moment. Moderate or severe acute illness is a temporary precaution to both live and inactivated vaccines. It is reasonable to defer vaccination until the acute condition has improved. So what do we mean by moderate or severe? As a rule of thumb any illness that may require hospitalization or additional medical care after the immunization visit is reason to delay the vaccine. The ACIP has never recommended a maximum temperature for giving vaccines. Fever may not be a very good indication of severe illness in an infant anyway. You will need to use your professional judgment about the severity of the acute illness. But minor illnesses with or without low grade fever are certainly not reasons to defer vaccination. Recent receipt of a blood product is a precaution to MMR and varicella vaccines because of possible interference with viral replication. Recent blood products have little or no effect on inactivated vaccines. This is a good example of the difference between a contraindication and a precaution. Giving measles vaccine shortly after a blood transfusion will not harm the vaccine recipient. But the antibody will probably inactivate the vaccine virus and no immunity will result from the vaccination. Recent blood products do not affect all live vaccines equally and some are not affected at all. Circulating antibody does not appear to affect zoster vaccine probably because the large amount of varicella zoster virus in the vaccine can overcome antibody in the serum. Antibody does reduce the response to rotavirus vaccine but the effect of the antibody is less because the vaccine is administered by mouth. Passive antibody does not affect live attenuated influenza vaccine because the vaccine viruses are often changed from year to year and antibody against a previous year's vaccine virus does not affect the current year's virus. Finally, few North Americans have antibody to yellow fever or typhoid so there is little or no antibody against these pathogens in the U.S. blood supply. There are a few other precautions which are specific to pertussis vaccine such as fever of 105 or a seizure following vaccination. We will discuss these in more detail when we talk about pertussis vaccine. Donna? We received many questions about vaccination of immunosuppressed persons so we would like to discuss this in a bit more detail. An immunosuppressed person may be more likely to have a serious adverse reaction to a live vaccine than a person with a normal immune system. There are both diseases and drugs which can cause significant immunosuppression. First, the diseases. Persons with congenital immunodeficiency, leukemia, lymphoma, or generalized malignancy should not receive live vaccines. Certain drugs and therapies may cause immunosuppression. For instance, people receiving cancer treatment with alkylating agents or anti-metabolites or radiation therapy should not be given live vaccines. Live vaccines can be given after chemotherapy has been discontinued for at least three months if the disease for which the therapy was given is in remission. Persons immunosuppressed from disease or chemotherapy may not respond well to inactivated vaccines and live vaccines can be harmful to them. However, in the absence of a bone marrow transplant neither the disease nor chemotherapy for the disease eliminates the immunologic memory of vaccines received before the disease or therapy. As a result, it is not necessary to revaccinate a person who has recovered from an immunosuppressive disease or chemotherapy. Persons receiving large doses of corticosteroids should not receive live vaccines. This would include those receiving 20 milligrams or more of prednisone daily or 2 milligrams or more per kilogram of body weight per day. Aerosolized steroids such as inhalers for asthma, topical preparations, alternate day or short high dose courses are not contraindications to vaccination. Short term means less than 14 days. For people who have received high dose steroids for more than 14 days, you should wait at least a month after discontinuation of therapy before administering a live virus vaccine. There are a variety of new drugs considered to be immune system mediators or modulators. Examples of these drugs include interferons and etanercept, tumor necrosis factor blocker marketed as inbrill. It is not known if or at what dose these drugs may cause safety concerns for live vaccines. Until more information is known about these drugs, we recommend they be treated like high dose steroids. Defer live vaccines for one month after discontinuation of therapy. Inactivated vaccines may be administered but may be less effective. Persons with HIV infection who are mildly immunosuppressed and not severely symptomatic should receive measles mumps rubella vaccine. This is because of the high risk of complications of measles disease in these persons. The ACIP also recommends that varicella vaccine be administered to persons with HIV infection with adequate CD4 T cell counts. Zoster, live attenuated influenza vaccine or LAIV and smallpox vaccine should not be given to persons with HIV infection regardless of symptom status. HIV infection is a precaution to the use of rotavirus vaccine. All inactivated vaccines may be administered to a person with HIV infection if indicated. Inactivated vaccines may be administered if indicated to any immunosuppressed person but to the vaccine may be poor. A good immune response to an inactivated vaccine requires a relatively functional immune system so the person may not be fully protected even if the vaccine has been given. But a little protection is better than none at all if you do not administer the vaccine. Bill? One additional issue related to immunosuppression is the vaccination of persons with high-poietic stem cell transplant. Stem cell transplant includes bone marrow transplant. Research has shown that antibody titers to vaccine preventable diseases decline during the one to four years after stem cell transplant if the recipient is not re-vaccinated. It has been common practice in transplant centers to re-vaccinate stem cell transplant recipients but vaccination protocols are still in place. In 2000, CDC published guidelines for the prevention of opportunistic infection including vaccine preventable infections among stem cell transplant recipients. These guidelines were developed in association with ACIP, the Infectious Diseases Society of America, and the American Society of Blood and Marrow Transplantation. Influence of vaccines should be administered prior to stem cell transplant if possible and resumed six months following transplant. Influence of vaccines should be administered annually thereafter. The series of all other inactivated vaccines recommended for the persons age group should be repeated. The repeat series should begin twelve months after transplantation. The inactivated vaccines that should be repeated include DTAP or adult TD age, IPV and hepatitis B vaccine. Re-vaccination with Hib vaccine is recommended for all age groups. Pneumococcal conjugate vaccine should be administered to children younger than five years. MMR is recommended and varicella vaccine should be considered at least 24 months after transplant if the person is immunocompetent. Immunocompetent means that the person is not on major immunosuppressive therapy and does not have graft vs. host disease. ACIP has not made a recommendation regarding the use of meningococcal and TDAP vaccines among stem cell transplant recipients. There are few data on the safety and efficacy of these vaccines in this population. Use of these inactivated vaccines should be a case-by-case by the clinician. An extremely important adjunct to prevention of vaccine preventable diseases in stem cell transplant recipients as well as other immunosuppressed people is to assure that family members, household contacts and healthcare personnel are immune. Healthy, susceptible household contacts of immunosuppressed persons should receive MMR and varicella vaccines as well as annual influenza vaccination. There is no risk of transmission of MMR vaccine virus to the immunosuppressed person and the risk of transmission of varicella vaccine virus is extremely small. If you do not vaccinate the healthy person they remain susceptible and may be infected with the wild virus particularly varicella and a person with the disease presents a real threat to an immunosuppressed household contact. Because of the risk of contact transmission smallpox vaccine should not be given to a person with an immunosuppressed household contact. Live attenuated influenza vaccine may be administered to the household contact of an immunosuppressed person as long as the immunosuppressed person is not hospitalized and not in protective isolation. Recommendations for vaccination of immunosuppressed persons are detailed in the general recommendations on immunization. There is also a table that lists vaccines that are indicated and contraindicated by specific immunosuppressive condition. We think you will find it very useful. These documents and the complete stem cell transplant document are available to download from the MMR website. But the stem cell transplant document is really long, 130 pages. So we extracted the background and vaccine recommendations and made a shorter version available on our updates and resources webpage. Andrew. The key to reducing the risk of a serious adverse reaction is screening for contraindications and precautions. Every person who administers vaccines should screen every person before giving the vaccine. Contraindications to vaccination can change from one dose of vaccine to the next dose. So everyone should be screened prior to every dose, even if they were screened during a prior visit. Many states have developed screening questionnaires for use in their clinics. You can develop your own sheet or you can adapt one that has already been developed. The Immunization Action Coalition has developed good one-page screening sheets for both children and teens, as you see