Vaccine preventable diseases and vaccination programs Adherence of the Public and stakeholders: ups and downs

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Vaccine preventable diseases and vaccination programs Adherence of the Public and stakeholders: ups and downs Catherine Weil Olivier Honorary Professor of pediatrics, University Paris 7, France Member of the Scientific Committee and trustee of the CLCI Brussels, May 2018

European Immunization Week (EIW) 23-29 April 2018 Prevent Protect Immunize «Vaccination is a right and responsibility for all»(and at all ages)

Global Vision of a national vaccination program Vaccine Recommendation Vaccine Vaccine coverage rate Respect of schedule Information / formation / Education/communication Around Vaccine/Vaccination Vaccine Reimbursment Vaccination Campaign Support of health authorities Vaccination coverage follow-up Surveillance of the targeted disease

Components of success of a vaccination programme Population households Health Professionnals Publique health Politics Adherence / Communication + Information + Formation, Education of health professionnals + Clear Support from authorities Chen RT, & al.vaccine1994;12(6):542 50

Tetanus, Diphtheria France 1975-2013 Morbidity, mortality Diphtheria in 2014 (EU/EEA Member States, latest data) 38 reported cases Notification rate 0.01 / 100 000 population Majority of cases due to C. diphtheria between 45 and 64 years (n=5) 65+ years cases mostly due to C. ulcerans (pets) http://ecdc.europa.eu/en/press/news/_layouts/forms/ne ws_dispform.aspx http://www.invs.sante.fr/dossiers-thematiques/maladies-infectieuses/maladies-a- prevention-vaccinale/tetanos ECDC report 2016 (data 2014)

Pertussis Infants < 3 months = THE risk group Incidence rate of pertussis cases in infants 0-2 months, Renacoq, 1996-2012

Wooping cough The risk not to vaccinate Changes to routine childhood pertussis immunization programs and notifications of pertussis disease (all ages) and vaccine coverage among children <2 years of age, England and Wales, 1940 2009. Campbell H & al, EID 2012;18:38-47

Measles in Europe (EU/EEA) year 2016 Over 14000 cases reported Age of cases (when known) Children under five: 35% Subjects 15+ years: 47% Vaccination status (when known)): 86% unvaccinated Comparisons between countries should be made with caution Countries report on measles and other vaccine-preventable diseases to TESSy at their own convenience because of dissimilar surveillance sensitivities, completeness of reporting and different reporting procedures under-notification is a well recognised limitation of nationwide mandatory notification systems. https://ecdc.europa.eu/en/publications-data/number-measles-cases-eu-and-eea-countries-2016-data

Measles elimination in Europe To reach elimination and protect those most vulnerable to severe complications and death from measles such as infants, 95% coverage of the population vaccinated with two doses of measles-containing-vaccine is needed. Vaccination coverage below 95% in 22 out of 29 EU/EEA countries for the 2nd dose of a measles-containing vaccine (WHO 2016 ) https://ecdc.europa.eu/en/publications-data/number-measles-cases-eu-and-eea-countries-2016-data WHO. Why immunization must remain a priority in the WHO European region. http://www.euro.who.int/ data/assets/pdf_file/0017/84302/seven_key_reasons.

«Interruption of endemic measles and rubella virus transmission for > 12 months, with high-quality surveillance (2015: all countries) Measles and rubella elimination verified by the Regional Verification Committee (2018: all countries)» http://www.euro.who.int/ data/assets/pdf_file/0008/276 659/EVAP-factsheet.pdf?ua=1

Meningococcal invasive diseases Transmission acquisition From M.Maiden Role of MenCC vaccine

Meningococcal invasive diseases Nowadays care With an early diagnosis and an adapted emergency care Therapeutic Hemodynamic Intensive care Neurologic A persistant and incompressible «plateau» of deaths and sequelae

Distribution of IMD incidence by age Europe 2014 and 2015 43,6% of cases in <4 year-olds 70% of cases in <24 year-olds In 2015: Age-specific IMD cases incidence Infants. : 10.0 / 100 000 1 4-years : 2.8 / 100 000

IMD outcome in European Member States Average case fatality in 2015: 9%1 unchanged since decades Higher CFR in adolescent and adults compared to infants, 2 toddlers and children Sequelae*: up to 1/3 of survivors3 life long impairment(6%): hearing loss, limb amputation, epilepsy; cognitive and/or behavioral disorders 1. ECDC. Annual epidemiological report for 2015. Stockholm: ECDC; 2017 2. ECDC. Annual epidemiological report for 2012. Stockholm: ECDC; 2015. 3.

