 Thomas F. Koinis, MD, FAAFP  Duke Primary Care Oxford  February 9, 2016

 Member, North Carolina Immunization Advisory Council, 1997-present  American Academy of Family Physicians, Commission on Health of the Public and Science,  Member, various ACIP workgroups,  Conflict of Interest - None

 What are Pneumococcal bacteria?  What problems do they cause?  How much of a problem are they?  What role do vaccines play?  How do we use these vaccines?

 Gram positive diplococcus bacteria  First identified in 1881 by Louis Pasteur  Initially found in patient with rabies  Original name: Diplococcus pneumonia.  1974: Name changed to Streptococcus pneumonia  Also known as Pneumococcus

 Polysaccharide capsule ◦ Allows bacteria to colonize and invade  Transmission ◦ Respiratory ◦ Resides in the nasopharynx, more often in kids ◦ Asymptomatic carriers – 40-50% of population  Most common cause of community acquired pneumonia (CAP)  Accounts for about 2/3 of bacteremic pneumonia

 Over 80 serotypes identified by 1940  Currently, there are more than 90 serotypes  Multiple diseases: ◦ Pneumonia, bronchitis, rhinitis, sinusitis, otitis media, conjunctivitis, meningitis, septicemia, osteomyelitis, septic arthritis, endocarditis, pericarditis, cellulitis, peritonitis, brain abscess

 Pneumococcal Polysaccharide Vaccine (PPSV) ◦ 1977: 14 Valent PPSV14 ◦ 1983: 23 Valent PPSV23  Pneumococcal Conjugate Vaccine (PCV ) ◦ 2000: 7 Valent PCV7 ◦ 2010: 13 Valent PCV13

 Otitis Media: 7,000,000  Pneumonia: 500,000  Bacteremia: 50,000  Meningitis: 3,000  Death: 40,000  Data from MMWR: 1997

 For adults age >50 ◦ Pneumonia: 442,000 ◦ Bacteremia: 7,000 ◦ Meningitis: 1,700

 Will refer to as IPD  Occurs when pneumococcal bacteria are invasive into body fluid that is usually sterile  Applies to blood - bacteremia- and cerebrospinal fluid (CSF) - meningitis

 Invasive disease, not just pneumonia  43,000 cases: 84% in adults  5,000 deaths: almost entirely adults  By 2007, IPD was down 45% over all ages  Herd Effect from vaccinating children with PCV 7 beginning in 2000

 Pneumococcal serotypes found in adult IPD cases studied  Adults age ◦ 49% of those were serotypes in PCV 13 ◦ 76% of those were serotypes in PPSV 23  Adults age > 65 ◦ 44% of those were serotypes in PCV 13 ◦ 66% of those were serotypes in PPSV 23

 Increased Risk of IPD in adults age with chronic diseases ◦ Diabetes – 3 times greater than healthy adults ◦ Chronic Heart disease – 3 times greater than health adults ◦ Chronic Lung Disease – 8 times greater than healthy adults

 Diabetes: Elevated sugars cause functional impairment of immune cells  Congestive Heart Failure (CHF): decreased cardiac output leads to increased pulmonary congestion  Chronic Obstructive Pulmonary Disease (COPD): chronic lung inflammation

 Reduced clearance of bacteria  Increased risk of infection from pneumococcal bacteria  Increased risk of invasive pneumococcal disease

 Pneumococcal Polysaccharide Vaccine (PPSV) ◦ 1977: 14 Valent PPSV14 ◦ 1983: 23 Valent PPSV23  Pneumococcal Conjugate Vaccine (PCV ) ◦ 2000: 7 Valent PCV7 ◦ 2010: 13 Valent PCV13

 PPSV 23: Pneumococcal Purified Polysaccharide Vaccine ◦ Stimulation of B Cells which release IgM without help from T Cells. ◦ Not Lifetime immunity ◦ Can prevent 60%-70% of IPD coming from included pneumococcal serotypes ◦ No consensus on ability to prevent non-bacteremic pneumonia – not really a “PNEUMONIA” vaccine

 PCV: Pneumococcal Conjugate Vaccine ◦ More robust immune response using both T Cells and B Cells ◦ Results in mucosal immunity ◦ 12 of the 13 serotypes are also included in PPSV 23

 1977: 14 Valent  1983: 23 Valent  Indications ◦ Age > 65 years old ◦ Age for High risk – DM, Chronic Heart Disease, COPD, Chronic Liver Disease, Alcoholism  2009: Smoking history (4x the IPD Risk) and Asthma (2x the IPD Risk) added as new indications

 Diabetes mellitus  COPD/Asthma  Smoking  Chronic Heart Disease: CHF/Cardiomyopathy  Alcoholism  Chronic Liver Disease

