 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 are 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. In this segment, we will discuss diphtheria and tetanus. It will be brief because there aren't many pressing issues with either of these diseases. We will include a discussion of the use of diphtheria and tetanus toxoids later in the program. Diphtheria is not a disease you're likely to ever see. Although it is rare in the United States, it's not gone. Because of this, and because it's more common in other countries, you need to be aware of it. Diphtheria is caused by a bacterium called carinobacterium diphtheriae. The bacteria infect mucus membranes, most commonly the nasopharynx. This leads to an exudative pharyngitis. Here's a picture of diphtheria involving the tonsils, the most common site of infection. The membrane is adherent to the tissue and is difficult to remove. The membrane may be so extensive it causes respiratory obstruction. As they grow, the bacteria produce a toxin that is absorbed into the bloodstream. The absorbed toxin causes most of the complications of diphtheriae, such as myocarditis, which is inflammation of the heart, and neuritis, which leads to abnormal nerve conduction. Fewer than five cases of diphtheriae have been reported each year in the U.S. since 1980. Only 28 cases were reported from 1990 through 2003, and no cases have been reported since 2003. Fifty-five percent of cases reported since 1980 were among adults 25 years or older. But the lack of cases does not mean the organism is gone. The organism is probably still circulating in some areas of the United States. In 1996, several infections with carinobacterium diphtheriae were documented among persons who had sore throats or ear infections. These infections occurred in a state where there had been a high incidence of diphtheriae during the 1970s. Many physicians have never seen a known case of diphtheriae. They may not even consider the diagnosis in a patient with membranous pharyngitis. Laboratories do not test for it unless a diphtheriae culture is specifically requested. So the organism is probably still out there. We just don't see it because we're not looking hard enough. Diphtheriae remains endemic in many other parts of the world and is estimated to result in 5,000 deaths globally per year. During the mid-1990s, there was a massive diphtheriae epidemic in the countries of the former Soviet Union. This outbreak went on for years with more than 115,000 cases and 3,000 deaths reported in the Russian Federation alone. Most cases and deaths occurred among adults. Many years of intensive international efforts eventually controlled the outbreak in the countries of the former Soviet Union. However, outbreaks have occurred in many other countries in Asia and Africa. Could an outbreak happen here? It's possible. Estimates are that up to 40% of adults in the U.S. lack protective antibody for diphtheriae. The message for you makes sure the adults in your care, especially international travelers, are up to date with their diphtheriae boosters. Like diphtheriae, tetanus is rare in the U.S. so our discussion of it will be brief. Tetanus is also an acute, often fatal disease caused by a toxin produced in this case by a bacterium called claustridium tetanide. The bacteria and their spores are found everywhere in the world that has dirt. We will never eradicate tetanus. Tetanus is a terrible disease. The toxin blocks the impulses in certain nerves, which leads to unopposed muscle contraction and spasm. This is a photograph of a man with tetanus. This posture is typical of generalized tetanus. It's caused by massive spasm of the hamstring, gluteus, and paraspinal muscles. This newborn has neonatal tetanus. Because the mother was never vaccinated, she had no tetanus antibody to transfer during gestation. So the infant was born without passive protection. Newborns are usually infected as a result of unsanitary birthing practices. The complications of tetanus include spasms of the respiratory muscles, which can lead to respiratory arrest. Muscle spasms can be so severe they break bones. One out of every four persons who develops tetanus dies. There are now fewer than 40 cases of tetanus reported per year in the United States. Only 27 cases were reported in 2005 and 41 in 2006. The disease occurs almost exclusively among adults. Neonatal tetanus is rare in the United States, but is estimated to kill more than 250,000 newborns throughout the world every year. Tetanus is unique among vaccine-preventable diseases because it is not contagious from person to person. Tetanus can only occur when the bacteria or their spores, which are in the environment, are introduced into the tissue of a susceptible person. So most cases are associated with injuries or wounds of some kind. This graphic shows the injuries and conditions reported in persons with tetanus in the United States from 1998 through 2000. Those are the last years for which we have compiled data. Wounds like punctures, lacerations, and abrasions accounted for two-thirds of the cases. Puncture wounds included stepping on a nail, splinters, injury from barbed wire, a tattoo, and a spider bite. Chronic wounds, such as abscesses and ulcers, accounted for 11 percent of cases. Fifteen percent of tetanus cases occurred among injection drug users, about a third or five percent of whom had no other known risk factor or injury. Twelve percent of cases occurred among persons with diabetes. There was one case of neonatal tetanus reported. The child's mother was unvaccinated because of a personal objection to vaccination. The infant's umbilical stump was treated with bentonite clay at home, which is how the tetanus spores were probably introduced. Fortunately, the child survived. Tetanus and diphtheria are both caused by toxins, so immunity requires antibodies against the toxin. Antibodies against the bacteria themselves are not necessary. So, the vaccine for both diphtheria and tetanus consists of formalin inactivated toxin known as a toxoid. We will talk more about tetanus and diphtheria toxoid later in the program. Pertussis or whooping cough is a disease that causes us great frustration. Despite a very high coverage level for pertussis vaccine among children, the number of cases reported in 2004 and 2005 was the highest in almost 50 years. Use of pertussis vaccine among adolescents and adults may now be helping to reverse this trend. Pertussis is caused by the bacterium bordetella pertussis. A vaccine has been available since the 1940s and has largely controlled pertussis in developed countries. But pertussis still takes a huge toll worldwide, with an estimated 294,000 deaths in 2002. Bordetella pertussis is a gram-negative bacillus that produces multiple antigenic and biologically active components. The best characterized and probably most important components are pertussis toxin, PT, and filamentous hemagglutinin, FHA. These two components, as well as others, play a role in the pathogenesis of the disease, but not all of them are important for immunity to pertussis. One of the problems with pertussis has been the complexity of the organism and an incomplete understanding of the disease process and immunity. Pertussis of research have allowed investigators to be reasonably certain which of the multiple antigenic products are most important for the immunity to the disease. These discoveries led to the development of improved vaccines. Pertussis is almost exclusively a respiratory disease. Lung infection leads to tissue damage. This damage may cause a decrease in pulmonary function, which leads to pooling of secretions and a characteristic cough. The incubation period of pertussis is relatively short. It is usually 5 to 10 days, but can be as long as 21 days. Initial symptoms are similar to a viral upper respiratory tract infection, with insidious onset of a nonspecific cough. Fever is usually minimal throughout the course of the illness. The first stage of pertussis is known as the cataral stage and lasts one to two weeks. The cough gradually worsens and the patient enters the paroxysmal cough stage, in which the typical severe episodes of coughing occur. The paroxysmal stage may last from one to six weeks. The cough then slowly subsides and convalescence may take weeks to months. The characteristic whoop of pertussis is the result of a strong inspiratory effort against a closed glottis. The sound of a whoop and the misery of a child with full-blown pertussis is something you do not quickly forget once you have seen it. Here is a videotape of a child in the paroxysmal stage, in case you have not seen or heard it before. These paroxysms of coughing may occur up to 30 times a day, and may be severe enough to cause cyanosis. A paroxysm of coughing typically ends with vomiting, and the child usually looks exhausted. Between attacks, the patient may not look very ill and is usually comfortable. Pertussis is not just a childhood disease as was believed in the past. Pertussis is a common cause of cough illness in adolescents and adults. Pertussis among adolescents and adults is often milder than in infants and children. The infection may be asymptomatic or may present as classic pertussis with paroxysmal cough or a whoop. Pertussis may not be considered by the person's clinician. Adolescents and adults with pertussis are often the source of infection for susceptible infants and children. This graphic summarizes complications of reported pertussis in 2001 through 2003. Because pertussis is predominantly a respiratory disease, the most frequent complication is pneumonia. This complication occurred in 4.9% of reported cases. Other complications included seizures in about 0.7% and encephalopathy in 0.1%, or once per thousand reported cases. The cause of encephalopathy is not known with certainty. Some experts think it is due to hypoxia. Others believe a toxin may be involved. About 16% of reported cases require hospitalization. Death is reported in 0.2% or 2 per 1000 cases and is usually due to pneumonia. The frequency of complications of pertussis varies inversely with age. The most severe disease and complications are reported among infants and young children. From 2004 through 2006, 82 pertussis-related deaths were reported to CDC. 27 in 2004, 39 in 2005, and 16 in 2006. Of these 82 pertussis-related deaths, 69 or 84% were infants younger than three months of age. In contrast, this age group accounts for less than 10% of reported cases. Pertussis is one of a few bacterial infections for which antibiotic treatment has little effect on the course of the illness. Treatment lessens the severity of pertussis if given early in the disease before the cough is well established. However, this is usually before the illness is recognized as pertussis. CDC published guidelines for the treatment and post-exposure prophylaxis of pertussis in MMWR in December 2005. A discussion of this issue is beyond the scope of this program, but we will include a link to the guidelines on the Updates and Resources webpage. Donna? The epidemiology of pertussis is complicated because of its high infectivity and atypical presentation in older children and adults. Humans are the only reservoir for pertussis. Transmission is by direct contact with respiratory droplets from an infected person. Maximum communicability occurs in the cataral stage when it seems like just a cold before the characteristic cough develops. People may transmit the disease in the paroxysmal stage as well. Pertussis is very contagious. The secondary attack rate among household contacts is up to 90%, which means that a person with pertussis will infect almost every susceptible person in the house. This graph shows the number of reported cases of pertussis by year since 1940. Notice the scale of the vertical axis. 250,000 cases between 1940 and 1945, an average of 175,000 cases and 2,700 deaths from pertussis were reported each year. With the widespread use of pertussis vaccine in the late 1940s, the number of reported cases began to drop, although not as rapidly as with some other diseases. Notice that cyclic peaks occurred every two to five years, even as the incidence was falling. This graph shows the number of reported cases by year since 1980. Notice that we are using a totally different scale on the vertical axis. The top is 30,000, not 250,000, like the last graph. The cyclic peaks continue to occur. Notice the peaks in 1985, 90, 93, and 2004 to 2005. A total of 25,827 cases was reported in 2004, the highest annual total since 1959. More than 25,000 cases were also reported in 2005. Reported cases declined to 10,600 in 2007. The provisional total for 2008 is about 9,500 cases. Pertussis vaccination rates have increased substantially since 1996. So why is pertussis still around? The answer to this question may be in who is being reported with pertussis. This stacked bar graph shows the number of pertussis cases reported by age group and year since 1990. Children younger than 11 years are shown in red. Cases among adolescents 11 through 18 years of age in blue and adults 19 and older are in gold. If you look at the far left part of the graphic, it shows that in the early 1990s, most cases were reported among children. Most of the bar is red. The bars representing adolescents and adults are very narrow. Contrast this to the far right side of the graph. The number of cases reported among children has increased slightly, but the number of cases reported among adolescents and adults has increased significantly. In 2007, more than 5,000 pertussis cases were reported in adolescents and adults, accounting for almost 55% of all reported cases. Although persons 11 years and older accounted for the largest proportion of cases, infants had the highest rates of pertussis by far. In 2006, the rate among infants younger than one year of age, shown in the far left bar on this graphic, was 49 per 100,000 population. This rate is more than four times higher than the rate among persons 5 to 14 years of age and more than 20 times higher than for persons 25 years and older. The number and proportion of reported pertussis cases among adolescents and adults increased significantly since the late 1990s. This increase could be partly due to changes made in the surveillance definition of pertussis. It could also be due to increased recognition and diagnosis of pertussis among older age groups. One factor that may be contributing to the rise in pertussis among older children and adults is waning vaccine-induced immunity. Protection declines as you get further away from the time you had your last dose. After 5 to 10 years, vaccine-induced immunity is probably minimal. At this point, even vaccinated persons may become infected and develop mild or undiagnosed disease, which could then be transmitted to incompletely vaccinated infants. So, has there been a true rise in pertussis in the last decade? Yes, probably. This rise may be due in part to better surveillance, waning immunity among adolescents and adults probably contributes as well. Two pertussis vaccines approved in 2005 for adolescents and adults provide us with a new tool to help prevent pertussis in older age groups, which may help prevent infection in very young infants. Yabo? Thanks, Donna. We're going to discuss pertussis vaccines in two parts. First, we'll discuss vaccines for children, then we'll discuss pertussis vaccination of adolescents and adults. Pertussis vaccines have a much longer history than most vaccines we use today. The development of pertussis vaccines began in 1906, when border teleprotussis was first grown on artificial media. The first crude pertussis vaccines were attempted about the time of the First World War. Pertussis vaccines made from a suspension of formalin and activated border teleprotussis cells and combined bacteria and tetanus toxoids became available in the mid-1940s. More purified pertussis vaccines were developed in the 1990s. These vaccines are called acelyla, since they do not contain whole pertussis cells. Only acelyla pertussis vaccines are available in the United States. Adolescent and adult formulations of acelyla pertussis vaccine were first approved for use in the United States in 2005. With the licensure of pertussis-containing vaccines for adolescents and adults, the nomenclature for these vaccines has gotten more confusing. We need to be careful when discussing these vaccines to be clear on which product we're talking about. You'll also need to be very careful in order to avoid administration errors. DTAP vaccine Big D, Big T, Little A, Big P is the pediatric formulation. DTAP is approved for children six weeks through six years of age, that is up to the seventh birthday. DTAP should not be administered to anyone seven years or older. DTAP contains the same amount of diphtheria and tetanus toxoid as pediatric DT vaccine. TDAP vaccine Big T, Little D, Little A, Little P is the acelyla pertussis vaccine for adolescents and adults. The Big T and Little D should help remind you that these are vaccines for older persons like adult TD. There are two brands available that have slightly different approved age indications. One vaccine is approved for persons 10 through 64 years. The other is approved for persons 11 through 64 years. Both these vaccines have less diphtheria toxoid and acelyla pertussis antigen than pediatric DTAP vaccines. These vaccines should not be used for anyone younger than 10 or 11 years depending on the brand. We will discuss TDAP vaccines in more detail a little later. Acelyla pertussis vaccines are available only as combined DTAP for children six weeks through six years of age and as combined TDAP for persons 10 through 64 years of age. Single antigen acelyla pertussis vaccine is not available in the United States. No pertussis containing vaccine distributed in the U.S. contains thimerosal as a preservative. There are currently three pediatric DTAP products available in the United States. Tripedia produced by Senefi Pasteur, Infanrix produced by GlaxoSmithKline, and Daptacell also produced by Senefi Pasteur. All three brands are licensed for all five doses of the DTAP series. These vaccines are also included in combination products which we'll discuss a little later. It