Immunisation schedule September 2016 Helen Sisson h.sisson@hull.ac.uk @hsisson1

After clean water, vaccination is the most effective public health intervention in the world for saving lives and promoting good health (HPA, 2013). January 2016

Focus of session Meningococcal vaccination Flu vaccination for children and 2016/17 season Vaccinating during pregnancy Administration of live vaccines January 2016

1st Sept 2015 January 2016

What is meningococcal disease? Invasive bacterial infection caused by Neisseria meningitidis, AKA the meningococcus Important clinical and public health problem: rare but serious disease onset is sudden and often dramatic The most common clinical presentations are meningitis and septicaemia: significant morbidity and mortality Significant case fatality rate ~10% but varies with age, capsular group, and clinical presentation: 1 in 8 survivors have long term complications Brain damage, deafness, epilepsy, limb/digit loss, cognitive deficit January 2016

http://www.bbc.co.uk/news/uk-england-35603938 http://www.bbc.co.uk/news/uk-england-london-35602045 January 2016

Meningococcal Capsular Groups There are 12 known meningococcal groups, each possessing a distinct outer polysaccharide (sugar) capsule. The organism is associated with both asymptomatic carriage and invasive disease >95% of cases are sporadic but occasional outbreaks occur, e.g. in families, schools, universities January 2016

Global distribution of invasive meningococcal disease Harrison LH, Trotter CL, Ramsay ME. Global Epidemiology of Meningococcal Disease, in Vaccines against Meningococcus, 2009; 27 Suppl 2:B51-63. January 2016

Laboratory confirmed cases invasive meningococcal disease England and Wales January 2016

MenB disease by age-group (England & Wales, 2008-13) January 2016

Meningococcal Disease in England The UK (and ROI) have the highest incidence of IMD in Europe In England, capsular groups B, W and Y are responsible for nearly all meningococcal infections across all age groups Routine meningococcal C (MenC) conjugate vaccination introduced in 1999 has nearly eliminated invasive MenC disease in England MenB still accounts for 70% of all laboratory-confirmed meningococcal cases in England and >90% of cases in children and adolescents January 2016

January 2016

Who are we vaccinating? Invasive meningococcal disease by age England & Wales (2006/07-2010/11)

The vaccines – Men B Bexsero® – developed with 4 antigens (OMV + 3 proteins) Reverse vaccinology Extensively trialled in infants & children – no safety concerns UK is first county to use this vaccine routinely Aim to provide protection at peak age of 5 months Protection to last into 2nd year of life Given at 2-4-12 months (with catch-up for those born between 1st May & 30th June) Men B PHE guidance: https://www.gov.uk/government/publications/menb- vaccination-introduction-from-1-september-2015

January 2016

Vaccination schedule Sept 2015 (up to 18 years) Age Diseases protected against 2 months Diphtheria, tetanus, whooping cough, polio, Hib, Pneumococcal, Rotavirus, and Meningococcal group B (Men B) 3 months Diphtheria, tetanus, whooping cough, polio, Hib, and Rotavirus 4 months Diphtheria, tetanus, whooping cough, polio, Hib, Pneumococcal and Men B 12-13 months Hib/Men C Pneumococcal, Measles, mumps & rubella (MMR) and Men B 2-6yrs 3yrs 4m Children’s flu vaccine Diphtheria, tetanus, whooping cough, polio MMR (pre-school immunisations) 12-13yrs HPV (cervical cancer) girls only 2 x doses 6 months apart 13-18yrs Diphtheria, tetanus, polio (school leavers immunisations) Men ACWY

Administration Left thigh (ideally on it’s own so that local reactions can be more accurately monitored) Accurate recording Bexsero® is associated with higher rates of local and systemic reactions when give with other routine infant vaccinations, but pattern predictable (peak at 6 hours and resolution the following day post vaccination)

January 2016

January 2016

January 2016

Laboratory confirmed cases invasive meningococcal disease England and Wales January 2016

