Biomedical_Infectious diseases_20231113_implementation.pdf

DEPARTMENT OF DIAGNOSTIC SCIENCES CENTER FOR VACCINOLOGY Vaccination programs and implementation of vaccines Chapter 6 2023-2024 Corinne Vandermeulen, MD, PhD Vaccinology 1. 2. 3. 4. 5. 6. 7. 8. Need for implementation strategies Organization of a vaccination program Recommendations Basic vaccin...

DEPARTMENT OF DIAGNOSTIC SCIENCES CENTER FOR VACCINOLOGY Vaccination programs and implementation of vaccines Chapter 6 2023-2024 Corinne Vandermeulen, MD, PhD Vaccinology 1. 2. 3. 4. 5. 6. 7. 8. Need for implementation strategies Organization of a vaccination program Recommendations Basic vaccination schedule Mandatory versus recommended vaccination Implementation of recommendations Evaluation of vaccination programs Registration of vaccinations 2 Why do we need to implement vaccines? 3 Why do we need to “implement” vaccine? ▪ To please the pharmaceutical companies so that they can make more money ▪ To insert nanochips in the entire population, so Bill Gates or the government can track you ▪ To create new diseases ▪ To create individual immunity for all vaccinated children 4 1. Need for implementation strategies Infection/epidemic Disease Protection                            Microbe          Vaccine Community immunity Or Herd immunity Individual protection = immunity INNATE IMMUNITY B cell or humoral immunity Antibodies T cell or cellular immunity Memory Effector cells Memory 5 Community immunity or herd immunity If >90-95% of a population is vaccinated  Develop protection for entire population: benefit for especially those who cannot be vaccinated and those who cannot develop protection after vaccination  ERADICATION of infectious diseases  ORGANIZED VACCINATION PROGRAMS = principle of solidarity 6 Community immunity or herd immunity 30% vaccinated           healthy           vaccinated ill Community immunity or herd immunity 90% vaccinated           healthy vaccinated ill Group or herd immunity 90% vaccinated           healthy           vaccinated ill Need for implementation strategies Effect of herd or community immunity first seen with smallpox WHO in 1967: only 31 countries with smallpox cases intensification of smallpox eradication efforts globally ➔ search and containment strategy  Last case of smallpox worldwide in 1977  World-wide eradication of smallpox declared in 1980 10 11 https://www.vaccines.com/ Result of community immunity Result of community immunity Ref: Leon Farrrante, Forbes – Talbird SE et all, Pediatrics 2022 Burden of disease in children <5 years of age Lancet 2017; 390: 1151–210 13 Poliomyelitis Poliomyelitis → most important cause of lifelong handicap in children in the prevaccination era. Because of lifelong handicap → memory of what polioviruses can cause. Everybody is susceptible → equity in the prevention of disease through vaccination Ref HGR polio: https://www.health.belgium.be/sites/default/files/uploads/fields/fpshealth_theme_file/hgr_9208a_polio_kinderen_adolescenten.pdf Poliomyelitis Cause - Enteroviruses – family of Picornaviridae → RNA viruses - Three different serotypes: type 1, type 2 and type 3 Transmission - Faeco-oral route (main route) - Droplet infection through human transmission Virus is present in the naso-pharynx and can be present for weeks after infection → through stools excreted → very infectieus (R0 5-7 personen) Incubation period 3-6 days In temperate climate: typical summer epidemics In tropical climate: no seasonal pattern Ref: https://en.wikipedia.org/wiki/Fecal%E2%80%93oral_route#/media/File:F-diagram-01.jpg https://www.mhlw.go.jp/english/topics/influenza_a/general_info.html Poliomyelitis Clinical signs and symptoms 70%: asymptomatic 24%: mild disease (low fever, throat ache) 5%: aseptic meningitis But infected persons shed the virus 1%: “flaccid paralysis” – eventually after mild disease Gastro-intestinal replication → invasion of virus in local lymphoid tissue → blood stream → infection of the cells of the central nervous system → destruction of motorneurons of the anterior horn of the spinal cord and the cells of the brain stem resulting in extensive paralysis