Immunizations. Update Immunizations through Time. Learning Objectives. Presenter Disclosure Information. 10:30 11:45am. Immunization Update

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1 10:30 11:45am Immunization Update SPEAKER John Russell, MD Presenter Disclosure Information The following relationships exist related to this presentation: John Russell, MD, serves on Speaker s Bureau Sanofi Pasteur. He also serves on Advisory Panel for Takeda and Valeant Pharmaceuticals. Off-Label/Investigational Discussion In accordance with pmicme policy, faculty have been asked to disclose discussion of unlabeled or unapproved use(s) of drugs or devices during the course of their presentations. Learning Objectives Immunization Update 2015 John Russell, M.D. Family Medicine Program Director Abington Memorial Hospital Clinical Professor of Family and Community Medicine Temple University School of Medicine Describe the new guidelines from the ACIP for the use of the conjugate pneumococcal vaccine Discuss changes to this year s influenza recommendations from the ACIP Review research on the use of high dose influenza vaccine Recognize the indications for the new meningococcal serotype B vaccine Immunizations through Time Immunizations through Time 1881 Anthrax vaccine 1894 First Polio Cases in US 1900 Walter Reed s team discovers cause of yellow fever 1921 Franklin Roosevelt develops polio 1925 race to get diptheria antitoxin to Nome inspires Iditatrod 1936 yellow fever vaccine developed 1939 pertussis vaccine developed 1945 influenza vaccine developed 1948 DPT developed 1953 Salk tests polio vaccine on himself and his family (1955 vaccine released) 1960 Oral polio released (Sabin)

2 Immunizations through Time 1963 Measles Vaccine licensed 1964 ACIP begun 1969 Rubella vaccine licensed 1971 MMR released 1972 US routine smallpox vaccination ceases 1977 pneumococcal multi serotype released 1977 last case of smallpox in the world 1981 Hepatitis B vaccine released 1981 Chickenpox vaccine released 1985 Hib Vaccine released 1994 Polio eliminated in the Americas 1995 Hepatitis A vaccine released 2000 Endemic measles eliminated from US Immunizations through Time 2000 Pneumococcal conjugate vaccine for children 2005 Meningococcal conjugate vaccine released 2006 Universal hepatitis A vaccine for children 2006 Rotavirus vaccine released 2010 PCV13 replaces PCV7 MMR Recommendations Currently, ACIP recommends 2 doses of MMR vaccine routinely for children with the first dose administered at age 12 through 15 months and the second dose administered at age 4 through 6 years before school entry. Two doses are recommended for adults at high risk for exposure and transmission (e.g., students attending colleges or other post high school educational institutions, health care personnel, and international travelers) and 1 dose for other adults aged 18 years. For prevention of rubella, 1 dose of MMR vaccine is recommended for persons aged 12 months. Pneumococcal Vaccines MMWR 2011;60[No. RR 7]). Background Streptococcus pneumoniae (pneumococcus) remains a leading cause of serious illness, including bacteremia, meningitis, and pneumonia among adults in the United States. An estimated 4,000 deaths occur in the United States each year because of S. pneumoniae, primarily among adults. The incidence of invasive disease ranges from 3.8 per 100,000 among persons aged years to 36.4 per 100,000 among those aged 65 years. Adults with certain medical conditions also are at increased risk for invasive pneumococcal disease (IPD). For adults aged years with hematologic cancer, the rate of IPD in 2010 was 186 per 100,000, and for persons with human immunodeficiency virus (HIV) the rate was 173 per 100,000 (CDC, unpublished data, 2012). The disease rates for adults in these groups can be more than 20 times those for adults without high risk medical conditions. PCV13 Background PCV13 has been used for children since 2010, when it replaced an earlier version targeting seven serotypes (PCV7) that had been in use since The routine use of PCV7 in infants and young children resulted in significant reductions in IPD caused by vaccine serotypes in children, and because of indirect effects, also in adults. Rates of IPD caused by vaccine serotypes in adults aged years without HIV decreased from six cases to one case per 100,000 during However, even after indirect effects of the pediatric immunization had been realized fully, the incidence of IPD caused by the serotypes included in PCV7 remained high in HIV infected persons aged years at 64 cases per 100,000 persons with acquired immunodeficiency syndrome (AIDS). Moreover, 50% of IPD cases among immunocompromised adults in 2010 were caused by serotypes contained in PCV13; an additional 21% were caused by serotypes only contained in PPSV23 (CDC, unpublished data, 2011). MMWR October 12, 2012