here, and for adults. They list all the screening questions that need to be asked. The form can be completed by the parent while waiting to be seen. On the back of the form, there is a paragraph explaining why each question is being asked. This is a very helpful feature and reminds staff why they are asking these questions in the first place. Effective screening is not difficult or complicated. It can be accomplished with just a few questions. It is important for you to understand the reasons for the questions on the screening form, so you would like to take a few minutes to review them and the rationale for asking them. The first question is simple. Is the child sick today? The first question addresses whether the child has a moderate or severe acute illness, which is a precaution to vaccination. If the child has been examined, this question may not be necessary or already may have been answered. There is no evidence that acute illness reduces vaccine efficacy or increases vaccine adverse reactions. But with moderate or severe acute illness, vaccines should be delayed until the illness has improved. This avoids confusing a symptom of the illness, such as fever, with a vaccine adverse reaction or vice versa. Mild illness, such as otitis media or an upper respiratory infection is not a contraindication to vaccination. Nor is taking antibiotics a reason to withhold a vaccine in a person who is otherwise not very sick. The second question is does the child have an allergy to any medication, food, or vaccine? A severe allergic reaction to a vaccine or vaccine component is a contraindication to subsequent doses of that vaccine or to a vaccine containing that component. For instance, an anaphylactic reaction to eggs is a contraindication to influenza vaccine. We suggest that you inquire about allergies in a generic way rather than read the parent a list of every component of every vaccine. Most parents will not recognize most of the components anyway, but they will know if the child has ever had an allergic reaction severe enough to seek medical attention, which is what you are trying to find out. If you do identify a person who has had a severe allergic reaction to a product that may be in a vaccine, the next challenge is to figure out which vaccines might contain that product. To make this task easier, you need a listing of vaccine contents. A comprehensive table of vaccine components, also called Excipients, is available from the Updates & Resources webpage and in an appendix of the course text. Remember that a local reaction, such as swelling or redness at the site of injection, is not a contraindication to subsequent doses of that vaccine. The third question is has the child had a serious reaction to a vaccine in the past? This open-ended question is intended to identify allergic reactions following previous vaccine doses. It can also help identify conditions following pertussis vaccine. In usual circumstances, vaccines are deferred when precautions are present, but situations may arise when the benefit of the vaccine outweighs the risk. For instance, a child who had a temperature of 105 following a prior dose of DTAP might still be vaccinated if there were an outbreak of pertussis in the community. The fourth question is has the child had a seizure, brain, or nerve problem? A history of encephalopathy within seven days following wholesale DTAP or DTAP vaccine is a contraindication to DTAP and TDAP. An undiagnosed neurologic problem is a precaution to the use of DTAP and TDAP. For children with a stable neurologic disorder, including seizures, unrelated to vaccination, or for children with a family history of seizure, you should vaccinate as usual. In these children, you should consider the use of acetaminophen or ibuprofen to minimize the fever. A history of Guillain-Barre syndrome is a precaution for tetanus containing influenza and meningococcal conjugate vaccines. The fifth question is has the child had a health problem with asthma, lung disease, heart disease, kidney disease, metabolic disease such as diabetes, or a blood disorder? This question is to identify possible contraindications to one of the two types of influenza vaccine. Children with any of these health conditions should not be given the intranasal live attenuated influenza vaccine. These children should be vaccinated with the inactivated injectable influenza vaccine. Donna? One of the most important conditions to identify during screening is the presence of immunosuppression. Since many different conditions and therapies can produce immunosuppression, there are two screening questions to probe for this. The first is does the child have cancer, leukemia, AIDS, or any other immune system problem? Live virus vaccines such as MMR and varicella are usually contraindicated in persons with severe immunodeficiency. However, MMR and varicella are recommended for persons infected with HIV who do not have evidence of severe immunosuppression. Varicella vaccine is contraindicated in persons with cellular immunodeficiency but may be administered to persons with humoral immunodeficiency. All inactivated vaccines may be given to immunosuppressed persons although the response to the vaccine may be suboptimal. Also, remember that having an immunosuppressed person in the household is not a contraindication to vaccination of a healthy child. The next question is also related to immunosuppression. Has the child taken cortisone, prednisone, other steroids or anti-cancer drugs or had x-ray treatments in the past three months? High daily doses of corticosteroids for more than 14 days can cause significant immunosuppression and increase the chance of an adverse reaction following a live vaccine. Live vaccines should not be administered for at least a month following prolonged high-dose steroid therapy or for at least three months following cancer chemotherapy. Persons receiving aerosolized steroids such as inhalers for asthma, topical preparations or low or moderate daily or alternate day doses of steroids for fewer than 14 days can receive live vaccines during treatment. As with other immunosuppressive conditions or therapies inactivated vaccines may be administered to a person receiving high-dose steroid therapy although the response to the vaccine could be reduced. The next question probes for recent receipt of antibody containing products. Has the child received a transfusion of blood or blood products or been given a medicine called immune or gamma globulin in the past year? Passively acquired antibody may reduce the effectiveness of MMR and varicella vaccines. MMR and varicella vaccines generally should not be given to persons who have recently received antibody containing blood products. This question might also lead to reported illnesses that might not have been revealed in earlier questions since blood products are usually given for specific indications. Depending on what product was administered and the dose it may be necessary to defer MMR and varicella vaccines for up to 11 months after the blood product. Rotavirus vaccine may also be deferred for as long as six weeks after receipt of an antibody table four in the general recommendations on immunization lists the most commonly used antibody containing preparations in the United States. It also lists the recommended waiting period between the blood product and administration of MMR or varicella vaccine. Every office should have a copy of this table which is included in the course text and on the resources webpage. This issue is discussed in more detail in the general segment of this program. The next question is is the child or teen pregnant or is there a chance she could become pregnant during the next month? This question should be asked of all females of childbearing age including young adolescents. MMR and varicella vaccines are contraindicated within a month of and during pregnancy due to the theoretical risk of virus transmission to the fetus. Sexually active females who receive MMR or varicella vaccine should be instructed to practice careful contraception for one month following receipt of either vaccine. With the exception of human papillomavirus vaccine and activated vaccines may be given to pregnant women when indicated. It is not necessary to inquire about pregnancy in household contacts. Having a pregnant woman living in the household has not a contraindication to administration of any vaccine to other household members except smallpox. The final screening question is has the child received any vaccinations in the past four weeks? The intent of this last question is to identify persons who recently received a live virus vaccine. The advisory committee on immunization practices recommends that two live virus vaccines on the same day be separated by at least 28 days. If the vaccine given recently was an inactivated vaccine such as DTAP or hepatitis B vaccine it is not necessary to defer any vaccine. In addition to the child and teen screening form the Immunization Action Coalition has developed a screening form for adults. It contains the same questions that are on the child and teen form. The child and adult screening forms as well as other vaccine related material for providers and patients are available free from the Immunization Action Coalition website. But whether you use the IAC form or some other form the important thing is that you ask these questions before administering vaccines to people of any age. Your patients are depending on you to make vaccines as safe as they can be. Screening every patient is one way to do this. The risk of an adverse reaction following vaccination can be greatly reduced with consistent and thorough screening for contraindications and precautions. However, despite screening adverse reactions will still occur. In this section of the program we would like to present an overview of the general types of adverse reactions. Let's begin by defining our terms. The intended effect of vaccination is to produce active immunity to specific antigen. An adverse