Dr Stewart Reid General Practitioner Ropata Medical Centre Wellington 7:15-8:10 Medicines New Zealand Breakfast Session Adult Vaccination The Poor Cousin
Adult Vaccination The poor cousin Stewart Reid June 2016
Conflict of interest In the past I have received support for vaccine work, clinical trials, presentation of papers and conference attendance from NZ Ministry of Health, US Government, Foundation Merieux, International Vaccine Institute, CSL, GSK, MSD, Novartis and Pfizer. Medicines NZ is paying me an honorarium for preparing and giving this talk 3 3
Outline Immune Senescence Demographic data Pregnancy 18-20 years - Meningococcal and HPV vaccines 20-64 years -Varicella vaccine >64 years - Influenza, Pneumococcal and Shingles vaccines
New Zealand Coverage At age 2 years 60% in 1992 77% in 2005 85% in 2009 12/2015-92.8% but only 80% on time Very small ethnic differences and some variability between DHBs MoH Data 5
Immunisation Coverage NZ 12/2015 6 Month 80.4% 8 Month 92.7% 12 Month 94.1% 18 Month 85.2% 2 years 92.8% 5 years 82.8% 6
Immunisation coverage NZ 2015 ethnic differences 12 month 24 month all 94.1 92.8 European 94.3 93.4 Maori 93.6 92.3 Pacifiic 96.9 96.1 Asian 96.4 95.8 Other 89.3 85.9
Demographics
New Zealand population Total Births Deaths 2014 4,509,700 57,242 31,063 2018 4,738,400 61,000 31,100 2023 4,948,800 63,200 33,200 2028 5,152,900 63,900 34,200 2048 5,761,100 52,300 52,300
New Zealand Population % Years 0-14 15-64 >64 >84 2014 20.2 65.3 14.4 1.7 2018 19.4 64.8 15.8 1.9 2023 18.7 63.3 17.9 2.1 2028 18 61.7 20.2 2.5 2048 16.4 59.7 24 5.5
Population issues 2000 turn 65 every day UK 11,000 - USA ~150 - New Zealand No of working people per elderly UK 1950-12 2000-9 2050-4
Vaccination is lifelong 18-20yrs. catch-up MMR, Hepatitis B, Td. Mening, HPV, Varicella, Influenza 20-64yrs- Tdap, Influenza, HPV, Hepatitis A, Varicella, Shingles 65+ yrs -Pneumococcal, Tdap, Influenza, Shingles Pregnancy Influenza, Tdap 12
Every Pregnancy Influenza is worse in pregnancy give vaccine in 2 nd trimester but can be given in first if in influenza season Tdap give in last trimester high 91% (95% CI 84-95%) efficacy for preventing Infant pertussis to age 3 months 1 1.Amirthalingan et al Lancet.2014:384(9953)1521-8
18-20 years Catch-up - MMR, Hepatitis B, Tdap. Mening, - communal living HPV, - Males Varicella, Influenza
Meningococcal disease NZ 2014 46 cases 1/100,000 38 confirmed - 36 typed Group B 26 epidemic strain 13 Group C 6 P1.5-1,10-8 5 Group Y 3 Group 29E 1 Which Vaccine for 18-20 years?
