11/17/2013 THE WHO, WHAT, WHEN, AND WHY OF ADULT VACCINATIONS. Pneumococcal Vaccines for Adults (PPV) Pneumococcal Vaccines

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1 THE WHO, WHAT, WHEN, AND WHY OF ADULT VACCINATIONS CAROL A. KAUFFMAN, MD VA ANN ARBOR HEALTHCARE SYSTEM UNIVERSITY OF MICHIGAN Will discuss: bacterial vaccines made of toxoids or polysaccharide capsular Ag virus vaccines made from capsid proteins live attenuated virus vaccines Will NOT discuss: influenza, hepatitis A & B vaccines 1977: 14-valent polysaccharide vaccine licensed 1983: 23-valent polysaccharide vaccine licensed ** 2000: 7-valent conjugate vaccine licensed 2010: 13-valent conjugate vaccine licensed ** for Adults (PPV) Large studies show efficacy in decreasing invasive disease, severity & complications of pneumonia Whether decreases non-bacteremic pneumonia still debated, but mainly an issue of study design Contains >80% serotypes causing disease in adults After decades, no replacement serotypes for Children (PCV) Clearly PCV a success in children, BUT also in adults!! Has decreased pneumonia, meningitis, otitis, bacteremia in infants & children Also decreases colonization in NP Decreased NP carriage decrease in invasive disease/pna in older adults Downside PCV: replacement serotypes Pneumococccal Infections in Children <5 years 1

2 Pneumococccal Infections in Adults >65 years for Adults PPV vs PCV PPV covers more serotypes PCV may give better Ab response generally true that conjugate better than polysaccharide, but data not yet firm PCV likely primes response to subsequent PPV enter the issue of timing of administration for Adults: PPV vs PCV Used to be so simple: one shot (or maybe 2) will do you NOW, complex and harder to set up a system in clinic or office to do this Can we simplify this? for Vaccine-Naive Adults When to use 1 dose PPV? > 65 yr old all adults with risk factors for PNA: smoking, EtOH, liver D, DM, COPD, asthma, cardiac D, LTCF residents In group that got vaccine <65 yr, give PPV again after 5 yr AND when >65 yr for Vaccine-Naive Adults When to give PCV, then PPV? asplenia, CSF leaks, cochlear implant immune compromised: HIV, CVID, Tx, heme/other CA, nephrotic S, CKD, MM, iatrogenic immunosuppression?? Give PPV at least 8 weeks after PCV Give another dose PPV 5 yr later 2

3 for PPV-Vaccinated Adults Who needs to receive PCV? > 65 yr NO chronic diseases NO asplenia YES CSF leak, cochlear implant YES immune suppressed YES Give PCV >1yr after PPV for Adults: PPV vs PCV Did I really simplify this???? Importantly, all this based on theoretical constructs with not very robust data to support the recommendations Are there major downsides if mistakes in timing made? NO for Adults: Remaining Issues How many serotypes can be placed on conjugate proteins? Will vaccine makers keep up with replacement serotypes? Do immunosuppressed patients really respond to either vaccine? for Adults Great Reference Musher DM. How effective is vaccination in preventing pneumococcal disease? Infectious Disease Clinics North America 2013; 27: THE expert on pneumococal disease! Pertussis: Resurgence of a preventable disease Complications highest for infants Epidemiology involving not only kids but also older adults, esp. grandparents Older adults more often hospitalized Worse disease in older adults who are obese & have asthma 3

4 Pertussis: Resurgence of a preventable disease Life-long immunity does not occur with infection or vaccine; has been endemic at low level for years in U.S. But, marked increase in recent years acellular vaccines (DTap & Tdap) safer, but not as effective as DPT parents not vaccinating kids more awareness & better Dx (PCR) Tdap: Who Should Get This Vaccine? Routine childhood vaccination (5 doses- DTap), then booster at yr (Tdap) All adults who have not received booster should get Tdap once, esp. if >65 yr Pregnant women with each pregnancy; give in 3rd trimester Remaining boosters every 10 yr and wound Rx can be with Td Pertussis and Tdap: Remaining Issues How many boosters & how often? Do we need to go back to DPT? Other Bordetella species (parapertussis and holmesii) not covered by Tdap as well as DPT? how important? Will companies continue to produce Td? No harm in giving Tdap instead of Td Papillomavirus Vaccines Vaccination recommended at yr, but can give until age 26 if not given before. So, internists do get involved Unique vaccine: made up of virus-like particles from recombinant capsid protein of various serotypes Major emphasis is to prevent cervical CA Now also use to prevent warts/anal CA 4