reaction is an unwanted extraneous effect caused by a vaccine. A synonym of adverse reaction is vaccine side effect. A vaccine adverse event on the other hand refers to any event that occurs following a dose of vaccine. So an adverse event may be a true adverse reaction or may be only coincidental with further research or study needed to distinguish between them. This terminology may be new to you and it's really not meant to be confusing. It's meant to increase the precision of discussions of vaccine safety. Adverse reactions are known to be caused by the vaccine. Adverse event is a more generic term that does not necessarily imply a cause and effect relationship with the vaccine. Vaccine adverse reactions fall into three general categories local, systemic and allergic listed here in order of decreasing frequency and increasing severity. The most common type of adverse reaction is a local reaction such as pain, swelling and redness at the side of injection. Local reactions may occur in up to 50% of vaccine doses depending on the vaccine. Local reactions are most common with inactivated vaccines, particularly those that contain an adjuvant such as DTAP and pneumococcal conjugate vaccines. Local adverse reactions generally occur within a few hours of the injection and are usually mild and self-limited. Occasionally, local reactions may be exaggerated. Some people refer to these as hypersensitivity reactions, which is really a misnomer since they're not allergy mediated as the term implies. These reactions are properly known as Artus reactions and are most commonly seen after tetanus and diphtheria toxoids. They are believed to be due to a very high concentration of antibody in the vaccine recipient, usually because of too many doses of toxoid in too short an interval. A second type of adverse reaction is referred to as systemic. These are more generalized symptoms and include fever, malaise, headache, myalgias or muscle pain, loss of appetite and others. You may notice that these symptoms are common and nonspecific and may occur in a vaccinated person because of the vaccine or may be caused by something totally unrelated to the vaccine like a concurrent viral infection. Systemic adverse reactions were relatively frequent with bacterial vaccines like DTP. However, they are much less common following inactivated vaccines currently in use including DTAP. We know systemic adverse reactions are not common because studies that compare vaccine and placebo recipients. The rates of systemic reactions are often similar in both groups indicating that few of the reactions are actually due to the vaccine. Systemic adverse reactions from live vaccines are a different situation. Live attenuated vaccines must replicate in order to produce immunity. The symptoms you would expect as side effects following live vaccines are basically those associated with a mild case of the disease. These adverse reactions occur after an incubation period of the virus, which is 7 to 21 days for MMR and varicella. As an example of a systemic adverse reaction to a live vaccine, consider measles. The most common symptoms of measles disease are fever and generalized rash. These symptoms, in a milder form, are also the most common adverse reactions following measles vaccine occurring in 5 to 10 percent of recipients. An exception to this general rule is, again, smallpox vaccine. Smallpox vaccine does not contain an attenuated smallpox virus. It contains vaccinia virus which is in the same family of smallpox virus that causes a much less severe illness. So the symptoms following smallpox vaccine are not like a mild case of smallpox. They are symptoms of infection with vaccinia virus. A third type of adverse reaction is a severe allergic reaction. The allergic reaction may be caused by the vaccine antigen itself or, more likely, by some other component of the vaccine, such as cell culture material, stabilizer, preservative or antibiotic used to inhibit bacterial growth. Severe allergic reactions to vaccines are rare, occurring at a rate of less than one and half a million doses. But they may be life threatening. The risk of an allergic reaction can be minimized by good screening prior to vaccination. So, to review, adverse reactions can generally be categorized as local, systemic or allergic. Local reactions are fairly common and usually mild. Systemic reactions, less common and allergic reactions are rare but can be severe. We will be talking about adverse reactions in much more detail as we talk about the specific vaccines. Bill, some adverse reactions to the categories of local, systemic or allergic reactions. For instance, thrombocytopenia following measles vaccine or Guillain-Barre syndrome following the 1976 influenza vaccination. How would you categorize those? Good question because reactions like this are obviously they're not local reactions and they're not really allergic in the typical sense, so they could be classified as systemic reactions but I think they almost belong to all of them idiosyncratic reactions. They're really rare occurrences and they're specific to just one vaccine into seception after roto shield, rotavirus vaccines, another example. We'll discuss these unusual adverse reactions again when we discuss the specific vaccines. Vaccines are among the most significant public health success stories of all time. However, like all pharmaceutical products, no vaccine is completely safe or effective. While almost all known vaccine adverse events are minor and self-limited, some vaccines have been associated with very rare but serious health effects. We usually give vaccines to healthy people including very young children and vaccines often are required by state immunization laws. So vaccines are held to a higher standard of safety than other medications. So it is critical that we do everything we can to ensure that vaccines are as safe as possible for public confidence in vaccines. To do this, we need to monitor closely the occurrence of adverse events, evaluate possible associations and respond appropriately to those risks. Monitoring adverse events following vaccination is especially important for newly licensed vaccines. Before licensure, vaccines undergo extensive testing and review for safety, immunogenicity and efficacy. Pre-licensure studies in particular Phase 3 clinical trials usually include unvaccinated comparison or control groups, so we can determine which reactions were actually caused by the vaccine. However, pre-licensure trials include a relatively small number of participants. Usually the vaccine has been given to only a few thousand people and usually they are monitored for a limited time period. And the studies are often conducted in homogenous populations meaning groups that are less diverse than those in which the vaccine is ultimately used. And finally, because the number of participants is relatively small, the sensitivity for detection of uncommon or rare adverse events before licensure is low. Because of the inherent limitations of pre-licensure testing, we cannot rely on pre-licensure studies to identify all the reactions that may occur once a vaccine is more widely used. For that, we rely on post-licensure surveillance which is the continuous monitoring of vaccine safety in the general population after licensure. The objectives of post-licensure safety monitoring are to identify rare reactions not detected during pre-licensure studies, monitor increases in known reactions, identify risk factors or pre-existing conditions that may promote reactions, identify vaccine lots with unusually high rates or types of events, and identify signals of possible adverse reactions that may warrant further study or affect current immunization recommendations. The National Childhood Vaccine Injury Act of 1986 requires healthcare professionals and vaccine manufacturers to report certain vaccine adverse events. In 1990, a reporting system was put into place to assist providers and families with this requirement. The system is called the Vaccine Adverse Event Reporting System or VAERS. VAERS is a cornerstone of post-licensure adverse events monitoring in the United States, so it is important that you understand how it works and what it does. We asked Dr. Angela Kalyugar, a vaccine safety expert and VAERS team lead in the Immunization Safety Office at CDC to tell us about the system. The Vaccine Adverse Event Reporting System or VAERS is a vaccine safety surveillance system. It was created to provide a single system for the collection and analysis of reports of adverse events following vaccination. VAERS was established in 1990 as part of the National Childhood Vaccine Injury Act. The Childhood Vaccine Injury Act requires healthcare providers to report the events listed on a table of the designated reportable events. However, VAERS depends on the reporting of different adverse events following immunization, most of which are not listed on the reportable events table. VAERS is the nation's frontline vaccine safety surveillance system. It relies on healthcare providers as well as patients and parents to report adverse events that they think are possibly related to vaccination. We are often asked what adverse events should be reported to VAERS. Any post-vaccination medical occurrence that is of concern to you or to the patient or parent should be reported even if you are not certain that the vaccine caused the event. VAERS is jointly operated by CDC and the Food and Drug Administration because VAERS is a national system, rare events more likely to be identified as patterns within the system and flagged rapidly for further study. This is one of the main strengths of VAERS. VAERS provides ongoing surveillance for vaccine safety. It relies primarily on voluntary reporting from the users and recipients of vaccines. So your contributions to VAERS in the form of electronic and hard copy reports are absolutely vital. VAERS cannot work without you. Now let's talk about how VAERS works. Many vaccine providers have heard