MenW cases by age group England, 2010/11-2014/15* January 2016

Men ACYW - JCVI recommendations: February 2015 In view of rapid increase in cases, known virulence of clonal complex 11 and international experience JCVI considered situation a public health emergency Optimal strategy difficult to decide based on wide age distribution Option to replace MenC doses with quadrivalent conjugate (ACWY) warrant urgent consideration Toddler dose is given as Hib-MenC – still need the Hib booster Teenagers are at high risk AND known to have high carriage rates Vaccination for school years 10-13 should have rapid impact on carriage and therefore have impact on disease in all age groups Speed of effect will depend on speed of catch-up campaign January 2016

Men ACWY – The vaccines Menveo® and Nimenrix ® are the two vaccines recommended for the routine MenACWY immunisation programme for adolescents Conjugate vaccines

January 2016

Administration – the schedule Catch up to run from Autumn 2015 into 2016 Aimed at adolescents in years 9, 10, 11, 12 & 13 and some university students Full details regarding the ACYW catch up see: https://www.gov.uk/government/uploads/system/uploads/at tachment_data/file/437901/150622_ACWY_bipartite_letter. pdf January 2016

Changes to Men C JCVI advised infants no longer need vaccination No Men C at 3 months from 1st July Hib/Men C at 12 months still to be given From 1st July no longer available as single Men C vaccine Invasive Men C disease hardly seen Men ACWY programme = herd immunity Vaccine update Issue 243, April 2016

Flu vaccination in the UK Late 1960s: annual flu immunisation recommended to directly protect those in clinical risk groups who are at a higher risk of flu associated morbidity and mortality 2000: flu vaccine policy extended to include all people aged 65 years or over 2010: pregnancy added as a clinical risk category for routine flu immunisation 2013: phased introduction of an annual childhood flu vaccination programme for all children aged 2-16y began with vaccine offered to all children aged 2 and 3 years and seven geographical pilots in primary school aged children 2014: phased introduction of childhood flu vaccination programme continued with vaccine offered to all children aged 2, 3 and 4 years and geographical pilots in primary and secondary school aged children 2015: offer to all 2, 3 & 4 year old children and children of school years 1 & 2 2016: offer to all 2, 3 & 4 year old children and children of school years 1, 2 & 3 January 2016

Why vaccinate children against flu? Extension of the seasonal flu vaccination programme to all children aims to appreciably lower the public health impact of flu by: Providing direct protection thus preventing a large number of cases of flu in children Providing indirect protection by lowering flu transmission from children to other children, to adults and to those in the clinical risk groups of any age Reducing flu transmission in the community will avert many cases of severe flu and flu- related deaths in older adults and people with clinical risk factors Annual administration of flu vaccine to children is expected to substantially reduce flu- related illness, GP consultations, hospital admissions and deaths It has been estimated that if just 30% of children had the flu vaccine, there could be 2000 fewer deaths and 11 000 fewer hospitalisations due to flu each year January 2016

Which vaccine? Two main types of vaccine available: Inactivated – by injection Live - by nasal application Trivalent vaccines = 2 x A and 1 x B virus types (most inactivated vaccines are trivalent) Quadrivalent vaccines 2 x A and 2 x B virus types As quadrivalent vaccines may be better matched and therefore may provide better protection against the circulating B strain(s) than trivalent flu vaccines, the live intranasal vaccine offered to children aged 2yrs and over is a quadrivalent vaccine, as is the inactivated vaccine recommended for children aged 3years and above who cannot received live vaccine January 2016

Fluenz Tetra® More effective than inactivated vaccines Attenuated whole live virus Q - So can it cause flu then? A - No - in addition to being attenuated, (weakened), the live viruses in Fluenz Tetra® have been adapted to cold so that they cannot replicate efficiently at body temperature Usual contraindications apply PHE flu in children guidance: https://www.gov.uk/government/publications/childhood-flu- programme-qa-for-healthcare-professionals January 2016