3 ACIP Recommendations for PCV13 and PPSV23 Use Adults with specified immunocompromising conditions who are eligible for pneumococcal vaccine should be vaccinated with PCV13 during their next pneumococcal vaccination opportunity. PCV13 in Adults Pneumococcal vaccine naïve persons. ACIP recommends that adults aged 19 years with immunocompromising conditions, functional or anatomic asplenia, CSF leaks, or cochlear implants, and who have not previously received PCV13 or PPSV23, should receive a dose of PCV13 first, followed by a dose of PPSV23 at least 8 weeks later. Subsequent doses of PPSV23 should follow current PPSV23 recommendations for adults at high risk. Specifically, a second PPSV23 dose is recommended 5 years after the first PPSV23 dose for persons aged years with functional or anatomic asplenia and for persons with immunocompromising conditions. Additionally, those who received PPSV23 before age 65 years for any indication should receive another dose of the vaccine at age 65 years, or later if at least 5 years have elapsed since their previous PPSV23 dose. Previous vaccination with PPSV23. Adults aged 19 years with immunocompromising conditions, functional or anatomic asplenia, CSF leaks, or cochlear implants, who previously have received 1 doses of PPSV23 should be given a PCV13 dose 1 year after the last PPSV23 dose was received. For those who require additional doses of PPSV23, the first such dose should be given no sooner than 8 weeks after PCV13 and at least 5 years after the most recent dose of PPSV23. Risk Group Underlying Medical Condition PCV13 Immuocompetent CAD x Lung Disease PPSV23 Recommend Recommend Revaccinate after 5 yrs x Risk Group Underlying Medical Condition PCV13 PPSV23 Recommend Recommend Revaccinate after 5 yrs Immunocompromised Immunodeficiency x x x HIV x x x Splenic Dysfunction DM x CSF leak x x Cochlear Implant x x Cirrhosis x Smoking x Sickle Cell x x x Other x x x Hemoglobinopathy CRF x x x Nephrotic Syndrome x x x Leukemia x x x Lymphoma x x x Hodgkin Dz x x x Generalized x x x Malignancy Iatrogenic x x x Immunodeficiency Organ Transplant x x x Asplenic x x x Multiple Myeloma x x x MMWR. October 12, 2012 / 61(40); MMWR. October 12, 2012 / 61(40); FAQs Can PPSV23 and PCV13 be administered at the same office visit? No. If PCV13 is indicated, administer it if at least 1 year has passed since the previous dose of PPSV23 or if no doses of PPSV23 have previously been received. Then wait at least 8 weeks to administer PPSV23 if no previous doses of PPSV23 have been received. If a previous dose of PPSV23 has been received and there is an indication for the second PPSV23 dose before age 65, wait 5 years since the previous dose of PPSV23 to administer the next dose of PPSV23. Then administer a third dose of PPSV23 at or after 65 years if it has been 5 years since the previous dose. FAQs If an adult has already gotten one or more doses of PPSV23, when should they get PCV13, if indicated? If indicated, PCV13 should be administered at least 1 year after the previous dose of PPSV23 was received. For those who require additional doses of PPSV23, the first such dose should be given no sooner than 8 weeks after PCV13 and at least 5 years since the most recent dose of PPSV23.

4 Case 1 How many doses of PPSV23 can an adult get in a lifetime? Who/when? Some adults may be recommended to receive up to 3 doses of PPSV23 in a lifetime. Two doses of PPSV23, given 5 years apart, are indicated for adults with functional or anatomic asplenia and immunocompromising conditions. Those adults should then receive a third dose of PPSV23 at or after 65 years, as long as it s been at least 5 years since the previous dose. A 28 year old woman with HIV infection received one dose of PPSV23 one year ago. Administer vaccines as follows: 1 dose of PCV13 now because one year has passed since receipt of PPSV23 A second dose of PPSV23 at age 32 (if it s been 5 years since previous PPSV23 and 8 weeks since PCV13 dose A third dose of PPSV23 at age 65 Case 2 A 42 year old man with cochlear implants who has not previously received any pneumococcal vaccines. Administer vaccines as follows: 1 dose of PCV13 now, at age 42 1 dose of PPSV23 at least 8 weeks after a dose of PCV13 A second dose of PPSV23 at age 65 Case 3 A 24 year old sees his doctor for a routine office visit. He has asthma and has not previously received any pneumococcal vaccines. Administer vaccines as follows: 1 dose of PPSV23 now, at age 24 1 dose of PPSV23 at age 65 Note: Asthma is not an indication for adult administration of PCV13 unless the patient has received long term systemic corticosteroids. This adult has an indication to receive a single dose of PPSV23 now. An additional dose of PPSV23 would be given at age 65 years or older. PCV13 ACIP August 2014 Meeting Voted 13 2 for the following recommendations CAPITA trial Recent data demonstrated a 75% reduction in vaccine type invasive pneumococcal disease (IPD) and 45% reduction in vaccine type nonbacteremic pneumonia (NBP). The indirect effects (herd effects) of PCV13 on children since its introduction in 2010 are decreasing IPD caused by vaccinetype serotypes and will decrease the need for PCV13 in the near future. The working group estimated there would be a decrease of CAP by 2019 by 86% due to this effect. They suggest that this recommendation should be re evaluated in Bonten M, Bolkenbaas M, Huijts S, et al. Community Acquired Pneumonia Immunization Trial in Adults (CAPiTA). Abstract no Pneumonia 2014;3:95. Available at