of VAERS and have seen a copy of the VAERS reporting form. Reporting through a secure website is available and encouraged. Users may find this a convenient way to submit a VAERS report. Online reporting also shortens the time to receive and process the reports. However, submitting a paper report is still an option. Report forms are available from the VAERS website at VAERS.hhs.gov or by calling the telephone number found on every vaccine information statement. The completed form can be faxed to a toll-free number or mailed. The VAERS form is postage paid with the address and instructions on the back. Once VAERS receives a report, a letter is sent out to the person who submitted it. The letter provides the assigned VAERS ID number and may request additional information. A team of nurses conducts follow-up on all reports considered serious. The follow-up is done to obtain complete clinical information about the reported event. In addition to the VAERS form, VAERS accepts hospital or clinical summaries or other medical records. This can be submitted with the original report or later accompanied by the VAERS ID number. Additional medical information is extremely useful in evaluating case reports. To illustrate how VAERS works, let me give the best example of why collecting reports that are only suspected to be related to a vaccination is vitally important. Before the first rotavirus vaccine was licensed, in the fall of 1998, investigators noted a few cases of a bowel disorder called intersusception in both vaccine recipients and those who received a placebo. Although the rate among vaccine recipients was slightly higher, it was not statistically significant. The vaccine was licensed but intersusception was included in product information among the list of possible adverse reactions. Once the vaccine was widely distributed, VAERS began to receive adverse event reports including cases of intersusception. The number of cases reported relative to the number of doses distributed was much higher than what was expected. This suggested but did not confirm that the vaccine might rarely cause intersusception. Subsequent control studies confirmed that the risk of intersusception was higher after vaccination and the rotavirus vaccine was withdrawn. The system worked. VAERS data indicated a possible problem which led to a more definitive study which led to policy action to protect the public health. The story of rotavirus vaccine highlights the importance of reporting events even when the reporter may be unsure that the vaccine was responsible. Vaccine safety concerns raised by VAERS will be carefully evaluated before any action is taken. So as the cornerstone of the country's vaccine safety monitoring system VAERS is always on call to receive case reports of any adverse event suspected to be related to any U.S. licensed vaccine. A few important points. VAERS accepts all reports of adverse events. Events that are related as well as those that are unrelated to vaccination will be reported. A report in VAERS concerning an adverse event does not prove that the event was caused by the vaccine. The event may be only coincidentally related to vaccination. VAERS reports are screened and evaluated on an ongoing basis by teams of researchers at the CDC and FDA. Concerns are identified and further assessed and illustrated by the example of interception. VAERS relies on the astute healthcare providers as well as patients and parents to notice and report adverse events that may be related to vaccination. Thank you for this opportunity to discuss the vaccine adverse event reporting system. All can contribute to the success of this system. In the end, the system works because you make it work. VAERS is a critical tool in CDC's vaccine safety surveillance system. However, it does have limitations. An important limitation of VAERS is that its data cannot be used to determine whether a reported adverse event was caused by the vaccine. This cannot be determined because VAERS contains no information about the occurrence of medical conditions or symptoms in persons who are unvaccinated. To obtain these data, it is necessary to study a large population that contains both vaccinated and unvaccinated persons. In such a population, the medical condition or symptoms that may indicate a vaccine adverse event can be counted and the rate of the condition can be compared for both vaccinated and unvaccinated persons. If a medical condition or symptom is significantly more common in the vaccinated group than in the unvaccinated group, then it is necessary to assess the vaccine might be responsible. The gaps that exist in the scientific knowledge of rare vaccine side effects prompted the CDC to develop the Vaccine Safety Datalink or VSD Project in 1990. The VSD Project involves partnerships with eight large health maintenance organizations to continually monitor vaccine safety. VSD is an example of a large linked database and immunization histories for more than five million people. All vaccines administered within the study population are recorded. Available data include vaccine type, data vaccination, concurrent vaccinations, those given during the same visit, the manufacturer, the lot number, and injection site. Medical records are then monitored for potential adverse events resulting from immunization. Since VSD includes medical records of both vaccinated and unvaccinated persons, rates of medical conditions can be generated and compared. The VSD Project allows for planned vaccine safety studies as well as timely investigations of hypotheses. At present, the VSD Project is examining potential associations between vaccines and a number of serious conditions. The database is also being used to test new vaccine safety hypotheses that result from the medical literature. VAERS changes in the immunization schedule or from the introduction of new vaccines. This project is a powerful and cost-effective tool for the ongoing evaluation of vaccine safety. We will include links to VAERS and additional information about the vaccine safety data link and other vaccine safety resources on our updates and resources webpage. We would like to present another case study that addresses issues that we have discussed on the program today. The case studies are available on the updates and resources webpage. Today's second case study is AIDEN. AIDEN is a 20-month old and is an established patient in your practice. AIDEN received MMR number 1, Varicella number 1, DTAP number 4, HIP number 4, PCV number 4 and Hepatitis A number 1 at 14 months of age. AIDEN's mother reports that he developed a temperature of 101 degrees for 2 days about 9 days after the vaccines. He had no other symptoms and did not require medical attention. At 17 months of age, AIDEN was diagnosed with a neuropathy that caused weakness of his left leg. He was treated with a 2-week course of prednisone and ibuprofen. 3 months later, he still has a visual weakness of his left leg. He has no other medical problems. Here are the questions about AIDEN. Was the fever 9 days after his last vaccinations caused by the vaccines? If so, which vaccine was responsible? Was the neuropathy caused by the vaccines? Should the fever and or the neuropathy be reported to VAERS? If you are viewing this program with a group, we suggest you pause the program now and discuss it among yourselves. We will return in a moment to discuss it with you. The AIDEN case study is a situation we hear about often. A person receives a vaccine, then a medical event occurs. The provider is uncertain about whether the vaccine caused the adverse reaction and what should be done about it. Here is the first question about AIDEN. AIDEN had a fever about 9 days after he received multiple vaccines. Was the fever caused by the vaccines? Well, possibly. Fever is not common but can occur after almost any vaccine. If so, which vaccine was responsible? In this case, the fever was most likely caused by the measles component of MMR. MMR and varicella vaccines can cause fever 7-10 days after vaccination. The timing of the fever relative to the vaccine gives us a hint about which vaccine might be the cause. Fever after live vaccines occurs after an incubation period of the virus. Fever following inactivated vaccines usually occurs within 48 hours of vaccination. Here is the next question about AIDEN. Was the neuropathy caused by the vaccines? Well, it's hard to say if the neuropathy was caused by the vaccine. Neuropathy of the leg has not been reported after vaccination. Brachial neuropathy has been reported after tetanus containing vaccine but it's rare. Also, the neuropathy occurred three months after his last vaccines which also makes vaccination less likely to be the cause of the symptoms. And here's the last question about AIDEN. Should the fever and or the neuropathy be reported to VAERS? It is not necessary to report the fever to VAERS. Fever is a recognized adverse event following MMR and varicella vaccines. However, the neuropathy definitely should be reported to VAERS. The main purpose of VAERS is to identify what are known as signals. Clusters of cases of previously unidentified adverse reactions that should be reported. The neuropathy may or may not be related to the vaccine but you don't need to know for sure. When in doubt, send in a VAERS report. When in doubt, send in a report. Excellent thing to take away a message from this. A good chance right now to talk about a few of the last questions that we get regarding the content that we've heard up to this point. And we have several and these are real questions. We don't make these things up. These are actually questions that have come to us at various times, mainly through NIP Info. The first question I'll direct to Andrew. We've talked about this now a couple of times today. Why is it, it seems counter-intuitive, why is it that blood products, transfusions, whatever do not affect Zoster vaccine the effect of varicella vaccine? Why is Zoster not included in the same group? Well Zoster is