Adult Pneumococcal Disease Education: Integrated Regional Learning Series

1. Adult Pneumococcal Disease Education: Integrated Regional Learning Series

2. Educational Learning Objectives Indicate the current burden of pneumococcal disease among adults and identify profiles of specific patients at greatest risk for these preventable diseases Identify the challenges facing adequate treatment of pneumococcal disease in adults, such as the emergence of non-vaccine serotype disease and trends in antibiotic resistance, and define how these elements impact clinical decision making Describe specific barriers that prevent the proper immunization of adults against pneumococcal disease, and define future strategies for overcoming these barriers

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4. Pneumococcal Disease Burden

5. Streptococcus pneumoniae Gram-positive bacteria 91 distinct capsular types identified Polysaccharide capsule important pathogenic factor for invasive disease; prevents phagocytosis Protection is serotype specific; some cross protection within serogroups

6. Pneumococcal Disease Second most common cause of vaccine-preventable death in the US (after influenza) Major clinical syndromes include Pneumonia Bacteremia Meningitis Invasive pneumococcal disease (IPD): isolation of S. pneumoniae from a normally sterile site (blood, CSF, pleural, pericardial, peritoneal, bone or joint fluid)

7. S. pneumoniae Infection Nasopharyngeal carriage of S. pneumoniae necessary for transmission of bacteria and invasive disease Person-to-person contact; respiratory droplets Autoinoculation Seasonal patterns

8. Pneumococcal Pneumonia 100,000 to 135,000 cases requiring hospitalization per year in USA Responsible for at least 1/2 of community-acquired pneumonias and less commonly can cause hospital-acquired pneumonias Common bacterial complication of influenza and measles Case-fatality rate 5%�7%, higher in elderly

9. Pneumococcal Bacteremia More than 50,000 cases per year in the United States Rates higher among elderly and very young infants Case-fatality rate ~20%; up to 60% among the elderly

10. Pneumococcal Meningitis Estimated 3,000�6,000 cases per year in the United States Case-fatality rate ~30%, up to 80% in the elderly Neurologic sequelae common among survivors Increased risk in persons with cochlear implant

11. Pneumococcal Disease in Children Bacteremia without known site of infection most common clinical presentation S. pneumoniae leading cause of bacterial meningitis among children younger than 5 years of age Highest rate of meningitis among children younger than 1 year of age Common cause of acute otitis media

12. Global Pneumococcal Deaths in Children

13. S. pneumoniae ABCs Provisional Data-2008

14. S. Pneumoniae ABCs Provisional Data-2008All Age Groups

15. Risk Factors for Invasive Pneumococcal Disease Extremes of age < 2 years; = 65 years Exposure to cigarette smoke, multiple children in household Comorbidities Alcohol abuse Congestive heart failure Chronic lung disease Cigarette smoking Asthma Recent influenza infection Diabetes mellitus Neurological disorders Certain ethnic groups American Indians, Alaska Natives, African Americans in the US Immune deficiencies B cell defects Deficiencies of early components of classical pathway of complement Asplenia Sickle cell disease Hematological or solid malignancies Organ transplant recipients HIV infection Immunosuppressive drugs

16. Risk Factors for Invasive Disease � Adults Ages 18 to 64 Years

17. Risk Factors for Death Due to Community-acquired Invasive Pneumococcal Pneumonia

18. Pneumococcal Vaccines

19. Pneumococcal Vaccines

20. Changes in Overall Invasive Pneumococcal Disease, 1998�2007

24. Rates of Invasive Pneumococcal DiseaseMetropolitan Atlanta, Georgia

25. PCV Efficacious in Reducing Radiologically Confirmed Pneumonia in Children

26. Efficacy of PCV in Children < 2 Years 11 publications of 6 randomized controlled trials N = 57,015 children received PCV; N = 56,029 received placebo or another vaccine Vaccine-serotype IPD; RR = 0.20 (0.10-0.42); P < 0.0001 All serotypes IPD; RR = 0.42 (0.25-0.71); P = 0.001 WHO X-ray defined pneumonia; RR = 0.73 (0.64-0.85); P < 0.0001 Clinical pneumonia; RR = 0.94 (0.91-0.98); P = 0.0006 All-cause mortality; RR = 0.91 (0.81-1.01); P = 0.07

