Small Group Discussion Guide Vaccine Safety Curriculum for Medical Residents

Case #1: Parents currently refusing all vaccines for their infant & considering an alternative schedule
Learning Objectives: a) Clearly explain the lack of scientific evidence for a causal relationship between vaccines and autism. b) List useful facts that can allay parental fears that multiple vaccines overwhelm the immune system. c) Clearly explain the risks of natural immunity. d) Identify resources to facilitate conversations with patients and to which you can refer patients. Case presentation: Both parents come into the office with their first-born daughter who is now 2 months old. They are here for a well-child exam. The child was born at term and the pregnancy and delivery were uncomplicated. The parents appear to be upper-middle class and well educated. The exam and discussion go well until you start to bring up the subject of immunizations. The parents state that they have decided to delay vaccination and are considering an alternative vaccine schedule in the future. Question 1: How do you start the conservation about the parents concerns? Answer: It is important to validate the parents concern, not to simply dismiss them. A helpful place to start is finding out what their specific concerns are and where the parents are getting their information. Frequently stated concerns among parents about vaccines that you might anticipate include: Vaccines cause autism Vaccines cause other developmental problems Vaccines overwhelm the immune system We give too many vaccines too soon Vaccine immunity in inferior and natural immunity is better The recommended vaccine schedule is manipulated by pharmaceutical companies to sell vaccine. The government and medical community are part of the conspiracy

Discussion: What can you say to address the concern that vaccines cause autism or other developmental problems?
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Small Group Discussion Guide Vaccine Safety Curriculum for Medical Residents
Cite the multiple epidemiologic studies that have shown no link between vaccines and autism. [http://www.cdc.gov/vaccinesafety/Concerns/Autism/Index.html] You can be very specific that MMR was not linked to autism in a large epidemiologic in Denmark comparing children who did and did not receive MMR. There was no difference in rates of autism. (Madsen et al, N Engl J Med 2002;347:1477) Similarly you can be very specific about the lack of a link between thimerosal and autism. Since thimerosal has been removed from pediatric vaccines in the California rates of autism have not changed. [Schechter et al, Arch Gen Psychiatry 2008;65:19-24) Cite the fact that autism is very heritable, more so than breast cancer.

What can you say to address the concern that vaccine overwhelm the immune system? No evidence that children get more infections in the period after they are immunized Your immune system responds to thousands of antigens every day Vaccine are more pure today than 20 years ago so even though we give more vaccines children are exposed to fewer antigens. What can you say to address the concern that we give too many vaccines too soon? We give vaccines as soon as we can in order to protect infants from diseases when they are most vulnerable Infants are the most susceptible to severe outcomes from infections because their organs are still developing Infants spend many hours per day in very close contact with others-a situation that leads to transmission of things like pertussis from family members to infants What can you say to address the concern that natural immunity is better? Acknowledge that for some diseases that is true (e.g. varicella) But also point out that natural immunity isnt better for other diseases (e.g. pneumococcus) for which the vaccine contains multiple serotypes. Natural infection only protects against the one serotype you happen to get Remind parents that natural immunity comes at a price-deafness, brain damage, death as a result of the disease. You are rolling the dice that your child will not be one of the ones who suffers severely from a vaccine preventable disease

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Small Group Discussion Guide Vaccine Safety Curriculum for Medical Residents
What can you say to address the concern that the vaccine schedule is a money-fueled conspiracy? Remind parents that the schedule is developed and endorsed by physicians and public health officials, not the companies Challenge them by saying, Do you really think all the pediatricians in the country are conspiring to promote a schedule that we dont think is safe and the best for children? Challenge them by saying, Do you really think I would recommend something that I didnt think was best for your child? Question 2: Where do parents with concerns about vaccines get their information? Answer: Likely sources include web sites (mostly anti-vaccine), blogs, television, popular magazines, playground discussions, relatives Exercise: Type Vaccines into Google and review the first 20 sites quickly. How many could be classified as anti-vaccine sites. Read and discuss some of the theories put forth on these sites. Discussion: How can you point out in a respectful way that the information parents are reading is not scientifically based and is incorrect? Point out some of the inconsistencies you find on these sites Ask them why they are taking medical advice from an celebrity, friend, relative, magazine instead of from their childs doctor Emphasize the lack of scientific studies and reiterate the basic tenet of science-an observation needs to be repeated by independent groups before we can really have confidence that it is correct. None of the claims about serious problems from vaccines have been reproduced.

What are the characteristics of a web site, specific article, or author that gives it/their credibility? The source of the information is reliable/stable (e.g. American Academy of Pediatrics, World Health Organization, National Library of Medicine, NIH) The individuals/groups posting the information are identified and provide contact information?