a great question. Zoster is very different from other live vaccines very different from other live vaccines because it's being given to people that already have varicella antibodies. They've already had natural chicken pox disease so they've had varicella antibodies so we don't expect that the since the vaccine has a much larger quantity of virus we don't expect that the virus to overcome the expected immunity in the recipient. So in other words it actually does affect the vaccine just like it does varicella vaccine virus but there's so much of it in there it just can is possible for it to just overwhelm whatever antibody might actually be there. Is that a good way to think about it? That's some way to think about it I suppose. And also we know from the clinical trials they'd all had chicken pox and they all most of them responded very well to the vaccine so very common question we get good to air that out we'll probably talk about it again later in the series. Donna here's a question about a similar one if passive immunity interferes with live vaccines then should live vaccines rotavirus, MMR, varicella vaccines be delayed if the mother is breastfeeding? That's a good question and we'll receive it very often. You're really talking about two different things passive immunity we're talking about Ig antibodies that are formed and passed on in maternal antibodies in the six to eight weeks the last part of the pregnancy that's different than the antibodies that you get from breastfeeding which are IgA antibodies so it really will not interfere with the antibodies to form after rotavirus, MMR, varicella so there's no reason to delay vaccination if the mom is breastfeeding breastfeeding is excellent we certainly recommend it and there's even some data that shows that it might enhance the response to some of the vaccines so mom should breastfeed and baby should be vaccinated on time. We do get that question a lot there's a major misconception that breastfeeding somehow enhances or extends or somehow improves passive immunity that a child gets but in fact that really is not true in most cases it's good for GI stuff IgA but generally not not too good for adding any passive immunity. Here's a screening type question that we receive fairly often since we just talked about screening a minute ago a lot of vaccines have gelatin in them there's several kinds of gelatin questions we get but one of the most common is screen how do you go about screening we said that well it's not the egg perhaps in MMR or mom's vaccine but it's the gelatin how do we screen for gelatin allergy another excellent question always start by asking your general screening questions when you have a patient that needs a vaccine does the child or this patient have an allergy to any foods or medications or vaccines and then if you hear back that the child or patient does have an allergy to gelatin probe a little further ask maybe if the child can eat Jell-O without any problem because you really want to anaphylactic allergy is very very rare so you really want to try to elicit the history of the anaphylactic allergy if it exists and only severe life threatening anaphylactic allergy is a contra indication to receipt of vaccines that contain gelatin I think gelatin is actually if you look in the excipient table gelatin is actually included in a lot of vaccines it's a stabilizer I believe they use it as stabilizer for sure it's in MMR and varicella and probably a lot of other ones too and would you expect what age would you expect the child to start kind of be exposed to gelatin when do babies start eating Jell-O well they may they may start in the first year of their life a lot of parents do start giving semi-solid foods you know after you know 6 to 8 months 9 months 10 months so it is very possible that a parent will know before you need to give these vaccines that usually aren't given before 12 months of age so it is an important thing to do and an important thing to ask about so most kids you can pretty much guess and most kids by the time they give their MMR have been exposed to Jell-O and if they haven't been to the hospital they'll go right ahead okay here's a not exactly related but here's a similar question we get fair amount if someone has talking about not revaccinating but what if somebody has had a major traumatic injury and had a lot of blood loss and required a lot of transfusions is a major blood loss event a transplant or a car crash is that something that would ever require now that's not a reason to revaccinate because they haven't lost their immune memory they may have lost a lot of blood but they haven't lost their immune memory because it's primarily housed in the bone marrow so unless someone has had their bone marrow wiped out with drugs or with radiation like for a bone marrow transplant then they still have their immune memory and it will kick in if they're exposed to the antigens so only with something like bone marrow transplant do we say that you have to revaccinate and then as mentioned earlier in the program there are recommendations for the timing of that I think one of the most common questions we get in that regard has to do with people who've gotten chemo or even transplants of solid organs we get a lot of those questions about people wanting to reapply somebody's gotten a case that has been immunosuppressed because of chemotherapy for a transplant for an organ transplant liver, heart and they want to revaccinate them but also that same situation they haven't lost their bone marrow so why could they do it? they're not, they don't need to be revaccinated one more thing to do with contraindications and precautions Andrew, you're getting disaster questions today shingles and zoster, we get tons of questions about that is shingles a reason not to give zoster vaccine can you give zoster vaccine after a case of shingles and if so when? in the context of the topics that we're discussing today the concern is precautions and contraindications is someone that has recently had a case of zoster disease can they receive zoster vaccine thereafter and so think of it in those terms if a person is not acutely ill then yes they can receive can receive a dose of this vaccine and there's a lot of other issues with zoster vaccine that will be discussed in the zoster session of the course a lot more questions that's a very very common set of questions we get and there's a lot of issues to it thank you Donna, thank you Andrew and we'll have time for questions later appropriate vaccine administration is critical for optimum vaccine effectiveness the recommended site, route and dosage for each vaccine is based on clinical trials practical experience and theoretical considerations vaccines may not protect your patient if they are administered incorrectly if the wrong site or needle length is used to administer a vaccine there may be an increased risk of a local adverse reaction so an education plan that includes competency based training on vaccine administration should be considered for everyone who administers vaccines delivering vaccine into the appropriate tissue promotes optimal antibody response to the vaccine and reduces the risk of a local adverse reaction so let's talk about route site and needle length subcutaneous injections are administered into the fatty tissue found below the dermis and above the muscle tissue subcutaneous tissue is present in most areas of the body the usual subcutaneous sites for vaccine administration are the thigh and the upper outer triceps area of the arm the upper outer triceps area can be used to administer subcutaneous injections to infants the recommended needle size for subcutaneous injection in all age groups is a 23-25 gauge 5-8 inch needle a longer needle could penetrate the muscle particularly if given at an incorrect angle to avoid reaching the muscle the fatty tissue is pinched up and the needle is inserted at a 45 degree angle a more perpendicular approach is used to reduce the muscular injection the majority of vaccines administered by injection are given by the intramuscular route incorrect intramuscular technique can reduce vaccine effectiveness and increase local adverse reactions so proper technique is critical intramuscular injections are administered into the muscle tissue below the dermis and subcutaneous tissue the amount of overlying subcutaneous tissue depends on the person and the site although there are several IM injection sites on the body the routinely recommended IM sites for vaccine administration are the vastus lateralis muscle in the anterolateral thigh and the deltoid muscle in the upper arm injection at these sites reduces the chance of involving neural or vascular structures the site depends on the age of the person and the degree of muscle development the deltoid muscle is most commonly used in older children and adults the deltoid muscle can be used in toddlers if the muscle mass is adequate it is important to use anatomical landmarks to locate the sites so the injection is given into the center of the muscle the gluteus should not be used as a site to administer vaccines injection in the gluteus risks injection into fat or damage to nerve tissue a 23-25 gauge needle is recommended for intramuscular injections the needle length must be adequate to reach the muscle and is based on the size of the individual a 5-8 inch needle may be considered for newborns in the first 28 days of life and for premature infants the recommended needle length for an infant is generally 1 inch the recommended needle length for an older child can range from 5-8 to 1 1⁄4 inch depending on the injection site the size of the muscle and the thickness of the fatty tissue at the injection site a 5-8 inch needle is adequate only for the deltoid muscle and only if the skin is stretched flat between the thumb and forefinger and the needle is inserted at a 90 degree angle to the skin a longer needle should be used for the adrolateral thigh for adolescents and adults the deltoid muscle is the