IMD by serogroup 2011-2015 ECDC report on IMD, 2015 data Notification rate of confirmed cases of IMD, Serogroup distribution of confirmed Serogroup distribution of confirmed cases of IMD, by age group, EU/EEA, by serogroup and year, EU/EEA, 2011 2015 cases of IMD, EU/EEA, 2015 2015 2016-ECDC annual report on IMD, 2015 data

Men C conjugate routine policies in Europe Year of introduction of routine childhood MCC vaccination among 25 European countries; respective MCC vaccine introduction group into which they were classified. R. Whittaker et al. / Vaccine 35 (2017) 2034 2041

Direct and indirect protection MenC conjugate vaccine routine program e.g. in the UK Direct and herd protection against MenC in the United Kingdom. Two major prerequisites Large catch-up campaign High coverage rate (> 90%), quickly achieved, maintained R. Borrow et al. J Inf 2017: 75, 1e11

Men C conjugate vaccines in France Incidence of IMD C per age groups, France 2005-2012 Recommendation (and reimbursment) since 2010 One dose any age between one and 24 years of age Coverage rate: 70 % at 2 years of age 32 % in the 10-14 years 7 % in the 20-24 years 2016-Rapport sur la concertation citoyenne Barret et al., BEH,2013

Meningococcal B vaccine program (Public Health England): the background of success Introduction of MenB immunisation has been supported by: Comprehensive media and communications campaign partnership with health partners and meningitis charities, leading to significant reporting in national, local and parenting media and social media. New patient information leaflets and posters Comprehensive guidance added to the NHS Choices website. Amendement of the existing children s immunisation information booklets and leaflets (new schedule reflected) Training factsheet and video for health professionals https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/677275/hpr0318_menb.pdf

Childhood PCVs vaccination impact on invasive pneumococcal disease (IPD) Indirect effect Direct effect Children < 5 years 2 4 6 8 10 Years post PCV7 introduction Shiri T et Al. Lancet glob health 2017 All age groups 12 2 4 6 8 Years post PCV7 introduction 10 12

AntiMicrobial Resistance rate in EOCD countries 2014 compared with 2005 EOCD report on antimicrobial resistance, 2016

Adolescent vaccination: HPV vaccines and Sites of HPV vaccination in different European Member Sates Gardasil Cervarix First Marketing Authorization in the world 01/06/2006 18/05/2007 European Marketing Authorization 3 dose schedule from 9 years 20/09/2006 20/09/2007 2 dose schedule from 9 years September 2014 September 2014 In the public sector in public health centres (Denmark, Italy, Netherlands and Portugal) school health services (Ireland, Norway, Slovenia, Sweden) or both (Latvia, Romania, Spain and United Kingdom). Through the private sector: 5 countries (France) Dorleans F et Al. Euro Surveill. 2010;15(47) Both public and private structures: 1 country ANSM, A.Jacquet, 8th REIVAC day, Paris 2014

Pharmacovigilance of vaccines in Europe The HPV vaccine case In terms of safety, European demands for vaccines are very high, compared with other drugs Pharmacovigilance is national, European, international The European Risk Management Plan is mandatory and followed up precisely: proactive, in «real life» On a national basis, diminution of the under-reporting of adverse events For HPV vaccines, anticipation of the risks (auto immune disorders) ANSM, A.Jacquet, 8th REIVAC day, Paris 2014

Distribution des virus influenza by age group (hospitalised cases) 2017-2018 Season https://flunewseurope.org/severity 24

Mortality due to confirmed influenza 2017 / 2018 season in Europe In Europe (22 countries or regions included) mortality significantly elevated in many European countries mainly affecting elderly people In France, (weeks 49/2017 to 12/2018) : mortalit y excess all causes and all ages estimated to 17 800 deaths of which 13 000 attribuable to influenza Pooled number of deaths by age groups; 2014-2018 0-4 years 15-64 years 5 14years 65 + years http://www.euromomo.eu; http://www.euromomo.eu/bulletin_pdf/2018/2018_17_bulletin.pdf 25

Influenza vaccine recommendations Europe 2007-08 up to 2014-15 Member States recommending seasonal influenza vaccine for children and adolescents 2007 08 2014 15 Member States recommending seasonal influenza vaccine for older age groups 2007 08 2014 15 https://ecdc.europa.eu/sites/portal/files/documents/influenza-vaccination-2007 2008-to-2014 2015.pdf

Proportion of Member States recommending seasonal influenza vaccine by chronic medical condition and / or pregnancy and HCPs 2007 08 to 2014 15 influenza seasons Pregnant women Any pregnancy trimester https://ecdc.europa.eu/sites/portal/files/documents/influenza-vaccination-2007 2008-to-2014 2015.pdf

Older age groups Seasonal influenza vaccination coverage rates in 29 EU/EEA Member States, 2007 08 to 2014 15 influenza seasons Healthy Children / Adolescents UK https://ecdc.europa.eu/sites/portal/files/documents/influenza-vaccination-2007 2008-to-2014 2015.pdf

Seasonal influenza vaccination coverage rates among individuals with chronic medical conditions and pregnant women Chronic medical conditions, 9 EU/EEA Member States influenza seasons 2007 08 to 2014 15 https://ecdc.europa.eu/sites/portal/files/documents/influenza-vaccination-2007 2008-to-2014 2015.pdf Pregnant women, 7 EU/EEA Member States, Influenza seasons 2010 11 to 2014 15