National flu immunisation programme 2016/2017 – Key messages flu immunisation is one of the most effective interventions we can provide to reduce harm from flu and pressures on health and social care services during the winter it is important to increase flu vaccine uptake in clinical risk groups because of increased risk of death and serious illness if people in these groups catch flu for a number of years, only around half of patients aged six months to under 65 years in clinical risk groups have been vaccinated influenza during pregnancy may be associated with perinatal mortality, prematurity, smaller neonatal size, lower birth weight and increased risk of complications for mother vaccination of health and social care workers protects them and reduces risk of spreading flu to their patients, service users, colleagues and family members by preventing flu infection through vaccination, secondary bacterial infections such as pneumonia are prevented. This reduces the need for antibiotics and helps prevent antibiotic resistance January 2016

Possible complications… Common: bronchitis otitis media (children), sinusitis secondary bacterial pneumonia Less common: meningitis, encephalitis, meningoencephalitis primary influenza pneumonia Risk of most serious illness is higher in children under six months, pregnant women, older people and those with underlying health conditions such as respiratory disease, cardiac disease, long-term neurological conditions or immunosuppression. Flu during pregnancy may be associated with perinatal mortality, prematurity, smaller neonatal size and lower birth weight Morbidity and mortality attributed to flu is a key factor in NHS winter pressures and a major cause of harm to individuals especially vulnerable people. The annual flu immunisation programme helps to reduce GP consultations, unplanned hospital admissions and pressure on A&E and is therefore a critical element of the system-wide approach for delivering robust and resilient health and care services during the winter. The national flu immunisation programme 2016/17

Vaccine eligibility: 2016/2017 flu season all children aged two, three and four years on 31 August 2016 all children of school years 1, 2 and 3 age all primary school-aged children in former primary school pilot areas those aged six months to under 65 years in clinical risk groups all pregnant women (including those who become pregnant during flu season) those aged 65 years and over (including those becoming 65 years by 31 March 2017 those living in long-stay residential care homes or other long-stay care facilities carers and household contacts of immunocompromised individuals Frontline health and social care workers should be provided flu vaccination by their employer. This includes general practice staff. January 2016

Morbidly obese patients JCVI has advised morbidly obese patients (BMI 40+) could benefit from flu vaccination those with morbid obesity (BMI>40) found to be at higher risk of hospitalisation and death following pandemic influenza infection many in this patient group already eligible due to complications of obesity that place them in another risk category practices need to use clinical judgement to decide whether to vaccinate this group of patients however, flu vaccinations for morbidly obese patients with no other recognised risk factor will not attract a payment in 2016/17 January 2016

Uptake rates 2012/13 – 2015/16 January 2016

Vaccines for clinical risk groups January 2016

Which vaccine and how many times? January 2016

2016/2017 Flu vaccine composition Trivalent vaccines will contain the following three viruses: • an A/California/7/2009 (H1N1)pdm09-like virus • an A/Hong Kong/4801/2014 (H3N2)-like virus • a B/Brisbane/60/2008-like virus In addition to the above, the quadrivalent vaccine will also contain: B/Phuket/3073/2013-like virus None of the influenza vaccines for the 2016/17 season contain thiomersal as an added preservative. More detailed information on the characteristics of the available vaccines, including age indications can be found in the Influenza chapter of the Green Book (Immunisation against infectious disease) and the product SPCs. January 2016

Egg allergy Most flu vaccines are prepared from viruses cultured in embryonated hens eggs Children Children with egg allergy may be safely vaccinated with the LAIV in any setting those with both egg allergy and clinical risk factors that contraindicate LAIV (eg immunosuppression) should be offered an inactivated flu vaccine with a very low ovalbumin content (less than 0.12μg/ml) children with a history of severe anaphylaxis to egg that has previously required intensive care, should be referred to specialists for immunisation in hospital Adults Those with egg allergy can receive vaccine with ovalbumin less than 0.12µg/ml Those with severe anaphylaxis refer for controlled adminstration There is no ovalbumin free vaccine available in the 2016/2017 flu season

Beware of product confusion!

