Childhood immunisation: An Update Helen Bedford Senior Lecturer in Children s Health UCL Institute of Child Health h.bedford@ucl.ac.uk June 11 th 2013
Immunisation Part of Healthy Child Programme HVs and SNs key role to play in advising parents and young people Administering vaccines Recent years some public loss of confidence in vaccines Trust is pivotal in maintaining and restoring confidence in vaccines HCWs can do much to build and maintain trust in their communications with parents Being well informed the foundation for effective communication 2
Plan Current routine UK schedule Confirmed changes to schedule in 2013 Introduction of rotavirus vaccine Change to timing of Men C vaccine Flu vaccine for all 2 year old children with pilots for other age groups Shingles vaccine for adults Latest on MMR vaccine and measles outbreaks Pertussis vaccine in pregnant women Possible future addition Men B vaccine 3
Routine Childhood & Adolescent Immunisation Schedule May 2013 0 BCG 0 Hepatitis B 4w. Hepatitis B 8w. Hepatitis B 8w. DTaP(5)/IPV/Hib & PCV 12w. DTaP(5)/IPV/Hib & Men C 16w. DTaP(5)/IPV/Hib & PCV & Men C 12m. Hepatitis B 12-13m. Hib/Men C & PCV & MMR 3yr 4 m MMR, DTaP(3)/IPV (or dtap(5)/ipv) Hepatitis B 12-13 yr HPV (girls) 13-18 yr Td/IPV 4
Routine Childhood & Adolescent Immunisation Schedule Confirmed changes in 2013 0 BCG 0 Hepatitis B 4w. Hepatitis B 8w. Hepatitis B 8w. DTaP(5)/IPV/Hib & PCV & Rotavirus 12w. DTaP(5)/IPV/Hib & Men C & Rotavirus 16w. DTaP(5)/IPV/Hib & PCV & Men C 12m. Hepatitis B 12-13m. Hib/Men C & PCV & MMR 2yr Influenza 3yr 4 m MMR, DTaP(3)/IPV (or dtap(5)/ipv) Hepatitis B 12-13 yr HPV (girls) 13-18 13-14 yr Td/IPV & Men C 13-14 yr Men C 5
Confirmed Change to schedule in 2013 Introduction of Rotavirus vaccine Most common cause of severe gastroenteritis in infants and young children Estimated 453,000 deaths pa more than 90% in resource poor countries In industrialised countries rotavirus main pathogen responsible for hospital admissions for diarrhoea In UK approx 750,000 episodes diarrhoea pa Cause of half of all gastroenteritis in children under 5 years olds By age 5, all children will have encountered it 6
Rotavirus by age in months
Estimated incidence rates and annual episodes due to rotavirus infection in children aged under 5 in England & Wales (Harris et al Vaccine 2007) Setting Non elective hospital admissions (from HES) Accident and emergency admissions (from London A&E) GP consultations (from RCGP consultation rates) GP Consultations (from GPRD consultation rates) Incidence per 1000 children (95% CI) Annual number of episodes 4.49 (4.23 4.76) 14,300 Annual cost to NHS 8.8 million ( 8.32-9.2m.) 9.3 (7.3 11.3) 29,700 1.7 million ( 1.3-2.1m) 28.4 (25.7 31.1) 90,600 44.3 (39.4-49.3) 133,400 3.7 million ( 3.3-4.1m) NHS Direct calls 11.8 (10.7 12.9) 37,496 0.56 million Total 14.8 million ( 13.3-16.0m) 8
Rotavirus vaccine in USA March 1998: RotaShield first recommended for use in USA July 1999: Use of Rotashield suspended because of suspected link with intussusception clustered 3-14 days after first dose October 1999: Link with intussusception confirmed and vaccine no longer recommended August 2006: RotaTeq recommended for use at 2, 4 & 6 months July 2008: Rotarix added to recommendations, to be given at 2 & 4 months Pre-licensure trials US - 60-70,000 infants 9
Rotarix Vaccine Live Attenuated vaccine Effective against 5 strains cause 98% disease Given orally First dose by 15 weeks Second dose by 24 weeks Efficacy Highly effective against severe rotavirus disease in 1 st year of life 100% protection against disease requiring hospitalisation Side effects Diarrhoea Irritability Intussusception (?1 or 2 extra cases per 100,000 doses) 10
Resources Joint letter from DH, PHE and NHS England April 2013: Important changes to the national immunisation programme in 2013/14: introduction of rotavirus vaccination for babies at 2 and 3 months Green Book Rotavirus chapter Q&As for healthcare professionals on PHE website NHS Rotavirus information factsheet, leaflet and flyer https://www.gov.uk/government/organisations/public -health-england/series/immunisation 11
Confirmed Changes to schedule in 2013 Change to timing of Men C vaccine Effectiveness and antibodies rapidly wane after Men C vaccination in infancy Evidence that effectiveness and antibody persist better after single dose in older age groups >>> booster @12 months introduced in October 2006 Now know antibody wanes rapidly after this booster Cohort entering adolescence who may be susceptible to Men C (one dose in 1999) Single dose in infancy is immunogenic Booster dose in adolescence much longer lasting protection into adulthood 1+1+1 schedule = direct protection for immunised + indirect protection via population immunity 12
Confirmed changes to schedule Introduction of routine influenza vaccine for 2 year old children Children are an important source of influenza infection for vulnerable patients and have a significant morbidity themselves Ultimately, universal for all children 2 years to 16 years Live attenuated nasal spray 2 doses on 1 st occasion if <9 years old Initially in 2013/14 All 2 year olds Further details awaited 13 BUT