Seasonal influenza vaccination coverage rates among healthcare workers, 17 EU/EEA Member States, influenza seasons 2007 08 to 2014 15 https://ecdc.europa.eu/sites/portal/files/documents/influenza-vaccination-2007 2008-to-2014 2015.pdf

Vaccine safety / side effects Vaccine side-effects and vaccine safety as the most commonly-cited reservation amongst the public Vaccine safety sentiment is more negative in the European and the Western Pacific regions, where 9/10 least confident countries are located (France, Bosnia & Herzegovina, Russia, Ukraine, Greece, Armenia, Slovenia, Japan, and Mongolia) Research stresses the emerging shift away from access to vaccines as the primary barrier to vaccination in many countries Yaqub, O.et Al. Soc. Sci. Med. 112, 1 11. http://dx.doi.org/10.1016/j.socscimed.2014.04. 018. Larson HJ et Al. EBioMedicine 12 (2016) 295 301

State of vaccine confidence 2016 67-country survey The European region performs poorly for vaccine importance, safety, and effectiveness-related skepticism with Southern and Eastern European countries performing notably poorly for vaccine safety, though France and Italy are notable exceptions. The South East Asian and Western Pacific Region have high levels of religious-based vaccine incompatibility, notably in Mongolia, Vietnam, and Thailand. Larson HJ et Al. EBioMedicine 12 (2016) 295 301

Vaccine confidence by world region and differences between perceived safety Vaccine World map of percentage negative ("tend to disagree" or "strongly agree") survey responses to the statement "overall I think vaccines are safe". Larson HJ et Al. EBioMedicine 12 (2016) 295 301

Worldwide levels of vaccine-safety skepticism Identified factors Age Aged 25 34 less likely to believe vaccines are safe compared to 18 24 year olds (OR 0.88, CI 0.77 1.00) Over 65s are more likely to report that vaccines are effective (OR 1.39, CI 1.11 1.76) Level of education Any level elevates positive views towards immunizations for vaccine importance, effectiveness, and religious compatibility Notably, not for vaccine safety Larson HJ et Al. EBioMedicine 12 (2016) 295 301

Vaccine Hesitancy in France The extreme negative sentiment around vaccine safety reported in France builds upon multiple strands of vaccine controversies and distrust that have evolved in France over the past 2 decades Hepatitis B vaccine and multiple sclerosis (Marshall, 1998) Physician-led petitions disputing the hexavalent vaccine for infants (until reimbursment) Aluminium and macrophage myofascitis HPV vaccine (Collange et al., 2016) and hesitancy amongst general practitioners: Nearly 1 / 4 consider that some vaccines recommended by the French public health authorities are not useful (Verger et al., 2015) Many report doubt in immunization programmes (Raude et al., 2016). Larson HJ et Al. EBioMedicine 12 (2016) 295 301

European Union initiatives Written declarations of Sept 2015 on: Infectious diseases of early childhood Vaccination campaigns Proposed resolution of April 2016 Considering the increase of the numbers of deaths due to meningitis in Europe The CoMO proposes to the European Commission to think of an action to sensitize European citizens to vaccination Council Conclusions on Vaccinations as an Effective Tool in Public Health, and the recent written declaration on vaccine campaigns that gathered 124 signatures of MEPs, the time is right for civil society intervention 3 6

European support by ECDC Stockholm, April 2012 Major keywords: in immunisation programmes Trust Transparency Communication. Major additional keyword: supporting HCPs http://ecdc.europa.eu/en/publications/publications/ter-immunisation-and-trust.pdf http://ecdc.europa.eu/en/publications/publications/lets-talk-about-hesitancy-vaccination-guide.pdf Stockholm, April 2016

Acceptance, conclusion Interconnectivity of vaccine confidence, confidence in the health system, public trust in government more broadly, and socio-economic status alongside the influences of religious and philosophical beliefs Measuring vaccine confidence can be a valuable window on bigger issues at play in the evolving health and development landscape. Larson HJ et Al. EBioMedicine 12 (2016) 295 301

Life Course Immunisation Example of a parents association : CoMO s directive line Partnership: a major Members keyword CSAG Public Health organisations Life Course Immunisation Strategy Change! The outcome of the Change Equation 3 9

Conclusion To address hesitancy issues and build confidence Importance of continued worldwide monitoring of confidence in vaccines To monitor the effects of policymakers interventions on immunization attitudes and acceptance To more effectively allocate resources Larson HJ et Al. EBioMedicine 12 (2016) 295 301

CoMO: Working Together X No fighting Work together 4 1

Take home messages Depending on diseases, eradication, elimination or an excellent controle are possible strongly linked with High, sustained vaccine coverage rates Respect of the vaccine schedule.. YES, WE CAN

Social Value VACCINES PHARMACEUTICALS Economic Value