2013 Meningococcal Data ESR Vaccine < 1 year 1-4 years 5-9 years 10-14 years 15-19 years 20+ years Total GROUP C Conjugate vaccine A C Y W 135 Conjugage vaccine 0 3 1 2 5 6 17 2 3 2 2 7 10 26
HPV vaccine? Universal
Global Burden of HPV lesions: 607,000 cancers Penile cancer 11,000 21,000 MALE Vulva and Vaginal cancer FEMALE Oropharyngeal cancer 17,000 4,400 Anal cancer 11,000 13,000 530,000 Cervical Cancer Genital warts 30,000,000* Cancer Epidemiology Research Program De Martel et al 2012 Lancet Oncol (cancers) and 2010 Dillner et al BMJ (genital warts) *Together with low-grade cervical intraepithelial neoplasia
20-64 years Tdap, Influenza, HPV, Hepatitis A, Varicella, Shingles - Zostavax licensed from age 50
Varicella house hold contact 42 year old male no Hx Daughter Chickenpox? Vaccinate
Epidemiology of Varicella Zoster Virus (VZV) Varicella occurs worldwide and equally affects both sexes and all races. 1,2 Varicella is highly contagious and infects at least 90% of the susceptible population. 1 In New Zealand 3 it is expected that 3% are infected during infancy 8-9% infected each year throughout childhood 90% by age 14 and 97% by age 40. 1. Whitley RJ. In: Harrison s Principles of Internal Medicine. 15th ed. New York: McGraw-Hill, 2001:1106 1108. 2. Straus SE et al. In: Fitzpatrick s Dermatology in General Medicine. 5th ed. Vol. 2. New York: McGraw-Hill, 1999:2427 2450.3.NZ Imm Handbook 2011. 21
Varicella exposure age 42 97% immune by age 40 75-90% of those with no Hx immune Some evidence vaccine protects if given within 3 and possibly 5 days of exposure Options are - do nothing, blood test and vaccinate if negative Vaccinate and blood test simultaneously and give second dose if seronegative Vaccinate 2 doses
65+ Years Tdap, Influenza, Shingles Pneumococcal
Influenza Vaccine efficacy >60 years Community Randomised Controlled Trial efficacy 58% - for those > 70 years efficacy - 57% Nursing home residents efficacy less - 20-40% Influenza related death efficacy 80% MMWR August 6, 2010 / 59(RR08);1-62
Influenza Vaccine efficacy >60 years Hospitalisation for Pneumonia and Influenza variable reported efficacy between 27% and 70% Non controlled studies indicating reductions in hospitalisation and death may be subject to confounding MMWR August 6, 2010 / 59(RR08);1-62
Shingles
Country-specific Zoster Rates Annual Incidence (per 1,000 person-years) 20 18 16 14 12 10 8 6 4 2 0 Hope-Simpson (UK) Brisson (UK) Gonzalez (France) Ultsch (Germany) Insinga (US) Yawn (US) Stein (Australia) Brisson (Canada) Jih (Taiwan) Choi (South Korea) 0 10 20 30 40 50 60 70 80 90 Age 27
New Zealand Epidemiology General practice, 20,000 patients, 5 year retrospective review. Population rate 2.97/1000/annum 70% aged > 50 years Female rate > 50-10% higher rate than male 6.38/1000/annum vs 5.75/1000/annum Rates all > 50 6.1/1000/annum > 60 8.1/1000/annum > 80 13.9/1000/annum Reid JS, Ah Wong B. N Z Med J. 2014 Dec 19;127(1407):56-60
IT S GETTING WORSE
Recent Australian Data Age 60+ increase in estimated rates between two time periods 2000-2006 and 2006-2013 Results 60+ incidence GP data 11.9 to 15.4/1000/Annum Prescription data 12.8 to 14.2/1000/Annum Macintyre et all. PLOS ONE DOI:10,1371/journal.pone0125025 April 30 2015
Zoster incidence >65 years http://annals.org/article.aspx?articleid=1784289
Immune Senescence and HZ Clinical Endpoint Efficacy (%) (years of age) 60-80+ 60-69 70-79 80 50-59 Herpes Zoster 51 64 41 18 70 Postherpetic neuralgia 67 66 74 42 -- The zoster vaccine may preserve QOL without preventing infection Schmader KE et al, Clin Infect Dis 2012; 54: 922-8; Oxman et al. NEJM 352; 2271. VACC-1075639-0059 06/2015 32
Age Group Effect of Zoster Vaccine on Preserving ADLs By Age -On total study population basis- Zoster Vaccine* Loss of Activity Placebo* Loss of Activity VE (95% CI) Prevention of Loss of Activity All ages 0.89 2.64 0.66 (0.55, 0.74) 60 to 64 0.52 1.95 0.73 (0.47, 0.86) 65 to 69 0.71 2.18 0.67 (0.44, 0.81) 70 to 74 1.16 2.96 0.61 (0.35, 0.76) 75 to 79 1.38 3.66 0.62 (0.30, 0.80) 80 2.11 5.16 0.59 (0.11, 0.81) *Vaccine n= 19254, HZ cases= 315; Placebo = 19247, HZ cases = 642 AUC ADLI Area-under-the-curve activities of daily living interference Schmader K et al. J Am Geriatr Soc 2010; 58: 1634-41.
How common is a second Scarce data episode of zoster? Small populations and short follow up periods Recent study: 6.2% recurrence over 8 years Recurrence more likely in women, the immune compromised and those with prolonged pain at initial episode (Yawn et al. Mayo Clin Proc. 2011; 86) Episode of zoster does not ensure protection against recurrence 34
Vaccination after Zoster A lady aged 68, who six months ago had an attack of ophthalmic shingles, wants to avoid another attack and requests vaccine. When should it be given? Alas, there is no clear answer to this question but probably 1-3 years post shingles.