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Small Group Discussion Guide Vaccine Safety Curriculum for Medical Residents
People with a scientific/medical background contribute the material or at least review it The information is dated and current-vaccine science changes quickly The scientific evidence is referenced with a citation, not just statements like studies show or it has been shown that... There is no obvious conflict of interest (e.g. selling a book) The site doesnt rely on anecdotes (e.g. My child got a vaccine and then got XXX) The purpose of the site is to provide accurate information. The purpose is not to sell something

Where can parents find credible information about vaccine safety, especially information about autism? NNII (www.immunizationinfo.org) VEC (www.vaccine.chop.edu) IAC (www.immunize.org) CDC/NIP (www.cdc.gov/nip) AAP (www.aap.org) AAFP (www.aafp.org/) IVS (www.vaccinesafety.edu) Vaccine Page (www.vaccines.org) Every Child by Two (www.ecbt.org) Exercise: Go to http://www.immunizationinfo.org/ and find the section on Evaluating Information About Vaccines on the Internet in the Immunization Issues section Question 3: Why is the Sears schedule unnecessary and what are the risks of seeking natural immunity? Answer: The Sears schedule is unnecessary because it is based on the premise that spreading out vaccines will avoid vaccine ingredients that are not linked to adverse outcomes (e.g. aluminum and autism). So you are taking steps to avoid something for no good reason. Discussion: What is wrong with following a delayed vaccine schedule like the Sears schedule? Following a delayed vaccine schedule does just that-it delays protection. Challenge the parent by saying, You dont delay putting your baby in a car seat, why do you want to delay protection from

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Small Group Discussion Guide Vaccine Safety Curriculum for Medical Residents
vaccines? Children remain susceptible to the disease that we can prevent through immunization. Some of them get them and suffer. Recent examples include the 5 Hib cases in Minnesota and published in 2009 (MMWR 2009;58:58-60) or [cite any recent local experiences here] Susceptible children contribute to outbreaks of disease Missed opportunities to immunize often stay missed and these children never get fully immunized. Sears schedule is wrong because it is untested with regard as to whether there is interference between vaccines that are given together in his schedule and not in the recommended one. Concomitant use studies must be done by Pharmaceutical companies before vaccines can be given together in patients to assure one vaccine does not inhibit the response of another. The Sears schedule ignores this possibility and could lead to impaired antibody responses in some cases.

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Small Group Discussion Guide Vaccine Safety Curriculum for Medical Residents
Case #2: Parents seeking a waiver for their 4-year old to enter preschool.
Learning Objectives: a) Describe what the school entry requirements are in your state b) Clearly describe the strengths and weaknesses of herd immunity. c) Concisely convey the risk/benefit ratio of deferring vaccines when vaccine-preventable diseases are still present in many communities. d) Allay parental concerns about common minor reactions to vaccines.

Case Presentation: Both parents come in, without their 4-year old child, to request that you sign a waiver of vaccination they need in order to enroll their child at a new preschool. The child has received some vaccines, but the parents have selectively refused certain immunizations, mainly the live-virus vaccines (MMR, Varicella, and Rotavirus). They have general concerns about vaccine safety including the concern that vaccines causing autism and about reactions their child has had to vaccines in the past. Question 1: What are the school entry requirements in your state? Can parents avoid immunizations required for school entry on the basis of a religious exemption? How does their religious exemption need to be documented? Can parents avoid immunizations required for school entry on the basis of a personal belief exemption? How does that need to be documented? Do all states allow exemptions from school entry requirements? Answer: Some states only allow medical exemptions. A minority allow exemption based on personal belief. What is the impact of exemptions from school entry requirements? Answer: Children who are exempted from vaccines have an 2-17-fold encreased risk of developing pertussis.[Feikin, JAMA, 2001;284:3145] Question 2: Why it is important for young children enrolled in childcare and school to be vaccinated? Answer: Herd immunity is crucial to prevent outbreaks of disease. Once immunization coverage levels drop below a threshold (e.g. 90% for measles) outbreaks of disease predictably occur. Outbreaks involve not only unimmunized children but immunized ones as well. This occurs because no vaccine is 100% effective so once an outbreak gets started even immunized

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Small Group Discussion Guide Vaccine Safety Curriculum for Medical Residents
(but still susceptible) children develop disease. Discussion: How can you convey the concept of herd immunity? Walk through a scenario where a child with measles is placed in a fully immunized classroom compared to one with a 30% exemption rate. Talk about the likelihood that unimmunized children will come in contact with the index case. Talk about how once an outbreak gets started, even immunized children can become infected since MMR vaccine is <100% effective. Talk about the amplification of an outbreak and spread outside of the classroom (playgrounds, sports teams, swim lessons). What level of herd immunity is adequate to prevent outbreaks? Depends on the specific disease. For measles immunization rates need to be >90% to prevent outbreaks (Hethcote HW. Am J Epidemiol. 1983;117(1):213) For pertussis the rate is probably similar to that required to prevent outbreaks of measles. What are some examples of what happens when herd immunity slips below an adequate level? Ongoing outbreaks of measles in UK, Switzerland other European countries Measles outbreak in San Diego in a school with very high exemption rates [Sugerman, Pediatrics 2010;125:747-755] Question 3: How can you convey to parents that by leaving their children unimmunized they are exposing them to greater risk than if they were immunized? Answer: It is important to simply and clearly convey the concept of risk/benefit. You need to make the risk of vaccine preventable diseases real. You need to convey just how rare any serious side effects are from vaccines. Discussion: How can you make disease risk real to parents? Discuss recent cases of vaccine preventable disease in your community (deaths, severe outcomes, recent large outbreaks). Discuss your personal experience with vaccine preventable diseases. How many cases of pneumococcal pneumonia or bacteremia have you seen? How many cases of severe vaccine side effects have you seen?

