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