is important to realize that these vaccines are different even though they share some similarities. They contain a different number of antigens in different concentrations. The antigens are manufactured and combined in different ways. Here's a table that illustrates this. It lists the vaccines and the quantity of each antigen they contain in micrograms. Tripedia contains two components, pertussis toxin, or PT, and filamentous hemagglutinin, or FHA, in equal amounts. Infanrix contains three antigens, mostly PT and FHA, and a small amount of protactin. Daptacell contains less PT, FHA, and protactin than the other two vaccines, but contains an additional antigen called the fimbria antigen. These vaccines have been studied in either blinded cohort studies or in case control studies. All three vaccines have an estimated three-dose vaccine efficacy of 80 to 85 percent against typical pertussis disease. Although the vaccines contain a different number and amount of pertussis antigen, there is no clear evidence that one is significantly more effective than the others. As a result, neither ACIP nor AAP has stated a preference for one of these vaccines. There are a few data on the interchangeability of the three pediatric DTAP vaccines. ACIP recommends that whenever feasible, the same DTAP vaccine should be used for all doses of the series. But if the brand of vaccine used for the earlier doses is not known or not available, then any brand may be used to complete the series. Use the same vaccine for all doses of the series if you can, but do not hesitate to administer a different brand if the brand used for earlier doses is not available or the brand is not known. The most current ACIP statement for DTAP was published in 1997. We have a link to the document on the resources webpage. We'll now discuss these recommendations beginning with the schedule. DTAP vaccine is recommended for all infants and children without contraindications. We will discuss contraindications to vaccination in a few minutes. A primary series in infancy is four doses, beginning at about two months of age. The first three doses are usually separated by two months. The fourth dose should follow the third by at least six months and should be given at 15 to 18 months of age. If an accelerated schedule is needed, the first dose can be given at six weeks of age, with the second and third doses given at four-week intervals. DTAP can and should be given simultaneously with all other childhood vaccines, using a separate syringe and in a different anatomic site. We receive many questions about the appropriate age for the fourth dose of DTAP. ACIP recommends that the fourth dose of DTAP be administered at 15 through 18 months of age, but the ACIP states that the fourth dose may be given earlier than 15 months in certain circumstances. Specifically, the fourth dose of any DTAP vaccine may be given earlier than 15 months of age if the child is at least 12 months of age and it has been at least six months since the third dose of pertussis vaccine, and in your opinion the child is unlikely to return for an additional visit at 15 to 18 months of age. The fourth dose of the DTAP series should not be administered prior to the first birthday. Also, the minimum interval between the third and fourth doses is six months. The fourth dose of the series should not be given less than six months after the third dose, even if the child is one year old. A fifth dose of DTAP at four through six years of age is recommended when the fourth dose is given before age four years. This final dose in the DTAP series should be administered no earlier than the fourth birthday and at least six months after the previous dose. You will encounter children who have received all five doses of DTAP prior to the fourth birthday. A booster dose of pertussis vaccine prior to school entry is important to maintain pertussis immunity through the school years. We recommend that children who receive the fifth dose prior to four years of age receive an additional dose of DTAP after age four, and at least six months after the previous dose. Andrew? Some children receive pediatric DT rather than DTAP. This could occur because of a true contraindication to pertussis containing vaccine or because of a parent's request. No matter what the reason may be, the DT schedule depends upon the age that the child receives the first dose of DT or DTAP vaccine. If the child received the first dose of DT or DTAP at younger than one year of age, a total of four doses of DT containing vaccine completes the series. Three doses are given at four to eight week intervals with the fourth dose six to twelve months after the third dose. Children who receive the first dose of DT or DTAP at one year of age or older should receive a total of three doses to complete the DT series. The first two doses should be separated by at least four weeks. The third dose should be administered six to twelve months after the second dose. A fourth or fifth dose at school entry is not necessary if pertussis vaccine is not being administered. The first routine booster dose of DT or DTAP would be given at 11 to 12 years of age. The reason that four doses are recommended if the first dose was administered prior to a year of age is to ensure that there will be no interference with the response to DT antigens from maternal antibodies. This recommendation can be found in the 1991 ACIP statement on wholesale DTP vaccine. There are occasional misguided parents who do not want their child to receive pertussis vaccine. So the series has started with pediatric DT. Some parents then change their mind and want pertussis vaccine most often because of a pertussis outbreak in the community. Since no single antigen pertussis vaccine is available in the United States, DTAP must be given. Since a minimum of three doses of pertussis containing vaccine are needed to provide protection, there may be concern that the child will receive too many doses of tetanus and diphtheria toxoid. For example, a child who has received four doses of DT will need three doses of DTAP for a total of seven doses of diphtheria and tetanus toxoid. Since at least 1991, the ACIP has recommended no more than six doses of tetanus and diphtheria toxoid before age seven years, the so-called six before seven rule. The six before seven rule is general guidance, not an absolute requirement. It is intended to reduce the frequency of local reactions, which occur more often with increasing doses of tetanus and diphtheria toxoid. If you get into a situation where a child may need more than six doses of DT containing vaccine before age seven, you should be sure the parents are aware of an increased risk of local reactions with increasing doses and agree that the benefit of pertussis immunity outweighs the risk and discomfort of a local reaction. There are four combination vaccines currently available that include DTAP. Trihibit, produced by Sanofi Pasteur, contains DTAP and Hib. This vaccine is currently licensed only for the fourth dose of the DTAP and Hib series. It is not currently licensed for the first three doses. It may also be used as the booster or final dose following a series of single antigen Hib vaccine or following Comvax, the combination Hepatitis B Hib vaccine. The second combination vaccine that contains DTAP is Pedirix, which is produced by GlaxoSmithKline. This product contains DTAP, inactivated polio, and Hepatitis B vaccines. The DTAP component is Infinerix and the Hepatitis B component is Enderix B. Pedirix is approved for the first three doses only of the DTAP and IPV series, which are usually given at about two, four, and six months of age. It is not approved for booster doses of the DTAP series, that is the fourth or fifth doses. The minimum age for the first dose of Pedirix is six weeks, so it cannot be used for the birth dose of the Hepatitis B series. Pedirix is also not approved for use in infants born to women who are Hepatitis B surface antigen positive or whose Hepatitis B status is not known. However, in 2003, ACIP recommended that Pedirix could be used to complete the series for high-risk infants as well as all other infants. We will discuss this issue again when we talk about Hepatitis B vaccines. An important thing to remember about Pedirix and all other combination vaccines for that matter is that the minimum interval between doses is dictated by the single antigen with the longest minimum interval. So the minimum intervals for Pedirix are determined by the Hepatitis B component. The minimum interval between the first two doses of Pedirix is four weeks, the same as for Hepatitis B. The third dose must be administered at least eight weeks after the second dose and should follow the first dose by at least 16 weeks. For the Hepatitis B component to be counted as valid, the third dose of Pedirix must be given on or after 24 weeks of age. The third combination vaccine that contains DTAP is Kinrix, produced by GlaxoSmithKline. Kinrix contains DTAP and inactivated polio vaccine. Kinrix is licensed only for the fifth dose of DTAP and the fourth dose of IPV for children four through six years of age. Kinrix should not be used for earlier doses in the DTAP or IPV series or for children younger than four years of age. The fourth combination vaccine that contains DTAP is Pentacell, produced by Sanofi Pasteur. The vaccine contains Liophilized Act Hib that is reconstituted with a liquid DTAP IPV solution. Pentacell is approved by FDA for doses one through four of the DTAP series among children six weeks through four years of age. Pentacell should not be used for the fifth dose of the DTAP series or for children five years or older. As we discussed earlier for Pedirix, the minimum intervals for a combination vaccine are determined by the component with the longest minimum intervals. In the case of Pentacell, the DTAP component determines the minimum interval between doses. As for DTAP, the first three doses must be separated by at least four weeks. The fourth dose must be separated from the third by at least six calendar months and not administered before 12 months of age. Pentacell is the second combination vaccine in which a Liophilized component, Hib, is reconstituted with another vaccine. This has led to many vaccine administration errors. Careless clinicians may administer the DTAP IPV component without using it to reconstitute the Hib component. The DTAP IPV doses can be counted as valid when this happens, but the stage is set for another vaccine administration error. When the DTAP IPV component is administered alone, a dose of Hib remains for which the clinician does not have diluent. Unfortunately, we have heard that many clinicians have used any available diluent to reconstitute the Hib dose. Often sterile water diluent for MMR or varicella has been used. Hib vaccine reconstituted with any diluent except Santa Fe's 0.4% sodium chloride act Hib diluent or Pentacell DTAP IPV solution is not valid and must be repeated. Please keep the DTAP IPV solution and the act Hib vials together in the original Pentacell carton and please instruct your staff to never use one component without using the other. Donna. In addition to the usual ones, DTAP vaccines have several unique contraindications and precautions. A severe allergic reaction to a vaccine component or following a prior dose is a contraindication to DTAP, pediatric DT, adult TD and every other vaccine. Encephalopathy within seven days of administration of pertussis vaccine that is not attributable to another identifiable cause is a contraindication to further doses of pertussis containing vaccine. This contraindication is a remnant from the wholesale pertussis days. Encephalopathy has not been associated with a cellular vaccines. Here are the precautions for DTAP as with all other vaccines moderate or severe acute illness is a precaution and vaccination should be deferred until the acute condition improves. If any of the next four events occur following pertussis vaccination, then additional doses generally should not be given. Temperature of 105 degrees Fahrenheit or higher, that is 40.5 degrees Celsius or higher within 48 hours with no other identifiable cause. Collapse or shock like state also known as a hypotonic hyporesponsive episode within 48 hours. Persistent inconsolable crying lasting three hours or more occurring within 48 hours and convulsions with or without fever occurring within three days. All of these precautionary conditions have been reported following both wholesale and a cellular pertussis vaccines. While they can be frightening especially for the parents, they do not result in permanent injury or predict more severe reactions in the future. DTAP has not been associated with any permanent brain injury. If one of these reactions occurred following a dose of any type of pediatric DTAP, you would not usually give additional doses. The series would be completed with pediatric DT. But remember that precautions require your judgment. You need to determine if the benefit of pertussis vaccine outweighs the risk of a recurrence of the adverse reaction. If so, you may choose to give the vaccine. For example, one of your patients is a normal six month old who had a fever of 105 the day after his second DTAP. Now there is a large community wide pertussis outbreak going on. You may choose to vaccinate this child because the risk from disease exceeds the risk from vaccination. The desire to reduce adverse reactions resulting from wholesale pertussis vaccines was the driving force behind the development of a cellular vaccines. As with other inactivated vaccines, the most common adverse reactions following DTAP and DT are local reactions such as swelling or redness. The more doses a person has received, the more likely they are to have a local reaction. 30 to 50 percent of children who receive a fourth or fifth dose of DTAP will report pain, redness or swelling at the injection site. Low grade fever is reported within 72 hours and one to five percent of children who receive DTAP. More severe systemic adverse reactions such as fever of 105 or higher, persistent crying and hypotonic hyporesponsive episodes are not common. These severe reactions are usually associated with pertussis vaccine and have been reported following DTAP. These reactions were more common after wholesale vaccine, which is no longer available in the U.S. In cephalopathy, which was a very rare adverse reaction to wholesale pertussis vaccines has not been associated with a cellular vaccine. Available data suggests an increase in the frequency and magnitude of local reactions with both the fourth and fifth doses compared to the first three doses. Here is an example. This graph shows the percentage of children reported with swelling, pain or fever of 101 degrees Fahrenheit or higher following administration of infant rigs. The green bar represents reactions following the first dose and the tan bar reactions following the fourth dose. Reports of these reactions were substantially higher following the fourth dose of the series. For instance, swelling at the site of injection shown on the left side of the graphic increased from 4% after the first dose to 35% following the fourth dose. The same pattern is seen for pain at the injection site and fever after vaccination. Although the data shown in the graph are for infant rigs, it appears that local reactions and fever are increased following the fourth and fifth doses of all brands of DTAP. In addition to these local reactions, there have also been reports of extensive limb swelling known as ELS after both the fourth and fifth doses. ELS has been reported in two to six percent of children receiving the fourth or fifth doses of DTAP. This reaction appears to be self-limited and resolves without sequelae. Parents should be informed of the increase in local reactions that has been reported following the fourth and fifth doses of DTAP. ACIP continues to recommend that a fifth dose of DTAP be administered before a child enters school. Because of the importance of this dose and protecting a child during school years, ACIP recommends that a history of extensive limb swelling after the fourth dose should not be considered a contraindication to receipt of a fifth dose at school entry. In summary, pertussis is a disease that affects persons of all ages in the United States. Adolescents and adults account for more than half of reported cases. Multiple pediatric DTAP vaccines are available in the United States, including combinations that also contain hepatitis B, Hib, and or IPV vaccines. These vaccines are very effective for protecting infants and young children from pertussis. Pertussis-containing vaccine license for use among adolescents and adults are expected to reduce the risk of pertussis in these groups as well. In this segment of the program, we're going to discuss pertussis vaccination of adolescents and adults. We will also discuss the use of tetanus and diphtheria toxoids since TD will continue to be an important vaccine for older children and adults. Earlier in the program, we discussed the increase in reported pertussis cases since the mid-1990s. More than 25,000 pertussis cases were reported in 2005. More than two-thirds, almost 15,000 cases were in adolescents or adults. And these were just the reported cases. Population-based studies estimate that more than a million symptomatic cases of pertussis occur each year among persons 11 years and older. The impact of pertussis among adolescents and adults is significant. Pertussis infection of an adolescent or adult can be asymptomatic, produce a mild cough illness, or can cause classic pertussis illness with severe cough and paroxysms. The illness can have a prolonged cough that can persist for three months or longer. Post-tussive vomiting may occur after a severe paroxysm of cough. Adolescents and adults often have multiple medical visits and may undergo extensive medical evaluation for the persistent cough before pertussis is even considered as the diagnosis. Complications of pertussis among adolescents and adults include pneumonia, rib fractures from violent coughing, pneumothorax, subconjunctival hemorrhage, and aspiration. The illness or complications may require