Vaccines are for adults too..and what’s new!

1. Vaccines are for adults too..and what’s new! Dr. Taj Jadavji Professor, Departments of Microbiology, Immunology & Infectious Diseases and Paediatrics Faculty of Medicine University of Calgary Infectious Disease Consultant – Alberta Health Services

2. Vaccines are for adults too..and what’s new! Disclosure: • Have received Honoraria from: - Glaxo Smith Kline - MSD - Abbott - Sanofi Pasteur - Novartis - Roche - Pfizer

3. Vaccination Motor-vehicle safety Safer workplaces Control of infectious diseases Decline in deaths from coronary heart disease and stroke Safer and healthier foods Healthier mothers and babies Family planning Fluoridation of drinking water Recognition of tobacco as a health hazard 10 Great Public Health Achievements – Industrialized Countries In the last 50 years Immunization has saved more lives than any other health intervention US Dept of Health and Human Service, MMWR 1999;48:241

4. Vaccines are for adults too! In the United States why do a 100 fold more adults die of vaccine-preventable diseases than do children? From Reid KC, Grizzard TA, Poland GA. Mayo Clin Proc. 1999;74:377–384 4

5. Vaccines & Older Adults • Immunosenescence is one of the main reasons for the increase in infections in the older adult.2 • Although childhood vaccines usually prevent clinical illness….. Most adult vaccines do not prevent illness but lessen the severity of infection.2 • Fulop, T, and Gemmill, I, Clinical update on adult immunization. 2007 • Aw, D., et al, Immunosenescence: emerging challenges for an ageing population. Immunology 2007. 120, 435–446.

6. May 2014 6

7. HPV

8. The Annual Burden of HPV in Canada ~510 deaths from cervical, vulvar and vaginal cancers6 ~1835 newly diagnosed cases of cervical, vulvar and vaginal cancers2,3 77,000newly diagnosed cases of genital warts, VIN VAIN 4,5 >325,000 abnormal Pap tests1 >4 million Pap tests 1 1. Akom E, Venne S. November 2002. 2. Statistics Canada. Table 103-0513. CANSIM [Canadian Cancer Registry]. 3. Canadian Cancer Society / National Cancer Institute. Canadian Cancer Statistics 2005:88-9. 4. BC Cancer Agency, 2006. 5. Statistics Canada. Accessed at http://www.40.statcan.ca/101/cst01/demo02.htm. 6. Statistics Canada. Table 102-0522. CANSIM [Vital Statistics – Death Database]. 31

9. 70% 9 Cancer Causes Control (2012) 23:1343–1348

10. NACI RecommendationsCCDR 2007 Feb vol 33 Vaccine recommended to: • 9-13 yr olds primary program • 14 yrs-26 yrs. catch • permissive use > 26yrs. • Including those with cervical abnormalities and genital warts

11. Mid-Adult Women Are At Continued Risk for Acquiring HPV Infection/Disease Incidence of New Genital Warts in Women by Age in US 7 6 5 4 Rate of New Genital Warts per 1000 Person-Years 3 2 1 0 <10 10-14 15-19 20-24 24-29 30-34 35-39 40-44 45-49 50+ Age (years) Insinga RP. Clin Inf Dis. 2003;36:1397-1403.

12. Primary Efficacy Results Combined Incidence of HPV 6/11/16/18-Related Persistent Infection or Cervical/Vulvar/Vaginal Disease – Per Protocol Efficacy Population Approved for ages 9-45yrs PYR = person years at risk; CI = confidence interval. Luna, IPV Nov 2009

13. Reduction in any Cervical Procedure due to any Causal HPV type 18,150 16-26 yr olds, RPCT x 3yrs ↓42% ↓22% ↓19% Colposcopy Cervical Biopsy Definitive therapy Cases Placebo 1077 950 230 Cases Vaccine 869 741 132

14. NACI recommendations on HPV vaccine in males Jan 2012 1.HPV4 (Gardasil) recommended in males 9 -26 years of age for the prevention of anal ,penile, perineal intraepithelial neoplasia ,cancers and anogenital warts 2. HPV4 (Gardasil) recommended in males who have sex with males (MSM) ≥9 years of age 3. HPV2 (Cervarix) not recommended in males at this time (NACI Recommendation Grade I).