 2000: PCV 7 for children. 4 dose series  2010: PCV13 introduced  2011: FDA approves PCV13 for all adults > age 50  2012: ACIP – recommends PCV13 in unvaccinated high risk adults, >age19  2013: ACIP – recommends PCV13 in unvaccinated children age 6-18 with immunocompromising conditions  2014: ACIP – recommends PCV13 in adults > age 65. Recommendation will be revisited in 2018

 Age <2: 47,000 Fewer pneumonia admissions annually. Reduction has been sustained over a decade  Age 85+: 73,000 Fewer pneumonia admissions annually  All age groups: 168,000 Fewer pneumonia admissions annually SOURCE: Griffin, et al. NEJM 2013; 369:

 By 2013, IPD from PCV Serotypes in adults >65 down by 50% from 2010  Still 13,500 IPD cases/year in adults >65  CAPiTA trial – studied PCV 13 in adults ◦ 45% efficacy vs vaccine type pneumonia ◦ 45% efficacy vs vaccine type bacteremia ◦ 75% efficacy vs vaccine type IPD

 Asplenia – functional and anatomic  CSF Leak  Cochlear Implant  Immunocompromising Conditions  Same list applies to PPSV 23, age 2-18

 Immunodeficiency  HIV  Chronic Renal Failure  Nephrotic Syndrome  Lymphoma  Hodgkin’s Lymphoma  Multiple Myeloma  Solid Organ transplant  Generalized Iatrogenic immunosupression

 One time vaccination for healthy adults >65  Vaccinate age with chronic disease conditions  Vaccinate age 2-18 with asplenia, CSF leak, cochlear implants, immunocompromising conditions

 Only revaccinate if received first dose before age 65 ◦ Once in 5 years for those with asplenia and immunocompromising conditions. ◦ For all other indications – Revaccinate at age 65; but needs to be given at least 5 years after first dose  Concern for multiple PPSV 23 dosing ◦ Lack of known benefit ◦ Increased reactions/side effects

 All Children: 2, 4, 6, and months  Unvaccinated children age months, healthy: single dose  Unvaccinated children age months, with high risk conditions: 2 doses, at least 8 weeks apart  Unvaccinated children age 6-18 years with high risk conditions: single dose

 All adults age >65 ◦ Will be looked at in 2018 to see if revisions to recommendations are needed ◦ Will assess burden of IPD and community acquired pneumonia (CAP) in adults  Adults age with high risk and immunocompromising conditions

 Complicated algorithm  Can not give together  Best to give PCV 13 first, then PPSV 23  Give PPSV 23 at minimum interval of 8 weeks after PCV 13

 In adults, studies showed: ◦ Shorter intervals between PCV 13 and PPSV 23 may lead to greater local reactions ◦ Longer intervals ( >1 year) may lead to better immune response to the common serotypes of the 2 vaccines

 Immunocompetent adults age >65 ◦ If given PCV 13 first then PPSV 23: 1 year (was 6-12 months) ◦ If given PPSV 23 first then PCV 13: 1 year ◦ ACIP changed PCV 13:PPSV 23 interval to both simplify recommendations and harmonize with Medicare payment

 PCV 13: PPSV 23 Sequence ◦ Age 2–64 years: 8 week minimum, for all PPSV 23 indications  PPSV 23: PCV 13 Sequence ◦ Age 2–18 years: 8 week minimum ◦ Age 19–64 years: 1 year minimum  These intervals for all PCV 13 indications

 PCV 13/TIV: safe  1 study showed slight decrease in pneumococcal titer and H3N2 titer  PCV 13/High Dose Flu: no data  No data for PCV 13 with either Tdap or Zoster

 PPSV 23 and Zoster: ideally give 4 weeks apart due to small decreased response to Zoster if given together  PPSV 23 and other vaccines: limited data though commonly given with influenza

 PPSV 23 ◦ Swelling/erythema/tenderness at injection site - common ◦ Myalgia/headache/fatigue – 5-15% ◦ Severe local reactions/fever - rare  PCV 13 ◦ For adults, similar to PPSV 23

 Based on 2009 National Health Interview Survey (NHIS), there were an estimated 59 million adults without PPSV 23 who had indications for being immunized with PPSV 23 ◦ 9 Million with Diabetes ◦ 11 Million with Chronic Heart Disease ◦ 11 Millions with Chronic Lung Disease

 Healthy People 2020 Goals ◦ PPSV 23 immunization rate: >90% in adults age >65  Rate has stayed in 60-65% range for a number of years  2014 NHIS – 61.3% ◦ PPSV 23 for Chronic Disease States/High Risk - > 60%  In 2013, was low at 21.2% for all disease states.  2014 NHIS – 20.2% for all disease states  No current goal for PCV 13

 Organizational Issues  Provider Reminders  Provider Education  Patient Reminders  Patient Education  Electronic Health Records  State Immunization Registries

 Current Vaccines cover limited number of serotypes  Pneumococcal bacteria can acquire DNA from other organisms and then can switch capsular serotypes  New work centers on targeting highly conserved proteins, some on the surface of the bacteria