Live attenuated influenza vaccines (LAIV) Fluenz (Flumist in USA) nasal spray Nasal administration: more acceptable for children Fewer side-effects (mainly nasal congestion / rhinorrhoea, but also decreased appetite, headache & malaise) Only LAIV has high efficacy in children only licensed from 2 years upwards so annual vaccination programme will target 2-16 year olds via schools (5-16) and GPs (2-4 year olds) 14
Confirmed changes to schedule Introduction of shingles vaccine for over 70 year olds Chickenpox Primary infection by a virus Most common in young children Transmitted through direct contact between people or indirectly via airborne droplets. usually a mild illness in children Greater risk of complications for infected neonates, adults, pregnant women or those who are immunocompromised 15
Varicella Zoster Disease (Shingles) Reactivation of chickenpox virus Follows the pattern of a sensory nerve Painful Can scar Is infectious, but cannot be caught About 50 deaths per year
Varicella Zoster Vaccine Live attenuated vaccine with high dose of virus Zostavax Single dose given subcutaneously Contraindications Anaphylaxis to an ingredient Immunosuppression Pregnancy (avoid for one month)
MMR vaccine where are we now?
Measles, mumps and rubella vaccines in UK 1968 live attenuated measles vaccine introduced at 12-18 months 1970 live rubella vaccine - prepubertal girls and nonimmune women (programme discontinued 1996) MMR 1 st dose at 12-13 months introduced in 1988 2 nd dose before school entry introduced in 1996 (or shorter interval) Protection from one dose of MMR Rubella-98%; Measles-90-95%; Mumps 85% 19
Measles, Mumps and Rubella Viral diseases Measles extremely infectious 1 in 15 have complications Mumps complications affects girls and boys Rubella innocuous in childhood but high risk of CRS if caught in first 12 weeks of pregnancy 20
Annual measles notifications & vaccine coverage England and Wales 1950-2010 Notifications ('000s) 800.000 600.000 400.000 200.000 Measles vaccine (1968) 2 nd MMR (1996) MMR vaccine (1988) MR campaign (1994) 100 80 60 40 20 Vaccine coverage (%) 0.000 0 1950 1960 1970 1980 1990 2000 2010 Year Sources: The Information Centre and Health Protection Agency 21
Measles - confirmed cases England and Wales 1996-2012 Source: Public Health England
Mumps incidence in England and Wales Laboratory reports and GP consultation rates 1200 1000 800 600 400 200 1960-2000 MMR introduced GP consultations Lab reports MR campaign 0 1960 1970 1980 1990 2000 Year 23
Number of laboratory confirmed mumps cases in England and Wales by year of birth and quarter Year of Birth Source: Health Protection Agency 2010
Mumps: Current Issues 2466 confirmed cases in 2012 Since 2004, the majority of the confirmed cases have been linkedwith outbreaks in universities Many confirmed cases are still unvaccinated or have had only onedose these cohorts were included in the MR catch-up campaign but were not part of the routine two-dose MMR schedule Recommend new entrants to universities and colleges have two doses of MMR before commencing their studies Analysis of the 2004-05 epidemic and data from US suggest that decline in protection with time (since vaccination) may also contribute to cases in university students One study showed 2-dose vaccine efficacy decreased from 99% among 5-6 year olds to 86% among 11-12 year olds 25
Congenital rubella births (NCRSP) 1971-2010 and rubella associated terminations* (ONS) 1971-2000 CR births (n) Terminations (n) 80 70 MMR CR births (England, Scotland, Wales) 1000 60 50 40 Rubella-associated terminations (England & Wales) 800 600 30 400 20 10 200 0 0 71 73 75 77 79 81 83 85 87 89 91 93 95 97 99 '01 '03 '05 '07 '09 *Terminations data not published since 2000 because of very low numbers
MMR - autism and bowel disease the research 1998 Wakefield et al. Lancet publication interpreted as showing link between MMR vaccine, autism and bowel disease 27
Press conference - Royal Free Hospital 1998 Andrew Wakefield made statement that he had enough doubt in his own mind about the safety of MMR vaccine to suggest that children should receive single measles, mumps and rubella vaccines separated by a year. Provided no evidence to support suggestion in 1998 2013 still stands by suggestion still has provided no evidence in support 28
MMR safety scare was biggest science story of 2002 1257 articles mostly written by non-expert commentators 29
MMR - autism and bowel disease the research 1998 Wakefield et al. Lancet publication interpreted as showing link between MMR vaccine, autism and bowel disease 1998 no studies had specifically looked at links between MMR vaccine autism and bowel disease no biological plausibility 1998-2013 - Significant body of research-at least 13 sound epidemiological studies + evidence reviewed by expert bodies in USA, UK, Canada etc Evidence of no link between MMR vaccine and autism and bowel disease. 30