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Small Group Discussion Guide Vaccine Safety Curriculum for Medical Residents
Paint the visual picture for how rare something is that occurs in 1:100,000. How can you convey the safety of vaccines? Describe how we know vaccines are safe. Talk about the Vaccine Safety Datalink [Baggs J, The Vaccine Safety Datalink: a model for monitoring immunization safety. Pediatrics 2011;127 Suppl 1: S45-S53; http://www.cdc.gov/vaccinesafety/Activities/VSD.html] Describe how many children have received MMR, hepatitis B, or whatever vaccine around the world over as many as 50 years!

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Small Group Discussion Guide Vaccine Safety Curriculum for Medical Residents
Case #3: Mother refusing HPV vaccination for her adolescent daughter.
Learning Objectives: a) Address parental and patient concerns about real safety concerns. b) Discuss vaccine safety topics in short and concise conversations. c) Clearly describe general testing and monitoring systems that ensure the safety of vaccines. Case Presentation: You are performing a physical for a 13-year old female to participate in cheerleading. The patient is accompanied by her mother today. The girl appears healthy and reports not participating in any high-risk behaviors such as substance abuse or sexual activity. The girl is up-to-date on all immunizations except HPV. The mother states she has heard the vaccine is unsafe and contains dangerous ingredients. She also has moral issues with the vaccine since it protects against an STD and will not allow her daughter to receive HPV vaccine until she is much older. Question 1: How can you convey the importance of HPV vaccine? Answer: Point out how common HPV infection is and that once someone is infected nothing can be done to eliminate the infection. A subset of infected people will go on to develop cancer from their HPV infection (MMWR, 2007; 56(RR02):1-24). Discussion: Discuss the fact that more than 3000 women die every year from HPVrelated cervical cancer. Point out that HPV infection usually occurs within a few years of sexual debut. Challenge the parents by asking Did you parents know when you started being sexually active? Review with parents that we immunize at a young age to make sure adolescents are protected before they become sexually active. Question 2: How can you concisely explain the testing and monitoring process for vaccines. Answer: Describe how vaccines are tested for safety including new electronic medical record based systems that allow much larger groups to be studied than before. Discussion: Discuss the clinical trial and FDA approval process. Vaccines are tested in thousands of individuals and in combination with other vaccines prior to licensure. Rigorous standards for both efficacy and safety need to be met before a vaccine can be licensed.

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Small Group Discussion Guide Vaccine Safety Curriculum for Medical Residents

Talk about post-licensure studies such as those conducted by the Vaccine Safety Datalink (Baggs J, The Vaccine Safety Datalink: a model for monitoring immunization safety. Pediatrics 2011;127 Suppl 1: S45-S53; http://www.cdc.gov/vaccinesafety/Activities/VSD.html). No clinical trial can detect rare adverse events (events with frequencies less than 1:2000-10,000). We now have robust postmarketing surveillance systems that take advantage of electronic medical records to scan large numbers of people for rare adverse events. As an example after the use of pandemic H1N1 influenza vaccine in 2009-2010, the medical records of more than 10 million vaccine recipients were evaluated for rare side effects.

Describe how many people have received MMR, hepatitis B, or whatever vaccine around the world over as many as 50 years! Billions of people have received some vaccines. If they clearly caused a significant side effect, we would know about it.

Question 3: What should you do in your clinic to ensure the patients safety? Answer: Standard immunization delivery includes precautions to avoid immediate adverse events such as syncope. Discussion: Syncopal reactions may occur in as many as 76% of adolescents receiving HPV vaccine. Vaccine providers, particularly when vaccinating adolescents, should consider observing patients for 15 minutes after vaccination to decrease risk for injury should they faint. (MMWR 2008;57:457-60) Patients should be observed seated or lying down to reduce the chance of a fall. More serious systemic reactions, such as anaphylactic reactions, are rare, especially following IPV immunization. Clinics should be equipped to manage them and have oxygn and epinephrine available should anaphylaxis occur. Question 4: Patients and parents cope with adverse reactions following vaccines if they are informed about what the patient might expect in the days following injection. What should you tell this patient and mother about what to anticipate in one to five days post vaccine?

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Small Group Discussion Guide Vaccine Safety Curriculum for Medical Residents
Answer: Mild to moderate pain (35-45%), swelling (6-8%) and redness (7-9%) at the injection site are seen following IPV vaccine in males and somewhat more often in females (61-63%, 10-15%, and 9-15% respectively.)