hospitalization. The medical costs, missed school and work, and impact on the public health system all contribute to the personal and societal burden of pertussis among adolescents and adults. So, pertussis can be a serious illness for adolescents and adults, but this isn't the only reason we want to prevent it in these groups. Adolescents and adults with pertussis are a source of infection for others, in particular, infants. In a study of infants with pertussis, an adult or adolescent with cough illness was the most likely source of infection for almost 80% of infants with a known source. Now, in case you still think pertussis in adolescents and adults is just a nuisance, have a look at this short video. Vaccination is the most effective strategy to reduce the burden of pertussis. Economic studies of the impact of pertussis among adolescents suggest that a vaccination program for adolescents and adults would be an effective strategy and is likely to be cost-effective as well. Protection from pertussis is the primary objective of our adolescent and adult vaccination program. The secondary objective is to reduce the reservoir of portatella pertussis in the adolescent and adult population. This could potentially reduce the incidence of pertussis in other age groups, particularly infants and in other settings, such as healthcare facilities. Two manufacturers produce Tdap vaccines. Boosterix Tdap vaccine is manufactured by GlaxoSmithKline. It was licensed in May 2005 for use as a single dose and as of December 2008 is approved for persons 10 through 64 years of age. Atticell Tdap vaccine is manufactured by Sanofi Pasteur. Atticell was licensed in June 2005 for use as a single dose in persons 11 through 64 years of age. Neither Tdap vaccine is approved or recommended for persons 65 years of age or older. The two Tdap vaccines are different. They contain a different number and quantity of pertussis antigens. Both vaccines contain a reduced quantity of pertussis antigen compared with the company's pediatric DTAP vaccine. Both vaccines contain the same amount of tetanus toxoid as the respective DTAP vaccine but a lower quantity of diphtheria toxoid. Neither vaccine contains thimerosal as a preservative. Both Tdap vaccines were approved by the Food and Drug Administration on the basis of the serologic response of the vaccine rather than clinical efficacy per se. The manufacturers compared the antibody response following a single dose of Tdap to the response of infants after three doses of the respective DTAP vaccine. The response after a single dose of each vaccine was similar to that following three doses of DTAP. So the assumption is that clinical protection will be similar as well. A clinical trial of the Glaxo formulation among 15 to 65 year olds estimated vaccine efficacy at 92 percent. Andrew. The ACIP recommendations for use of Tdap vaccines among adolescents 11 through 18 years of age were published in the MMWR in March 2006. Recommendations for the use of Tdap among adults were published in December 2006. A few general principles apply to the use of Tdap and Tdap in both adolescents and adults. The recommendations address vaccination to protect against tetanus, diphtheria, and pertussis. ACIP is not stated a preference for one brand of Tdap although each vaccine should be used within its approved age range. In most situations, Tdap is preferred to Td to provide protection against pertussis. Tdap vaccines are not approved for use as a primary series or for persons who have not completed a full series of DTAP or DTP. Both Tdap vaccines are approved by the Food and Drug Administration as a single booster dose in persons who have previously received a full series of four or five doses of pediatric DTAP or DTP. Future studies will address the immunogenicity and safety of subsequent booster doses, for example, a second or third dose of Tdap. Here is the current vaccination schedule for persons seven through 18 years of age. The recommendation for this age group is at the top of the column labeled 11 through 12 years. The recommendation is simple. Adolescents 11 through 12 years of age should receive a single dose of Tdap instead of Td if they have completed the recommended childhood DTAP vaccination series and have not yet received a Td booster. Ketchup doses are indicated on this schedule by the light green bars. The ACIP also recommends that adolescents 13 through 18 years who have not received Tdap should receive a single dose as their ketchup booster dose instead of Td if they have completed the recommended childhood DTAP vaccination series and have not received Td. ACIP recommends that adults 19 through 64 years of age receive a single dose of either brand of Tdap to replace a single dose of Td for booster immunization. Special emphasis should be placed on Tdap vaccination of adults who have close contact with infants, such as child care and health care personnel and parents. Both Tdap vaccines were approved by the Food and Drug Administration as a booster dose for persons who have previously received a documented series of DTP or DTAP. However, as you know, many adolescents and adults do not have a record of having previously received these vaccines. They may not have a vaccination record at all. All adolescents and adults should have documentation of having received an age-appropriate series of pediatric DTAP, DTP, DT, or adult Td. Persons without documentation of this or with an incomplete series should receive or complete a series of three doses. The preferred schedule for persons without documentation is a single dose of Tdap followed by a dose of Td at least four weeks later and a second dose of Td at least six months after the prior Td dose. Although this is the preferred schedule, Tdap may be substituted for any one of the three Td doses in the series. The use of Tdap in a person without a history of DTP or DTAP is an off-label recommendation, but it has been endorsed by the ACIP. Let me emphasize. Persons 11 years and older who have not received a complete series of pediatric pertussis vaccination should receive one dose of Tdap. Do not administer two or three doses of Tdap vaccine. We must await more data and a change in the labeling of the vaccines to administer more than one dose of Tdap to anyone. You will also encounter adolescents and adults who completed the recommended childhood vaccination series for tetanus and diphtheria toxoids with pediatric DT or adult TD vaccine rather than pediatric DTP or DTAP. That is, they received diphtheria and tetanus toxoids but no pertussis vaccine. The ACIP recommends that these persons generally should receive Tdap according to the routine recommendations for adolescents. Remember that the minimum age for Tdap is 10 years for Bustrix and 11 years for Atticell. Tdap vaccine is not approved for children 7 through 9 years of age and ACIP does not recommend off-label use of either Tdap vaccine for this age group. When tetanus and or diphtheria toxoid is needed for this age group, it must be given as adult TD without pertussis. Some adolescents and adults may already have received a TD booster. The ACIP encourages adolescents who received a TD booster to receive a single dose of Tdap to provide protection against pertussis if they have completed the recommended childhood DTAP vaccination series. A five-year interval between the TD and Tdap is encouraged to reduce the chance of a local reaction. However, this five-year interval between TD and Tdap is not set in stone. The two vaccines can be separated by intervals shorter than five years. The benefits of protection from pertussis should generally outweigh the risk of a local reaction in settings with increased risk from pertussis. These settings might include a pertussis outbreak in the community or having an infant in the household. Two Canadian studies evaluated local reactions in more than 6,000 students who received Tdap at various intervals after they had already received TD or five doses of DTP or DTAP. Intervals as short as two years were found to be acceptably safe. The ACIP did not define an absolute minimum interval between a dose of TD and a subsequent dose of Tdap in order to give maximum flexibility to providers. The provider will need to decide when to administer Tdap based on whether the benefit of pertussis immunity outweighs the hypothetical increase in risk of a local adverse reaction, a sore arm. For example, during a community outbreak of pertussis or a household in which there is an infant younger than 12 months of age, a clinician should strongly consider administration of Tdap to persons 10 through 64 years of age, even if TD was received in the previous two years. Donna. The ACIP recommends the administration of all indicated vaccines at the same visit. This fundamental vaccination strategy increases the likelihood that a person will receive each of the vaccines recommended for his or her age or situation. There are two issues that relate to simultaneous and non-simultaneous administration of vaccines at the adolescent visit. Meningococcal conjugate vaccine or MCV is also recommended for all children at the 11-12 year visit. The ACIP recommends that providers administer Tdap and MCV to adolescents during the same visit if both vaccines are indicated and available. Meningococcal conjugate vaccine contains diphtheria toxoid as its carrier protein. The amount of diphtheria toxoid in MCV is similar to that in pediatric DTAP. Tdap, TD, and MCV all induce antibody responses to diphtheria, although MCV is not indicated for immunization against diphtheria. There is concern that the risk of a local reaction could be increased when two diphtheria containing vaccines are administered within a short interval, such as a few days apart. Schedules administering Tdap and MCV in various sequences are being studied. To date, acceptable rates of local reactions have been found in clinical studies of TD and MCV administered simultaneously. TD followed one month later by MCV and MCV followed three years later by a second dose of MCV. Immunity to both pertussis and meningococcus is very important for adolescents. No evidence to date indicates that non-simultaneous administration of these two vaccines is harmful. Simultaneous administration of MCV and Tdap is preferred but not always possible due to vaccine supply or other factors. The ACIP recommends that if simultaneous administration of Tdap and MCV is not possible, these vaccines can be administered at any time before or after each other. There is no absolute minimum interval recommended between these two important vaccines. Obviously, this issue will continue to be studied. You may know that the American Academy of Pediatrics issued their recommendations on the use of Tdap in December 2005. In that document, AAP suggested an interval of one month between Tdap and MCV if the two vaccines were not administered on the same day. They had concerns about the immunogenicity and safety of two vaccines containing diphtheria toxoid that were not shared by the ACIP. Another issue concerning simultaneous administration of vaccines to adolescents is the administration itself. Providers need to be aware that syncope can occur after vaccination and may be more common among adolescents. Be sure to have the person sit down when being vaccinated. You may also want to consider a 15 to 20-minute observation period after vaccination as discussed in the 2006 General Recommendations on Immunization. The ACIP struggled with recommendations for vaccination of pregnant women. On one hand, if the woman received Tdap before or during pregnancy, her passive immunity might help protect the newborn from pertussis. But on the other hand, there are few safety data for pregnant women given Tdap and there are concerns by some experts that the passive pertussis antibody could interfere with the infant's response to DTAP. After extensive discussion of this issue, ACIP recommended that because of these uncertainties, Tdap is generally preferred during pregnancy for women who need protection against tetanus and diphtheria. However, all women should receive a dose of Tdap in the immediate postpartum period, preferably before leaving the hospital if they have not previously received it. Any woman who might become pregnant is encouraged to receive a single dose of Tdap. However, ACIP recommends that a clinician may choose to administer Tdap to a pregnant woman in certain circumstances, such as during an outbreak of pertussis in the community. In this situation, the benefit of boosting pertussis immunity outweighs the hypothetical risk for the mother or infant. Both the package inserts and the ACIP recommendations state that pregnancy is not a contraindication for vaccination with Tdap. Healthcare personnel are also a high priority group for tetanus, diphtheria, and pertussis vaccination. Pertussis can be a serious, sometimes fatal disease in infancy. Because of the possibility of healthcare personnel transmitting pertussis to their patients, special consideration is given to healthcare personnel regarding the scheduling of Tdap. Healthcare personnel who work in hospitals or ambulatory care settings and have direct patient contact should receive a single dose of Tdap as soon as feasible. Priority should be given to vaccination of healthcare personnel who have direct contact with infants 12 months of age and younger. Other healthcare personnel such as those not working in hospitals or ambulatory care settings or without direct patient contact should receive a single dose of Tdap to replace the next scheduled Tdap. A two-year interval or less from the previous dose of tetanus-toxoid-containing vaccine may be used. Please make Tdap vaccination of your staff and yourself a priority. This will help you protect yourself from an infection you do not want and help protect your vulnerable patients as well. Also, please be aware that the recommendations for post-exposure antimicrobial prophylaxis for healthcare personnel have not changed. The same recommendations apply whether or not the person has received Tdap. Andrew? The contraindications and precautions for Tdap are different than those for either pediatric DTAP or adult TD. As with all vaccines, a severe allergic reaction to a vaccine component or following a prior dose is a contraindication to subsequent doses. The tip and rubber plunger of the boosterx-prefilled syringe contains dry natural latex rubber, so a person with an anaphylactic latex allergy should not receive boosterx in this packaging. A boosterx-prefilled syringe may be used for persons with less severe latex allergy, such as contact allergy to latex gloves. The single dose vials of both boosterx and adicel do not contain latex. If a person experiences a serious allergic reaction following a dose of Tdap or TD, an allergy workup should be considered to determine which component might be responsible. This is to avoid unnecessarily labeling the person as allergic to tetanus and diphtheria toxoids because booster doses are needed for the rest of the person's life. The second contraindication is encephalopathy within seven days of administration of a pertussis vaccine, including wholesale DTP and DTAP that is not attributable to another identifiable cause. This condition is a contraindication to pediatric DTAP, but not to adult Td. In addition to contraindications, there are several precautions for Tdap. I will remind you that if a precaution is present, the decision to vaccinate must be made based upon a case-by-case risk versus benefit consideration. The first precaution is a history of a serious or exaggerated local reaction, also known as an Arthus type reaction, following a prior dose of tetanus or diphtheria toxoid containing vaccine. Persons who experience a serious local reaction following a prior dose of tetanus toxoid or Td usually have high serum tetanus or diphtheria antitoxin levels. These persons should not be given a dose of Tdap or Tdap more frequently than every 10 years, even if they have a tetanus prone wound. A second precaution is a progressive neurologic disorder, uncontrolled epilepsy or progressive encephalopathy until a treatment regimen has been established and the condition has stabilized. If a decision is made to withhold pertussis vaccination, then Td may be used instead of Tdap. A history of Guillain-Barre syndrome within six weeks after a prior dose of tetanus toxoid containing vaccine is a precaution to Tdap. This is also a precaution for other tetanus toxoid containing vaccines. Finally, a moderate or severe acute illness with or without fever is a precaution, as it is with all other vaccines. It is worth mentioning here that some conditions that are precautions to the use of pediatric DTAP are not precautions to the use of Tdap. ACIP believes that these conditions are unique to young children and are not expected to be an issue among adolescents. These conditions occasionally occurred following pediatric DTAP or DTP, but are not precautions for Tdap. Temperature 105 degrees Fahrenheit or higher, which is 40.5 degrees Celsius within 48 hours, collapse or shock-like state, also known as hypotonic hyporesponsive episode, persistent crying lasting three hours or longer, convulsions with or without fever occurring within three days, and finally a history of an extensive limb swelling reaction. Other conditions that are not precautions to Tdap include a stable neurologic disorder, pregnancy, breastfeeding, and immunosuppression, including persons with HIV infection. The immunogenicity of Tdap in persons with immunosuppression has not been studied and could be suboptimal. Finally, concurrent minor illness and antimicrobial use are not precautions to Tdap. Clinicians should be careful to use only valid contraindications and precautions when screening a Tdap candidate. To withhold Tdap for an inappropriate reason could jeopardize not only the person but his or her close contacts as well. Donna. For the definitive clinical trials that led to licensure of both boostrics and adisal, the Tdap products were compared to standard adult Td for immunogenicity and safety of the Td component. This graphic shows the adverse reactions and events reported by recipients of Tdap in the manufacturer's