15. Australia Free 12-18 yrs &< 26yr 2007-2009 Sex.Trans.infect 2011 Sex.Trans.infect 2011

16. Take home points • HPV is on rise at both ends of the GI track • For cancer protection we have 2 excellent anti-cancer vaccines that are not comparable • Gardasil only vaccine that prevents genital warts. • ‘Best vaccine’ is the one that a patient takes! 1 word summary:immunize! 16

17. Influenza

18. N Engl J Med 2008;359. 340  3rd trimester RDBPC influenza vs 23 valent pneumococcal vaccine 63% reduction of influenza in infants for up to 6 months and 36% reduction of febrile respiratory illnesses in mothers

19. Seasonal influenza mortality UK 2001-2009

20. Vaccine 2013 xxx-xxx • 282 participants; most in long-term care & >85 yrs ;open label ; pcr confirmation of influenza • Fluad and TIV vaccine; each given in a different district in BC • Results: - Fluad 60% effective • - TIV not effective

21. Clinical Infect Dis 2012 55:951 Case control study 2010-11 season N= 1040 influenza vs 3700 controls Efficacy: 69 % 6m-8yrs 51 % 9-64yrs 38 % >65 yrs Immunizing your parents and grandparents is less likely to protect them than immunizing yourself DO BOTH! 21

22. Take home points • Influenza vaccine , especially for high risk groups including pregnant women, babies and bubies • 3 new vaccines: intranasal (live) ,intradermal (killed) & adjuvented • new vaccines for elderly are here; they are more immunogenic but are they more effective than TIV? • influenza vaccine may prevent MI 22

23. Pneumococcus 23

24. Major Clinical Forms of Pneumococcal Disease PneumococcalDisease Noninvasive(Mucosal) Invasive Meningitis Bacteremia Pneumonia Acute Otitis Media Sinusitis • Pneumococcal disease can be broadly grouped into categories of invasive disease and noninvasive (also termed mucosal) disease1 • Noninvasive forms of disease may become invasive (eg, pneumonia when accompanied by bacteremia)2 • Serotype is associated with disease severity and invasiveness3 • WHO. Acute Respiratory Infections (Update September 2009).www.who.int/vaccine_research/diseases/ari/en/print.html. Accessed December 20, 2010. • CDC. Epidemiology and prevention of vaccine-preventable diseases. 11th ed. 2009;217-230. • Jansen AG et al. Clin Infect Dis. 2009;49:e23-e29.

25. S. pneumoniae disproportionately affects those at the extremes of age Incidence of IPD and Associated Mortality Rates (USA, 2010) Cases of IPD/100,000 Deaths associated with IPD/100,000 Age (years) IPD = invasive pneumococcal disease, and includes meningitis, bacteremia, and pneumonia when accompanied by bacteremia. Centers for Disease Control and Prevention. 2012. Active Bacterial Core surveillance Report, Emerging Infections Program Network, Streptococcus pneumoniae, 2010.

26. Incidence rate (per 100,000) of invasive pneumococcal disease by age group, Canada, 2011 IPD rate per 100,000 An Advisory Committee Statement (ACS) National Advisory Committee on Immunization (NACI) Statement on the Use of Conjugate Pneumococcal Vaccine – 13 valent in Adults (Pneu-C-13), April 4th, 2013

27. Reported number of cases and incidence rate of invasive pneumococcal disease, Canada, 2001-2011 27 Canadian Notifiable Disease Surveillance System

28. Risk Factors for Invasive Pneumococcal Disease (IPD) * Including chronic obstructive pulmonary disease, emphysema, and asthma. CDC. Morb Mortal Wkly Rep. 2010;59(34):1102-1106. Rahier JF et al. Rheumatology (Oxford). 2010;49(10):1815-1827. CDC. Prevention of Pneumococcal Infections Secondary to Seasonal and 2009 H1N1 Influenza Viruses Infection. 2009. CDC. Morb Mortal Wkly Rep. 2001;50(33):707-710.

29. Current vaccine options Two types of pneumococcal vaccines licensed for adults in Canada (3 products) The two types of vaccine contain 12 serotypes in common * PCV13 replaced the previous version of PCV, known as PCV7, which included 7 pneumococcal serotypes. ** 6A serotype is unique to PCV13 Lang Kau, Cheryl A. Sadowski, Christine Hughes. Vaccinations in older adults: Focus on pneumococcal, influenza and herpes zoster infections. Canadian Pharmacists Journal. 2011, 144(3):132-141.