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Small Group Discussion Guide Vaccine Safety Curriculum for Medical Residents
Case #4: Immunizations for immunosuppressed patients (child & adult versions)

Learning Objectives: a) Clearly describe why live-virus vaccines should generally be avoided in immunosuppressed patients, but other vaccines are safe and recommended. b) Concisely explain the safety of household contacts receiving livevirus vaccines. c) Clearly convey the importance of cocooning an immunosuppressed patient. d) Describe the risk/benefit ratio of receiving vaccines when immunosuppressed. Case Presentation (child): A 5-year old child is accompanied by his parents for a routine check-up following treatment for ALL. He was diagnosed at 3 years of age and successfully completed chemotherapy 30 days ago. The family has survived a harrowing struggle and wants to make sure their son is healthy and safe in the future. As you talk about the effects of the chemotherapy and returning to a normal life, you introduce the topic of the child receiving vaccines. The parents have concerns about the safety of an immunosuppressed child and the people around that child getting vaccines because they are afraid the vaccines will make the child sick because of his weak immune system. Case Presentation (adult): A 43-year old patient is being seen today for a routine check-up following a lumpectomy. Stage II breast cancer was removed 3 months prior with no complications and the patient is currently undergoing radiation therapy. As you talk about the effects of the radiation and returning to a normal life, you introduce the topic of vaccines. The patient has concerns about the safety of an immunosuppressed person, and contacts, getting vaccines because she is afraid the vaccines will make her sick because of her weak immune system. Question 1: Why are some vaccines safe and others arent for immunosuppressed patients? Answer: Some vaccine are live-attenuated vaccines that can replicate and potentially cause disease in immunosuppressed individuals (CDC General Recommendations on Immunization, MMWR 2011;60:1-60) Discussion: Which vaccines are live attenuated vaccines?

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Small Group Discussion Guide Vaccine Safety Curriculum for Medical Residents
MMR Varicella vaccine Zoster vaccine LAIV Yellow fever vaccine Rotavirus vaccine (selected patients)

Question 2: Is it safe for household contacts to receive live vaccines? Answer: Yes, all of the live vaccines except oral polio vaccine (no longer used in the U.S.) can be given to household contacts of immunosuppressed patients. The Centers for Disease Control monitors the use of live vaccines among high risk populations to ensure that such events are identified. There is no evidence that household transmission from household contacts has resulted in severe infection among the immunocompromised member of the household. Discussion: What are the recommendations for use of LAIV (nasal infleuza vaccine) in household contacts of immunosuppressed patients? The only restrictions for use of LAIV in contacts of immunosuppressed patients are for severely suppressed individuals (e.g. bone-marrow transplant patients in a protected environment (MMWR, 2010;59(rr08):1-62). Can healthcare workers who work with oncology patients receive LAIV? Yes, healthcare workers who work with general oncology patients (see restriction for bone marrow transplant patients), ICU patients, NICU patients, and HIV-infected patients can receive LAIV (MMWR, 2010;59(rr08):1-62). Are there any published reports of a healthcare worker receiving LAIV, transmitting to a patient, and making them ill? No, there are no published examples of such transmission (MMWR, 2010;59(rr08):1-62). Can healthcare workers receive varicella or zoster vaccine and still work? Yes, however rarely recipients of these vaccine develop a rash after vaccination (typically 1-2 weeks after vaccination). These rashes may contain live vaccine virus and thus individuals with rash may be contagious and should take appropriate precautions.

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Small Group Discussion Guide Vaccine Safety Curriculum for Medical Residents
Question 3: What are the risks involved when immunosuppressed patients receive vaccines? Answer: Live attenuated vaccines can cause disease similar to the natural infection. Discussion: What might happen if an HIV-infected patient with a CD4 count of 100 was given MMR vaccine? Cases of measles have occurred in severely suppressed individuals immunized with MMR vaccine. Therefore, these children must receive immunoglobulin after any exposure to measles disease because they are susceptible to measles and could develop severe and potentially fatal infection. Similarly, immunosuppressed individuals that receive varicella vaccine can develop varicella disease. Fortunately these cases can be treated with acyclovir since the vaccine strain of VZV is susceptible to antiviral medications. Can a patient on steroids for rheumatoid arthritis receive zoster vaccine? Persons with impaired humoral immunity may be vaccinated. No data have been published concerning whether persons without evidence of immunity receiving only inhaled, nasal, or topical doses of steroids can be vaccinated safely. However, clinical experience suggests that vaccination is well-tolerated among these persons. Persons without evidence of immunity who are receiving systemic steroids for certain conditions (e.g., asthma) and who are not otherwise immunocompromised may be vaccinated if they are receiving <2 mg/kg of body weight or a total of <20 mg/day of prednisone or its equivalent. Certain experts suggest withholding steroids for 2--3 weeks after vaccination if it can be done safely (MMWR, 1996;45(RR11):1-25). Persons who are receiving high doses of systemic steroids (i.e., >2 mg/kg prednisone) for >2 weeks may be vaccinated once steroid therapy has been discontinued for >1 month, in accordance with the general recommendations for the use of live-virus vaccines (MMWR 2011;60:1-60). Vaccination of leukemic children who are in remission and who do not have evidence of immunity to varicella should be undertaken only with expert guidance and with the availability of antiviral therapy should complications ensue. Patients with leukemia, lymphoma, or other malignancies whose disease is in remission and whose chemotherapy has been terminated for at least 3 months can receive live-virus vaccines. When immunizing persons in whom some degree of immunodeficiency might be present, only single-antigen varicella vaccine should be used.