5 Papillomavirus Vaccines Bivalent: HPV 16 & 18 - for girls to prevent cervical CA (~70% cervical CA) Quadrivalent: HPV 16,18, 6,11 - for girls and boys to prevent cervical CA, anal CA, genital warts (~90% CA and warts) Most warts & most respiratory papilloma due to HPV 6,11 (non-oncogenic types) Papillomavirus Vaccines Newest recommendations are to give to males up to age 21 & MSM up to age 26 MSM are high risk for warts & anal CA 3-dose vaccination over 6 months If don t finish series, give catch up doses Safe to give to immune suppressed pt Papillomavirus Vaccines Has to be given before exposure to specific HPV type-prevents infection but does not modify course once infected Even if (+) Pap, give because will protect against other serotypes Not clear if any benefit against oral HPVrelated CA or respiratory papillomatosis Papillomavirus Vaccines: Remaining Issues Uptake slow-not too surprising not exactly a childhood disease & costly Age recommendations in men make little sense (21 for some, 26 for others)? Duration of protection thought to be long, but not really known (true for most new vaccines) LIVE VIRUS VACCINES 5

6 Incidence 1000 person-yr Incidence 1000 person-yr Burden of Illness Score 11/17/2013 Rationale For Use Of VZV Vaccine In Elderly CMI to VZV with age Vaccine boosts CMI to VZV CMI will prevent shingles Zostavax Clinical Trial Design Blinded randomized placebo-controlled trial VA/Merck Study - 22 sites Eligible > age 60 years Enrollment = 38,546 pts Stratification yrs (20,747) and > 70 yrs (17,799) Endpoint - burden of illness due to zoster Oxman et al. NEJM 2005;352:2271 Zostavax Efficacy Herpes Zoster Episodes Zostavax Efficacy Burden of Herpes Zoster Overall Efficacy 51.3%, p<.001 All Age Age > 70 Efficacy 63.9% 37.6% P<.001 Vaccine (n=315) Placebo (n=642) 9 Overall Efficacy 61.1%, p < All Age Age > 70 Efficacy 65.5% 55.4% Vaccine (n=315) Placebo (n=642) Zostavax Efficacy Post-Herpetic Neuralgia Zostavax: Who Should Get This Vaccine? Overall Efficacy 66.5%, p<.001 All Age Age > 70 Efficacy 65.7% 66.8% Vaccine (n=27) Placebo (n=80) All persons > 60 yr ACIP approved Make sure no contraindications No VZV serology needed Better response before >70 yr 6

7 Zostavax: Who Should Get This Vaccine? All persons > 50 yr FDA approved, but not ACIP approved Company could not supply drug for >60 was main reason for ACIP disapproval Cost high, risk lower than >60, but ~20% cases occur in yo Response ~70% vs 64% in yo & 38% in >70 yo Zostavax: Who Should Not Get This Vaccine? Chemotherapy Zostavax: Problems Must be kept frozen at -15 o C Need to dilute right after removal from freezer with diluent kept at RT or in frig Give immediately after reconstituted & if not given in 30 minutes, discard Expensive!! Zostavax: Remaining Issues What is the length of protection? Unpublished data: 6867 persons from SPS study show protection declines over 10 years Will a booster be required? Should pt with prior zoster get zostavax? Safe, but less risk of zoster Is there a stable refrigerated vaccine? Yes, approved in Europe, not here? Will the cost come down??? VARICELLA Major risk for severe D: pregnant women, immune compromised persons Major concern for spread: family contacts immune compromised, teachers, day care staff, staff in institutional settings HCW especially need to be immune (high risk for exposure & transmission) Varicella Vaccine: Who Should Get This Vaccine? All adults never immunized or no Hx VZV if no Hx, get Ab - often immune born <1980, most immune 2 doses, 4 weeks apart Cannot vaccinate during pregnancy-start series right after delivery so immune if get pregnant again 7

8 Measles, Mumps, Rubella Major risk for severe D: immune compromised persons (measles) Major concern for spread: schools with non-immunized students, overseas travel Recent upsurge in measles; mumps outbreaks a few years ago HCW especially need to be immune (high risk for exposure & transmission) MMR: Who Should Get This Vaccine? All adults never immunized and born >1957 (if born before 1957, consider immune) if born after 1957, Hx of infxn not adequate proof must do Ab tests to prove immunity Several early vaccines (measles & mumps) inadequate & repeat vaccination needed 2 doses, 4 weeks apart 8

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