School Health Workshop Robert S. Bal2more, M.D. Professor of Pediatrics and Epidemiology Yale School of Medicine Yale School of Public Health

Transcription

1 School Health Workshop Robert S. Bal2more, M.D. Professor of Pediatrics and Epidemiology Yale School of Medicine Yale School of Public Health Three Issues 1. Uptake of Human Parvovirus Vaccine (HPV) 2. New Recommenda2ons for Meningococcal Vaccines. Meningococcal serogroup B 2. Management of Latent Tuberculosis. Who to test. When to test. What about treatment? HPV Vaccina5on Coverage: Current status of uptake and strategies to increase coverage 1

2 HPV Vaccina5on Coverage SLIDES THANKS TO Linda M. Niccolai, PhD Associate Professor Yale School of Public Health HPV vaccines approved for use in US Quadrivalent Bivalent 9-valent Brand name Manufacturer Gardasil Merck Cervarix GlaxoSmithKline Gardasil 9 Merck Approved HPV types 6,11,16,18 16,18 6,11,16,18, 31,33,45,52,58 HPV-associated diseases 65% cervical cancer 90% genital warts 65% cervical cancer 80% cervical cancer 90% genital warts Acceptable safety profiles From RCT and several post- licensure monitoring efforts by federal agencies and vaccine manufactures CDC Merck Vaccine Safety Datalink Postmarketing commitment to FDA >600,000 doses No statistically significant increase in risk of outcomes monitored >340,000 doses HPV4 vaccine associated with syncope of the day of vaccination and skin infections in the 2 weeks after vaccination. No other vaccine safety signals detected. MMWR

3 High- grade cervical lesions in CT High-grade cervical lesions among young women in CT Number of cases years 24 years 23 years 22 years 21 years Significant declines: 25% 33% 49% 55% CT HPV-IMPACT (unpublished data). Current status of coverage: Subop&mal Lower than other vaccines for adolescents Lower than other high income countries Low uptake of HPV vaccine in US Most other high-income countries have higher coverage than US. Country Coverage with 3 doses among adolescent females in 2010 Portugal 81% Scotland 81% England 76% Australia 72% Denmark 70% New Zealand 40% United States 33% France 28% Hopkins

4 Low uptake of HPV vaccine in US Tdap MCV4 HPV1-F HPV1-M HPV3-F HPV3-M MMWR Current recommenda5ons Rou2ne HPV vaccina2on at ages 11 or 12 years For girls (2-, 4-, or 9- valent) and boys (4- or 9- valent) Can be started at age 9 years Catch- up vaccina2on years for females years for males years for men who have sex with men and for men who are immunocompromised MMWR Does not contain whole virus 4

5 Reduc5ons in HPV infec5ons Sexually ac5ve females ages years 25 Prevalence of HPV 6/11/16/ Overall: 53% reduction 9.0 Vaccinated: 82% reduction 3.1 Unvaccinated: 28% reduction Markowitz High efficacy in randomized trials When administered to HPV- naïve individuals Quadrivalent: 99% efficacy against HPV 16/18 associated high- grade cervical lesions 9- valent: 97% efficacy against HPV 31/33/45/52/58 associated high- grade cervical, vaginal, or vulvar disease Schiller Joura Coverage by age 13 years Greater reliance on catch-up for HPV compared to MCV4 and Tdap. Percent coverage HPV vaccination coverage among adolescents males and females ages 13 and 17 years, US Tdap MCV4 HPV1 - F HPV1 - M HPV3 - F HPV3 - M Age 13 years Age 17 years MMWR

6 Coverage steady in CT since 2009 HPV vaccination coverage among females with 1 dose, United States and Connecticut, United States Connecticut US CT Early evidence of vaccine impact HPV infections Genital warts High-grade precancerous cervical lesions Genital warts in US Among women ages years: 38% reduction from 2006 to 2010 Among women ages years: 13% reduction from 2006 to 2010 Flagg