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Small Group Discussion Guide Vaccine Safety Curriculum for Medical Residents
Case #5: Immunizations for pregnant women
Learning Objectives: a) Clearly describe what is known about the safety of administering vaccines during pregnancy. b) Define the risks of complications from diseases and the benefit of receiving vaccines during pregnancy. c) Clearly convey the importance of cocooning infants. d) Explain the importance and safety of vaccine ingredients. Case Presentation: A 20-year old pregnant woman complains of mild congestion. She is 20 weeks pregnant and not taking any medications. She is single and lives with her parents and younger brother. After examining her and discussing her current complaint, you review her chart and notice she is missing Tdap and influenza vaccines. When you suggest she be vaccinated she expresses concerns about receiving vaccine during pregnancy. Question 1: How can you describe the risk/benefit ratio of vaccinating during pregnancy when there is limited data to support it? Answer: Although in general it is best to avoid medications and immunizations during pregnancy, there are certain diseases to which pregnant women are more susceptible than non-pregnant women of the same age. There is actually quite a bit of experience with use of some vaccines during pregnancy (e.g. influenza vaccine, Td vaccine) even though in many cases they have not been studied in clinical trials. Women should discuss the benefits and the potential risks of each vaccine when considering immunization during pregnancy. Discussion: What vaccines are specifically recommended during pregnancy? Influenza vaccine and Tdap; others (e.g. hepatitis B vaccine) should be considered if otherwise indicated. Influenza disease is more severe in pregnant women and maternal immunization not only protects the pregnant woman but also confers immunity to the infant (Louie JK et al. ,N Engl J Med 2009;362:27-35; Zaman K, N Engl J Med 2008;359:15551564; Eick A, et al. , Arch Pediatr Adolesc Med 2010;165(2): E1-E8). No unusual adverse events associated with influenza vaccine during pregnancy have been reported to the VAERS system (Moro P, Broder KR et al. , American Journal of Obstetrics and Gynecology 2011;204(2):146.e1-e7).

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Small Group Discussion Guide Vaccine Safety Curriculum for Medical Residents
What vaccines are contraindicated during pregnancy? MMR, varicella, LAIV, zoster. These are live virus vaccines and thus pose a theoretical risk of infecting the fetus. However it is important to note that there have been no published reports of MMR, Varicella, LAIV, or zoster vaccine leading to infection of the fetus and no adverse fetal outcomes have been reported. Have any vaccines been shown to harm the fetus? No. Obviously many women are inadvertently immunized while pregnant, in many cases before they know they are pregnant. This has been happening for more than 40 years with MMR vaccine and no adverse fetal outcomes have ever been reported. Similarly influenza vaccine has been recommended for pregnant women for many years now and there are no reports of adverse fetal outcomes related to influenza vaccine. Can we infer anything from the lack of reports of adverse events during pregnancy in the VAERS system? The VAERS system serves to identify possible vaccine adverse events. Since it is a passive reporting system one cannot interpret a lack of reports as an indication that no adverse events have occurred. However, VAERS does usually identify adverse events well.

Question 2: What is the purpose of vaccine ingredients and how do we know they are safe? Answer: Each ingredient is there to preserve vaccine potency or sterility or enhance the immune response. Discussion: What is thimerosal and why is it in vaccines? What do we know about its toxicity? Thimerosal is a mercury-based preservative that has been in vaccines for decades. There is no known toxicity related to thimerosal exposure as a result of immunization. Thimerosal has been voluntarily removed from most vaccines based on theoretical concerns rather than based on any demonstrated toxicity. What is alum and why is it in vaccines? Alum is an aluminum-based adjuvant that has been in vaccines for decades. Without alum, many vaccines would not induce an adequate immune response. There is no known toxicity related to alum exposure through immunization.

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Small Group Discussion Guide Vaccine Safety Curriculum for Medical Residents
What are squalene-based vaccine adjuvants? Squalene is a naturally occurring organic compound (produced by plants, fish and other animals (including humans) that is used as a component of some vaccine adjuvants. As with aluminum and thimerasol, there has been no toxicity demonstrated as a result of exposure to squalene. It has been a component of influenza vaccines in Europe since 1997. To which vaccine ingredients are pregnant women exposed from other sources? Pregnant women are exposed to many of the ingredients in vaccines through interaction with their routine environment. For example consuming seafood (especially tuna) results in more exposure to mercury than does immunization. Aluminum is ubiquitous in the environment.

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Small Group Discussion Guide Vaccine Safety Curriculum for Medical Residents
Case #6: Hospital healthcare worker refusing Tdap and Influenza vaccine