routinely recommended site although the adrolateral thigh can be used the needle length generally ranges from 1 inch to 1 1⁄2 inch depending on the person's sex weight the size of the muscle and the amount of fatty tissue at the injection site and the technique used this can all seem really complicated unfortunately there is a table in the general recommendations on immunization that would be table 7 that lays all this out it's yet another reason to get a copy of the general recommendations and read it to avoid injection into subcutaneous tissue the skin of the selected site can be spread-taught between the thumb and forefinger isolating the muscle another technique is to grasp the tissue and bunch up the muscle the needle should be fully inserted into the muscle at a 90 degree angle remember injection technique is the most important parameter to ensure efficient intramuscular vaccine delivery this is a list of vaccines that should be administered by the subcutaneous route vaccines given sub-q include Japanese encephalitis measles, mumps rebella containing vaccines either as trivalent vaccine or in combination with varicella vaccine meningococcal polysaccharide varicella zoster and yellow fever this is a list of vaccines that should be administered by the intramuscular route vaccines given im include anthrax any product containing diphtheria, tetanus and pertussis hemophilus influenza type b hepatitis a hepatitis b inactivated influenza pneumococcal and meningococcal conjugate rabies and typhoid vi vaccines two vaccines inactivated polio and pneumococcal polysaccharide vaccines can be administered by either the subcutaneous route or the intramuscular route for these two vaccines neither the vaccine manufacturer or the acip recommends one route or the other with ipv and pneumococcal polysaccharide the clinician can choose the route for all other vaccines the manufacturers recommended route should be used there are a few other issues related to vaccine administration that seem to generate a lot of questions and andrew will review these andrew other important vaccine administration issues such as infection control sites for simultaneous administration and latex allergy hand hygiene is recommended between each patient when working at a site where it is not feasible to wash your hands before each patient an alcohol based waterless antiseptic can be used between patients and in situations where your hands become soiled gloves are not required by the occupational health and safety administration or OSHA for vaccine administration unless there is the potential for exposure to blood or body fluids the person administering the injection has open lesions on the hands or it is an agency policy just remember gloves cannot prevent a needle stick injury you should never ever detach, recap or cut a used needle before disposal all used syringe and needle devices should be placed in a puncture proof container to prevent needle sticks and reuse the equipment should be disposed of as infectious medical waste safety needles or needle free injection devices also can reduce the risk for injury and should be used whenever available here are a few more points about vaccine administration it is not necessary to change needles between drawing or reconstituting vaccine and administration unless the needle is contaminated or bent use a new syringe and needle to draw up each vaccine to be administered when administering multiple vaccines never mix vaccines in the same syringe unless they are approved for mixing by the food and drug administration and no attempt should ever be made to transfer vaccine from one syringe to another vaccines approved for mixing will be packaged together or indicated in the package insert if more than one vaccine is to be administered in the same limb the injection sites should be separated by at least one inch if possible this separation allows any local reactions to be differentiated vaccines that contain tetanus and diphtheria toxoids may cause more soreness than other vaccines so you may want to give this vaccine alone or in the limb with a subcutaneous injection we receive many questions about spacing of injections in a single limb this spacing is a recommendation and not an absolute rule considering the number of injections needed at each visit in the first two years of life there may be circumstances where separation of each site by one inch or more is not feasible we are not aware of any evidence that less than one inch separation between injection sites reduces the effectiveness or safety of a vaccine but you should try to put the most reactive vaccines tv containing vaccines and pneumococcal conjugate vaccine into different limbs if you can you should also develop a system so that everyone in your office can get the same vaccine into the same anatomic location this way if a local adverse reaction occurs anyone can easily determine which vaccine is most likely to be responsible a standardized vaccine administration map can help you do this here is an example of such a map it suggests the anatomic area for each injection this version was provided to us by the michigan department of community health and the alliance for immunization in michigan they have graciously allowed us to show it to you and to post it on the resources web page please consider using this site map or one similar to standardize the vaccine administration procedures in your office aspiration is the process of pulling back on the plunger of the syringe prior to injection to ensure that the medication is not injected into a blood vessel aspiration is not required before administration of a vaccine although this practice is advocated by some experts and most nurses are taught to aspirate before injection there is no evidence that this procedure is necessary there are no reports of any person being injured because of failure to aspirate in addition the veins and arteries within the reach of a needle in the anatomic areas recommended for vaccination are too small to allow an intravenous push of vaccine without blowing out the vessel a 2007 study from Canada compared infants pain response using slow injection aspiration and slow withdrawal with another group using rapid injection no aspiration and rapid withdrawal based on behavioral and visual pain scales the group that received the vaccine rapidly without aspiration experienced less pain no adverse events were reported with either vaccination technique a link to the study results is included on the program page we have been downplaying the need for aspiration since the issue is addressed in the 2002 edition of the general recommendations on immunization we have been impressed with the passion with which some nurses particularly nursing instructors defend this procedure but I will repeat that we consider aspiration an option or preference not a requirement if you prefer to aspirate and blood appears the needle should be withdrawn the dose discarded and a new needle syringe and vaccine dose used to administer the injection at a different site one way to avoid the need to discard an expensive dose of vaccine and possibly minimize the patient's pain is just not to aspirate in the first place many people particularly healthcare personnel claim to have latex allergies latex allergy is most often a contact type allergy we have been one published report of an anaphylactic allergic reaction following vaccine administration in a patient with known severe allergy to latex a person with an anaphylactic allergy to latex should not generally receive vaccines supplied in vials or syringes that contain natural rubber persons with latex allergies that are not anaphylactic such as contact allergy to latex gloves can receive vaccines supplied in vials or syringes that contain dry natural rubber or natural rubber latex with the number of injections that we are giving in immunization practice today both healthcare providers and parents are concerned about adequate pain control comfort measures and distraction techniques may help children cope with the discomfort associated with vaccination remember that pain is a subjective phenomenon influenced by multiple factors including a person's age, anxiety level previous healthcare experiences and culture a variety of measures ranging from topical anesthetics to diversionary techniques are discussed in the general recommendations on immunization another event to be aware of is fainting referred to medically as syncope this may have come to the attention of providers because most of our newest vaccines are recommended for adolescents a cdc fda analysis of recent VAERS data indicates that females aged 11 to 18 years contributed most to an increase in the number of post-vaccination syncope reports although rare serious injuries occurred to reduce the risk of syncope and injury resulting from syncope the acip recommends that providers strongly consider observing patients for 15 minutes after they are vaccinated in fact we recommend that you have patients and adults seated during vaccination and the observation period to decrease the risk of injury should they faint Donna? We would like to end our discussion of vaccine administration with a few words about non-standard vaccination practices and vaccine administration errors we have become increasingly concerned about the growing number of questions we receive asking what to do when the wrong vaccine or the wrong vaccine dose has been administered or the wrong route was used the first type of vaccine administration error is administration of the wrong formulation since the approval of Tdap and Zoster vaccines we have heard of several instances where the wrong vaccine was administered when young children receive Tdap instead of DTAP they do not receive adequate amounts of diphtheria toxoid and pertussis antigens young infant who has not completed a primary series of DTAP at increased risk for pertussis if an adolescent or adult receives DTAP instead of Tdap they are at increased risk for an exaggerated local