7 Arguments against HPV vaccine Side effects and the vaccine s overall safety record are cause for concern. The verdict is s7ll out as to whether the vaccine is effec7ve at preven7ng cervical cancer. Because the cancer takes 10 to 20 years to develop, it s too early to look at the effect of HPV vaccina7ons on cancer outcomes. The recommended 3- shot series over a 6- month period is difficult for families to follow. Cost Promo7on of promiscuity. parents' religious and personal beliefs that adolescent sexual ac7vity will increase with HPV vaccina7on Challenges for uptake and how to address Lack of urgency Concern about dura2on of protec2on Preference for alterna2ve dosing schedules An2cipated parental hesitancy Limited awareness of full range and severity of HPV- associated outcomes Addressing urgency: Importance of immuniza5on prior to sexual ac5vity Current HPV vaccines have no known therapeu2c effect Efficacy in pre- licensure trials: 98% for HPV- naïve women 44% for all women, including a substan2al propor2on (~25%) who had already been exposed to HPV Parents (and maybe HCP) underes2mate sexually ac2vity among adolescents 47% of mothers inaccurately report that their adolescent child is not sexually experienced Liddon The Future II Study Group

8 Dura5on of clinical effec5veness FEMALES Number followed Number of cases Rate per 100 person-years Persistent infection Cervical disease Warts or vaginal/vulvar disease MALES Clinically effective protection is durable up to 5 years. Vaccine effectiveness in preventing HPV 6/11/16/18 persistent infections and disease: 5 year follow-up in boys and girls vaccinated at ages 9 15 years Persistent infection Related disease Ferris Addressing parental hesitancy HCP underestimate the importance of HPV vaccine to parents. Healy An5cipated parental hesitancy If you have an 11- year old boy and I m supposed to talk about HPV, they are going to ask me why I am recommending it. So few 11 year olds are physically mature to be sexually aceve, that it s, I find it s almost sort of an awkward conversaeon. Perkins

9 Addressing alterna5ve dosing schedules All three vaccines recommended for adolescents can be given at same visit. HPV only HPV + MCV4 + Tdap GMT for HPV Seroconversion 100% 100% Adverse events Injection site Systemic Serious Serious vaccine-related Non- inferior immune response and acceptable safety profile of co- Noronha Reisinger administra2on in a review of 9 clinical trials Parent opinions about the most important factor in immuniza5on decisions Importance of number of shots at a single visit among parents is overestimated by HCP. Healy Median number of injections per visit that parents felt comfortable with is three Under- es5ma5on of severity of HPV- associated outcomes I don t get as scared of cervical cancer just because So, the other things just feel more dramaec to me and it s not like HPV is going to kill the boys. Perkins

10 Human papillomavirus Most common sexually transmiied infec2on 80% life2me risk 38% risk of acquiring from first sex partner Associated with six types of cancer Virtually 100% cervical cancer 90% of anal cancers 60% of oropharyngeal cancers 40% of vaginal, vulvar, and penile cancers Also cause most genital warts Hariri Winer Jemal Other HPV- associated cancers Substantial and significant cancers other than cervical cancer that are associated with HPV. 10,400 cervical cancer compared to 16,500 other cancers No routine screening for other types of cancer Oropharyngeal and anal cancers are increasing in incidence Precancerous cervical lesions Psychological impact Fear and worry, anxiety, distress, depressive symptoms, concern about sexual rela2onships Clinical follow- up and management ~ 20 months, 7-8 visits Treatment- associated impact 2- to 3- fold increased risk for preterm deliveries among women treated with excisional procedures (8% vs. 3.5%) Insinga Rogstad Sadler

11 Strategies to increase coverage Bundling of recommenda5ons for all three adolescent vaccines Treat them all the same. All three vaccines have important characteris2cs in common. Safe, effec2ve, and recommended. Today your son is due for three shots including Tdap, HPV, and the meningococcal vaccine. Do you have any queseons? Some differences HPV is sexually transmiied Focus on (substan2al) cancer outcomes Related to bundling No requirement for school Primary ra2onale to vaccinate is to prevent disease Related to bundling 11