trials. Local reactions such as pain, redness and swelling at the site of injection are the most common reaction and was reported in 21 to 75 percent of recipients of both vaccines. Temperature of 100 degrees Fahrenheit or higher within 14 days of vaccination was reported in 3 to 5 percent of recipients. Systemic events such as headache and fatigue were reported in 30 to 40 percent of recipients. No unusual or unexpected adverse reactions were identified for either vaccine. The percentage of Tdap recipients reporting these symptoms was very similar to reports from persons receiving only Td. Tdap is a relatively new vaccine. As is the case with all new vaccines, VAERS reports for persons who receive Tdap will be monitored very carefully to detect any unanticipated adverse events as the vaccine becomes more widely used. One final note about Tdap. Many offices are now stocking both pediatric DTAP and Tdap in the same refrigerator. This has led to many vaccine administration errors. Pediatric DTAP has been administered to persons seven years of age or older and Tdap has been administered to children. This has happened so much that ACIP addressed it in both the adolescent and adult Tdap statements. We do not have time on this program to discuss the management of these errors. You can get that from the ACIP statements, but we would like to point out a resource to help you prevent these mistakes. The California Immunization Branch has produced a poster titled Check Your Viles. The poster shows images of the DTAP and Tdap brands and reminds your staff to look carefully before administration of one of these products. Vaccine administration errors are not acceptable practice. We encourage all of you to discuss this issue with your staff and download a copy of the Check Your Viles poster from the California Immunization Branch and post it on the front of your refrigerator. We will provide a link to the poster on the Updates and Resources webpage. One additional comment about adult Tdap, you have probably encountered older persons who claim to be allergic to tetanus shots. Many described severe reactions to something they were given for tetanus years ago. Their allergic reaction may actually have been serum sickness, a reaction to equine antitoxin. Equine antitoxin was the only product available for the prevention of tetanus prior to the mid-1940s. It was used for post-exposure prophylaxis until the late 1950s when tetanus immune globulin was introduced. Tetanus toxoid has never contained any horse protein. If you come across someone with a history like this, do not just write it off as allergy to tetanus toxoid. Try to find out when it happened, the nature of the reaction, and the circumstances when it occurred. If the reaction seems to be truly anaphylactic, you should strongly consider referring your client to an allergist for evaluation. No one should be allowed to remain susceptible to tetanus. That can be a fatal error. 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. Jarek is a seven-year-old who you're seeing for the first time in July. He recently moved to the United States from Poland with his family. He was born six weeks premature and has a history of eczema, which is controlled with the use of a topical steroid cream. Otherwise, he's healthy with no other medical conditions. His mother reports he has not had chicken pox. His mother is five months pregnant. Jarek's written vaccination record from Poland indicates that he received BCG vaccine at seven days of age, DTP, oral polio vaccine, OPV, and hepatitis B vaccine at two, three, four, and 18 months of age. He received MMR and HIP vaccines at 15 and 18 months of age. So here are three questions about Jarek. What, if any, vaccines does he need today? Does he have any contraindications to the vaccines he needs today? And when should Jarek return and what vaccines will he need at his next visit? 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 two main issues with Jarek. First, his previous vaccines were given on a schedule that's typical in Europe. You'll need to look closely at the timing and spacing of the vaccines he received in Poland to determine if they will comply with U.S. minimum ages and intervals. Second, you need to determine if he has any contraindications or precautions to the vaccines he needs today. So here's the first question for Jarek. What, if any, vaccines does he need today? At today's visit, Jarek needs his first dose of varicella vaccine. He could also receive his first dose of hepatitis A vaccine if your state or county has a catch up program for hepatitis A. You will need table one to determine if the doses of vaccine he received in Poland can be counted. After consulting table one, you determine that the doses of DTP and oral polio vaccine given at two, three, four, and 18 months meet the U.S. minimum intervals and ages and can all be counted. For tetanus and diphtheriotoxoids, he received the four-dose series recommended if the first dose was given before the first birthday. Here is the catch. Some states have laws that require a dose of tetanus-containing vaccine and or polio vaccine on or after age four years. If this is the case in your state, your only option would be to give Jarek a dose of adult TD since at age seven, he's too old for DTAP and he's too young for TDAP. If there's a four-year polio rule in your state, you would administer a single dose of IPV to be in compliance. The dose of hepatitis B vaccine he received at four months of age was not a valid third dose because it was given before 24 weeks of age. But he got another dose at 18 months, so his hepatitis B series is complete. The doses of MMR were both given after the first birthday and separated by at least four weeks, so they can both be counted. Finally, he got the two doses of Hib vaccine recommended when a child's first dose is given after the first birthday, so his Hib series is also complete. Now here is the second question about Jarek. Does Jarek have any contraindications to the vaccines he needs today? No, he doesn't have any contraindications to varicella or hepatitis A vaccines. The only considerations for contraindications or precautions are his eczema, the treatment of the eczema with topical steroids, and his mother's pregnancy. None of these are contraindications to either varicella or hepatitis A vaccine. Here then is the third question about Jarek. When should he return and what vaccines will he need at his next visit? Jarek needs a return in three months for his second dose of varicella vaccine. You're seeing Jarek now in July and in three months it'll be October and his mother will be nearing delivery of her baby. So this will be a convenient time for Jarek and everyone else in the household including his mother to receive their influenza vaccine. Jarek could receive either inactivated or live attenuated influenza vaccine. One of the idiosyncrasies of the new two-dose varicella recommendation for children is that the doses need to be separated by three months rather than four weeks. We will discuss this issue in more detail in the varicella segment of the course. His mother's pregnancy is not a contraindication to the use of live attenuated vaccine for Jarek or other household members although his mother should only receive inactivated influenza vaccine. Children younger than nine years of age receiving influenza vaccine for the first time need two doses in their first vaccination year. So Jarek will need a second dose of influenza vaccine a month after the first dose since he has no history of prior influenza vaccination. And he will need to return in six months for his second dose of Hepatitis A vaccine. Thanks Bill. Now what we would like to do is address some of your most frequent questions that we receive. Bill, I'm going to address this one to you and we hear this a lot and that is that someone goes usually for a wound prophylaxis to an urgent care center or to the emergency room and they receive tetanus toxoid. So what do you do then? Do they need to be revaccinated? Yeah, we we do hear that a lot more than we like. It depends on what what you do depends. If the ACIP of course recommends that only TD or TDAT be used when tetanus or diphtheria is necessary but and if there are no contraindications of course to the other vaccines but it's already given and there's nothing you can do about it. So if the person is basically a U.S. resident and not traveling you can wait at the minimum interval or wait till the next dose and then give him or her TD or TDAP but there are exceptions to this. An international traveler needs to be protected against diphtheria. A person with an infant in the household or a health care worker needs to be protected against pertussis. So if those conditions are present you need to give either the TD or the TDAP right now and not wait five or ten years for their next round for TD. Okay thanks. Andrew here's another one that we get. We're talking about giving this TDAP booster to adolescents and adults but what if they have a history of having had pertussis do you then do you just give them TD? Well actually in most circumstances you'll probably want to give TDAP you know it documented culture confirmed pertussis disease probably provides natural immunity for a period of five to ten years but in most circumstances you won't really be able to obtain a culture you may not be able to obtain a culture but we know that immunity does wane so regardless of when this history when this event occurred in most cases immunity will probably have waned or you won't have a culture to confirm it so in most cases you'll likely need to give TDAP. If you have a culture if it happened recently within the past three to five years then maybe you can get away with giving TD but in most circumstances TDAP. Okay good thanks. Bill here's another one what do you do if someone over 64 or like a kid who's between seven and nine years of age that didn't get all their pertussis if they get TDAP? This also happens a lot of course TDAP is not approved for seven eight or nine year olds and it's not approved for people 65 and older that would be off-label to use it in those situations. Having said that TD is pretty much TD so we would recommend that the dose not be repeated as TD because the person would have gotten all the T and D that they need in those doses. Okay good we get a lot of questions about tetanus diphtheria and pertussis and here's another one and this this is more with like usually elderly patients if they're admitted to a nursing home they may not remember what vaccines they've had or have any immunization record so what do you do about their tetanus diphtheria and all this? Well a TD dose is only valid if it's documented so if you don't have a documented dose then you will need to provide a vaccination either a booster or a primary series but you need the documentation. If it ain't written it wasn't done right? Exactly. Thanks Andrew and thank you Bill. Homophilus influenzae type B is a disease that most healthcare providers will never see again. 20 years ago there were children with Hib meningitis or epiglottitis in the hospital almost all the time then a vaccine came and the disease became a rarity thousands of children are alive today because of this vaccine. Homophilus influenzae type B or Hib was once the leading cause of bacterial meningitis among children younger than five years of age. Approximately one in 200 children developed some form of invasive Hib disease almost all invasive infections were among children younger than five years of age. Homophilus influenzae was first described by Robert Pfeiffer in 1892 in the sputum of patients with influenza so he believed that this bacteria was the cause of influenza. Influenza is actually caused by a virus but that was not known until 1933. The microbiology of homophilus including the importance of the capsular polysaccharide was established in the 1930s. The polysaccharide was not purified and characterized until the 1970s. In 1985 the first vaccine was licensed and the first conjugate vaccine was licensed in 1987. With widespread use of conjugate vaccines invasive Hib disease is now rarely seen. Homophilus influenzae is an aerobic gram negative bacterium. The polysaccharide capsule is responsible for the organism's virulence and for immunity to it. There are six different serotypes of polysaccharide capsule designated as A through F. There are also non-typeable strains that colonize the respiratory tract and are a major cause of otitis media and bronchitis. But 95% of invasive disease is caused by type B which we will refer to as Hib. We will focus solely on it. Some persons are colonized with Hib without ill effects. Unfortunately, some of these colonized persons develop invasive disease. What triggers invasive disease is not well understood but it may be something as minor as an upper respiratory infection. Hib invasive disease can affect many different organ systems. This pie chart shows the different clinical manifestations of invasive Hib disease in the pre-vaccine era. As you can see, Hib can cause bacteremia, can infect skin as cellulitis, the joints as septic arthritis, and the bones as osteomyelitis. It can also cause pneumonia. 15 to 20% of invasive Hib disease was epiglottitis, inflammation of a tissue flap at the opening of the airway. But by far the most common clinical manifestation was meningitis. Meningitis accounted for approximately 50 to 65% of cases of invasive Hib disease. Before a vaccine was available, Hib was the most common type of bacterial meningitis in infants. Hearing impairment or neurologic sequelae occurred in 15 to 30% of survivors. The case fatality rate was 2 to 5% even with effective antimicrobial therapy. With the disappearance of Hib meningitis, Streptococcus pneumoniae, or pneumococcus, is now the most common cause of bacterial meningitis in infants. Pneumococcal meningitis has not become more common. In fact, it has become less common since pneumococcal conjugate vaccine became available. But since Hib meningitis now rarely occurs, what was number two has become number one just by default. Hemophilus influenzae is a human disease, and the reservoir is infected humans who are usually asymptomatic. The epidemiology of Hib disease is complex because of transmission from asymptomatic carriers. In the pre-vaccine era, studies suggested that 5 to 15% of children were colonized at any given time. Carriage could persist for months. Most children were infected by the age of 5 and, presumably, developed immunity to the bacteria from these subclinical infections. Respiratory transmission of Hib occurs through the spread of infected droplets. Communicability of Hib is limited. This means that secondary clinical cases are unusual, but communicability may be higher in some circumstances, such as close contact with a symptomatic case in childcare. Invasive Hib disease became nationally reportable in 1991, so historical data before that is estimated. Before an effective vaccine became available, there were an estimated 20,000 invasive Hib infections each year, with up to 1,000 deaths. This is a graph of the incidence of invasive Hib among children younger than five years since 1989. The rate per 100,000 children is shown along the vertical axis and the year on the horizontal axis. Incidence was estimated between 25 and 60 cases per 100,000 in the pre-vaccination era. The rate fell rapidly after introduction of the conjugate vaccine. By 1994, the incidence of Hib among children younger than five years of age had decreased by 95% compared with the pre-vaccination era. By 2005, the incidence had declined by more than 99%. From 2002 through 2006, a total of 123 confirmed Hib cases have been reported among children younger than five years, an average of about 20 cases per year. This is a rate of less than one case per million population. About half of children with invasive Hib disease are younger than six months of age, so they were too young to have completed the two or three dose primary Hib vaccination series. Of the children who are six months of age or older, about one-third had received a complete primary series, and some had received a booster dose at 12 to 15 months of age. The cause or risk factors of these apparent vaccine failures is not known. So, although Hib vaccine failure can occur, the majority of children who develop invasive Hib disease are too young to be vaccinated or older children who are incompletely vaccinated. Donna? The first Hib vaccine was licensed in 1985. It was purified Hib polysaccharide. Polysaccharides are not very immunogenic. They do not stimulate the immune system very well. As a result, polysaccharide vaccines are not effective, including the first Hib vaccine in children younger than 12 months of age, and the effectiveness in older children is variable. This is a serious problem if the disease you wish to prevent occurs in infants. The limited effectiveness of polysaccharide Hib vaccine was improved by a process known as conjugation. The idea is to link a poor antigen, the polysaccharide, to a good one, protein. Conjugation enhances antibody production, especially in young children. Repeat doses elicit a booster response, so antibody titers go up with every dose. And the antibody that is produced has increased biologic activity, which means it works better. What happens with conjugation is that the protein polysaccharide complex elicits a T cell dependent response. That means that T cells become involved in the immune response instead of the T independent response characteristic of pure polysaccharide. The original pure polysaccharide Hib vaccine is no longer produced. Only conjugated polysaccharide Hib vaccines are available now in the United States. There are two Hib conjugate vaccines licensed for use in infants in the United States. These vaccines are chemically and immunologically different. However, available data suggests three doses of any combination confers protection. PRPT Hib vaccine is marketed as Act Hib and is included in the combination's trihibot and pentacel. PRPOMP is marketed as P-vax Hib and is included in the combination Comvax. We will talk more about the combination vaccines a little later. A third Hib