Poliomyelitis Paralytic polio → especially children <5 years of age, but if older more severe cases - 79%: spinal polio → lower limbs - 2%: Bulbonic form → destruction of central nerves and innervation of the diaphragm (important for breathing) - 1%: bulbospinal form → Late complications and post-polio syndrome Poliomyelitis Poliomyelitis Diagnosis - Viral culture of stool → in case polio is observed → confirmation through RT-PCR and determination of sequence for serotyping - Preferably 2 stool samples with minimum interval of 24h and within 14 days after start of symptoms. Treatment Supportive and symptomatic Poliomyelitis - vaccins Inactivated vaccin – Jonas Salk - Mixture of 3 polioviruses serotype 1, 2 en 3 (respective strains: Mahoney, MEF-1, Suakett) - Produced from wild-type poliovirus strains of each serotype → inactivated (killed) with formalin - In combination with other vaccines: diphtheria, tetanus, pertussis, hepatitis B, Hib - Or also separate: Imovax - Parenteral (IM) administration → but still able to provide antibodies to the gut where prevention is necessary Poliomyelitis - vaccins Oral polio vaccine – Albert Sabin - Initially also a mixture of 3 polioviruses - Mix of live attenuated strains of the poliovirus of each of the 3 serotypes, - Serotypes selected because of their ability to imitate the immune response after infection with wild-type poliovirus, with a strong attenuated incidence to migrate to the central nervous system. - Stronger local immune response (gut), where the wild-type virus also entries the human body CAVE: conversion to Wild-type poliovirus → Vaccine-derived Poliovirus (VDPV) causing Vaccine-associated paralytic polio (VaPP) Poliomyelitis - vaccins Oral polio vaccine – nOPV2 To better address the evolving risk of type 2 circulating vaccine-derived poliovirus (cVDPV2) → novel oral polio vaccine type 2 (nOPV2) was developed = modified version of the type 2 monovalent OPV (mOPV2), → comparable protection against poliovirus while being more genetically stable and less likely to be associated with the emergence of cVDPV2 in low immunity settings. This means that nOPV2 has the potential to be a significant tool to help stop outbreaks more sustainably. Currently deployed under WHO Emergency Use Listings Procedure (EUL) since 2 years Summary of new polioviruses update 25-Oct-2023, cases and positive environmental isolates: • Pakistan: one WPV1 case and 17 positive environmental samples • DR Congo: two cVDPV1 cases • Egypt: three cVDPV2-positive environmental samples • Kenya: one cVDPV2 case • Madagascar: six cVDPV1 cases and three positive environmental samples • Zimbabwe: four cVDPV2-positive environmental samples Ref: https://polioeradication.org/this-week/ Poliomyelitis - Belgium Epidemiology – pre-vaccination Epidemiology postvaccination: last case - Dates from the last non-imported case of poliomyelitis in 1979 - Dates from the last imported case of poliomyelitis in 1989 - Became the last case of poliomyelitis with the vaccin-derived poliovirus, after the administration of an oral vaccine reported in 1999 - since 1989 no cases of polio were reported through the PediSurv network or mandatory reporting of infectious diseases Ref: https://www.sciensano.be/nl/gezondheidsonderwerpen/poliomyelitis-polio/cijfers#poliomyelitis-in-belgi- Poliomyelitis - global https://polioeradication.org/ Epidemiology – global - 1988: each day 1000 children were paralysed by polio → launch of Global Polio Eradication initiative - 1994: North- and South-America declared polio-free - 1996: Africa: still 76.000 paralyses due to polio - 2000: Western-Pacific polio-free - 2002: Europe polio-free - 2014: 11 countries in SO-Asia polio-free - 25-aug-2020: Africa transmission of wild-type polio stopped - 2021: start of use of new polio-vaccine to combat VDVP • • • Because of VDVP: only bivalente oral poliovaccines (type 1 and 3) are used since 2016 Wild-type Polio-type 2 and 3 have been eradicated (resp. 2015 and 2019), only wild polio type 1 is still circulating Implementation of at least 1 dosis of IPV to create immunity to polio serotype 2 Community immunity or herd immunity: necessary? Example: Spread of polio in 2013 25 Poliomyelitis – VaPP and VDPV Ref: https://polioeradication.org/polio-today/polio-now/ Poliomyelitis – VaPP and VDPV 1. World-wide organisation of vaccination programs 28 2. Organisation of vaccination programs: worldwide Define burden of disease Define target population Sustain high vaccination coverage How to reach target population? Reach high vaccination coverage 29 2. Organisation of vaccination programs: worldwide Initial focus of vaccination programs: Children: highest morbidity and mortality WHO: expanded program on immunization (EPI) in 1974 - assist developing countries ➔ routine vaccination service - focus: children <12 months - initially 6 vaccines: BCG, polio, DTP and measles - establishing necessary infrastructure and training - monitoring vaccination coverage: initial goal 80% 30 2. Organisation of vaccination programs: worldwide WHO: Vaccination programs ⇔ building blocks for strengthening the health system in the world’s poorest countries 1. 2. 3. 4. 5. 6. Health delivery system Health care workers Logistics and supply systems Health financing Health information and monitoring Leadership and governance Since 2000: GAVI: Global Alliance for Vaccine and Immunization GAVI will support the world’s poorest countries - Improve training - Provide vaccines - Sustain health care facilities 31 - Zero-dose children - integrated portfolio of support - Multi-year approvals - Differentiated approach https://www.youtube.com/watch?v=UTfwXBuS_TE&t=225s 32 Ref: https://www.gavi.org/sites/default/files/support/guidelines-2023/Gavi_Programme_Funding_Guidelines_ENG.pdf 2. Organisation of vaccination programs: worldwide 2. Organisation of vaccination programs: worldwide 33 3. Recommendations by NITAGs 34 3. Recommendations: introduction of new vaccines Vaccines: recommendations made per country NITAG = National Immunization Technical Advisory Group Vaccination schedules differ from country to country based on - Epidemiology - Current vaccination program - Country-specific tradition: e.g. number of vaccines/consultation - Resources: cost-effectiveness studies for Belgium - Scientific approach of NITAG Europe: every country it’s own vaccination schedule → ECDC: http://vaccine-schedule.ecdc.europa.eu/Pages/Scheduler.aspx 35 3. Recommendations: introduction of new vaccines: Belgium Superior High Council: scientific advisory group of the ministery of Public Health, Safety of the food chain and environment. The council is a link between the Belgian authorities and the scientific community regarding all domains that are linked to public health. ➔ Permanent working group for vaccinations ➔ federal recommendations = Belgian NITAG https://www.health.belgium.be/nl/vaccinatie Financing of vaccination program → regional - Prevention = competence of the different communities in Belgium - Each community can decide for itself which recommendations will be reimbursed and to which degree, based on specific epidemiology - Partly funded by federal government. 36 4. Basic vaccination schedule 37 4. Basic vaccination schedule: 1958 3m OPV1 4m 5m OPV2 13m OPV3 15m 5-6 yr 10-12 yr 14-16 yr 1985 3m 4m 5m DTP1 DTP2 DTP3 DTP4 DT1 OPV2 OPV3 OPV4 OPV1 13m 15m MMR1 5-6 yr 10-12 yr 14-16 yr T2 R 1996-1999 3m 4m 5m DTP1 DTP2 DTP3 DTP4 DT1 Hib1 Hib2 Hib3 Hib4 OPV4 OPV2 OPV3 HBV2 HBV3 OPV1 HBV1 13m 15m 5-6 yr 10-12 yr dT2 HBV1/2/3 MMR1 14-16 yr MMR2 2006 2m 3m 4m 12m DTaP1 DTaP2 DTaP3 DTaP4 dTap1 IPV1 IPV2 IPV3 IPV4 IPV5 Hib1 Hib2 Hib3 Hib4 HBV1 HBV2 HBV3 HBV4 PCV1 PCV2 PCV3 PCV4 Rota1 Rota2 (Rota3) MMR1 MenC 14m 5-6 yr 10-12 yr 14-16 yr dT2 HBV1/2/3 MMR2 2009-2010 8w 12w 16w DTaP1 DTaP2 DTaP3 DTaP4 dTap1 IPV1 IPV2 IPV3 IPV4 IPV5 Hib1 Hib2 Hib3 Hib4 HBV1 HBV2 HBV3 HBV4 PCV1 Rota1 PCV2 Rota2 12m 14m 5-6 yr 10-12 yr 14-16 yr dTap2 PCV3 (Rota3) MMR1 MMR2 MenC ♀:HPV1/2/3 2022 8w 12w 16w DTaP1 DTaP2 DTaP3 DTaP4 dTap1 IPV1 IPV2 IPV3 IPV4 IPV5 Hib1 Hib2 Hib3 Hib4 HBV1 HBV2 HBV3 HBV4 PCV1 Rota1 PCV2 Rota2 12m 14m 5-6 yr 7-9 yr 10-13 yr dTap2 PCV3 (Rota3) MMR1 14-16 yr MMR2 MenC/QMen HPV1/2 Vaccination schedule adults - 2023 ➢ Healthy adults - 18+ years: - ≥60/65 year: - Diphtheria-Tetanus-Pertussis (dTap): every 10 years Influenza: yearly Pneumococci: 1 time (PCV20 or PCV15 + PPV23) Zoster/zona: 1 time (2 doses) vanaf 60 jaar RSV: op individuele basis aan risicopersonen vanaf 60 jaar ➢ Pregnant women: every pregnancy - Flu: 2nd trimester - Pertussis: 24 – 32 weeks - RSV (in future?) ➢ Persons with chronic diseases: no age limit - Diphtheria-tetanus-pertussis: every 10 years - Influenza: yearly - Pneumococci: 1x and after 5 year 1 repeat - Zoster/zona: 1 time (2 doses) ➢ Travel vaccines - meningococcal vaccines, hepatitis A vaccine, yellow fever, rabies, tyhpoid fever, Tick-borne encephalitis, Dengue 5. Mandatory versus recommended vaccination 45 5. Mandatory versus recommended What is the situation in Belgium? What do you think is best? - All vaccines Only in certain situations Only certain groups National versus EU versus global Mandatory Recommended 46 5. Mandatory versus recommended Mandatory vaccination: legal obligation to be vaccinated What is the effect of legal obligation? - on immunization coverage - on public perception towards vaccination e.g. Italy, France, US Recommended: no legal obligation, but highly recommended Mandatory or recommended does not mean free of charge… 47 5. Mandatory versus recommended vaccination 48 Ref: WHO data feb 2015 6. Implementation of vaccination programs 49 6. Implementation of vaccination programs ➢ Vaccine delivery to vaccinees: health care system - Individual vaccination: e.g. tetanus for adults - Organized vaccination: - At well-baby clinics - In schools - Flu vaccination campaigns in hospitals - Mass vaccination campaigns - High income countries: e.g. Pandemic flu, SARS-CoV-2 - Low income countries - Vaccination days e.g. Polio - Door-to-door campaigns - Outbreak actions 50 6. Implementation of vaccination program ➢ Elaborated vaccination system necessary to reach entire cohorts - < 18 years: - > 18 years: - Well-baby clinics School-based vaccination programs General practitioners and pediatricians General practitioners and specialists Occupational health services 6. Implementation of vaccination program ➢ Vaccine delivery to vaccinees: logistics Cold chain needs to be preserved at all times - Vaccines: 2-8°C - During transport At pharmacy At home At vaccinator practice → Vaccines that do not work will not protect New vaccines → -20°C and -70°C 52 6. Implementation of vaccination ➢ Cold chain needs to be preserved at all times System needs to be in place to keep the cold chain at all times Difficult in low-income countries !!! - Transport to communities which are difficult to reach - How to maintain cold chain in absence of reliable access to electricity? - Batteries – batteries replacement? - Solar systeems 53 Ref: https://www.who.int/teams/immunization-vaccines-and-biologicals/essential-programme-on-immunization/supply-chain/supply-chain-tools 6. Implementation of vaccination 54 Ref: https://www.who.int/teams/immunization-vaccines-and-biologicals/essential-programme-on-immunization/supply-chain/supply-chain-tools 6. Implementation of vaccination Ethical dilemmas with implementation of SARS-CoV-2 vaccination programs? 1. Manufacturing of billions of doses 2. Who will get the first vaccine on a global scale? ▪ Who is most needing? ▪ Who is developing the vaccine? ▪ Who will take care of developing countries? 3. Within a country: who will get the first vaccines? ▪ Health care workers ▪ Safety personnel: police, border control ▪ Vulnerable population ▪ Healthy adults to prevent spread of disease 55 Decisions on reimbursement of vaccines 56 Decisions on reimbursement of vaccines Disease A - Occurrence: high (±400 000 cases/year) especially in children, but morbidity and mortality high in elderly. - Vaccination in children helps to prevent disease in elderly Eg. Influenza Disease B - Occurrence: high in children (50 000 to 75 000 cases/yr) Mortality: 1:2500 Encephalitis: 1:1000 Hospitalization: 20% - Vaccination protects children eg. Measles 57 Decisions on reimbursement of vaccines Disease A - Terrible disease: - High mortality (10%), often severe complications - Very quick evolution from healthy to very sick - Occurrence