Why not use single vaccines? Regimen of single vaccines never been given in way suggested - at yearly intervals any where in the world no evidence from either trials or use to show efficacy and safety of single vaccines used in this way scientific evidence for appropriate interval? scientific evidence for order to give vaccines? any gap leaves individual child at risk lower uptake likely ( 6 injections vs 2) - allow diseases to circulate loss of herd immunity puts susceptible people at risk pregnant women, infants, immunosuppressed to eliminate rubella and CRS need high uptake in young children? uptake of single vaccines 5.8% in MCS study (8% in London) 52% completed full course (BMJ 2008) 31
Other events 2007- Andrew Wakefield and two colleagues referred to General Medical Council - 2007 Concerns over ethics of research and financial irregularities 2010- Andrew Wakefield and one colleague struck off medical register 2010- Lancet paper retracted 2011 - Three part BMJ series in which investigative journalist Brian Deer provided evidence that MMR scare was a fraud. No single case of the 12 reported in 1998 paper could be reconciled with the medical records-i.e. facts altered to provide the results wanted. 32
COVER data (Public Health England, Public Health Wales and Health Protection Scotland) MMR1 reported uptake by 24 months, 1996-2012
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Measles outbreaks - 2013 Measles notifications Wales 1 November 2012-30 May 2013 1362 35
COVER data (Public Health England, Public Health Wales and Health Protection Scotland) MMR1 reported uptake by 24 months, 1996-2012
Daily Express. Feb 7th 2002 37
Measles cases 2012 by age Source: Public Health England 38
COVER data for selected PCTs with uptake of MMR2 at 5 years Oct-Dec 2012 London PCTs overall 80.7% Kensington and Chelsea 69.7% Southwark 77.4% Sutton and Merton 67.6% Wandsworth 76.9% Tower Hamlets 92.0% England 87.5% 39
Preventing further outbreaks of measles Two doses - after age of 18 months gap 1 month Nice guidance 2009 Offer MMR opportunistically Check immunisation status of children entering daycare, schools (primary and secondary) Children in hospitals, A&E? Offer more accessible catch up immunisation clinics Be positive about MMR encourage parents 40
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Incidence of laboratory confirmed pertussis by age group 1998 to 2012* (*provisional) 250 <3 months 3-5 months 6-11 months 200 150 1-9 years 10-14 years 15-24y >=25 years 100 50 0 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 43
Pertussis cases in infants 44
Pertussis vaccine programme in pregnant women rationale and recommendations Mothers an important source of infection their immunity will be boosted so less likely to infect baby Mother s antibodies cross the placenta and may protect the newborn until first dose of vaccine @ 2 months Evidence of increased antibodies in breast milk of recently vaccinated women (unclear if protective) Offer a single dose of Repevax (dtap/ipv) between 28-38 weeks pregnancy (if not poss offer anytime up to baby receiving first dose) Offer in every pregnancy Outbreak response measure 45
Laboratory confirmed pertussis cases between January 2012 and January 2013, England & Wales 1800 All ages 25+ years <3 months 60 Total cases 1600 1400 1200 1000 800 600 400 200 50 40 30 20 10 Total cases (<3 months of age) 0 Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec Jan 0 46
Current view of impact of vaccine programme Reduction in cases since Sept 2012? Due to vaccine programme Early and very provisional calculations of vaccine effectiveness are encouraging Maternal attitudes are encouraging Vaccine coverage is encouraging 60% Challenges Temporary programme - when do we stop? (continuing in 2013/4) Evaluation of the programme Long term strategies to optimise pertussis control 47
Observations on recent rise in Pertussis disease Increased recognition in adults Protective effect of the vaccine is known to wear off as is immunity from natural infection Acellular vaccine may wane quicker/more than whole cell Build up of susceptibles Could different strains of the organism be prevalent? ******** Adults may act as a reservoir for disease that can be transmitted to unvaccinated infants Could immunisation of adolescents and/or parents reduce disease in infants? Pertussis is a complicated disease! 48
Possible future addition to programme Men B vaccine Serogroup B meningococcus now causes 88% of all Invasive meningococcal disease in England and Wales. Serogroup Y meningococcus accounts for much of the remainder of IMD (4.2% of all IMD in England and Wales); the majority of serogroup Y cases are in people aged 45 years and over, often with comorbidities; a small number of cases of serogroup Y disease are seen in teenagers. 49
Possibleaddition of Men B vaccine to routine infant schedule 4 component meningococcal B (4CMenB) vaccine Trials at many ages in childhood have shown: Good immunological responses Good tolerability, but high rates of low grade fever and local reactions 3 doses at 8, 12 and 16 weeks Now licenced Cost effectiveness, and therefore price, will be the main consideration 50
Sources of information for health professionals https://www.gov.uk/government/organisations/public-healthengland/series/immunisation