Learning Objectives: a) Clearly explain how vaccines cannot cause disease in a healthy adult. b) Allay concerns of common minor reactions to vaccines. c) Address the social responsibility of healthcare workers to protect their patients against disease through vaccination. d) Effectively address an individuals personal right to refuse vaccination. Case Presentation: A healthy 43 yo male is in your office because of a minor work injury. He is a healthcare worker employed at a long-term care facility. The laceration on his forearm requires wound management prophylaxis with Tdap. You also suggest he gets a flu vaccine while hes in the office, but he refuses because he says the flu shot gave him the flu a few years ago. Question 1: Why do healthcare personnel think that the flu shot gives them the flu? Can it? Answer: Myalgia and fever can occur after influenza vaccine, particularly the first time someone is immunized. In addition many people dont really know what the symptoms of influenza are and misinterpret symptoms related to other viral infections (e.g. gastrointestinal disturbances, rhinorhea) as being from their influenza vaccine (LaVela SI et al, Infect Control Hosp Epidemiol 2004;25:933-40; Mah MW et al, Am J Infect Control 2005:33:24350). Discussion: What is the frequency of myalgia and fever following influenza vaccine? Does the frequency decrease with subsequent doses? In placebo-controlled studies among adults, the most frequent side effect of vaccination was soreness at the vaccination site (affecting 10%--64% of patients) that lasted <2 days. These local reactions typically were mild and rarely interfered with the recipients' ability to conduct usual daily activities. Placebo-controlled trials demonstrated that among older persons and healthy young adults, administration of TIV is not associated with higher rates for systemic symptoms (e.g., fever, malaise, myalgia, and headache) when compared with placebo injections. Among adults vaccinated in consecutive years, reaction frequencies declined in the second year of vaccination. In clinical trials, serious adverse events were reported to occur after vaccination with

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Small Group Discussion Guide Vaccine Safety Curriculum for Medical Residents
TIV at a rate of <1%. The potential association between TIV and GBS has been an area of ongoing research (see Guillain-Barr Syndrome and TIV). No elevated risk for prespecified events after TIV was identified among 4,773,956 adults in a VSD analysis (MMWR 2010; 59(rr08):1-62) http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5908a1.htm? s_cid=rr5908a1_e. Solicited injection-site reactions and systemic adverse events among persons aged 65 years were more frequent after vaccination with a vaccine containing 180 mcg of HA antigen (Fluzone High-Dose, sanofi pasteur) compared with a standard dose (45 mcg) (Fluzone, Sanofi pasteur vaccines) but were typically mild and transient. In the largest study, 915 (36%) of 2,572 persons who received Fluzone High-Dose reported injection-site pain, compared with 306 (24%) of the 1,260 subjects who received Fluzone. The pain was of mild intensity and resolved within 3 days in the majority of subjects. Among Fluzone High Dose recipients, 1.1% reported moderate to severe fever; this was substantially higher than the 0.3% of Fluzone recipients who reported this systemic adverse event). During the 6-month follow-up period, SAEs were reported in 6% of the High-Dose recipients and 7% of the Fluzone recipients (MMWR 2010; 59(rr08):1-62) http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5908a1.htm? s_cid=rr5908a1_e. What symptoms can LAIV cause? LAIV, unlike the injectable flu vaccine, can cause runny nose or sore throat. Low-grade fever is another occasional adverse event associated with LAIV. Among adults, runny nose or nasal congestion (28%--78%), headache (16%--44%), and sore throat (15%--27%) have been reported more often among vaccine recipients than placebo recipients (346,360Should this be the MMWR reference, for simplicity?). In one clinical trial among a subset of healthy adults aged 18--49 years, signs and symptoms reported significantly more often (p<0.05) among LAIV recipients (n = 2,548) than placebo recipients (n = 1,290) within 7 days after each dose included cough (14% and 11%, respectively), runny nose (45% and 27%, respectively), sore throat (28% and 17%, respectively), chills (9% and 6%, respectively), and tiredness/weakness (26% and 22%, respectively) (MMWR 2010; 59(rr08):1-62). http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5908a1.htm? s_cid=rr5908a1_e

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Small Group Discussion Guide Vaccine Safety Curriculum for Medical Residents
What are some common reasons healthcare personnel give for not getting a flu vaccine? Healthcare personnel claim: The flu vaccine made me sick I never get sick so I dont need a flu shot Im not in a group recommended to get a flu shot The flu vaccine doesnt work Add in other reasons from your own experience.. None of these are valid reasons to avoid immunization. Question 2: Why is it especially important that healthcare workers receive vaccines? Answer: Duh, they give their patients the flu! And they are potentially at higher risk for contracting influenza due to contact with ill patients (Potter J et al, J Infect Dis 1997;175:1-6). Discussion: Why do HCP give their patients influenza? Unimmunized HCP are susceptible to influenza and are exposed to influenza in their workplace HCP still come to work when they are ill and as a result transmit infections to patients Individuals with influenza are contagious up to 24 hours before they have symptoms and thus unknowingly spread infection before they know they are sick. HCP do not wash their hands frequently enough to control nosocomial infections What percent of healthcare personnel receive an influenza vaccine every year? In 2009 (the year of H1N1 vaccination) only 60% of HCP received any type of influenza vaccine (MMWR 2010;59(12):357-362). http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5912a1.htm? s_cid=mm5912a1_e%0d%0a Question 3: Should we mandate HCP influenza vaccination? Answer: Many hospitals have turned to mandatory policies because voluntary programs have not been successful in achieving adequate HCP vaccination rates. (Babcock HM, et al. 2010, Clinical Infectious Disease 2010;50:459-64) Discussion: What vaccines are already mandated for HCP? Most HCP are already required to be immunized with MMR, hepatitis B,
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and varicella vaccines if not already immune. What about people with medical or religious reasons not to get vaccinated? Exemptions to influenza vaccination mandates should be allowed only for medical contraindications to vaccination, specifically allergy to eggs and prior allergic or severe adverse reactions to influenza vaccine. Most religions do not prohibit vaccination. What about HCP who request a personal belief or philosophical exemption to influenza vaccination, eg, for those who do not believe in the need for influenza vaccination or for those who are opposed to the concept of mandatory vaccination? Personal belief or philosophical exemptions should not be allowed. The allowance of personal belief exemptions for schoolentry vaccination requirements has been associated with an increased risk of the acquisition and transmission of vaccinepreventable diseases. Although a few facilities and systems have been successful in achieving high vaccination rates in the setting of personal belief exemptions, allowance of personal belief exemptions runs counter to the concept that HCP influenza vaccination is a core patient safety intervention from which the HCP cannot merely opt out, particularly given the known safety and efficacy of influenza vaccination. http://www.jstor.org/stable/10.1086/656558 Wont vaccine mandates be overturned by the courts or labor relations boards? No, influenza vaccine mandates for HCP have been in place in some large institutions in the U.S. since 2006 and have withstood legal challenge. In many case some accommodation has been required for HCP who wont be immunized (e.g. allowing them to wear a mask all day long while working) but the fundamental policies have been upheld.