low → 100 cases/yr eg. Meningococcal disease Disease B - Mild disease, but - main cause of unisensorial deafness (1:20.000 cases of mumps) - Orchitis in men (20-30%) → infertility (1%) - High occurrence → 25.000 cases/yr eg. mumps 58 7. Evaluation of vaccination programs 59 7. Evaluation of vaccination programs 1. Epidemiology of vaccine preventable disease a. Pre-vaccine era b. Post-vaccine era 2. Vaccination coverage studies 3. Seroprevalence studies 4. Vaccinovigilance: adverse events reporting 60 7.1. Evaluation of epidemiology of vaccine-preventable diseases 61 7.1. Pre-vaccine era - Monitoring of reported cases of infectious diseases ➔ Determine burden of disease and mortality: necessity for vaccination ➔ Determine which age groups are affected most ➔ Determine how epidemics are moving through a population ➔ Determine cost-effectiveness ➔ Difficulties: - Depends on willingness of medical doctors and laboratories to report cases - Collaboration over frontiers and borders !! ➔ ECDC, CDC, WHO 62 7.1. Evaluation of epidemiology of vaccine-preventable diseases Example: Spanish flu 1918-1919 63 7.1. Evaluation of epidemiology of vaccine-preventable diseases Example: Haemophilus influenza type b 64 7.1. Post-vaccine era - Monitoring of reported cases of vaccine-preventable diseases ➔ Important to measure impact of vaccine recommendations ➔ Detect outbreaks of vaccine preventable disease ➔ Monitor outbreaks → e.g. flacid paralysis monitoring • age-related problem • risk group • vaccine efficacy ➔ Difficulties: - Due to vaccination: less cases: disease symptomatology becomes unknown - Due to vaccination: shift of cases to older age groups: different symptomatology - Depends on willingness of medical doctors and laboratories to report cases - Collaboration over frontiers and borders !! ➔ ECDC, CDC, WHO 65 7.1. Evaluation of epidemiology of vaccine-preventable diseases Example: measles outbreaks Wallonia, Belgium, 2016-2017 - Especially unvaccinated persons - Age distribution: - 29%: <5 years of age - 52% >15 years of age - 43% was hospitalised - >10% health care workers 66 Ref: https://epidemio.wiv-isp.be/ID/Pages/Rougeole.aspx 7.1. Evaluation of epidemiology of vaccine-preventable diseases Age shift in mumps outbreaks 67 Ref: N. López-Perea et al./Vaccine 35 (2017) 4339–4345 7.2. Evaluation of vaccination coverage 68 7.2. Evaluation of vaccination coverage 1. Vaccination coverage studies - Necessary to know whether population intended to be vaccinated is reached - Which factors influence vaccination coverage? - Different for different age cohorts? - Are there pockets of unvaccinated persons? - Which are your risk groups? - If outbreaks of vaccine preventable disease: was coverage high enough? 69 7.2. Evaluation vaccination coverage Ref: Rapport Vlaamse Vaccinatiegraadstudie, 2020 70 7.2. Evaluation vaccination coverage Ref: Rapport Vlaamse Vaccinatiegraadstudie, 2020 71 7.2. Evaluation vaccination coverage 2 3 4 5 6 7 Total Number of pupils with questionnaire 241 317 77 178 113 315 602 1843 Number of pupils with vaccination data 235 77 177 112 314 593 1825 Vaccination coverage at start of outbreak (%) 83.4 92.1 81.8 94.4 93.1 93.9 92.0 91.8 N mumps cases 95/96 19 43 10 13 3 15 2 105 0.3 5.7 % mumps cases during this outbreak 15 1 10 317 0 5 Percentage with mumps School 20 Mumps outbreak in Bruges 0 7.9 13.6 1 13.0 2 3 4 7.3 5 6 2.7 7 years since last vaccination 8 9 4.8 10 Ref: Vandermeulen et al. Vaccine 2004 72 7.1. Evaluation vaccination coverage Measles outbreak in Antwerp in Orthodox Jews 73 Ref: Asnong et al, PIDJ 2011, Lernout et al, Eurosurveillance 2009 7.2. Evaluation vaccination coverage Example: measles outbreak US, 2014-2015 74 Ref: CDC website 2015: http://www.cdc.gov/measles/cases-outbreaks.html 7.3. Evaluation of seroprevalence of antibodies: Seroprevalence studies 75 7.3. Evaluation of seroprevalence of antibodies - Vaccination coverage studies important to know how well population is vaccinated - BUT: most vaccines: - No 100% seroprotection - Waning of antibodies and possible protection over time is possible Seroprevalence of antibodies: - Measurement of