conjugate vaccine, Hib Titer, is no longer available in the U.S. Hib vaccination should be started for all infants, including premature infants at two months of age. Hib vaccine can and should be administered simultaneously with all other childhood vaccines. A primary infant series of Hib vaccine consists of two or three doses depending on the vaccine. PRPT or Act Hib is a three-dose primary series at two, four, and six months of age. PRPOMP or P-vax Hib is a two-dose schedule at two and four months. A dose of P-vax Hib at six months is not required. For both vaccines, a booster dose should be given at 12 to 15 months of age. The minimum age for the last dose of the Hib series is 12 months. At the time this program was updated, February 2009, Merck's Hib vaccine, P-vax Hib, is not available in the U.S. During the shortage, CDC recommends that the booster dose of Hib vaccine, usually administered at 12 to 15 months of age, be deferred except for children at increased risk of Hib disease. This group includes children with asplenia, sickle cell disease, immunodeficiency, including HIV infection and cancer, and American Indian and Alaska Native children. Details of this recommendation are available in the December 21, 2007 edition of Morbidity and Mortality Weekly Report. Updates on the Hib vaccine supply are also available on the CDC Vaccines and Immunizations website. The first dose of Hib vaccine is usually administered at two months of age, but may be given as early as six weeks. Available data suggests that vaccination before six weeks of age may induce what is known as immunologic tolerance to Hib antigen. That means that doses given before six weeks of age may cause the child to be incapable of responding to subsequent doses, and that is not a good thing. Based on limited data, it appears that the earlier in life the vaccine is given, the more likely that tolerance will occur, so the minimum age for all Hib vaccines is six weeks. Unfortunately, we frequently hear about Hib vaccine administered before six weeks of age. The ACIP has no specific recommendations for management of the child if this happens. The dose before six weeks of age should not be counted as valid, and the child should receive the Hib vaccine series on schedule. The first two or three doses of the series should be separated by two months, but a minimum interval of four weeks may be used if an accelerated schedule is needed. The booster dose should be given on or after the first birthday and should be separated from the preceding dose by at least two months. Children younger than two years of age do not reliably develop immunity following invasive Hib disease, so these children should be vaccinated as usual after they recover. Fortunately, Hib disease is now rare in the United States, so you will not need to manage this situation very often. Bill? There are times when you encounter a child who received Hib vaccine from another office or clinic. You may not know or may not stock the Hib vaccine the child received for the earlier doses. Fortunately, studies have shown that an excellent immune response is achieved when different brands of Hib vaccine are interchanged in the primary series. So, ACIP recommends that all Hib containing vaccines except trihibid are interchangeable for both the primary series and the booster dose. Trihibid is interchangeable only for the last or booster dose in the Hib series. Here, though, is the caveat. Three doses should be given as the primary series if more than one brand of vaccine is used. In particular, if Merck's vaccine, P-Vax Hib, is given in a series with ACTIB, the child should receive three doses and a booster, not two doses and a booster. This recommendation seems to cause some confusion, and it's important that you're clear on this because this will be a common situation if one brand of Hib vaccine is in short supply or not available. This recommendation only applies to the primary series given before 12 months of age. If a child receives different brands of Hib vaccine for the two and four month doses, then a dose at six months is needed. For example, a child who receives P-Vax Hib at two months then receives ACTIB at four months, a third primary dose at six months should be administered. Likewise, if the child receives ACTIB at two months then P-Vax Hib at four months, a six month dose should be administered. Any Hib vaccine can be administered as that six month dose. Where this recommendation does not apply is for the booster dose after 12 months of age. If the child receives P-Vax Hib at two and four months, any Hib vaccine can be used as the single booster dose at 12 to 15 months. In this situation, mixing and matching vaccine brands does not mean the child needs a fourth dose. Now it shouldn't happen but sometimes children are late getting started with the vaccination schedule including Hib. If the child gets started before seven months of age they should receive the full series of doses. But unvaccinated children seven months of age and older starting the series late may not need the entire three or four dose series. The number of doses a previously unvaccinated child requires depends on their current age that is the age at which the series is being started. Unvaccinated children 15 to 59 months of age need only one dose of any licensed conjugate vaccine. Here's a table outlining the number of Hib doses by the age at the first dose. This information is in the Hib ACIP statement and is also included in the course text. Notice that P-Vax Hib has its own row because it's a two-dose schedule. Also note that Hib Titer is on this table but is no longer available. A more common situation is when a child has received one or two doses of Hib vaccine on schedule but has since fallen behind. This is referred to as a lapsed series. These situations are similar to those when the child is starting the schedule late. Depending on the child's age now he or she may not need a full series of three or four doses. You can use the catch-up schedule to figure out how many if any additional doses of Hib vaccine a child may need. Here is the current catch-up schedule published in January in MMWR. If you have a copy of it handy please get it out now. This part of the catch-up schedule tends to confuse people so I'd like to work through an example with you. Suppose you have a 14 month old child in your office with a record of one dose of Hib vaccine at six months of age. The first question is whether the child needs any more doses of Hib vaccine. To determine this go to the dose one to dose two column and follow it down to the Hib row. There are three entries in the Hib row in this column. The one that applies here is the first one. Your patient received his first and only dose at six months of age. A second dose is needed a minimum of four weeks after the first if the first dose was administered at less than 12 months of age. Since the minimum interval has elapsed you should give the second dose today. Next question does the child need a third dose? To determine this you move to the next column labeled dose two to dose three and follow this column down to the Hib row. There are also three entries in this cell. Reading through them you find the one applicable to your patient is the second entry. If the current age is 12 months or older and the second dose was given at an age younger than 15 months then a third and final dose is recommended at least eight weeks after the dose you gave today. So you make the child a return appointment for two months for the third dose of Hib. Children behind on Hib vaccine are probably behind schedule for other vaccines as well. So be sure the parent understands the importance of returning for the next Hib dose and the other vaccines the child needs. Donna. Another Hib vaccine issue that we frequently receive questions about is vaccination of older children and adults. Hib vaccination is generally not recommended for persons older than 59 months of age because there is very little Hib disease in older persons. Presumably this lack of disease in older children and adults is because of immunity acquired through asymptomatic infection as children. Although none of the current Hib vaccines are specifically approved for this indication ACIP recommends that Hib vaccination be considered for certain high risk older children and adults. This would generally include persons with anatomic asplenia those who have had their spleen removed or functional asplenia those who spleen is not functional such as children with sickle cell disease. Vaccination can also be considered for persons with immunodeficiency including HIV infection. Older children and adults who are at high risk of Hib disease should receive only one pediatric dose of any Hib conjugate vaccine. A series of three doses of Hib vaccine is recommended for all persons who have received an hematopoietic stem cell transplant. Now that we have discussed the specifics of the use of single antigen Hib vaccines let's move on to combination vaccines that contain Hib. Three combination vaccines that include Hib are currently available in the United States. There is a hepatitis B Hib combination, COMVACS. We will come back to COMVACS in a moment. There are also two licensed DTAP Hib combination vaccines Pinticell and Trihibot. Pinticell is a sanofi-pasture vaccine that contains lyophilized ACTIB that is reconstituted with a liquid DTAP IPV solution. Pinticell is licensed by FDA for doses one through four of the DTAP series among children six weeks through four years of age. Pinticell should not be used for the fifth dose of the DTAP series or for children five years or older. We discussed the Pinticell schedule in more detail in the DTAP segment of the program. As we mentioned earlier, we expect the supply of the Merck Hib vaccine, P-Vax Hib, will be limited through at least the first half of 2009. CDC continues to recommend that the last or booster dose of the Hib series be deferred in healthy children in order to conserve the Hib vaccine supply. The availability of Pinticell has improved the Hib vaccine supply situation in the United States. However, the availability of Pinticell is not sufficient to reinstate the last or booster dose of the Hib vaccine series. Although Pinticell is licensed by FDA for the fourth dose in the DTAP IPV and Hib series, providers should not use it for the fourth dose until there is further improvement in the Hib vaccine supply later in 2009. Until the Hib supply improves, Pinticell should be used only for the first three doses of the DTAP IPV and Hib vaccination series, except for children at increased risk of Hib disease or who have not completed a primary Hib schedule. More information on the Hib shortage is available on the CDC vaccine and immunizations website. Trihibot is ACTIB reconstituted with Santa Fe Pasteur's DTAP vaccine, Tripedia. This vaccine can be used for the last dose of the DTAP Hib series only. Trihibot is not approved by FDA for the primary series at two, four or six months of age. The currently licensed trihibot should not be used for the first three doses of the series regardless of the child's age. Now you may encounter children who received trihibot inappropriately for one or more of the first three doses of the series. If so, the primary series Hib doses given as trihibot should be disregarded. You can count the DTAP doses as valid. You should revaccinate the child with single antigen Hib vaccine appropriate for their age. You may need to use the catch-up schedule to determine how many doses of single antigen Hib the child needs. This conservative approach assures that the child is truly protected against invasive Hib disease. We also receive many questions about the use of trihibot as the last dose of the Hib series when a different brand of Hib vaccine was used for the primary series. The Hib footnote of the childhood schedule helps clarify this situation. Although not in the package insert, ACIP recommends that while trihibot cannot be used for the primary series, it may be used as the booster or final dose at 12 months of age or older following any Hib vaccine series, including a Comvax primary series. So to use trihibot, the child must be at least 12 months of age and have received at least one prior dose of Hib vaccine. Trihibot should not be used if the child has received no prior Hib doses regardless of the child's current age. Another combination vaccine that contains Hib is Comvax. Comvax is a hepatitis B Hib combination. It contains a standard dose of P-vax Hib and standard 5-microgram pediatric dose of Merck's hepatitis B vaccine, Recomba-vax HB. As with other combinations, the vaccine can be used when either antigen is indicated and the other component or components are not contraindicated. As we discussed earlier, Hib vaccine should not be given to infants before six weeks of age because of the potential of immune tolerance to Hib. So Comvax also cannot be used in infants younger than six weeks of age. That means it cannot be used when an infant receives hepatitis B vaccine at birth or at one month of age. Technically, Comvax is not approved by the Food and Drug Administration for use when the infant's mother is hepatitis B surface antigen positive. However, in 1997, ACIP recommended that Comvax could be used to complete the series for high-risk infants as well as all other infants. We will discuss this further during the hepatitis B segment later in the course. Since Comvax contains Merck's P-vax Hib, the routine schedule is three doses at two, four, and 12 months of age. If a child has received a birth dose of hepatitis B vaccine, Comvax may still be given at two, four, and 12 months of age. Bill? One of the most common questions we receive about Comvax concerns the interval between doses, particularly the second and third doses. The confusion is caused by the wording on this issue in the package insert. This is the Comvax package insert. In the section on dosage administration, there's a sentence that says the interval between the second and third dose should be as close as possible to eight to 11 months. Some providers have interpreted this to mean the minimum interval is eight months between the second and third doses. This is not the case. The package insert implies an eight to 11 month minimum interval between the second and third Comvax doses. This interval only applies if the child is on schedule and the second dose was given at four months of age, because the minimum age for the third dose is 12 months. The minimum interval if the child is not on schedule is two months, the same as P-vax Hib and other Hib vaccine brands. But remember that the minimum age is 12 months, and for the last Hib dose to be valid, it needs to meet both the minimum interval two months and the minimum age of 12 months. Also, remember that if more than one brand of Hib vaccine is given, the child needs three doses and a booster after the first birthday. So, if a child gets Comvax at two months, then you switch to Act Hib at four months, a third dose is recommended at six months of age and a booster after the first birthday. Likewise, if the child starts with Act Hib at two months, then gets Comvax at four months, a third dose of Hib vaccine should be given at six months with a booster dose after the first birthday. Now, since Hib vaccines are inactivated, contraindications and precautions are also predictable. As with all vaccines, a severe allergic reaction to a vaccine component or following a prior dose is a contraindication. Moderate or severe acute illness is a precaution and the vaccination should be deferred until the acute illness improves. Because of the risk of immunologic tolerance, age younger than six weeks is a contraindication to all Hib containing vaccines. Adverse reactions following Hib vaccines are similar to those following other inactivated vaccines, but adverse reactions following Hib vaccine are remarkably mild. Local adverse reactions such as swelling, redness and pain are reported in five to thirty percent of recipients. These symptoms usually resolve within 24 hours. Systemic reactions such as fever are infrequent and serious adverse reactions are rare. So that's the story with hemophilus influenza type B. It's a great vaccine and has practically eliminated Hib disease as a threat to infants in the United States. We now would like to present a case study that addresses some of the issues that we have discussed on the program today. The case studies are available on the updates and resources webpage for this program. Rob is a 25-year-old male nurse who works in the emergency department of an urban hospital. He reports that he had a temperature of 105 degrees Fahrenheit after his first dose of wholesale DTP vaccine at two months of age. Since that time, he has received a full series of pediatric DT and adult TD booster doses. His last TD booster dose was 16 months ago. He is up to date for all other vaccines. Rob reports that there is a pertussis outbreak occurring in the community served by the hospital where he works. Several cases have been seen recently in the emergency department and two hospital staff members have been diagnosed with pertussis in the last month. Here are the questions we would like you to consider. Does Rob have an indication for Tdap? Can Rob receive Tdap considering his past reaction to DTP? And, if Rob can receive Tdap, when should it be administered? 