27. Estimated Changes in Rates of Pneumonia Hospitalizations Post PCV7

28. PCV7 and Community Acquired PneumoniaRetrospective Cohort of Children and Adults - Washington State HMO

29. Invasive Pneumococcal Disease in Children < 2 years

30. Invasive Pneumococcal Disease Penicillin Non-susceptible (> 2 years)

31. Invasive Pneumococcal Disease in Children and Older Adults

32. Change in Serotype-specific Incidence of Invasive Pneumococcal Infections

33. Invasive Pneumococcal Disease Serotype 19A

34. IPD and S. pneumoniae Serotypes

35. ABC Incidence of Pneumococcal Meningitis by PCV7 ST Group Over Time

36. Most clinically significant resistance: 6A, 6B, 9V, 14, 19A, 19F, 23 F Antibiotic Resistance in S. pneumoniae

37. Revised Penicillin Breakpoints for Treatment of S. pneumoniae Infection 90-95% of all S. pneumoniae strains will have MIC results in the susceptible range

38. Pneumococcal Polysaccharide Vaccine Coverage � Elderly Adults, 1989�2007 (US)

39. Pneumococcal Polysaccharide Vaccine in Older Adults, US Retrospective cohort study; N = 47,365; = 65 years; 1998-2001 Pneumococcal bacteremia Reduced risk: HR = 0.56 (0.33-0.93); P = 0.03 Hospitalization for pneumonia Slightly increased risk: HR:1.14 (1.02-1.28); P = 0.02 Outpatient pneumonia HR: 1.04 (0.96-1.13); P = 0.31 Community-acquired pneumonia HR: 1.07 (0.99-1.14)

40. Prospective cohort study, N = 11,241; = 65 years; 2002�2005 Overall pneumonia: HR = 0.79 (0.64-0.98); P = 0.032 Pneumococcal pneumonia: HR: 0.55 (0.34-0.88); P = 0.013 Outpatient pneumonia: HR: 0.90 (0.59-1.37); P = 0.619 Risk of hospitalization for pneumonia: HR = 0.74 (0.59-0.92); P = 0.007 Risk of death due to pneumonia: HR: 0.41 (0.23-0.72); P = 0.002 Invasive pneumococcal disease: HR: 0.60 (0.22-1.65) [incidence was low]; P = 0.324 Pneumococcal Polysaccharide Vaccine in Older Adults, Spain

41. Efficacy of PPV Against Invasive Disease

42. Effectiveness of PPV23 in Adults2008 Meta-analysis 22 studies; 15 Randomized controlled trials (RCTs), N = 48,656 patients; 7 non-RCTs, N = 62,294 patients Results from RCTs Invasive pneumococcal disease (IPD) Strong evidence of protection (74%); OR 0.26 (95% CI 0.15�0.46); P < 0.00001 No statistical heterogeneity All-cause pneumonia Inconclusive efficacy (29%); OR 0.71 (95% CI 0.52�0.97); P = 0.029 Substantial statistical heterogeneity All-cause mortality No evidence of protection; OR 0.87 (95% CI 0.69�1.10); P = 0.25 Adults with chronic illness Evidence is less clear Results from non-RCTs IPD Evidence of protection (52%); OR 0.48 (95% CI 0.37�0.61); P < 0.00001