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Small Group Discussion Guide Vaccine Safety Curriculum for Medical Residents
Case #7: Senior refusing vaccines

Learning Objectives: a) Clearly describe general testing and monitoring systems that ensure the safety of vaccines. b) Define the risks of complications from diseases and the benefit of receiving vaccines. c) Clearly explain how vaccines cannot cause disease in a healthy adult. d) Discuss vaccine safety topics in short and concise conversations. Case Presentation: A 66-year old woman is being seen today for a follow-up visit for new blood pressure medications that were started 30 days ago. When you suggest she receive influenza, pneumococcal and zoster vaccines, she states she does not want them. She has concerns about their safety and begins to tell you a number of stories about acquaintances who have experienced various problems with vaccines. Question 1: How do you know vaccines are safe? Answer: Describe the basic elements of vaccine safety monitoring. Discussion: Discuss the clinical trial and FDA approval process. Vaccines are tested in thousands of individuals and in combination with other vaccines prior to licensure. Rigorous standards for both efficacy and safety need to be met before a vaccine can be licensed. No clinical trial can detect rare adverse events (events with frequencies less than 1:2000-10,000). We now have robust postmarketing surveillance systems that take advantage of electronic medical records to scan large numbers of people for rare adverse events. As an example after the use of pandemic H1N1 influenza vaccine in 2009-2010, the medical records of more than 10 million vaccine recipients were evaluated for rare side effects. Talk about post-licensure studies such as those conducted by the Vaccine Safety Datalink (http://www.cdc.gov/vaccinesafety/Activities/VSD.html) [Baggs J, Pediatrics 2011; 127 No. Supplement 1:S45 -S53] The Vaccine Safety Datalink (VSD) project is a collaborative project between the Centers for Disease Control and Prevention and 8 managed care organizations (MCOs) in the United States. Established in 1990 to conduct

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Small Group Discussion Guide Vaccine Safety Curriculum for Medical Residents
postmarketing evaluations of vaccine safety, the project has created an infrastructure that allows for high-quality research and surveillance. The 8 participating MCOs comprise a large population of 8.8 million members annually (3% of the US population), which enables researchers to conduct studies that assess adverse events after immunization. Each MCO prepares computerized data files by using a standardized data dictionary containing demographic and medical information on its members, such as age and gender, health plan enrollment, vaccinations, hospitalizations, outpatient clinic visits, emergency department visits, urgent care visits, and mortality data, as well as additional birth information (eg, birth weight) when available. Other information sources, such as medical chart review, member surveys, and pharmacy, laboratory, and radiology data, are often used in VSD studies to validate outcomes and vaccination data. Since 2000, the VSD has undergone significant changes including an increase in the number of participating MCOs and enrolled population, changes in data-collection procedures, the creation of near real-time data files, and the development of near real-time postmarketing surveillance for newly licensed vaccines or changes in vaccine recommendations. Recognized as an important resource in vaccine safety, the VSD is working toward increasing transparency through data-sharing and external input. With its recent enhancements, the VSD provides scientific expertise, continues to develop innovative approaches for vaccine-safety research, and may serve as a model for other patient safety collaborative research projects. Describe how many people have received MMR, hepatitis B, or whatever vaccine around the world over as many as 50 years! Billions of people have received some vaccines. If they clearly caused a significant side effect, we would know about it

Question 2: If vaccines arent as efficacious in seniors, why should they get vaccinated? Answer: Some protection is better than none. Discussion: What is the efficacy of influenza vaccine in seniors? Point out that influenza vaccine, although not perfect, still decreases the severity of influenza in most people. Influenza vaccine efficacy declines with age. The only randomized controlled trial among community-dwelling persons aged 60 years reported a vaccine efficacy of 58% (95% CI = 26%--77%) against laboratory-confirmed influenza illness during a season when the vaccine strains were considered to be well-matched to circulating strains (Govaert TM, JAMA 1994:272:1661Page 23 of 26