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. Recommendations for adult vaccination often need to take into account factors like occupation. This decision process typically occurs after deciding whether a dose of vaccine is recommended universally for an adult of a given age or gender. Based on age, gender, and previous vaccination history, you determine that no vaccines are universally recommended for Rob. But of course, this is employee health and you must be aware of other factors like healthcare occupation. Here is the first question about Rob. Does Rob have an indication for Tdap? Yes. In fact, he has several indications, including his age and occupation. He should receive Tdap and can receive either brand. Tdap is recommended universally for persons 11 years through 64 years of age, so Tdap is indicated on the basis of Rob's age. Recommendations for Tdap are driven in part by a need to prevent transmission of pertussis to children, especially young infants. For this reason, ACIP gives preference for Tdap vaccination of healthcare personnel. This is especially important for those who care for children since they are at high risk for a complication from pertussis. Rob works in the ED of an urban hospital where he certainly cares for children. Rob's occupation might indicate the need for additional vaccines as well, and we hope the employee health provider recognizes this. But at a minimum, he needs Tdap and he can receive either brand. Also note that even though the package insert states that this vaccine is indicated as a booster dose, ACIP recommends its use, even if a primary series of pertussis-containing vaccine has not been previously given, as is the case with Rob. Here is the second question about Rob. Can Rob receive Tdap considering his past reaction to DTP? The answer is yes. Rob can receive Tdap. A fever of 105 degrees Fahrenheit following a dose of DTP or DTAP is neither a contraindication nor a precaution to Tdap. We will assume Rob's high fever and infancy occurred within two days of his two-month dose of DTP vaccine. This was and is considered a precaution for subsequent doses of either pediatric DTP or DTAP vaccine. This precaution is based on the association between doses of pertussis-containing vaccine and high fever, particularly the older, wholesale DTP vaccine. Persistent crying and hypotonic, hyporesponsive episodes also rarely follow DTP. The occurrence of one of these reactions following pertussis-containing vaccines is considered to be a precaution for further doses of pediatric pertussis-containing vaccine. This is why some people, like Rob, have a history of receiving DT vaccine instead of DTAP. Reactions such as hypotonic, hyporesponsive states and persistent crying appear to occur mainly among infants who receive DTP or DTAP. The cause of these reactions is not known, but there is no evidence that they led to chronic neurologic damage. Adolescents and adults are not considered to be at risk for these reactions, so a past history of one of these reactions in infancy is not considered to be a contraindication or precaution to Tdap. Here is the third question about Rob. If Rob can receive Tdap, when should it be administered? The answer is Rob should receive his Tdap today. ACIP recommends that adults routinely receive a dose of Tdap 10 years after the previous tetanus-toxoid-containing vaccine. This interval is recommended to reduce the risk of local reactions. However, a 10-year interval is not set in stone. Since pertussis vaccine is only available combined with tetanus and diphtheria toxoids, an adolescent or adult who needs a boost in pertussis immunity has no alternative but to receive Tdap. Clinical studies have demonstrated an acceptable rate of local reactions when Tdap is given as soon as two years after a dose of adult Tdap. ACIP has not recommended a specific minimum interval between Tdap and Tdap in situations where there is a definite risk of acquisition and transmission of pertussis. This includes healthcare personnel that care for children, anyone in contact with an infant, and anyone involved in a pertussis outbreak. Rob is a healthcare provider that works with children, there is a pertussis outbreak in the community, and there is pertussis transmission occurring in the urban hospital as evidenced by cases among children and staff. Rob needs Tdap now. Donna? We get a lot of questions about these DTAP and Tdap and we talked about the upper age limit on Tdap being 64 years of age. Well, what do providers do about these grandmas and grandpas that are over 64 and they're going to be around, you know, little babies and children? What about their pertussis protection? It's a great question. Tdap is not currently recommended for a person 65 years of age and older, and this gets back to the issue of the groups that the manufacturer studied in the pre-licensure trials, which of course leads to the FDA package insert. So the vaccine is not licensed for persons 65 years of age and older, and so CDC and ACIP do not recommend this vaccine specifically. It's a difficult situation. The manufacturers say they're looking at this to see if it can possibly be used, but currently it cannot be used in persons over that age. So probably the best thing to do is to make sure that all of those members of the family that can receive it do receive it, and that can also help then with the herd immunity and that barrier of protection, not only for the little ones, but also for the grandparents. Yabo, one of the new combinations we have is the kinrix, the DTAP and IPV combination. Sometimes a provider will run into a child that's their over four years of age, not yet seven, but they haven't received all of their vaccine doses and they may be behind in their DTAP and IPV and need several doses. So can they use this combination so they only have to give one stick for DTAP and IPV? Great question, Donna. We are hearing this question a little bit more often now, and really as the name implies, kinrix is licensed for the kindergarten dose of vaccine. It is licensed only for the fifth dose of DTAP and the fourth dose of IPV. It is not to be used for subsequent doses. It's a one-time dose only. The same scenario could also be likened to the penicill issue where penicill is only licensed for the first four doses of the series of DTAP. It should not be given for the fifth dose of DTAP. So it's important for providers when these vaccines first come into their office that they really check out that package insert and make sure that staff are oriented to these new vaccines and the specific indications for them. Absolutely. Andrew, a little bit different topic here. Hib disease. Sometimes, unfortunately, we hear about children that still get hib disease. So if they have actually had the disease, should they be vaccinated against hib? Yes, they actually do still need to be vaccinated. Hib disease, natural hib disease, does generate an immune response. It's not as high as we like to think of with other organisms and other natural diseases. And so there is still some benefit that can be derived from vaccinating with hib vaccine even in a child that has had hib disease already. Now, just to emphasize that we don't routinely recommend hib vaccine for children five years of age and older. So what we're talking about are children younger than five years. Yeah, and that's because they're the ones that are at greatest risk for the disease, right? Okay. Yaddle, you mentioned Pentacel. That's the DTAP-IPV-HIB combination. We hear that some providers are just using the DTAP and IPV separately. What about that? What do you think? Right, Donna. That is a very concerning problem. This is a medication error and it's happening much too often. The component should never be used separately. The DTAP-IPV should be used to reconstitute the hip component. If it is inadvertently done, which we discussed earlier in the program, the DTAP-IPV component will be considered valid. However, the problem becomes what to do with the hip component. Now, there's no diluent available to mix with it. The only approved diluents to mix with the hip component are the act hip from Santa Fe or the DTAP-IPV. So we definitely recommend not splitting the contents. Okay. Thank you, Yaddle. Thank you, Andrew. It's all the time we have right now. Streptococcus pneumoniae or pneumococcus was first isolated by Lewis Pasteur in 1881. It was confused with other causes of pneumonia until the invention of the gram stain in 1884. By 1940, more than 80 serotypes had been described. The first attempts at producing a pneumococcal vaccine began about the time of the First World War. It would be almost 70 years before the first pneumococcal vaccine was licensed in 1977. Streptococcus pneumoniae is a gram-positive bacterium. There are 90 known serotypes, as with other encapsulated organisms, the polysaccharide capsule is an important virulence factor, and capsular-type specific antibody is protective. Although all serotypes may cause serious disease, a relatively limited number of serotypes cause the majority of invasive infections. Overall, the 10 most common serotypes are estimated to account for about 60 percent of invasive disease worldwide. But the ranking and serotype prevalence differs by age group and by geographic area. Among children younger than six years of age in the U.S., seven serotypes account for 80 percent of isolates from blood or cerebral spinal fluid. In contrast, these same seven serotypes account for only about 50 percent of isolates from older children and adults. Pneumococcus is a frequent inhabitant of the upper respiratory tract and may be isolated from the nose, throat or both of about 10 percent of persons at any given time. Colonization of children may be even more frequent. Nearly all persons are colonized with pneumococci at some time during the course of a year. We do not understand why some of these persons go on to develop invasive disease. Host factors like underlying illness are probably important, but persons without any underlying illness may also develop invasive pneumococcal disease. The most common clinical presentation is pneumococcal pneumonia. Among adults an estimated 100,000 to 135,000 cases of pneumococcal pneumonia requiring hospitalization occur annually in the U.S. Pneumococcus is responsible for up to one-third of community acquired pneumonias and up to half of hospital acquired pneumonias. Pneumococcal pneumonia is also a common complication of influenza and of measles. Pneumococcal bacteremia can be a severe disease with an estimated 50,000 or more cases per year. Pneumococcal meningitis is much less common. There are three to six thousand cases per year, but pneumococcal meningitis is often fatal and survivors may have permanent neurologic damage. This is a basilar view of the brain of a person who died from pneumococcal meningitis. The cerebellum is on the right. All the white material you see is purulent material. That's pus. This type of purulent meningitis is very difficult to treat with antibiotics. The person is likely to have residual neurologic deficits if he or she survives. Pneumococcus alone is responsible for up to one out of every five cases of bacterial meningitis in the U.S. Now that hemophilus influenza is well controlled, pneumococcus is the most common cause of bacterial meningitis in infants. For all these syndromes, fatality rates are higher in older adults. For example, the fatality rate from pneumococcal meningitis is up to 40 percent in person 65 years of age and older. The CDC active bacterial core surveillance system estimates that about 41,000 cases and 4,900 deaths from invasive pneumococcal disease occurred in the United States in 2006. Bacteremia without a known site of infection is the most common invasive clinical presentation among children younger than two years of age. Bacteremia accounts for about 70 percent of invasive disease in this age group. With the decline of invasive hip disease, pneumococcus has become the most common cause of bacterial meningitis among children younger than five years of age in the United States. The highest rate of meningitis is among children younger than one year of age, approximately 10 cases per 100,000 population. The burden of pneumococcal disease among children younger than five years of age is significant. In the pre-vaccination era, an estimated 17,000 cases of invasive disease occurred each year. 13,000 of these were bacteremia without a known site of infection and about 700 were cases of meningitis. An estimated 200 children died every year as a result of invasive pneumococcal disease. Although not considered invasive disease, it was estimated that five million cases of acute otitis media occurred each year among children younger than five years of age. Before pneumococcal conjugate vaccine was available, more than 60 percent of children had at least one episode of acute otitis media by their first birthday. Otitis media was the most frequent reason for pediatric office visits in the United States and resulted in more than 20 million visits annually. Pneumococci are also an important cause of pneumonia in children. In two perspective studies, 17 to 28 percent of community-acquired pneumonia was diagnosed as pneumococcal. This translates into tens of thousands of cases each year. Bill? The epidemiology of pneumococcal disease is complicated because nasopharyngeal colonization with the bacteria is relatively common and not all colonized persons develop invasive disease. The reservoir of pneumococcus is believed to be the nasopharynx of humans who are colonized with the organism. As mentioned earlier, up to 10 percent of persons are colonized with pneumococci at any given moment. Transmission probably occurs mostly from asymptomatic colonized persons by respiratory droplets. For this reason, a vaccine that could reduce nasopharyngeal colonization could indirectly protect unvaccinated contacts. The communicability of pneumococci is not known with certainty, but transmission can probably occur as long as the organism is present in respiratory secretions. Much of our knowledge of the incidence and risk factors for invasive pneumococcal disease comes from special studies and surveillance systems. One such special surveillance system is CDC's active bacterial core surveillance known as ABCs. This graph shows the incidence of invasive pneumococcal disease by age group in 1998 based on data from ABCs. The vertical axis shows incidence expressed as rates per 100,000 population. The horizontal axis shows age groups. The highest rates are among children younger than five years, particularly children two years and younger shown in the bar at the far left, and among adults 80 years and older shown in the bar at the far right of the graph. Incidence falls to its lowest point among children five to 17 years of age. After age 49, the incidence of pneumococcal disease rises steadily with increasing age. Although pneumococcal infections occur in healthy persons, there are medical and other factors that increase the risk significantly. Age is an important risk factor for invasive pneumococcal disease. Children two years of age and younger are at highest risk. Persons 65 years and older are at increased risk, although the rates overall in this age group are less than half that in young children. Many underlying medical conditions increase the risk of invasive pneumococcal disease, and we'll come back to this in just a moment. Recipients of a cochlear implant are a group recently recognized to be at increased risk for invasive pneumococcal disease. A cochlear implant is an electronic device utilized by persons with profound hearing loss that cannot be corrected by hearing aids. There are estimated to be about 25,000 recipients of these devices in the United States. Since 2002, more than 50 cases of meningitis and at least two deaths have been reported in individuals who have had a cochlear implant. Two-thirds of these infections were in young children. The reason why the implant appears to predispose the recipient to meningitis is not known. Conditions that increase the risk of invasive pneumococcal disease include decreased immune function from disease or drugs, functional or anatomic asplenia, chronic heart, pulmonary, including asthma, liver or renal disease, smoking cigarettes, and cerebral spinal fluid or CSF leak. For children out of home group child care has been shown to increase the risk of invasive pneumococcal disease and acute otitis media. The risk for children in these settings is increased two to three fold among children younger than five years of age. Children of certain racial and ethnic groups have increased rates of invasive pneumococcal disease. These include African American children, Alaska Native and American Indian children who live in Alaska, Arizona or New Mexico, and Navajo children who live in Colorado and Utah. The rate of invasive disease for these children is three to four times higher than for other healthy children at every age. The reason for this increased risk is not clear. Socioeconomic factors may account for some of the increased risk, but some studies have reported increased risk even when controlling for income. Data collected by the Active Bacterial Core Surveillance System suggests that the conjugate vaccine is already having an impact on invasive pneumococcal disease in young children. In 2006, the rate of invasive pneumococcal disease caused by all serotypes in children younger than five years of age was 24 cases per 100,000 population, down from 100 cases per 100,000 population before the vaccine was licensed. The rate of invasive pneumococcal disease caused by vaccine serotypes has fallen even further, from 82 cases per 100,000 to 0.4 cases per 100,000, a 99% reduction. In the last three years, there's been an increase in invasive disease caused by serotypes, not in the vaccine. We'll come back to this issue in just a moment. So, with more than 100,000 cases of pneumonia and 5,000 deaths each year, pneumococcal disease is one of the most common causes of vaccine-preventable death in America. The highest risk is among children younger than two, older adults, and persons with certain underlying medical conditions. Obviously, this is a disease worth preventing. Andrew. The first pneumococcal vaccine was licensed in 1977. It contained polysaccharide from 14 serotypes of pneumococcus. In 1983, a 23-valent polysaccharide vaccine was licensed, which replaced the earlier vaccine. The first pneumococcal conjugate vaccine was licensed in 2000. Pneumococcal polysaccharide vaccine contains purified, capsular polysaccharide antigen from 23 types of pneumococci. These 23 serotypes account for 88% of bacteremic pneumococcal disease and cross-react with types causing an additional 8% of disease. The efficacy of the polysaccharide vaccine has been estimated at 60 to 70% against invasive disease, but appears to vary to some extent with underlying disease. The duration of immunity is at least six years, and the schedule is one dose, with selective