43. Efficacy of Pneumococcal Vaccination in Adults

44. PPV23 and PCV7 Adverse Reactions

45. Safety and Acceptability of PPV23 in Nontraditional Settings

46. Safety and Acceptability of PPV23 in Nontraditional Settings Local redness or swelling higher w/ re-vaccination (P = 0.001) Re-vacc: 13.1% First time: 4.4% Unsure: 1.4% In multivariate analyses: Local symptoms ? fever (OR 13.15, P < 0.001) Re-vaccination ? local symptoms (adjusted OR 3.77, P < 0.001) Patient satisfaction: Very convenient 96.2% Very satisfied 97.0% Would recommend to family/friend 99.4%

47. Safety of 3rd Dose of PPV23 Retrospective analysis of 316,995 elderly members of 3 HMOs participating in Vaccine Safety Datalink project Medical encounters associated with potential injection site reaction 0.3% of 1st dose recipients 0.7% of 2nd dose recipients 0.5% of 3rd dose recipients Conclusion: no suggestion of increased risk of medically attended injection site reactions for a 3rd dose compared with 1st or 2nd doses of PPV

48. PPV Prevention of Pneumonia in Elderly Patients Cohort studies suggest protection against IPD Some cohort studies suggest protection against pneumonia, while others do not No randomized trials have demonstrated efficacy against pneumonia in the elderly

49. Investigation of Pneumococcal Conjugate Vaccine for Adults

50. Influenza and Pneumococcal Pneumonia

52. 1918 Influenza and Pneumococcal Pneumonia Sequential Infection

53. 1918 Pneumonia Deaths � All of 58 Autopsies Reviewed in 2008 Showed Evidence of Bacterial Infection

55. Improving Immunization Rates

56. Adult Immunization Schedule: US 2010

57. Pneumococcal Polysaccharide Vaccine (PPV23)

58. Gaps Persist Between Vaccination Rates and Healthy People 2010 Goals

59. IPD � Missed Opportunities for Vaccination 1878 cases of IPD in adults from ABCs program 1177 had an indication for vaccination 617 were unvaccinated 92% had 1 or more missed opportunities 54% hospitalized (median # of visits = 1) 58% had ED visits (median # of visits = 1) 76% had PC visits (median # of visits = 6) Conclusion: 1 or more missed opportunities were documented in almost all unvaccinated IPD adults with a vaccine indication Implementation of systems strategies in outpatient settings would increase vaccine uptake

60. Patient Issues for Vaccination Awareness Disease Vaccine Personal risk Provider recommendation Misconceptions/fears About vaccine About health care system Access and ability to pay

61. Medicare Coverage for Influenza and Pneumococcal Polysaccharide Vaccines

62. Strategies to Improve Immunization Rates Standing orders Computerized record reminders Chart reminders Performance feedback Home visits Mailed/Telephoned reminders Expanding access in health care settings Patient education Personal health records

63. Improving Vaccination Rates:Provider Issues Know the facts Recommend vaccinations to your patients Get organized and use systems approaches Ensure offering and administration of vaccine Automatic processes that empower nurses are effective Address convenience, efficiency, durability Evaluate and provide feedback Consider new paradigms New venues Extend vaccination season Practice what we preach (get vaccinated!)

64. Standing Orders Are Among the Most Effective Strategies Nonphysicians offer and administer vaccinations No direct MD involvement at the time of the visit Established with physician-approved policies and protocols Locations: Clinics and hospitals

65. Success of Standing Orders as Part of a Multifaceted Program

66. Provider Recommendation Can Overcome Negative Attitudes Among Patients

67. Interventions That Improve Vaccination Rates for Adults

68. Inpatient Computer-Based Standing Orders vs MD Reminders

69. Summary Conjugate Vaccine Changing epidemiology of IPD Effectiveness in children Herd immunity Antibiotic resistance Serotype replacement PPV23 in Adults Effectiveness against IPD On the Horizon Expanded serotype coverage: PCV13 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F Conjugate vaccines for older adults? Protein vaccines that include universal protein antigens (not serotype specific) Strategies to Improve Vaccination Coverage

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