30. NACI Recommendations: PPSV23 for High Risk Individuals • Including chronic obstructive pulmonary disease, emphysema, and asthma. • National Advisory Committee on Immunization (NACI). Canadian Immunization Guide, Public Health Agency of Canada, 2012. Accessed Feb 2, 2013 at http://www.phac-aspc.gc.ca/publicat/cig-gci/p04-pneu-eng.php#ru

31. PCV13 vaccine for adults:Current status • In Canada, PCV13 was approved in January 2012 1 • indicated for active immunization for the prevention of invasive pneumococcal disease (sepsis, meningitis, bacteraemic pneumonia, pleural empyema and bacteraemia), • in adults 50 years of age and older, • caused by Streptococcus pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F. 1 • In Jan 2014 the indication was expanded to include2 • Children, Adolescents and Adults. Pneumococcal 3-valent Conjugate Vaccine (Diphtheria CRM197 Protein) Product Monograph. Pfizer Canada, Jan 2012 Health Canada. Notice of Compliance. Accessed July 10, 2013 at http://webprod5.hc-sc.gc.ca/noc-ac/info.do?no=14512&lang=eng

32. Always give PCV13 before polysaccharide 23; follow with polysaccharide 2 mo-2 yrs later Non-naive: wait 1 year before PCV13

33. Oct 2012 “for adults >18 with immunocompromising conditions...PCV13 should be administered in addition to PPSV23” (off label <50yrs.)

34. ACIP Feb .12 34

36. Varicella

37. Shingles risk factors Advancing age: - Decreased CMI with age Immunosuppression: - HIV-AIDS - Organ transplants - Malignancy - Immunosuppressive therapy - autoimmune rheumatic diseases

38. Shingles: Canadian epidemiology 30% lifetime risk * 15% of cases Post-herpetic neuralgia (PHN) of whom 70% have moderate to severe pain * * Brisson M. CIC 2004

39. 33%

40. Frequency of PHN (> 3mo) and duration of Pain Increase With Age 100 >1 yr 6 - 12 mo 80 1 - 6 mo 40 30 15 <1 mo 60 Percent of patientsreporting pain 40 20 0 0-19 20-29 30-39 40-49 50-59 60-69 ≥79 Age (years) Kost R et al. N Engl J Med. 1996;355:32-42.

41. Treatment of Herpes Zoster Antivirals(given early): - modestly shortens the rash - do NOT prevent PHN Corticosteroids: - decreases severity of acute pain - do NOT prevent PHN Once zoster develops treatment does not prevent PHN 41

42. The Shingles Prevention StudyVaccineEfficacy: HZ Incidence by age 14 Vaccine Placebo 12 10 Incidence of HZ 8 * 6 4 2 0 All 60-69 yr ≥70 yr *P <0.001 Adapted from Oxman M et al. N Engl J Med. 2005;352:2271-2284.

43. 2.5 Vaccine 2.0 Placebo 1.5 Incidence of PHN 1.0 0.5 0.0 All Subjects 60-69 yr ≥70 yr The Shingles Prevention StudyVaccineEfficacy: PHN Incidence * *P <0.001 Adapted from Oxman M et al. N Engl J Med. 2005;352:2271-2284.

44. 9 8 Vaccine 7 Placebo 6 5 HZ burden of illness 4 3 2 1 0 All 60-69 yr ≥70 yr The Shingles Prevention Study Vaccine Efficacy: Severity/duration Illness * *P <0.001 Adapted from Oxman M et al. N Engl J Med. 2005;352:2271-2284.

45. Clinical Infectious Diseases 2012;55(10):1320 N= 38,500 SPS vs.14,000 STPS over 7 years Comparison SPS vs STPS SPS (2.5 y) STPS (7y) HZ 51% 40% PHN 66% 60%N/S PHN BOI 61% 50% Conclusion : complete vaccine efficacy for ~ 5 yrs. 45

46. Contraindications Who can I give Zostavax to? • lymphoproliferative disorders : • Solid tumour cancers : • immunosuppressants: • immune modulators : NO YES MAYBE NO 46

47. NACI January 2014 • Herpes zoster vaccine is recommended for the prevention of herpes zoster and its complications in persons 60 years and older • Herpes zoster vaccine may be used in patients aged 50 to 59 years • Herpes zoster vaccine may be administered to individuals ≥ 50 years old with a prior history of herpes zoster • Herpes zoster vaccine can be administered concomitantly with pneumococcal vaccine 47

48. Take home points • Shingles is increasing and is a BAD disease esp in older population • PHN lasts for months to years • Zostavax provides at least 50% protection against infection, incidence and severity of PHN. • mild immunosuppression not C/I • Now approved >50 yrs. of age esp. prior to immunosuppression • Recommended over 60 yrs. 48

49. Pertussis

50. Vaccine efficacy decreased by 42% each year after 5 years N Engl J Med 2012;367:1012-9.