Immunisation Vaccines Immunisation programme Immunisation strategy

Importance of immunisation The most effective intervention (most effective public health intervention after clean water) Globally, 3 million deaths per year and 750,000 children disabled by vaccine- preventable infections 1 in 4 children (~30 million) have no access to vaccination for 6 EPI diseases (measles, polio, pertussis, diphtheria, tetanus, TB)

Types of Immunisation Passive – Temporary protection, e.g. immunoglobulin (specific protein substance produced by plasma cells to fight infection) – Taken from infected individuals, good for people whose immune systems are not strong Active – Longer term protection leading to the formation of antibodies Exploring new delivery systems e.g. aerosols, ‘edible’ vaccines, topical

Types of vaccine Live vaccine – Live but weakened organism or virus; replicates in the host – Single dose, long duration of immunity, may revert to virulent strain and can cause disease in immuno- suppressed – E.g. oral polio vaccine, MMR, yellow fever Inactivated vaccines – Killed micro-organism or their toxins or subunit vaccines – Conjugate (a vaccine where a polysaccharide antigen is chemically joined with a protein molecule to improve the immunogenicity of the polysaccharide) – Multiple doses & booster, short immunity and stable – E.g. DTaP/IPV/Hib, Men C, Hepatitis B Vaccine (HBV) and Hepatitis A Vaccine (HAV)

Vaccines Aim of vaccine is to induce long term immunological memory Interrupts transmission of the infection (for infections transmitted person to person)

Contra indications to immunisation Very few real contra-indications 1. A confirmed anaphylactic reaction to a previous dose of the vaccine 2. A confirmed anaphylactic reaction to a component of the vaccine 3. Immunosuppression (live vaccines) Check Green Book for national recommendations; WHO recommendations & manufacturer’s data sheet

Vaccine failure Primary – An individual fails to make an adequate immune response to the initial vaccination Secondary failure – An individual makes an adequate immune response initially but then immunity wanes over time

Designing/developing a Vaccination Programme Is there a suitable vaccine? Is there a need?

The need for a vaccination programme depends on: 1. Disease epidemiology – Disease incidence – Age distribution of disease – Disease trends – Disease complications – Mortality 2. Vaccine type safety and efficacy 3. Aim, cost & benefit of programme 4. Cultural attitudes and practices 5. Political expedience 6. Facilities available for delivery 7. Provision of trained primary care providers 8. Population accessibility

Vaccine Trials Pre-licensePhase 1 studiesSafety studies, in health adult volunteers (10-20) Phase 2 studiesAssess common reactions and immunogenicity – in target population ( ) Phase 3 studiesProtective efficacy – in target population (large) Post-licensePhase 4 studiesSurveillance, to detect (rare) adverse events

Vaccine Trials May also be pharmo-economic studies at phase 3 (i.e. cost benefit analysis, cost effective analysis) Phase 4 surveillance is needed to detect rarer adverse events due to variability in preparation, storage and vaccines are used in different groups than pre-license studies.

Evaluation - Targets Coverage Targets set by WHO, DoH and Local EPI European Region targets are – high coverage (over 95% overall; over 90% in all geopolitical areas) – Better surveillance – Laboratory support

Factors associated with low coverage 1. Socio-demographic variables Deprived, inner city areas Mobile families (i.e. don’t register with GP or miss appointments) Larger family size Children with chronic illness Ethnic status

Factors associated with low coverage 2. Personal Variables – Parental attitudes to disease, to vaccine – Professional knowledge and attitudes to disease, to vaccine – Misconceptions of contra-indications 3. Media stories 4. Health service variables – Poor co-ordination – Unclear responsibility – Access to guidelines and protocols – Accuracy of information – Computerisation, default lists

Developing immunisation strategy Mass immunisation or selective immunisation Selective: – travel, e.g. HAV – occupational, e.g. HBV for health care workers – Chronic disease, e.g. pneumococcal – outbreak, e.g. HAV

Developing immunisation strategy Mass immunisation’s aim is to eradicate (e.g. small pox) – Disease and its casual agent have been removed worldwide eliminate (e.g. polio) – Disease has disappeared from one region but remains elsewhere contain (e.g. Hib) – Point at which the disease no longer constitutes a ‘significant public health problem’

Prioritising vaccines WHO Global expanded Programme on immunization (EPI) – Diphtheria – Tetanus – Pertussis – Measles – TB – Poliomyelitis – Hepatitis B – Yellow fever Countries decide their own immunisation programmes depending on incidences of diseases within the countries Other priority diseases in EU are rubella and mumps and Hib Aim for WHO European Region to eliminate measles in every country by 2010.

Implementation of vaccination policy Choice of policy (mass or selective) Publish recommendations (‘green book’) License vaccine Purchase vaccine Media campaign and start giving vaccinations

Delivery of programme Central roles 1. Choice of vaccine policy (DH following recommendations from JCVI) 2. Publication of policy and recommendations (Green Book) 3. Licensing of vaccine (MHRA) 4. Control of vaccine (NIBSC) 5. Purchase of vaccine (DH) 6. Storage and distribution of vaccine (Farillon on behalf of DH)

Delivery of programme Local contract from commissioner (PCT) Provider – GP practice (practice nurse) – Community clinics (CMOs, health visitor) – Others (e.g. occupational health) UK immunisation service is excellent – Birth notification enters child on child health system in each district – Consent for vaccination obtained by health visitor – Scheduled for vaccination by child health system (or GP) – Invitation and appointment to parent and list of appointments to clinic or GP – Record of vaccinations given entered on child health system

Systems for delivery elsewhere Compulsory vaccination e.g. France, Italy Physicians must deliver vaccines e.g. France, Italy Separation of prescribing and dispensing, e.g. France

UK initiatives on immunisation coverage 1986 – district immunisation co-ordinators 1990 – GP contract (good practice payment) Others: special immunisation clinics, target health promotion campaigns, national and local education material

Surveillance Surveillance of vaccine delivery needs to follow vaccine policy Surveillance of vaccine preventable disease 1. Disease incidence 2. Vaccine coverage 3. Serological surveillance 4. Adverse events

Objectives of surveillance Pre-implementation – Estimate burden – Decide strategy Post-implementation – Monitor effectiveness, predict impact Nearing elimination – Identify pockets of susceptible – Certification process

1. Disease incidence (routine) Main sources of data – Statutory notification No lab confirmation/case definition required so poor for assessing efficacy; incomplete so low sensitivity as disease declines – Laboratory reporting – Death registration Other sources – Hospital episodes – Sentinel physician reporting More complete data linked to denominator so good for burden – Paediatric surveillance Complete, stimulated reporting so good for detailed follow up

2. Surveillance of vaccine coverage COVER Computerised child health register in each area; quarterly request to immunisation co-ordinator; national and regional aggregation of data published in CDR; SHA/PCT data fed back at regional and local levels Uses: 1. Evaluate vaccination programme 2. Feedback to public health professionals 3. Targeting areas of low coverage 4. Vaccine effectiveness/efficacy 5. Outcome measurement (risk factors for vaccine failure; impact on age and other groups) 6. Modelling, planning and policy

Surveillance Cont’d 3. Serological Surveillance Representative samples of target population, can be ad- hoc or routine Opportunistic samples Collected annually for 1-15 years; five yearly for adults; age and sex coded 4. Adverse events following immunisation (AEFI) This is any event that follows immunisation that negatively affects health passive reporting (i.e. yellow card) active reporting – used for rare serious adverse events; British Paediatric Surveillance Unit – aseptic meningitis following MMR eventually led to withdrawal of Urabe vaccine