revaccination. The problem with polysaccharide vaccines is that they are not effective in young children. Basically, polysaccharide is a T-cell independent antigen and does not establish good immunologic memory. Polysaccharide vaccines are generally not effective among children younger than two years of age, and subsequent doses do not produce a substantial boost in antibody level. Conjugation of a protein to the polysaccharide improves the response to the vaccine. Pneumococcal conjugate vaccine, Prevnar, contains purified pneumococcal polysaccharide conjugated to a non-toxic variant of diphtheriotoxin known as CRM197. It contains the polysaccharide of seven serotypes of pneumococci. The seven serotypes included in PCV account for 86% of bacteremia and 83% of meningitis among children younger than six years of age. Additional pneumococcal conjugate vaccines containing additional serotypes are being developed. Pure polysaccharide vaccine does not generate a significant immune response in young children. Conjugating the polysaccharide to a protein overcomes this problem. PCV is very effective in children. The efficacy trial included almost 38,000 children in the Northern California Kaiser Permanente system. The vaccine was 97% effective against invasive disease caused by vaccine serotypes. It was 73% effective against clinically diagnosed pneumonia in children with x-ray evidence of an area of consolidation. Vaccinated children also had a significant reduction in visits for acute otitis media. Overall, there was a 7% reduction in all episodes of acute otitis media. Frequent otitis media was reduced by 9 to 23% depending on the definition of frequent and vaccinated children had 20% fewer tympanostomy tubes placed than unvaccinated children. Studies in various populations of children subsequent to the clinical trial have shown a decline of up to 28% in frequent otitis media and tympanostomy tubes. This translates to thousands fewer office visits and thousands fewer prescriptions for antibiotics. Another benefit of PCV may be its effect on nasopharyngeal carriage of pneumococci. This is important because if carriage could be reduced it would indirectly protect unvaccinated contacts of vaccinated children. Several studies indicate that conjugate vaccines reduce nasopharyngeal carriage of vaccine type pneumococci by about one half. Nearly all studies have found that carriage of pneumococcal serotypes not included in the vaccine is higher among vaccinated children. A small increase in invasive disease caused by non-vaccine serotypes has been reported, particularly serotype 19a. This is called replacement disease. However the decline in invasive disease caused by vaccine serotypes far exceeds the increase in disease caused by non-vaccine strains. Obviously this issue will continue to be monitored. The next few graphics list the recommendations for use of pneumococcal polysaccharide vaccine. All adults 65 years of age and older should be vaccinated even if they do not have an underlying illness. PPV is also recommended for persons two years and older with normal immune systems who have chronic illness. Examples of targeted chronic illnesses are cardiovascular or pulmonary disease, diabetes, and alcoholism. In addition persons with cerebrospinal fluid leak or a cochlear implant are considered to be at high risk and should be vaccinated. In 2008 ACIP added two new indications for pneumococcal polysaccharide vaccine for adults 19 years of age and older. These new indications are asthma and cigarette smoking. These groups were added because of evidence of an increased risk of invasive pneumococcal disease. Available data do not support asthma or cigarette smoking as indications for PPV among persons younger than 19 years. PPV is also recommended for persons two years and older who are immunocompromised. Asplenia is a unique type of immunosuppression. Persons with functional or anatomic asplenia are at very high risk of pneumococcal bacteremia and should be vaccinated. Persons with chronic renal failure and nephrodic syndrome are relatively immunocompromised and should be vaccinated. Immunosuppression also includes Hodgkin's disease, lymphoma, and multiple myeloma. Vaccination is also recommended for persons with HIV infection. The majority of persons eligible for PPV will only need a single dose in their lifetime. A few persons at very high risk of pneumococcal infection should receive a second dose. We will discuss re-vaccination in more detail a little later. Donna? Pneumococcal conjugate vaccine is approved for children six weeks through nine years of age. However, the ACIP recommends the vaccine only through age 59 months. The vaccine is not routinely recommended for older children or for adults. Older children and adults are candidates for pneumococcal polysaccharide vaccine. Use of pneumococcal conjugate vaccine in children five through nine years should be reserved for unvaccinated children at the highest risk of invasive pneumococcal disease, such as those without a functional spleen or who are immunosuppressed. The ACIP recommends routine vaccination with PCV for all children younger than 24 months of age. The vaccine should be integrated into the routine schedule and administered during the same visits as other routine childhood immunizations. Routine vaccination is also recommended for unvaccinated children 24 to 59 months of age with a high risk medical condition. The second recommendation for catch-up vaccination of children two to five years of age was important when the PCV recommendations were first published in 2000. PCV was added to the childhood immunization schedule in 2001, so there should now be very few unvaccinated older children, since most will have received PCV with their other routine vaccines. But you might encounter a child two to five years of age from a country that does not routinely use PCV. These children deserve to be protected. So your policy should be to vaccinate all unvaccinated children up to age five years regardless of whether they have an underlying medical condition. The routine vaccination schedule for PCV is three primary doses at two, four, and six months with a booster dose at 12 to 15 months. The first dose may be given as early as six weeks of age. If an accelerated schedule is needed, a minimum interval of four weeks should separate each of the first three doses. At least eight weeks should separate the third and fourth doses. Children who begin the series of PCV after seven months of age will need fewer doses than children who begin the schedule at two months of age. In this way, the vaccine is similar to Hib conjugate vaccine. This table shows the recommended number of doses for children who start the vaccination series late at seven months of age and older. Children who receive their first dose at seven to 11 months will receive two doses separated by at least four weeks and a booster dose two months after the second dose. Children beginning the series at 12 to 23 months of age should receive two doses separated by at least eight weeks with no booster dose. Healthy unvaccinated children 24 to 59 months of age need only one dose. Unvaccinated children 24 to 59 months of age at high risk of invasive pneumococcal disease, such as those with HIV infection or asplenia, should receive a total of two doses separated by eight weeks. You will encounter children who began the PCV series on time but have since fallen behind schedule. We receive many questions on this issue. If a child is more than one month behind schedule, you will need to use the catch-up schedule to determine how many doses the child needs. The catch-up schedule is published with the routine childhood schedule in January of each year. We receive so many questions about the PCV catch-up schedule we want to work through an example with you. Now, suppose you have a healthy 14-month-old child in your office who has a record of one dose of PCV at nine months of age. The first question is whether the child needs any more doses of PCV. To determine this, go to the dose one to dose two column and follow it down to the pneumococcal row. There are three entries in the PCV row in this column. The one that applies here is the first one. Your patient received his first and only dose at nine months of age. A second dose is needed a minimum of four weeks after the first if the first dose was administered at less than 12 months of age. Since the minimum interval has elapsed, you should give the second dose of PCV today. Next question, does the child need a third dose? To determine this, you move to the next column labeled dose two to dose three. Follow this column down to the pneumococcal row. There are also three entries in this cell. Reading through them, you find the one applicable to your patient is the second entry. If current age is 12 months or older than a third and final dose is recommended for healthy children at least eight weeks after the dose you gave today. So you make the child a return appointment for two months to receive the third dose of PCV. If the child is behind on PCV, he or she is probably behind on other vaccines as well. So be sure the parent understands the importance of returning for this and the other vaccines the child needs. Bill? There are situations in which children two years of age and older with high risk medical conditions could benefit from vaccination with both pneumococcal conjugate vaccine and pneumococcal polysaccharide vaccine. Some children 24 to 59 months of age with high risk medical conditions such as HIV infection or sickle cell disease may have already received pneumococcal polysaccharide vaccine. The polysaccharide vaccine has the advantage of containing a larger number of serotypes of pneumococci, but the conjugate vaccine has the advantage of better immunologic priming and induction of immune memory. ACIP recommends administration of pneumococcal conjugate vaccine to children at high risk of invasive pneumococcal disease who have already received pneumococcal polysaccharide vaccine. These children should receive two doses of PCV. The two doses of PCV should be separated by eight weeks and should be given at least eight weeks after the pneumococcal polysaccharide dose. A more common situation now is that children with high risk conditions have already received a series of PCV. Children who complete the PCV series before two years of age and who are at high risk of invasive pneumococcal disease should also receive pneumococcal polysaccharide vaccine. These children will benefit from the larger number of pneumococcal serotypes contained in the polysaccharide vaccine. ACIP recommends that children at high risk of invasive pneumococcal disease receive pneumococcal polysaccharide vaccine. These children should receive one dose at two years of age at least eight weeks after the last dose of pneumococcal conjugate vaccine. Children at highest risk, such as those with HIV infection or a splenia, will also receive a second dose of pneumococcal polysaccharide vaccine five years after the first dose. All this may seem complicated at first, but the recommendations for use of pneumococcal polysaccharide vaccine in high-risk children have not changed. Pneumococcal conjugate vaccine has just been added to the schedule for children younger than 59 months of age. We receive many questions about revaccination with pneumococcal polysaccharide vaccine. We've heard of clinicians who want to administer it every 10 years or every five years or even every year along with influenza vaccine. The basic problem is that multiple doses of polysaccharide vaccine do not provide a significant boost in antibody titer. In addition, there is little evidence that more than one dose protects any better than just one dose. Routine revaccination of immunocompetent persons is not recommended, regardless of the person's age. Revaccination is recommended for persons at highest risk of serious pneumococcal infection and for those who are likely to have a rapid decline in pneumococcal antibody levels. I'll define these groups a little further in a moment. Revaccination is a one-time event. Data for the safety and efficacy of more than two doses are not available, so only one revaccination dose should be given. This single revaccination dose should be given five years or longer after the first dose. This revaccination interval applies to persons of all ages. Persons who are candidates for revaccination are those at highest risk of severe disease. This includes persons with functional or anatomic asplenia and persons with immunosuppression from either disease or drugs. Disease immunosuppression occurs with HIV infection, leukemia, lymphoma, and other malignancies. Therapeutic immunosuppression occurs with cancer chemotherapy, post-transplantation immunosuppressive drugs, and high doses of corticosteroids. Additional candidates for revaccination include persons with chronic renal failure and for persons who have conditions that result in a rapid decline in antibody level, such as nephrodic syndrome. Persons vaccinated before age 65 years should also be revaccinated. Revaccination of healthy persons 65 years of age and older is not routinely recommended, but persons 65 years of age and older should be revaccinated if they received their first dose five or more years earlier and were younger than 65 years of age at the time of that first dose. Also, if a healthy person receives the first dose of pneumococcal polysaccharide vaccine at 65 years of age, then develops a condition that increases the risk for pneumococcal disease, immunosuppression, for instance, a second dose five years or more after the first dose would be appropriate. Persons 65 years of age and older, whose vaccination status is not known, should receive one dose of vaccine. Andrew. Contraindications and precautions for pneumococcal conjugate vaccine are the same for both pneumococcal polysaccharide and pneumococcal conjugate vaccines. A history of a severe allergic reaction to a vaccine component or following a prior dose is a contraindication to vaccination. Moderate or severe acute illness is a precaution and vaccination should be delayed until the acute illness improves. Adverse reactions following pneumococcal vaccines are similar to other inactivated vaccines. Local reactions, such as pain and redness, are reported in 30 to 50 percent of recipients of PPV. In the clinical trials, local reactions such as redness, swelling, or tenderness were reported in 10 to 23 percent of recipients of PCV, depending on the dose. In three to four percent, pain was severe enough to interfere with limb movement. Systemic reactions such as fever and myalgia are uncommon in PPV recipients, being reported in fewer than one percent of recipients. Fever defined as a temperature of 100.4 degrees Fahrenheit or higher within 48 hours was reported in 15 to 24 percent of PCV recipients. But in these studies, PCV was often administered simultaneously with wholesale pertussis vaccine. Many of these febrile episodes may have been attributable to the wholesale pertussis vaccine, not the pneumococcal conjugate vaccine. In another study in which a cellular pertussis vaccine was given simultaneously with PCV, 11 percent of recipients had temperatures of 100.4 degrees Fahrenheit or higher, which is 38 degrees Celsius or higher. Serious adverse reactions are rare for PPV and have not been attributed to PCV. One final note about pneumococcal vaccines. Many offices are now stocking both pneumococcal conjugate and polysaccharide vaccines. Having two types of pneumococcal vaccine in the same refrigerator does increase the risk of a vaccine administration error. We have already heard of several instances in which polysaccharide vaccine was given to an infant and conjugate vaccine was given to an older child or adult. Pneumococcal polysaccharide is not recommended for children younger than two years of age because it is not effective in this age group. Conjugate vaccine is not recommended for persons older than five years of age. The larger number of serotypes in the polysaccharide vaccine is advantageous to older persons. Providers always need to verify the correct vaccine is being given before injecting it. We all want to avoid administration errors. If a child is inadvertently given a dose of polysaccharide vaccine, you should administer the correct vaccine as soon as the error is discovered. If an adult receives conjugate vaccine, ACIP recommends waiting two months before giving the polysaccharide vaccine. Widespread use of pneumococcal conjugate vaccine is preventing invasive pneumococcal disease among both children and their close contacts. It is likely that additional vaccines with even more serotypes will be licensed in the future. Hopefully, the incidence of pneumococcal disease in infants will continue to fall and the disease will become a rarity, the same way Hib conjugate vaccine has made Hib disease a rarity. Donna. Thanks, Andrew. We do receive a fair amount of questions about pneumococcal disease and the vaccine, so we'll go over a few of those now. Andrew, you know, providers are seeing so many kids with asthma now and we say that it's an indication for influenza vaccine. What about pneumococcal vaccine? Well, actually, asthma is not associated with pneumococcal disease, so asthma alone is not an indication. If someone has chronic obstructive pulmonary disease or other types of chronic diseases that we've discussed, heart disease, diabetes, those would be indications for the pneumococcal vaccines, but asthma alone, no. Thanks. Bill, what about children who've actually had pneumococcal disease? Do they still need to be vaccinated? Good question. There are a lot of different serotypes of pneumococcus and just because a person has an infection with one, even if it is documented and often it's not, even if it is documented, that does not necessarily mean that they'll be immune to one of the many other strains, one of the other serotypes of pneumococcus. So, yes, we do recommend that even if a person has culture-confirmed pneumococcal disease that they should, if they have an indication of child, for instance, they should in fact go ahead and receive the entire vaccination series with pneumococcal