5 PCV 13 Adults aged 65 years and older who have not previously received pneumococcal vaccine or whose previous vaccination history is unknown should receive a dose of PCV13 first, followed by a dose of PPSV23 (Pneumovax Merck) A dose of PPSV23 should be given 6 to 12 months following a dose of PCV13. The two vaccines should not be coadministered PCV 13 Adults aged 65 years and older who have not previously received PCV13 and who have previously received one or more doses of PPSV23 should receive a dose of PCV13 at least 12 months following the PCV23 PCV 13 CMS would not likely be able to cover two pneumococcal vaccines during this upcoming season. It takes about 1 year to make a policy change based upon legal requirements, including public comment. Two vaccines would not be paid for by CMS, if given this year, because only one pneumococcal vaccine (type not specified) is already covered. Zoster Vaccine ACIP voted to make no change to VZV vaccine age recommendations (> 60 yrs of age) 2014 Influenza Vaccine Composition for the Season Influenza For , U.S. licensed influenza vaccines will contain the same vaccine virus strains as those in the vaccine. Trivalent influenza vaccines will contain hemagglutinin (HA) derived from an A/California/7/2009 (H1N1) like virus, an A/Texas/50/2012 (H3N2) like virus, and a B/Massachusetts/2/2012 like (Yamagata lineage) virus. Quadrivalent influenza vaccines will contain these antigens, and also a B/Brisbane/60/2008 like (Victoria lineage) virus

6 Influenza B Virus: Disease Burden 1 3 Represents ~20 25% of circulating strains Circulating B lineage may vary between countries in the same year Causes influenza epidemics about every 2 4 years Symptoms of influenza A and B infection are similar Influenza B associated hospitalization and mortality rates are lower than influenza A/H3N2, but more severe than influenza A/H1N1 Substantial burden of influenza B in children and young adults 1 3 Overall, a significant cause of absenteeism, clinic visits, hospitalizations and deaths across all age groups References: Robert Couch, VRBPAC Presentation, February S2_11_files/frame.htm 3. Simonsen, et al., JID 2000;181:831. Historical Circulation of Influenza B Lineages Influenza B Viruses subdivided into two lineages B/Yamagata B/Victoria Before 1980s: Single dominant strain globally Mid 1980s early 1990s B/Victoria/87 like strains dominant, B/Yamagata present Early 1990s 2000 B/Yamagata strains dominant, B/Victoria also in Asia 2000 present: Both lineages worldwide, variable dominance Vaccine mismatches occurred in 6 of past 12 years Different lineages may predominate in different countries within the same region during the same season References: 1.VRBPAC meeting, February Silva ML. Presenting symptoms of influenza B patients; A prospective study in France and Turkey. ESWI Sept A116P. B lineage Mismatch in 6 of the Past 12 Seasons Season % B % Yamagata % Victoria Vaccine Yamagata Yamagata Victoria Victoria Yamagata Yamagata Victoria Victoria Yamagata Victoria Victoria Victoria Red indicates B lineage mismatch between vaccine strain and predominant circulating strain Influenza For , ACIP recommends the following: 1.All persons aged 6 months should receive influenza vaccine annually. 2.When immediately available, LAIV should be used for healthy children aged 2 through 8 years who have no contraindications or precautions (Category A). If LAIV is not immediately available, IIV (inactivated influenza vaccine) should be used. Vaccination should not be delayed to procure LAIV. This recommendation should be implemented for the season as feasible, but not later than the season. MMWR. August 15, 2014 / 63(32); References: 1. C. Reed et al. Vaccine 30 (2012): Accessed 22 July High Dose Flu Vaccine Seniors have smaller antigen response to flu vaccine High Dose Flu vaccine have 4 times more antigen than standard vaccine (15 mcg vs 60mcg) For season ACIP has stated no preference for seniors Only indicated for those over 65 years NEJM study August % more effective than standard dose flu vaccine in study of over 30K pts Post vaccination GMT, a Fluzone Vaccine, b Younger vs Older Adults 1 GMT Years of Age 65 Years of Age GMT A(H1N1) B 0 A(H3N2) a GMT = Geometric Mean Titers. b Fluzone (Influenza Virus Vaccine); 15 mcg of hemagglutinin per strain. 1. Sanofi Pasteur Inc. Data on file (Annual study GRC41), November MKT20203.