antibodies in left-over samples of blood samples taken in hospitals (specified sort of samples) or red cross blood drives - All age groups can be sampled - Define which are critical infectious diseases to be monitored ➔ Reliable source of information to estimate risk of infectious disease over different age groups and predict risk 76 7.3. Evaluation of seroprevalence of antibodies Seroprevalence of antibodies for diphtheria and tetanus Ref: Theeten et al. Epidemiol Infect 2011 77 7.3. Evaluation of seroprevalence of antibodies Seroprevalence (%) Antibody titers diphtheria, tetanus, pertussis in adult patients with chronic conditions (n= 1052) 100 90 80 70 60 50 40 30 20 10 0 Correctly vaccinated Correctly vaccinated Age Age Correctly vaccinated 95,3 83,1 85,2 79,2 80 79,6 82,6 72,3 45,9 28,9 55,8 53,1 46,1 44,8 47,1 42,9 45,9 31,2 41,3 22,1 22,1 21,5 17,1 23 Diphtheria (≥0.1IU/ml) Tetanus (≥0.1IU/ml) All patients (n=1052) DM type 1 (n=172) DM type 2 (n=77) COPD (N=170) Heart failure (N=77) HIV (n=196) Pertussis (≥ 5IU/ml) CKD (N=130) 78 SOT (n=230) Ref: Boey et al, 2020 7.3. Evaluation of seroprevalence of antibodies Antibody titers diphtheria, tetanus, pertussis in pediatric patients with chronic conditions (n=222 ) Age-appropriate vaccination 100 90 80 70 60 50 40 30 20 10 0 93 57 61 60 56 93 88 97 89 93 93 67 69 57 Diphtheria (≥0.1 IU/ml) All patients (n=222) Diabetes (n=58) SOT (n=28) Number of doses Time since last vaccination Time since last vaccination 57 50 53 Tetanus (≥ 0,1 IU/ml) Allergy (n=14) Cystic fibrosis (n=9) 56 50 57 39 Pertussis (≥ 5IU/ml) Congenital heart disease (n=25) PID (n=88) 79 Ref: Boey et al, 2021 7.3. Evaluation of seroprevalence of antibodies Antibody titers measles, mumps, rubella in pediatric patients with chronic conditions (n= 222) Age-appropriate vaccination Age-appropriate vaccination Age-appropriate vaccination SOT 100 90 80 70 60 50 40 30 20 10 0 100 79 80 93 83 83 Measles (≥150 IU/ml) All patients (n=222) Diabetes (n=58) SOT (n=28) 86 64 78 80 78 78 86 83 81 68 57 Mumps (≥230 labU/ml) Allergy (n=14) Cystic fibrosis (n=9) 86 78 86 61 Rubella (≥10 IU/ml) Congenital heart disease (n=25) PID (n=88) 80 Ref: Boey et al, 2021 7.4. Evaluation of adverse events in vaccination programs: Vaccinovigilance 81 7.4. Evaluation of adverse events in vaccination programs Pharmacovigilance: adverse event (AE) reporting = the science and activities related to the detection, assessment, understanding and communication of adverse events following immunization and other vaccine- or immunization-related issues and to the prevention of untoward effects of the vaccine or immunization Goal: - To trigger accurate risk assessment (benefit vs. harm vs. effectiveness) and appropriate response (risk-management to the problem). - Minimization of negative effects to individuals: improve patient care and safety - Lessen the potential negative impact on immunization programs Vaccines given to healthy persons, often children ➔ NO serious AE acceptable 82 http://vaccine-safety-training.org/vaccine-pharmacovigilance.html 7.4. Evaluation of adverse events in vaccination programs The objectives for an effective AEFI surveillance system are to: 1. Identify problems with vaccine lots or brands leading to vaccine reactions caused by the inherent properties of a vaccine 2. Detect, correct and prevent immunization errors caused by errors in vaccine preparation, handling, storage or administration 3. Generate new hypotheses about vaccine reactions that are specific to the population of your country/region, 4. Estimate rates of occurrence of AEFIs in the local population compared with trial and international data, particularly for new vaccines that are being introduced. 