GSK Shingles vaccine N Engl J Med 2015; 372:2087-2096May 28, 2015 Inactivated vaccine 2 doses 2 months apart RCT 15411 adults > 50 7698 Vaccine 7713 placebo Follow Up 3.2 years Efficacy 6 cases vaccine group 210 cases control group 97.2% (95%CI 93.7% -99%) stable across age groups
GSK Shingles vaccine N Engl J Med 2015; 372:2087-2096May 28, 2015 Adverse events Injection Site Reactions vaccine group more than control group type 3 events which involve interference with activity 17% vaccine group 3.2% control group
GSK Shingles vaccine GSK press release publication to follow RCT 14,800 subjects aged 70 years + over 3-4 years? Efficacy against Shingles 90% (95% CI 84-94%) PHN 89% (95% CI 69-97%) Adverse events not fully analysed but data on >14000 recipients from 2 RCTs indicate Injection site reactions, muscle pain, fatigue and headache commonest events
Pneumococcal vaccine 65+ years Controversial Conjugate and polysaccharide vaccines Current recommendations age 65 PCV13 followed 8 weeks or more later by PPV23 but not funded
NZ Invasive Pneumococcal Disease quarterly report to December 2015 Age Cases 2015 RATE/ 100,000 Cases 2014 RATE/100,000 <2 18 15.1 34 28.5 2-4 12 6.3 21 11.1 5-64 209 5.9 216 6.1 >64 218 33.5 218 33.5
Invasive Pneumococcal Disease - ESR Annual report 2014 2006/7 compared to 2014 In children < 5 years 66.7% reduction in all IPD 95.6% reduction in IPD caused by PCV10 Serotypes >64 years 69.9% reduction in disease caused by PCV 10 serotypes > 64yrs 2009 all IPD rate 44.0/100,000 2015 all IPD rate 33.5/100,000
Invasive Pneumococcal Disease - ESR Annual report 2014 2006/7 2014 IPD rates/100,000 in those aged > 64 years caused by serotypes in PCV7 22.2 4.3 PCV10 23.5 7.1 PCV 13 28.0 16.0
Epidemiology Summary Substantial reduction in IPD caused by vaccine serotypes in vaccinees Reduction in IPD caused by vaccine serotypes in older age groups who have not received vaccine i.e herd effect Despite some serotype replacement by non vaccine types there is an overall reduction in IPD in all age groups
PNEUMOCOCCAL PS VACCINE EFFICACY IN ADULTS: META-ANALYSIS (RCT) PPV 23 efficacy in preventing invasive pneumococcal disease in adults 11 studies (events/n): 15/18,634 (vaccine), 63/17,855 (controls) OR [95% CI] = 0.26 [0.14, 0.45]; efficacy = 74% PPV 23 efficacy in preventing all cause pneumonia 16 studies (events/n): 978/22,643 (vaccine), 1,547/25,091 (controls) OR [95% CI] = 0.72 [0.56, 0.93]; efficacy = 28% Holden MS, Tatham DP. Cochrane Collaboration, 2013
PPV23 efficacy General agreement efficacy demonstrated against Invasive Pneumococcal Disease Variable reported efficacy against pneumonia (Cochrane review considers efficacy against pneumonia not proven 1 ) Efficacy in adults with chronic illness not defined Prevention of IPD alone is sufficient reason for vaccinating all elderly adults with PPV23 2 1.Holden MS, Tatham DP. Cochrane Collaboration, 2013 2.Fedson D et al Expert Rev Vaccines 2011:10(8):1143-1167
PCV 13 adults > 64 years efficacy N Engl Med J 2015;372:1114-25 Capita study - RCT Netherlands 85,000 subjects followed between 2008-13 Efficacy against IPD 75% ( 95% CI 41.4% - 90.8%) Efficacy against PCV13 type pneumonia 45.6% (95% CI 21.8% - 62.5%)
For those aged >64 Pneumococcal Conclusion PCV13 followed by PPV23 for those who can afford it For those who cannot PPV23 if affordable As incidence of IPD caused by PCV13 serotypes declines in elderly -?just give PPV23
Summary points Vaccination is lifelong adults need vaccines too The increasing numbers of elderly in population require all the prevention available including vaccines of modest efficacy Influenza and Tdap vaccines are important in pregnancy Males should receive HPV vaccine Shingles vaccine can reduce severity of shingles even in those aged > 80
Standing Orders for adult vaccines E.G. RMC has standing orders for nurses to administer the following adult vaccines Hep A, Hep B, Hep A/typhoid, Hep A/B Influenza Typhoid Zostavax Varicella IPV Tdap
Thank you for your attention