7 Number of HPV Attributable Cancer Cases per Year HPV Vaccine Recent U.S. population based studies conducted by CDC show that 66% of cervical cancers, 55% of vaginal cancers, 79% of anal cancers, and 62% of oropharyngeal cancers are attributable to HPV types 16 or 18. Each year in the United States, an estimated 26,000 new cancers are attributable to HPV, about 17,000 in women and 9,000 in men MMWR January 31, 2014 / 63(04);69 72 CDC: National Program of Cancer Registries Available HPV vaccines HPV2 Protects against two serotypes 16 and 18 that causes cervical cancer Only for female patients 0, 1 2, 6 months 0.5ml IM HPV4 Protects against serotypes Protects against cervical cancer as well as genital warts and cancers of anus, vagina and vulva For females and males 0,1 2, 6 months 0.5ml IM FDA approves HPV 9 for prevention of certain cancers caused by five additional types of HPV The U.S. Food and Drug Administration today approved HPV9 (Human Papillomavirus 9 valent Vaccine, Recombinant) for the prevention of certain diseases caused by nine types of Human Papillomavirus (HPV). Covering nine HPV types, five more HPV types than HPV4 (previously approved by the FDA), HPV9 has the potential to prevent approximately 90 percent of cervical, vulvar, vaginal and anal cancers. FDA News Release Dec 10, 2014 HPV 9 HPV2, HPV4 and HPV9 all protect against HPV types 16 and 18, types that cause about 66% of cervical cancers and the majority of other HPV attributable cancers in the United States. HPV9 targets 5 additional cancer causing types, which account for about 15% of cervical cancers in the United States. HPV4 and HPV9 also protect against HPV types 6 and 11, types that cause genital warts. For protection against genital warts in addition to cancer causing HPV types, vaccination is recommended with HPV4 or HPV9. When HPV4 is no longer available, HPV9 can be used to complete a series begun with HPV4. HPV 10,575 cases of invasive cervical cancer were included in the study, and 8977 (85%) of these were positive for HPV DNA. The most common HPV types were 16, 18, 31, 33, 35, 45, 52, and 58 with a combined worldwide relative contribution of 8196 of 8977 (91%, 95% CI 90 92). HPV types 16 and 18 were detected in 6357 of 8977 of cases (71%, 70 72) of invasive cervical cancer. HPV types 16, 18, and 45 were detected in 443 of 470 cases (94%, 92 96) of cervical adenocarcinomas. Unknown HPV types that were identified with sequence analysis were 26, 30, 61, 67, 69, 82, and 91 in 103 (1%) of 8977 cases of invasive cervical cancer. Women with invasive cervical cancers related to HPV types 16, 18, or 45 presented at a younger mean age than did those with other HPV types (50 0 years [ ], 48 2 years [ ], 46 8 years [ ], and 55 5 years [ ], respectively). Lancet Oncol Nov;11(11):

8 HPV 9 Will be reviewed at February 2015 ACIP meeting Issues to be determined Overall Recommendation Dosing schedule Males over 15 Meningitis B Describing the Burden Meningitis Serogroup B Disease Epidemiology Adolescents College students and other young adults High Risk Groups