5. Prevent false blame arising from coincidental adverse events following immunization, which may have a known or unknown cause unrelated to the immunization 6. Maintain confidence by properly responding to parent/community concerns, while increasing awareness (public and professional) about vaccine risks and safety 83 http://vaccine-safety-training.org/vaccine-pharmacovigilance.html 7.4. Evaluation of adverse events in vaccination programs Vaccine pharmacovigilance relies on three steps Any adverse events which is plausibly related to a vaccine or vaccination should be reported Especially if they are - Serious - Associated with new vaccines - Events causing significant parental or community concern 84 http://vaccine-safety-training.org/vaccine-pharmacovigilance.html 7.4. Evaluation of adverse events in vaccination programs Vaccine pharmacovigilance relies on three steps 1. Confirm the diagnosis (or propose other diagnoses) and determine the outcome of the adverse event 2. Identify specifications of implicated vaccine(s) used to immunize patient(s) 3. Examine operational aspects of the immunization program, which may have led to immunization errors 4. Justify the search for other AEFI cases/clustering 5. Compare background risk of adverse event (occurring in unimmunized people) to the reported rate in the vaccinated population. 85 http://vaccine-safety-training.org/vaccine-pharmacovigilance.html 7.4. Evaluation of adverse events in vaccination programs Example: Rotashield®: rotavirus vaccine introduced in US in 1998 Case-control analysis: 429 infants with intussusception and 1763 matched controls. 74 of 429 infants with intussusception (17.2 percent) and 226 of1763 controls (12.8 percent) had received RRV-TV (P=0.02). An increased risk of intussusception 3 to 14 days after the first dose of RRV-TV was found in the case–control analysis (adjusted odds ratio, 21.7; 95 percent confidence interval, 9.6 to 48.9). Case-series analysis: 432 infants with intussusception in a caseseries analysis, the incidence-rate ratio was 29.4 (95 percent confidence interval, 16.1 to 53.6) for days 3 through 14 after a first dose. There was also an increase in the risk of intussusception after the second dose of the vaccine, but it was smaller than the increase in risk after the first dose. We estimated that 1 case of intussusception attributable to the vaccine would occur for every 4670 to 9474 infants vaccinated. Figure 1. Interval between Vaccination with RRV-TV and Intussusception in 74 Infants. Ref: Murphy TV et al, NEJM 2001 Ref: 86 1st dose 100000 98000 96000 94000 92000 90000 88000 86000 84000 82000 80000 78000 76000 74000 72000 70000 68000 66000 64000 62000 60000 58000 56000 54000 52000 50000 48000 46000 44000 42000 40000 38000 36000 34000 32000 30000 28000 26000 24000 22000 20000 18000 16000 14000 12000 10000 8000 6000 4000 2000 0 Año 2009 .. .. . . .. . . .. . . . . . . . . Ene Feb .. Mar Abr May 2nd dose . . . . . . . . . .. ... .. . . . . . . .. . . .. . . Jun Jul Ago Sep Oct Nov Dic 50-60 adolescents (9-18 years) per each 100.000 are yearly admitted with diabetes debút Courtesy Pierre Van Damme 87 Martinón-Torres, GENVIP 2014 7. Evaluation of adverse events 88 8. Registration of vaccinations 89 8. Registration of vaccinations Immunization information systems (IIS) are: - confidential - population-based - computerized databases that record all immunization doses administered by participating providers to persons residing within a given geopolitical area. 90 8. Registration of vaccinations Advantages: IIS are effective in increasing vaccination rates and reducing vaccinepreventable disease through their capabilities to: At the individual level: 1. Determine patient vaccination status → clinicians, health departments, and schools At the population level: 2. Guide public health responses to outbreaks of vaccine-preventable disease 3. Inform assessments of vaccination coverage, missed vaccination opportunities, invalid dose administration, and disparities in vaccination coverage; and 4. Facilitate vaccine management and accountability. 5. Create or support effective interventions such as client reminder and recall systems, provider assessment and feedback, and provider reminders. 91 8. Registration of vaccinations 92 Vaccine hesitancy Vaccine hesitancy is increasing world wide → Vaccines are seen as not natural However! By using vaccines we maximize our own natural defense by maximally using our personal immunological potential. 93 "A boat doesn't go forward, if each one is rowing their own way.“ Swahili proverb 94 95