Katherine Julian, MD Professor of Clinical Medicine, UCSF July 9, - PDF document

Katherine Julian, MD Professor of Clinical Medicine, UCSF July 9, 2014

Vaccines Generally Available in the U.S.  Tetanus  Hepatitis B  Diptheria  Hepatitis A  Pertussis  Haemophilus influenzae type B  Measles  Rotovirus  Mumps  Inactivated polio  Rubella  Rabies  Varicella  Typhoid  Meningococcus  Yellow fever  Pneumococcus  Japanese encephalitis  Human Papillomavirus  Influenza Vaccines Generally Available in the U.S.  Tetanus  Hepatitis B  Diptheria  Hepatitis A  Pertussis  Haemophilus influenzae type B  Measles  Rotovirus  Mumps  Inactivated polio  Rubella  Rabies  Varicella  Typhoid  Meningococcus  Yellow fever  Pneumococcus  Japanese encephalitis  Human Papillomavirus  Influenza

Vaccines for Special Populations  Plague  Tularemia  Smallpox  Anthrax  Botulism  Tuberculosis – BCG  Adenovirus Key Website Centers for Disease Control and Prevention http://www.cdc.gov/vaccines

MMWR, Feb 7, 2014;63(05):110-112 Case I  45 yo woman here for regular visit. PMH: Healthy SH: smoker Vaccine history: “all the regular vaccines as a child”, but last vaccine was given “as a teen”. What vaccines should be given now?  1) Td  2) Tdap  3) Pneumovax  4) #1 and #3  5) #2 and #3

Pertussis…Not Just for Kids  41,880 pertussis cases and 14 infant deaths in 2012  Classic Sx: post ‐ tussive emesis and inspiratory “whoop”  Residual immunity from prior vaccination may modify the clinical presentation  Among adults, prolonged cough may be the only manifestation of pertussis  13 ‐ 32% of adolescents/adults with cough >6 days have serologic evidence of infection with pertussis ACIP. MMWR, 2013;62 Cornia PB, et al. JAMA, 2010;304(8) Pertussis…Not Just for Kids  Highly contagious to home contacts  Adults may act as reservoirs of the disease to vulnerable populations  Majority of deaths in infants <2 months  Immunity for pertussis wanes after childhood vaccination Hewlett EL et al. NEJM, 2005;35:12

Pertussis Vaccine  In 1980’s, acellular vaccine created  Contains purified, detoxified pertussis antigens  Childhood DTaP: diptheria toxoid, tetanus toxoid, and acellular pertussis (full dose)  Adult/adolescent Td and Tdap: tetanus toxoid (full dose) and reduced dose diptheria toxoid +/ ‐ reduced dose acellular pertussis antigens  Adacel: age 11 ‐ 64  Boostrix: >10 years Pertussis Vaccine – How Effective?  2781 subjects aged 15 ‐ 65 randomized to reduced dose of acellular pertussis vaccine or hepatitis A placebo  Followed for 2.5 years  Based on primary pertussis definition (cough and positive culture/PCR), vaccine 92% effective Ward JL et al. NEJM, 2005;353(13)

Tdap Recommendations  Adolescents: give Tdap instead of Td at routine 11 ‐ 12 year visit  Adults >19 years: Tdap regardless of interval since last tetanus (if never had Tdap)  Older Adults: recommended for all >65 yo  Does not depend on contact with young children  Both Adacel and Boostrix appear to be immunogenic  If a choice, give Boostrix for now  Health care workers with patient contact Tdap Recommendations  If pregnant woman  Administer Tdap during EACH pregnancy, preferably during between 27 ‐ 36 weeks  If not administered during pregnancy, Tdap should be administered immediately postpartum  Adolescents and adults with close contact with an infant aged <12 months should receive a single dose of Tdap if they have not received Tdap previously  JAMA 2014: 48 pregnant women—no adverse outcomes and babies with higher Ab rates when mother vaccinated in 3 rd trimester Munoz FM, et al. JAMA, 2014;311(17)

Pneumococcus ‐ Background  Gram + diplococcus, polysaccharide capsule  Over 90 serotypes  Colonizes the upper respiratory tract  Causes 40,000 deaths annually in the U.S.  Mainly transmitted by direct contact with respiratory secretions (ex: household) Pneumococcus ‐ Background  Risk factors for invasive disease  Age >65 or <2 years  People with chronic illness, immunocompromised  Crowding, PPI’s  Antecedent respiratory infection and recent Abx  Smokers

Pneumovax Polysaccharide Vaccine (PPSV23)  23 purified capsular polysaccharide antigens  Represent at least 85 ‐ 90% of the serotypes that cause invasive pneumococcal infections  Shorter Ab duration  Decreases pneumococcal bacteremia  Retrospective cohort 47K people >65 yrs; HR 0.56  Likely no effect on PNA Jackson LA. NEJM, 2003;348:18. Pneumovax Polysaccharide Vaccine PPSV23 ‐ Recommendations  Age >65  People > 2 years old** with chronic illness  Chronic cardiovascular disease  Chronic pulmonary disease including ASTHMA  Chronic liver disease, ETOH  Diabetes  Immunocompromising conditions  Smokers  People aged 2 ‐ 64 living in environments in which the risk for invasive pneumococcal disease is increased (no longer American Indians or Alaskan natives)