12 Presump5ve approach Provider communication is effective in increasing parental acceptance of immunizations. Presump2ve approach results in 74% acceptance We have to do some shots. Par2cipatory approach results in 17% acceptance What do you want to do about shots? Opel HCP persistence in face of parental hesitancy results in subsequent 47% acceptance He really needs these shots. An addi5onal possible benefit Immune response is 1.7 to 2.7 2mes higher when given at younger ages Geometric mean titers 7 months after vaccination HPV 16 Girls years Boys years Females years Block Automated clinical decision support for health care providers Clinician- focused interven2on included educa2on, programmed electronic health record alerts, and audit & feedback at primary pediatric prac2ces in NJ and PA Clinician intervention Control P-value HPV 1 24% 16% <.01 HPV 2 64% 65%.70 HPV 3 67% 63%.20 Fiks Pediatrics

13 Reminder/recall systems for pa5ents Leier or phone reminders to families of unimmunized adolescent females at primary care prac2ces in NY state Mail Phone Control HPV 1 27% 27% 21% HPV 2 26% * 26% * 18% HPV 3 18% * 19% * 14% * p-value <.05 for difference from control group Szilagyi Text message reminders Parents of adolescent females at 9 pediatric prac2ces in NYC could opt- in for text reminders for 2 nd and 3 rd doses Percent receiving next dose On time Within 4 months Text reminder Opt-out control Historical control Kharbanda Vaccine Concluding remarks HPV vaccines are very good news that could be much beier. Pediatricians are important for increasing coverage. Informa2on and strategies provided in this presenta2on may help you to promote the future good health of your pa2ents. 13

14 Meningocococcal Vaccines Role of New Meningococcal Serotype B Vaccines Available meningococcal vaccines Trade name Type of Vaccine Bexsero Recombinant B Menactra Conjugate A, C, W, Y MenHibrix Conjugate Menomune Polysaccharide A, C, W, Y Menveo Conjugate A, C, W, Y Trumenba Recombinant B Meningococcal Serogroups Covered C, Y (and Haemophilus influenzae type b [Hib]) Age- and Serogroup- Specific Meningococcal Disease Incidence United States, Cases per 100,000 persons mos 5-11 mos 1 yr 2-4 yrs 5-10 yrs yrs yrs yrs Age Serogroup B Serogroup C Serogroup Y Serogroup W-135 Other Shepard CW, et al. Pediatrics. 2005;115:

15 Builds on the success of the Haemophilus and Pneumococcal conjugate vaccines. Es7mated annual incidence* of invasive Haemophilus influenzae type b (Hib) disease in children aged <5 years United States, ACIP Recommenda2ons (CDC) Recommenda7ons A MenB vaccine series may be administered to adolescents and young adults aged years to provide short- term protec7on against most strains of serogroup B meningococcal disease. The preferred age for MenB vaccina2on is years (recommenda2on Category B). MenB vaccine should either be administered as a 3- dose series of MenB- FHbp or a 2- dose series of MenB- 4C. The two MenB vaccines are not interchangeable; the same vaccine product must be used for all doses. On the basis of available data and expert opinion, MenB- FHbp or MenB- 4C may be administered concomitantly with other vaccines indicated for this age, but at a different anatomic site, if feasible. In February 2015, ACIP recommended rou2ne use (recommenda2on Category A)** of MenB vaccines in certain groups of persons at increased risk for serogroup B meningococcal disease, including during outbreaks of serogroup B meningococcal disease (20). College campuses that have recently experienced an outbreak of serogroup B meningococcal disease should con2nue to follow the recommenda2ons for use of MenB vaccines in outbreak seungs that recommend vaccina2on for persons aged 10 years. Category B recommenda2ons are made for individual clinical decision making. ** Category A recommenda2ons are made for all persons in an age- or risk- factor- based group. [All of these must be covered by insurance carrirs and by VFC] 15