reaction because they have received excess diphtheria toxoid and pertussis antigens even more concerning is when we hear about a young toddler receiving Zoster vaccine instead of Varicella vaccine this exposes the child to a dose of vaccine virus 14 to 15 times the prescribed dose another concern related to administering the correct vaccine is using the correct diluent with vaccines that require reconstitution we frequently receive questions about the effectiveness of a vaccine when the wrong diluent has been used vaccine safety and efficacy data are based on using the prescribed diluent vaccine manufacturers and CDC do not test vaccine using the wrong diluent to find out what will happen we almost always recommend that doses reconstituted with the wrong diluent be repeated you must not only carefully check the label on the vaccine to administer but also the diluent to ensure that the appropriate product is used remember standard medication guidelines require that the medication label is checked at least three times before administration similarity in product names and packaging also increase the risk of medication errors we suggest that you do not store products with similar names or packaging close to each other in the refrigerator or freezer a third administration error we hear about is the wrong route of administration earlier we discussed several factors involved in ensuring that a vaccine is injected into the correct tissue the first step in this process is verifying the route that should be used for a particular vaccine for example a common error we are hearing about is inadvertent administration of meningococcal conjugate vaccine by the subcutaneous route meningococcal polysaccharide vaccine should be administered by the subcutaneous route but the newer meningococcal conjugate vaccine should be administered by the intramuscular route we also have received several reports in which purified protein derivative or ppd used for tuberculin skin testing and td have been confused resulting in intradermal administration of td administration errors like these not only increase the risk of adverse reactions and suboptimal immune response but they also diminish the trust and confidence that parents and patients have in their healthcare provider be sure that staff are adequately trained in standard vaccine administration practices and are oriented to the proper administration of new vaccine products remember your patients are counting on you Don and Andrea as you know we receive many many questions about vaccine administration issues one of the most common Don I'll point this one at you do you have any questions about vaccine administration or if it's an open lesion or if it's an agency policy so if you if you do wear a large clinic when you're like a big flu clinic when you're giving a lot of vaccines the thing is that you know ACIP says you really only need to wear vaccines or wear gloves I'm sorry if there's a risk of exposure to blood so if you do wear gloves you still have the whole issue of hygiene and so it would we would say yes you need to wash your hands between patients and if that means you know changing the gloves then that's what you have to do okay better maybe just not to wear gloves in the first place if you don't have to another very very common question is partial doses if a patient moves his arm and somehow manages to dislodge the needle before the whole vaccine dose has gone in do you have to repeat it do you repeat it then what do you do it's really a judgment call on the part of the health care provider if a provider feels like that there was vaccine loss during the procedure then this is counted as a partial dose and the vaccine must be repeated general rule is if partial doses are given they are invalid and you should repeat the dose one more quick one for Donna is there a risk for pregnant staff people to administer live virus vaccines no a pregnant person can administer any live virus vaccine except smallpox vaccine this question comes up a lot with rotavirus and influenza vaccine like the leiv vaccine and there's no problem there for one thing the health care provider should have been vaccinated already against influenza if they are administering influenza vaccine and that should not be an issue and rotavirus is not a concern either they most likely have antibodies to it very helpful thank you very much Andrew and Donna thank you the success of efforts against vaccine preventable diseases is attributable in part to proper storage and handling of vaccines exposure of vaccines to temperatures outside the recommended ranges can adversely affect their potency and reduce the protection they provide storage and handling errors can cost your practice thousands of dollars in wasted vaccine and revaccination they can also result in the loss of patient confidence in your practice when repeat doses are required vaccines are fragile and must be kept at the temperatures recommended by the vaccine manufacturers at all times it is better not to vaccinate than to administer a dose of vaccine that has been mishandled live vaccines can usually tolerate freezing temperatures in fact all vaccines that contain varicella virus must be stored in a continuously frozen state at the recommended freezer temperature until administration MMR vaccine is usually stored in the refrigerator but it can also tolerate freezing temperatures live attenuated influenza and rotavirus vaccines must be kept at refrigerator temperature live virus vaccines deteriorate rapidly after they are removed from storage on the other hand inactivated vaccines are damaged when exposed to freezing temperatures inactivated vaccines exposed to freezing temperatures should not be used however they can tolerate short times out of refrigeration although potency can be adversely affected if left out too long vaccines must be stored properly from the time they are manufactured until they are administered to your patients the cold chain begins with the manufacturer and continues with the transfer of vaccine to the distributor transfer from the distributor to the provider's office and administration to the patient proper storage temperatures must be maintained at every link in the chain all healthcare providers who administer vaccines must evaluate their cold chain procedures to ensure that vaccine storage lines are being followed each office should develop and maintain a detailed written storage and handling protocol assign storage and handling responsibilities to one person designate a backup person and provide training on vaccine storage and handling vaccine storage units must be selected carefully and used properly refrigerators without freezers and standalone freezers are usually better at maintaining the required temperatures however a combination refrigerator freezer unit sold for home use is acceptable for vaccine storage if the refrigerator and freezer compartments each have a separate external door any refrigerator or freezer used for vaccine storage must be able to maintain the required temperature range throughout the year it must be large enough to hold the year's largest vaccine inventory and must be dedicated to the storage of biologics food and beverages should not be stored in vaccine storage units keeping food and beverages in the storage unit leads to frequent opening of the door which leads to temperature instability the CDC discourages the use of small single door or dorm style refrigerators like this this type of unit may be used for storing small quantities of activated vaccines or MMR rotavirus or live attenuated influenza vaccine but only if the refrigerator compartment can maintain a constant temperature it is impossible for the freezer compartment in this type of unit to maintain the required temperature range and must not be used to store varicella, MMRV and zoster vaccines most vaccines require refrigerator storage temperatures of 35 to 46 degrees Fahrenheit which is 2 to 8 degrees Celsius with the desired average temperature of 40 degrees Fahrenheit or 5 degrees Celsius vaccines that are stored in the freezer must be kept at 5 degrees Fahrenheit which is minus 15 degrees Celsius or colder both types of influenza vaccine, TIV inactivated vaccine and live attenuated influenza vaccine must be stored in the refrigerator LAIV no longer requires freezer storage all vaccines that contain live varicella virus must be stored in the freezer at 5 degrees Fahrenheit or colder this includes single antigen varicella vaccine, MMRV and zoster vaccine MMR may be stored in either the freezer or the refrigerator if you're using both the refrigerator and freezer vaccines be careful not to make the freezer so cold that the refrigerator temperature drops below the recommended temperature range Andrew proper temperature monitoring is key to proper cold chain management check the temperatures twice a day once in the morning and once before you leave at the end of the work day post a temperature log like this on the door of the refrigerator or freezer and record the temperature readings twice daily it is important to keep temperature logs for at least three years unless state statutes or rules require a longer period as the refrigerator or freezer ages you can track recurring problems or identify how long problems have existed while it is important to document the temperatures, documentation is not enough equally important is taking immediate action when the temperatures fall outside the recommended ranges remember any mishandled or incorrectly stored vaccines should not be administered it is especially important that inactivated vaccine that has been exposed to freezing temperature not be administered if you discover that your refrigerated vaccine has been exposed to freezing temperature even if the vaccines do not appear to have been frozen you should segregate the exposed vaccine so it will not be used and contact the manufacturer or your state immunization program for advice temperature rises above 5 degrees Fahrenheit during