Revaccination with Pneumococcal Polysaccharide Vaccine (PPSV23)  One ‐ time vaccination after 5 years for immunosupression, asplenia, renal failure/nephrotic syndrome, long ‐ term corticosteroids  If at least 65 yrs, one ‐ time revaccination if vaccinated >5 yrs prior and age less than 65 yrs at the time of initial vaccination  Max 3 doses Pneumococcal 13 ‐ Valent Conjugate Vaccine for Adults (PCV13) – Prevnar 13  Conjugates the bacterial capsular polysaccharide to a carrier protein. Longer Ab duration.  FDA data comparing PPSV23 vs. PCV13  Ab titers for PCV13 equal or higher in adults 60 ‐ 64 yrs  Adults 50 ‐ 59yrs given PPSV23 first had lower antibody titers when given PCV13 booster compared to those given PCV13 for 2 doses  Similar result for PPSV23 vs. PCV7 in HIV+ patients ACIP. MMWR, 2012; 61(40).

Pneumococcal 13 ‐ Valent Conjugate Vaccine (PCV13) ‐ Recommendations  Age >19 AND  Immunocompromising conditions  HIV, Chronic renal failure, nephrotic syndrome, malignancy, transplant  Functional or anatomic asplenia  CSF leaks  Cochlear implants Pneumococcal Boosters – More Complicated…  No history of pneumovax  If indication for PCV13: give PCV13 first and then PPSV23 booster 8 weeks later  Then give PPSV23 booster 5 years later  Previous vaccination with PPSV23 AND indication for PCV13:  Give PCV13 dose at least 1 year after previous pneumovax  People >65 years with chronic illness should get PPSV23 booster 5 years after first vaccine dose (if first dose was given before they were 65).

Pneumovax…Future Changes?  13 ‐ valent conjugate vaccine in all adults?  Functional antibody responses higher than for polysaccharide vaccine  Prevnar 13 approved by the FDA Dec 2011 (for adults >50 years) but not yet recommended by ACIP aside from immunocompromised  CAPiTA Trial – 85K subjects in Netherlands >65 yrs  46% fewer vaccine type pneumococcal CAP  75% fewer vaccine type invasive pneumococcal dz March 2014 Press Release Case I  45 yo woman here for regular visit. PMH: Healthy SH: smoker Vaccine history: “all the regular vaccines as a child”, but last vaccine was given “as a teen”. What vaccines should be given now?  1) Td  2) Tdap  3) Pneumovax  4) #1 and #3  5) #2 and #3

Bonus Question to Case I  What type of pneumovax should she have? 1) Polysaccharide vaccine (PPSV23)? 2) Conjugate vaccine – Prevnar 13 (PCV13)? Case 2 63 yo woman PMH: htn, DM Meds: HCTZ, metformin SH: Married, non ‐ smoker What vaccine(s) does she need? 1) Hepatitis B Varicella Zoster vaccine 2) 3) Seasonal Influenza #2 and #3 4) 5) All of the above

Varicella ‐ Background  After primary VZV infection (chickenpox), latent infection is established in the sensory ‐ nerve ganglion  Decline in cell ‐ mediated immunity with age predisposes to zoster  Zoster develops in 30% of people over a lifetime  Post ‐ herpetic neuralgia 13 ‐ 40%; directly correlated with age Kimberlin DW, et al. NEJM, 2007;356(13). Zoster Vaccine  Live attenuated virus vaccine  Older adults need higher titer of live attenuated virus to produce a durable increase in cell ‐ mediated immunity  Zoster vaccine contains more plaque ‐ forming units/dose than the chickenpox vaccine  Vaccine “boosts” older adults’ waning immunity to prevent reactivation of varicella

Varicella Zoster Vaccine…The Evidence  Randomized, double ‐ blind, placebo ‐ controlled trial of 38,546 adults > 60 yrs  Zoster vaccine vs. placebo  Primary endpoint: “burden of illness” due to zoster  Incidence, severity of pain, duration of pain  Secondary endpoint: incidence of post ‐ herpetic neuralgia (pain >120 days) Oxman MN et al. NEJM, 2005;352(22) Varicella Zoster Vaccine…The Evidence  Results: followed median 3.12 years  Incidence of zoster reduced by 51.3%  Incidence of post herpetic neuralgia decreased by 66.5%  Burden of illness due to zoster decreased by 61.1%  Higher efficacy ages 60 ‐ 70  Efficacious in 75K community dwellers 6.4/1000 person ‐ years vs. 13/1000 (HR 0.45) Oxman MN et al. NEJM, 2005;352(22) Tseng HF et al. JAMA, 2011;305(2)