16 Polysaccharide capsule (serogroup Outer membrane complex Two protein- based meningococcal serogroup B vaccines. Equally effec2ve (we think). Summary of evidence for MenB- FHbp and MenB- 4C vaccina7on of healthy adolescents and young adults, including college students United States Evidence type* Outcome MenB- FHbp MenB- 4C Benefits Short- term immunogenicity 2 2 Persistence in immunogenicity 4 3 MenB immunogenicity with concomitant 2 vaccina2on Harms Serious adverse events 2 2 Serious adverse events following concomitant 2 vaccina2on * Evidence type: 2 = moderate level of evidence; 3 = low level of evidence; 4 = lowest level of evidence. Not assessed because of lack of available data. 16

17 The Advisory Commiiee on Immuniza2on Prac2ces recommenda2ons regarding meningococcal vaccines The Advisory Commiiee on Immuniza2on Prac2ces recommends rou2ne vaccina2on of all adolescents aged years with a quadrivalent meningococcal conjugate vaccine (MenACWY). A single dose should be administered at age 11 or 12 years with a booster dose at age 16 years for persons who receive the first dose before age 16 years. Rou2ne vaccina2on of certain persons at increased risk for meningococcal disease with MenACWY and serogroup B meningococcal (MenB) vaccine is also recommended. Who should get it rou2nely? These vaccines are recommended rou2nely for people 10 years or older who are at increased risk for serogroup B meningococcal infec2ons, including: People at risk because of a serogroup B meningococcal disease outbreak Anyone whose spleen is damaged or has been removed Anyone with a rare immune system condi2on called persistent complement component deficiency Anyone taking a drug called eculizumab (also called Soliris ) Microbiologists who rou2nely work with N. meningiedis isolates These vaccines may also be given to anyone 16 through 23 years old to provide short term protec2on against most strains of serogroup B meningococcal disease; 16 through 18 years are the preferred ages for vaccina2on. 17

18 The Advisory Commiiee on Immuniza2on Prac7ces recommenda7ons for serogroup B meningococcal vaccines The Advisory Commiiee on Immuniza2on Prac7ces recommends rou7ne vaccina7on of all adolescents aged years with a quadrivalent meningococcal conjugate vaccine (MenACWY). A single dose should be administered at age 11 or 12 years with a booster dose at age 16 years for persons who receive the first dose before age 16 years. Rou2ne vaccina2on of certain persons at increased risk for meningococcal disease with MenACWY and serogroup B meningococcal (MenB) vaccine is also recommended. Two serogroup B meningococcal vaccines were recently licensed by the Food and Drug Administra2on and approved for use in persons aged years. The evidence suppor2ng the use of MenB vaccines in adolescents and young adults was evaluated using the Grading of Recommenda2ons, Assessment, Development, and Evalua2on framework. The recommenda2on was designated as Category B (recommended for individual clinical decision making). A MenB vaccine series may be administered to adolescents and young adults aged years to provide short- term protec2on against most strains of serogroup B meningococcal disease. The preferred age for MenB vaccina2on is years. Management of Latent Tuberculosis. Who to test. When to test. What about treatment? Tuberculosis in Connec2cut Sixty cases of tuberculosis (TB) were reported in 2014, a 3% decrease from 2013 (62 cases). Forty- one (68%) cases were pulmonary, while 19 (32%) were extra- pulmonary. The case rate was 1.7/100,000 for both 2013 and Na2onally, the provisional case count for 2014 is 9,412 (corresponding to a 2014 provisional case rate of 3.0/100,000). 18

19 Tuberculosis in Connec2cut Age Distribution of Reported TB Cases by Country of Birth Age in Years (Active tuberculosis) AGE US-Born Foreign-Born < Total Tuberculosis in Connec2cut Towns repor2ng five or more cases in 2014 included (case rate reported per 100,000 town popula2on): Town Cases Rate Har ord Norwalk New Haven It is recommended that at each mandated examina7on, an assessment be made of the risk of exposure to tuberculosis. Students not already known to have a posi2ve test should be tested if they have any of the following risk factors for tuberculosis infec2on: a) were born in a high risk country of the world and do not have a record of a tuberculin skin test performed in the US; b) have travelled to a high risk country since the previously required examina2on; c) have had extensive contact with persons who have recently come to the US since the previously required examina2on; d) had contact with person(s) suspected to have tuberculosis; e) have been living in a homeless shelter; or f) have HIV infec2on. Schools should assure that all students originally from high risk countries who are entering school in Connec7cut for the first 7me receive a tuberculin skin test. A history of BCG vaccinaeon is not a contraindicaeon to teseng nor should it be considered in interpretaeon of the skin test result. 19