conjugate vaccine. And if they have an indication for polysaccharide vaccine, they should receive it as well when they're two years or older. Okay, good. Andrew, I hate to talk about administration errors, but we do get questions about this. And we say if an infant inadvertently receives pneumococcal polysaccharide vaccine, that we, they can go ahead right then as soon as they discover it and give the conjugate vaccine. But on the other hand, with older children or adults, if they have vice versa, if they've received the conjugate vaccine, then we say they need to wait eight weeks before giving the polysaccharide. What's the rationale for that difference? Great question. The infant is not going to respond at all to the pure polysaccharide vaccine, because as I mentioned before, pure polysaccharide vaccines do not work well in infants. So, you need to give the conjugate vaccine to the infant or a child ASAP. Whereas in the adult situation, if an adult by mistake receives the conjugate vaccine, there is this concern of local reactions, which are more common with frequent dosing of pneumococcal vaccines. So, hence the recommendation to wait two months to give the polysaccharide vaccine. Okay. I think that might help some people in understanding why we have that difference in the recommendation. Bill, here's another one. Is there ever a situation where we would give pneumococcal conjugate vaccine to an adult? No, basically no. Two reasons. Number one, the vaccine is only approved for children older than nine and actually recommended only through age five. There's much more benefit for pneumococcal polysaccharide vaccine in older people and adults because of the large number of strains that are contained in the polysaccharide vaccine. Okay. Good. Andrew, one last question here. You know, pneumococcal, a lot of providers will say this is the pneumonia shot. So, if a person has a history of pneumonia, is that a high risk situation or an indication to get the pneumococcal vaccine? Good question. A history of pneumonia alone is not considered a high risk. Again, it's those chronic diseases, chronic obstructive pulmonary disease, heart disease, other chronic conditions that are a recommendation, but a history of pneumonia alone is not considered to be an indication for the pneumococcal vaccine. Good. I'm glad we addressed that because I think there is some confusion about that. A lot. Okay. Thank you. Thank you, Andrew. Thank you, Bill. Okay. Myelitis is a disease few healthcare providers in the United States will ever see. Wild-type polio virus transmission was interrupted in the United States almost 30 years ago. With our exclusive use of inactivated polio vaccine in the United States, vaccine-associated polio also no longer occurs in this country. So, we are going to limit our discussion today primarily to polio vaccine issues. Poliomyelitis is caused by an interovirus. There are three distinct serotypes of polio virus, one, two and three. There is minimal heterotypic immunity between serotypes, which means that the immunity to one serotype does not protect you very much from other serotypes. So, that's why there are three viruses in the vaccine. The infection is acquired through the mouth. The virus initially replicates in the pharynx and GI tract, then spreads to the lymphatics and other tissues, including the central nervous system. Most polio virus infections are asymptomatic. However, about one in 200 infected persons develop permanent paralysis. The paralysis caused by polio virus is usually asymmetric and sensory function is intact. Persons initially paralyzed may recover some or all motor function. Overall, from two to five percent of paralytic polio cases are fatal. In general, the severity of polio increases with age and older children and adults are more likely to be paralyzed or die than infants. This graphic shows the number of reported cases of polio by year since 1950. Polio peaked in 1952 with more than 58,000 total cases and more than 21,000 paralytic cases, which are shown on this slide. The number of reported cases was falling even before the introduction of the first polio vaccine in 1955. By the time oral polio vaccine was licensed in 1963, the number of cases was only a fraction of that reported in the pre-vaccination era. The last documented cases of paralysis caused by while polio transmitted in the United States were in 1979. These cases were part of an outbreak among the Amish in the Midwest. The virus responsible for this outbreak had been imported from the Netherlands. The elimination of indigenous transmission of wild polio virus in the United States helped stimulate the development of a global polio eradication program. Even after the last cases of paralysis from wild-type polio virus in 1979, cases of paralytic polio continued to be reported. This graph shows the number of paralytic polio cases reported in the United States by year since 1980. Between 1980 and 1999, 158 paralytic cases were reported, an average of about eight cases per year. Six of the 158 cases were acquired in other countries and imported into the U.S., and the cause of two cases was uncertain. These eight cases are shown in tan on the graph. The last imported case occurred in 1993. The remaining 150 cases, or 95 percent of all cases reported since 1980, were caused by polio vaccine virus, shown in the green bars on the graph. In fact, every case of paralytic polio acquired in the United States in 1980 through 1999 was caused by vaccine virus. Because oral polio vaccine is no longer used in the U.S., the last known case of vaccine-associated paralytic polio acquired in this country occurred in 1999. The single vaccine-associated paralytic polio case in 2005 at the far right of the graph, shown in red, was unique because it was a U.S. citizen who acquired the infection outside the country. This case is a 22-year-old woman from Arizona who was believed to have been infected with polio vaccine virus in Costa Rica in January 2005. She had never received polio vaccine because of a religious exemption. She represents the first case of vaccine-associated paralytic polio in a U.S. citizen since 1999 and the first imported vaccine-associated case ever documented in the U.S. This case illustrates that international travel by an unvaccinated person, even to a country without indigenous polio virus transmission, is not without risk. Details about this case and the investigation were published in the February 3, 2006 edition of Morbidity and Mortality Weekly Report. Another OPV-related issue emerged in 2005. A seven-month-old infant with a severe immunodeficiency was found to be infected with a type 1 polio virus that was derived from the vaccine strain. The child was unvaccinated and lived in a community in Minnesota where many children and adults were unvaccinated. Investigations identified seven additional infections in the community. Four children in the community were shedding the same virus in their stool and three of the child's siblings had serologic evidence of recent polio virus infection. None of the infected children were paralyzed or had other symptoms related to their infection. The virus was vaccine-derived because of mutations. It is called this because it is clearly different than vaccine virus. This was the first identification of a vaccine-derived polio virus in the United States. Vaccine-derived polio viruses have caused outbreaks on the island of Hispaniola in the Philippines and in Indonesia as recently as 2005. Testing of the virus suggested that it had been circulating for at least two years, meaning that the virus was older than the infant who had the index case. The source of the virus has not been identified. The takeaway message from this is that unvaccinated persons are at risk of polio virus infection even if they live in a country with no endemic circulation of wild virus and where OPV is not used. Details of this investigation were published in the October 21, 2005 edition of MMWR. Bill? The first polio vaccine, the inactivated vaccine developed by Jonas Salk was licensed in 1955 and the demand for it was enormous. Millions of doses of Salk vaccine were administered in the late 1950s. Trivalent oral polio vaccine was licensed in 1963. OPV rapidly became the polio vaccine of choice. An enhanced version of IPV was licensed in 1987 and the original Salk IPV was taken off the market in 1988. Production and distribution of oral polio vaccine was discontinued in the United States in 2000. Oral polio vaccine was responsible for the elimination of wild polio virus from the United States. OPV continues to be used extensively throughout the rest of the world and will eventually be the vaccine that eliminates polio from the planet. But OPV no longer plays a direct role in polio vaccination policy in the United States. So the remainder of our discussion will concentrate on the use of inactivated polio vaccine. Enhanced IPV, which we will refer to simply as IPV, is an excellent vaccine that is highly effective in producing immunity to the three types of polio virus. Like many other inactivated vaccines, most recipients do not become immune after a single dose. But 90% of recipients are immune to all three polio types after two doses. 99% are immune after three doses. There are three combination vaccines that contain inactivated polio vaccine. PediaRx is produced by GlaxoSmithKline and contains DTAP, Hepatitis B, and IPV vaccines. It is licensed for the first three doses of the DTAP series among children six weeks through six years of age. KinRx is also produced by GSK and contains DTAP and IPV. KinRx is licensed only for the fifth dose of DTAP and the fourth dose of IPV among children four through six years of age. Pentacel is produced by Sanofi Pasteur and contains DTAP, Hib, and IPV. It is licensed for the first four doses of the component vaccines among children six weeks through four years of age. Pentacel is not licensed for children five years or older. We discuss additional details for the use of these vaccines in the DTAP segment of this program. The schedule recommended by the ACIP and the American Academies of Pediatrics and Family Physicians is four doses of IPV beginning at two months of age. The first dose may be given as early as six weeks of age. The second dose should be given at four months of age and the third may be given as early as six months of age. A fourth dose of IPV is recommended at school entry at four to six years of age. If an accelerated schedule is needed, the current minimum interval between all four doses of IPV in the series is four weeks. These minimum intervals are being discussed by ACIP and could change in the future. It is preferable to administer the fourth dose at school entry. However, it may be given as early as 18 weeks and be counted as a valid dose depending on the age and spacing of the earlier doses. This is one of the most common questions we receive now about polio vaccine. According to table one of the general recommendations, the minimum age for the last dose of IPV is 18 weeks. However, some states have requirements that mandate a dose of polio vaccine on or after age four years. So if you encounter a child who has received four doses of polio vaccine before the fourth birthday and you live in a state that mandates a dose after age four years, the simplest solution is just to administer a fifth dose after age four years. Serial logic testing is an option, but the testing is expensive and you'll need to test for antibody against all three serotypes and the results can be very difficult to interpret. We suggest you just give a fifth dose and be done with it. Children who receive three doses of either OPV or IPV before the fourth birthday should receive a fourth dose of polio vaccine at the time of school entry. But if the third dose was given honor after the fourth birthday, a fourth dose is not required. However, this rule only applies to children whose first three doses were either all OPV or all IPV. If the child received any combination of both OPV and IPV, then a total of four doses are recommended regardless of the age when the third dose was given. Now this will no longer be an issue soon for U.S. born children since distribution of OPV was stopped in the United States in 2000. A related issue is that of children who received OPV for their early doses and are now due for their school entry dose. We've gotten many calls and emails with questions about how many doses to administer in this situation. Remember that IPV is the only polio vaccine available in the United States. You may still occasionally encounter a child who began the series with OPV, such as an immigrant from another country. These children should receive IPV to complete the polio vaccination series. Any combination of four doses of IPV and OPV by four to six years of age constitutes a complete series. You do not need to add any extra doses. Four total doses are all that is needed. Now we want to make sure you're clear on this point. A total of four doses is recommended if a child received any combination of IPV and OPV. This recommendation is for all children through 17 years of age, that is, until the 18th birthday. The only situation in which three doses are acceptable is when all three doses are the same type of vaccine and one or more of those doses was administered on or after the fourth birthday. Andrew. Polio vaccination of adults generates a lot of questions, mostly from international travelers and travel health providers. Routine polio vaccination of U.S. residents 18 years of age and older is not recommended. The only adults for whom vaccination should be considered are those who travel to polio endemic areas of the world and selected laboratory workers who may come into contact with wild polio viruses. Endemic areas currently exist only in Africa and Asia. Vaccination of adults would also be appropriate in the event of an outbreak of vaccine derived polio virus has occurred in Minnesota in 2005. Unvaccinated adults, including those who cannot document prior vaccination, should receive three doses of IPV each separated by at least four weeks. If travel is imminent, less than four weeks, an unvaccinated person should receive a single dose of IPV. The remaining doses of the series should be administered later if the person remains at risk. Persons with the documented incomplete series should receive the remaining doses of the series. It is not necessary to restart or add doses to the series because of a lapse in the series. Adults who can document a complete series of any type of polio vaccine in the past should receive a single booster dose of IPV. This booster dose is only given once in an adult's lifetime. Contraindications and precautions to an activated polio vaccine are also very limited. As with all vaccines, a severe allergic reaction to a vaccine component or following a prior dose is a contraindication to IPV. Moderate or severe acute illness is a precaution and vaccination should be deferred until the person's condition improves. Pregnancy is not a contraindication to the use of IPV, but since routine polio vaccination of Americans 18 years and older is not recommended, pregnancy will not be a common issue except for those of you who see travelers. An activated polio vaccine is one of, if not the safest vaccine available. As with any injected vaccine, local reactions such as pain, redness or swelling at the site of injection occurs in 2.8% of recipients after any of the first three doses of IPV. Severe adverse reactions are rare and are mostly allergic reactions. In the past, almost all adverse reactions following polio vaccine were due to oral polio vaccine. Vaccine associated paralytic polio was a rare occurrence, but it led to the discontinuation of use of OPV in the United States. However, OPV is still being used extensively outside the United States and could be encountered by travelers as we described earlier. It is likely that in the near future polio will become the second virus intentionally eradicated from the planet. The last known case of paralytic disease caused by wild polio virus in the United States occurred in 1979. The Pan American Health Organization devised an aggressive and successful OPV mass vaccination program in 1985. The last case of wild polio virus in the Western Hemisphere occurred in Peru in 1991. Due largely to the success of the polio elimination program in the Americas, the World Health Organization established a polio eradication program in 1988. At the end of 2006, polio was considered to be endemic in only four countries shown on this map in red, Afghanistan, Pakistan, India, and Nigeria. In 2006, a total of 1,997 confirmed cases of polio were reported from the four endemic countries and 13 other countries where the virus was reintroduced due to importation. The total for 2006 was about the same as the total for 2005 due primarily to a large outbreak in Northern India. This outbreak resulted in the reintroduction of polio into areas of India that had been polio-free and 10 times as many cases in 2006 as in 2005. In 2006, Nigeria accounted for more than half the polio cases reported worldwide. Transmission is mainly occurring in three Northern states. However, due to intense vaccination efforts in Nigeria, the number of polio cases dropped in the second half of 2006 and in the first five months of 2007. Transmission of polio virus continued in Pakistan, mainly along the border with Afghanistan. Transmission is also occurring in the southern region of Afghanistan. There have been challenges during the past three years, in particular the outbreak in Nigeria with subsequent importation into previously polio-free areas and the 2006 outbreak in Northern India. But strategies continued to be refined and the world moved closer to eradicating polio in 2006. With continued progress, we look forward to the day when the scourge of polio is relegated to the history books. More information about the global polio eradication program and opportunities to volunteer for short-term assignments in the program are available on the Updates and Resources webpage. 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.ph.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.