other than the normal defrost cycle both the refrigerator and freezer compartments should have their own thermometer here are some examples of thermometers that can be used including biosafe liquid continuous graphic and minimum maximum if you are using a continuous recording thermometer even though it is recording the temperatures for you it should still be checked twice each day to make sure the temperatures are in range thermometers are a critical part of good storage and handling practice the CDC recommends using only certified calibrated thermometers for measuring vaccine storage unit temperatures more information about these thermometers is available on the updates and resources web page to keep the refrigerator and freezer cold the unit must be in good working condition and it must have power at all times there are several things you can do to prevent problems your refrigerator should have a plug guard or a safety lock plug so that it cannot be inadvertently pulled out you may want to install a temperature alarm to alert staff to after hours emergencies particularly if large vaccine inventories are maintained label the circuit breakers to alert janitors and electricians not to unplug the vaccine storage unit or turn the power off you can do this by posting a warning sign like this at the plug on the refrigerator and at the circuit breaker box you can help stabilize the temperature in the refrigerator by keeping containers of water inside this liquid bulk helps keep the temperature stable particularly when the refrigerator is being opened and closed all day remove the vegetable bins and shelf and put your water containers in their place as you see here the same principle applies to the freezer store extra cold packs or blue ice in the freezer not only will they help keep the temperature stable with frequent opening and closing of the door they will also help keep the temperature stable in the event of a power failure providers should also never store vaccines in the door of the freezer or the refrigerator or in the vegetable bins the temperatures in these areas are not stable use these areas to store liquid bulk and cold packs we are frequently asked about storing biologic specimens such as blood and urine in the same storage unit as vaccine we prefer that vaccines be kept in a dedicated storage unit but we understand this is not possible in some offices if you must store biologic specimens in the same unit as the vaccines be sure the specimens are stored on a lower shelf than your vaccine supply this is to assure that if a specimen leaks your vaccine will not be contaminated another common inquiry we receive concerns pre-filling or drawing up doses of vaccine before they are actually needed we strongly discourage filling syringes in advance for a number of reasons the most important reason to avoid this practice is that filling a syringe before it is needed increases the risk for administration errors once in the syringe it is difficult to tell which vaccine is which pre-filling syringes also increases vaccine wastage unused syringes you have pre-filled should be discarded at the end of the clinic day finally pre-filling syringes may result in bacterial growth in the vaccines that do not contain a preservative such as vaccines supplied in single dose vials as an alternative to pre-filling syringes consider using manufacturers supplied pre-filled syringes for large immunization events such as community influenza clinics syringes other than those filled by the manufacturer are designed for immediate administration and not for vaccine storage however if you have a reason to draw up more than one dose of vaccine you should only pre-fill a few syringes at a time which you will administer yourself any syringes of vaccine other than those filled by the manufacturer should be discarded at the end of the clinic day vaccine inventory control is a critical part of vaccine quality management as part of inventory control providers should conduct a monthly vaccine inventory to be sure they have enough to meet their needs however avoid stocking excessive vaccine supplies because this can lead to vaccine wastage when vaccines become outdated also include diluents in the stock control procedures and ensure adequate diluent supplies are available vaccines may only be reconstituted with the specified diluent diluents are not interchangeable except the sterile water used to reconstitute MMR varicella MMRV and zoster vaccines providers should monitor the expiration date of their vaccines and diluent supplies rotate stock to avoid waste from expiration expired vaccine and diluent should never be used it is critical that every clinic have a written emergency vaccine retrieval and storage plan the most important part of this plan is to identify a location with a backup generator where a provider can move their vaccine in the event of an emergency such as an equipment failure or power outage consider contacting a local hospital the Red Cross or a long term care facility is a backup site information to assist in developing a written plan is available on the CDC vaccines and immunization website there are also useful storage and handling resources in an appendix of the course text including temperature logs vaccine storage requirements and warning signs for your electrical plugs and breaker box other helpful tools are available at the CDC a vaccine storage and handling toolkit with detailed storage and handling guidelines videos, forms, posters and an interactive game is available on the vaccines and immunization website this is the main page of the online toolkit a CD version of the toolkit is included with this DVD set and is also available from our online catalog check the updates and resources on the page for information on how to order a copy for your office in order for patients to be protected by vaccines vaccines must be stored and handled with care with a few simple steps and good practices to maintain proper vaccine storage and handling we can ensure that the full benefit of immunization is realized Donna could you comment on aging is there a time that they should be arbitrarily replaced or does CDC have a preference for say stand-alone units as opposed to combination units for households well the CDC requirement really is that you know as was mentioned earlier that you've got external doors on the two different compartments if you're using a single unit that has freezer and refrigerator that it can maintain the temperature year-round in each compartment and that it can handle your largest amount of vaccine stock that you have in a year some states now do have tighter requirements than that and frankly because of problems that they've seen I will say that if you're storing varicella vaccine it's tough in a single unit to make sure that you've got the temperature that you need in the freezer without getting the vaccines in the refrigerator compartment too cold so usually you know stand-alones are better because then you don't have to worry about the temperature of one compartment affecting the other if you do have a stand-alone it's not only good I mean if you're using the one that has refrigerator and freezer you not only should think about external doors but the fact that they have separate thermostats for each compartment and of course that you have certified calibrated thermometers in each compartment as far as aging you know sometimes we're asked we're not allowed to use units that's you know more than 10 years old well the thing is older units just may not maintain the temperature as well but check with your state immunization program especially if you're a VFC provider thank you Donna, thank you Andrew this brings us to the close of this session of epidemiology and prevention of vaccine preventable diseases we would like to remind you of resources that you can use to get more information or to contact us here's the companion book for this program the public health foundation is the sole source for a printed copy the book costs $35 plus shipping and handling and is a useful resource for any office that administers vaccine to persons of any age you can contact the public health foundation through their toll free number at 877-252-1200 you can also order materials online from their website at bookstore.phf.org if your patients or their parents have immunization related questions you can refer them to the CDC Info Contact Center you can reach the contact center toll free at 800-CDC-INFO the CDC Info Contact Center is staffed 24 hours a day 7 days a week if you or your staff have questions you should direct them to us at the National Center for Immunization and Respiratory Diseases by email our email address is nipinfo at cdc.gov throughout this program we've mentioned additional immunization resources available to you on the updates and resources web page the address is www.cdc.gov front slash vaccines click on education and training then the self study link choose this program from the list to find all the materials we've discussed during this program we want you to have the most current immunization information at your fingertips an easy way to do this is to have the information available on your computer we've compiled all the current ACIP statements, vaccine information statements the course text and much more on a CD called immunization works the CD is a great way to have all your current immunization information together in one place immunization works is distributed free of charge by the CDC the updates and resources web page has a link to order it continuing education credit is available for viewing this program details and instructions can be found in the continuing education chapter of the DVD or on the updates and resources web page thank you for joining us for this session of epidemiology and prevention of vaccine preventable diseases please join us for other programs in this series when we discuss specific vaccine preventable diseases and the vaccines to prevent them until then goodbye