Small Group Discussion Guide Vaccine Safety Curriculum for Medical Residents
5). Additional information from this trial published separately indicated that efficacy among those aged 70 years was 57% (95% CI = -36%--87%), similar to younger persons. However, few persons aged >75 years participated in this study, and the wide confidence interval for the estimate of efficacy among participants aged 70 years could not exclude no effect (i.e., included 0) (Thijs C, Lancet Infect Dis 2008;8:460-1). Influenza vaccine effectiveness in preventing MAARI among the elderly in nursing homes has been estimated at 20%--40%, and reported outbreaks among wellvaccinated nursing home populations have suggested that vaccination might not have any significant effectiveness when circulating strains are drifted from vaccine strains (MMWR 2010; 59(rr08):1-62). http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5908a1.htm? s_cid=rr5908a1_ What is the risk of serious illness from influenza in seniors? Emphasize the risk as you discuss the value of inluenza vaccine with seniors.

Hospitalization rates during typical influenza seasons are substantially increased for persons aged 65 years compared with younger age groups. One retrospective analysis based on data from managed-care organizations collected during 1996--2000 estimated that the risk during influenza season among persons aged 65 years with underlying conditions that put them at risk for influenza-related complications (i.e., one or more of the conditions listed as indications for vaccination) was approximately 560 influenzaassociated hospitalizations per 100,000 persons compared with approximately 190 per 100,000 healthy persons aged 65 years. Persons aged 50--64 years who have underlying medical conditions also were at substantially increased risk for hospitalizations during influenza season compared with healthy adults aged 50--64 years (MMWR 2010; 59(rr08):162) http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5908a1.htm? s_cid=rr5908a1_e. What is the efficacy of zoster vaccine? Emphasize the severity of zoster and that a greater than 50% reduction in the chance that you will get zoster is significant.

The vaccine reduced the risk for developing zoster by 51.3% (95% CI = 44.2--57.6; p<0.001. The vaccine was 66.5% (95% CI = 47.5--79.2; p<0.001) efficacious for preventing PHN. When the definition of PHN was changed from 30 days of pain to 182 days of pain following rash onset, vaccine efficacy increased from 58.9% to 72.9%. Zoster vaccine had an independent effect of reducing PHN among patients who developed zoster (39% [95% CI = 7%-59%]). The mean severity-by-duration of zoster was reduced by 57% (p = 0.016) in vaccine recipients who developed PHN. (MMWR 2008;57(05);1-30).
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Small Group Discussion Guide Vaccine Safety Curriculum for Medical Residents
These findings were recently reproduced in a large observational study of 75,800 vaccinees (Tseng , JAMA 2011 ; ). In this study vaccine effectiveness at preventing zoster was 55% and effectiveness at preventing zoster-linked hospitalization was 65%. http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5705a1.htm? s_cid=rr5705a1_e. Question 3: How can you address other concerns seniors might have about immunization? What can you say to address the concern that the vaccine schedule is a money-fueled conspiracy? Remind patients that immunization recommendations are developed and endorsed by physicians and public health officials, not the companies Challenge them by saying, Do you really think all the physicians in the country are conspiring to promote a schedule that we dont think is safe and the best for you? Question 4: Where do people with concerns about vaccines get their information? Answer: Likely sources include Web sites (mostly anti-vaccine), blogs, television, popular magazines, community discussions and relatives Exercise: Type Vaccines into Google and review the first 20 sites quickly. How many could be classified as anti-vaccine sites. Read and discuss some of the theories put forth on these sites. Discussion: How can you point out in a respectful way that the information they are reading is not scientifically based and is incorrect? Ask them why they are taking medical advice from an celebrity, friend, relative or magazine instead of from their childs doctor Point out some of the inconsistencies you find on these sites Emphasize the lack of scientific studies and reiterate the basic tenet of science-an observation needs to be repeated by independent groups before we can really have confidence that it is correct. None of the claims about serious problems from vaccines has been reproduced. What are the characteristics of a Web site, specific article or author that

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Small Group Discussion Guide Vaccine Safety Curriculum for Medical Residents
gives it/them credibility? The source of the information is reliable/stable (e.g. American Academy of Pediatrics, World Health Organization, National Library of Medicine, NIH) The individuals/groups posting the information are identified and provide contact information? People with a scientific/medical background contribute the material or at least review it The information is dated and current - vaccine science changes quickly The scientific evidence is referenced with a citation, not just statements like studies show or it has been shown that.. There is no obvious conflict of interest (e.g. selling a book) The site doesnt rely on anecdotes (e.g. My child got a vaccine and then got XXX) The purpose of the site is to provide accurate information. The purpose is not to sell something Where can patients find credible information about vaccine safety, especially information about autism? NNII (www.immunizationinfo.org) VEC (www.vaccine.chop.edu) IAC (www.immunize.org) CDC/NIP (www.cdc.gov/nip) AAP (www.aap.org) AAFP (www.aafp.org/) IVS (www.vaccinesafety.edu) Vaccine Page (www.vaccines.org) Every Child by Two (www.ecbt.org)

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