9 Outbreaks of Meningococcal Disease Meningococcal outbreaks are rare, historically causing ~2 3% of US cases 1 Five serogroup B meningococcal disease clusters/outbreaks on college campuses Princeton: 1400 fold increased risk; 7,500 recommended vaccine UCSB: 200 fold increased risk; 20,000 recommended vaccine Threshold for vaccination for serogroup B outbreaks in institutional settings 2 2 cases in population <5,000 persons 3 cases in population 5,000 persons Summary: Epidemiology of Serogroup B Meningococcal Disease With widespread use of conjugate vaccines in adolescents and young adults, serogroup B now causes 40% of all meningococcal disease cases in this age group Approximately 50 cases annually among year olds Approximately one third of cases among year olds occur in college students Recent outbreaks on college campuses have been due to serogroup B 1 National Notifiable Diseases Surveillance System 2http:// guidance.pdf Groups at High Risk for Meningococcal Disease High risk medical conditions: Persistent complement component deficiencies Functional or anatomic asplenia Microbiologists Outbreak at risk populations Recent University Based Serogroup B Clusters/Outbreaks University Outbreak Period Number of cases University 1 Feb Mar University 2 Nov University 3 Jan 2008 Nov Princeton University Mar 2013 Mar UC Santa Barbara Nov Two MenB Vaccines for Persons years of age Trumenba 3 dose series (0, 2, 6 months) Licensed in the U.S. on October 29, 2014 Bexsero 2 dose series (0, 1 6 months) Licensed in Europe, Australia and Canada in 2013 for 2 months of age Expanded access investigational new drug protocol to control two recent university outbreaks Granted Priority Review designation with announcement regarding licensure expected by early 2015 Assessment of Immunogenicity: Primary Endpoints Bexsero proportion of subjects with hsba titers 1:4 or 1: % of adolescents demonstrated protective titers following two doses Immunity wanes by 5 25% at two years Trumenba proportion of subjects with hsba titers four fold increase from baseline (minimum titer 1:16); composite endpoint (hsba 1:8 or 1:16) % demonstrate protective titers following 3 doses No long term immunogenicity data available ACIP Oct2014 meeting

10 Options for Use of MenB vaccines??? Future ACIP Meetings Meningococcal Serotype B Recommendation for high risk groups only Medical conditions high risk for meningococcal disease Persistent complement component deficiencies Anatomic or functional asplenia Microbiologists Outbreak response Routine recommendation for expanded groups Adolescent recommendation College recommendation TO BE DETERMINED February 2015 GRADE for high risk groups Use of MenB vaccines in persons 10 years of age with high risk medical conditions, microbiologists, and outbreaks Planned vote on high risk groups June/October 2015 Review of evidence for expanded target groups GRADE Economic and impact analysis Updated outbreak guidelines for all serogroups Tdap in Pregnant Women Tdap ACIP Recommendations for Pregnant Women ACIP recommends that providers of prenatal care implement a Tdap immunization program for all pregnant women. Health care personnel should administer a dose of Tdap during each pregnancy, irrespective of the patient's prior history of receiving Tdap. Guidance for Use Administration is between 27 and 36 weeks gestation although Tdap may be given at any time during pregnancy. For women not previously vaccinated with Tdap, if Tdap is not administered during pregnancy, Tdap should be administered immediately postpartum. MMWR Feb 22, 2012 Tdap in Pregnant Women Special Situations Pregnant women due for tetanus booster. If a tetanus and diphtheria booster vaccination is indicated during pregnancy (i.e., >10 years since previous Td), then Tdap should be administered. Wound management for pregnant women. For wound management in a pregnant woman if 5 years have elapsed since the previous Td booster. If a Td booster is recommended for a pregnant woman, health care providers should administer Tdap. Pregnant women with unknown or incomplete tetanus vaccination. To ensure protection against maternal and neonatal tetanus, pregnant women who never have been vaccinated against tetanus should receive three vaccinations containing tetanus and reduced diphtheria toxoids. The recommended schedule is 0, 4 weeks, and 6 through 12 months. Tdap should replace 1 dose of Td, preferably between 27 and 36 weeks gestation to maximize the maternal antibody response and passive antibody transfer to the infant. MMWR Feb 22, 2012 Tdap safety In Pregnancy (ACIP) There is no elevated frequency or an unusual occurrence of adverse events among pregnant women who have received Tdap vaccine, or in their newborns. Tdap vaccine is recommended after 20 weeks gestation because that optimizes antibody transfer and protection at birth. The immune response to the vaccine peaks two weeks after administration. Both tetanus and diphtheria toxoids (Td) and tetanus toxoid (TT) vaccines have been used extensively in pregnant women worldwide since the 1960s to prevent neonatal tetanus. Td and TT vaccines administered during pregnancy have not been shown to harm either the mother or baby/fetus. CDC ACIP guidelines

11 Tdap Cocooning Vaccination with Tdap during pregnancy is ideal. However, if a woman does not get vaccinated during pregnancy, administer the vaccine immediately postpartum, before she leaves the hospital or birthing center. In addition to vaccinating your patients, you should educate them about encouraging others including dads, grandparents and other caregivers to get vaccinated with Tdap at least two weeks before coming into contact with their infants. MMWR Feb 22, 2012