20 CT DPH Defini7on of High Risk Countries. All countries in Africa, Asia (including former Soviet Union), Central and South America, Dominican Republic and Hai2. Recommended Tes7ng Schedule Rou2ne tuberculin tes2ng at each of the required examina2ons is not recommended. The current low rates of transmission of tuberculosis in all parts of Connec2cut do not jus2fy it. Interferon- gamma release assays (IGRAs) e.g. Quan&feron, T- spot Interferon- gamma release assays (IGRAs) are diagnos2c tools for latent tuberculosis infec2on (LTBI). They are surrogate markers of Mycobacterium tuberculosis infec2on and indicate a cellular immune response to M. tuberculosis. IGRAs cannot dis2nguish between latent infec2on and ac2ve tuberculosis (TB) disease, and should not be used as a sole method for diagnosis of ac2ve TB, which is a microbiological diagnosis. A posi2ve IGRA result may not necessarily indicate ac2ve TB; however, a nega2ve IGRA result rules out the possibility of both ac2ve and latent tuberculosis. 9 months 4-6 months 20

21 Dosage for a combina7on regimen of isoniazid and rifapen7ne in 12 once- weekly doses under direct observa7on for trea7ng latent Mycobacterium tuberculosis infec7on In the randomized clinical trial of this regimen, a pa2ent was considered to have completed treatment if they took at least 11 doses within 16 weeks with all doses separated by at least 72 hours (2). Pa7ents for whom INH- RPT is not recommended. INH- RPT is not recommended for the following pa2ents: children aged <2 years, because the safety and pharmacokine2cs of RPT have not been established for them; HIV- infected pa2ents receiving an2retroviral treatment, because the drug interac2ons have not been studied; pregnant women or women expec2ng to become pregnant during treatment, because safety in pregnancy is unknown; and pa2ents who have LTBI with presumed INH or RIF resistance Fin 21

22 Barriers to uptake Population Practice/ Provider Patient Policies Media Social norms Access to health care US health care system Relationships and communication with health care providers Practice-based systems Demographic factors Knowledge and attitudes Motivation and skills Past experiences Brewer 2007, Ferrer 2014, Garcini 2012, Hendry 2013, Holman 2013, Katz 2012, Kessels Genital warts in Australia Among women ages <21 years: 93% reduction from 2007 to 2011 Among women ages years: 73% reduction from 2007 to 2011 Ali Lack of urgency I d be shocked if they became sexually aceve at a really young age, and to bring this all up with the parents who have 20 other things they want to talk about, it seems low down on the list. I got a queseon from a provider He is reluctant to follow the recommended schedule for year olds because he queseons whether the immunity is sell going to be sufficient by the Eme young women in parecular reach age 26. He doesn t discourage people from pu[ng it off unel they are a li]le bit older. Perkins Personal communication. 22

23 Addressing concerns about dura5on of protec5on Antibody titers are sustained for up to 8 years. Percent seropositive at 8 years among 9 15 year old boys and girls HPV 6 HPV 11 HPV 16 HPV 18 Males Females Ferris The importance of strong and consistent recommenda5ons Health care provider (HCP) recommenda2ons salient predictor of HPV immuniza2on Adolescents more than 4 2mes as likely to be immunized if they received HCP recommenda2on Many adolescents not receiving recommenda2ons 47% in a na2onal sample What are the challenges? How can they be addressed? Ylitalo Offer at ages 9 10 years FDA approved ACIP recommenda2ons state can be started beginning at age 9 years Anecdotally, this strategy is currently being used by some pediatricians in Connec2cut. Can provide an2cipatory guidance at this age, then follow- up at subsequent visits if necessary Reminder/recall and electronic health alerts 23

24 Projected an5body 5ters Antibody titers are projected to last at levels above naturally induced immunity for at least 20 years. Einstein Safety of HPV Vaccine 24