Full PHE flu 2016/2017 slideset: https://www.gov.uk/government/publications/national-flu-programme-training-slide-set-for-healthcare-professionals

Why vaccinate during pregnancy? Pregnant women may be greater risk if infection is acquired Passive protection is important for newborns PHE Flu in pregnancy guidance: https://www.gov.uk/government/publications/influenza- vaccination-in-pregnancy-advice-for-healthcare-professionals PHE Pertussis in pregnancy guidance: https://www.gov.uk/guidance/pertussis-whooping-cough- immunisation-for-pregnant-women-resources-and-training January 2016

What happens in the pregnant immune system? Innate immunity Same immediate response Non specific Fast Adaptive immunity Highly specific T & B cells Antibody production Takes time January 2016

Administration of antibodies Passive immunity Transfer of maternal antibodies Administration of antibodies January 2016

Transfer of maternal antibody (passive immunity) IgG crosses the placenta – most after 32 weeks and reaches maternal levels by 33 weeks IgG1, IgG2, IgG3, IgG4 Relies heavily on quantity and ability of transfer but can provide newborn with passive protection against many vaccine preventable diseases (VPDs) – tetanus, polio, measles, HBV, mumps, diphtheria…. Predominantly IgA in breast milk January 2016

Flu Flu infection during pregnancy maternal complications May be associated with preterm birth and SGA babies Immunisation with inactivated vaccine recommended Any stage of pregnancy – with each pregnancy WHO recommendations for uptake are 75% January 2016

January 2016

Lab confirmed pertussis cases in England 1998-2014 January 2016

Vaccine update: Issue 249, July 2016 January 2016

Pertussis vaccination (in pregnancy) Vaccination containing low dose (d not D) diphtheria 28-32 weeks ideally STOP PRESS Uptake? Data from PHE April 2014-March 2015 Prenatal pertussis vaccine coverage in England January 2016

JCVI advised vaccination from 16 weeks Maternal vaccination in 2nd trimester = neonatal antibodies Bigger window for vaccination Advised after 20 week scan Still okay after 32 weeks although protection for infant not as effective Vaccine Update Issue 242, March 2016

Interval Spacing of vaccines Doses of the same inactivated vaccine – 4 weeks apart (or 8w for PCV) Live vaccines (same or different) – 4 weeks apart No interval need be observed between: live and inactivated vaccines doses of different inactivated vaccines No evidence exists that inactivated vaccines interfere with the immune response to other inactivated vaccines or to live vaccines An inactivated vaccine can be administered either simultaneously or at any time before or after a different inactivated vaccine or live vaccine January 2016

April 2015 January 2016

Recommendations for giving more than one live attenuated vaccine in current use in the UK Vaccine combinations Recommendations Yellow fever & MMR 4 weeks between NOT on same day Varicella (and zoster) & MMR OR okay to be given on same day Mantoux testing & MMR If recent MMR given then wait 4 weeks before Mantoux If Mantoux initiated then delay MMR until after test read UNLESS measles protection urgently required All other live vaccines (BCG, rotavirus, LAIV, oral typhoid, yellow fever, varicella, zoster & MMR) and Mantoux testing Apart from combinations listed above can be given at any time before or after each other. January 2016

Thank you! With acknowledgement to Public Health England for use/adaptation of slides January 2016

Further reading/resources Green Book online: https://www.gov.uk/government/collections/immunisation -against-infectious-disease-the-green-book Algorithm for uncertain/incomplete vaccination status: https://www.gov.uk/government/publications/vaccination- of-individuals-with-uncertain-or-incomplete-immunisation- status January 2016