Deaths/yr Efficacy Use Prev Deaths/yr. Influenza 36,000 70% 60% 18,000. Pneumonia 40,000 60% 40% 20,000 HBV 6,000 90% 30% 4,000

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1 Tetanus, Diptheria, Pertussis,! Measles, Mumps, Rubella, Varicella, HPV, Polio Meningococcus, Pneumococcus,! Influenza, Hepatitis B, Hepatitis A,! H influenza, Rabies, Typhoid,! Yellow Fever, Japanese encephalitis, Typhoid! Deaths/yr Efficacy Use Prev Deaths/yr Influenza 36,000 70% 60% 18,000 Pneumonia 40,000 60% 40% 20,000 HBV 6,000 90% 30% 4,000 Tetanus-D < 25 99% 80% < 15 MMR < 30 95% varies < 30

2 a) Order tests for rubella, measles, and varicella antibodies before immunizing! b) Obtain detailed clinical history of possible childhood infections! c) Offer vaccines without tests given that immunization rate is low! d) Obtain medical record documentation or immunization card! e) Ask about possible social contacts before giving live viral vaccines! a) Tetanus booster if more than 10 years from last dose! b) Influenza vaccine! c) Hepatitis A vaccine in two doses if not previously given or one dose if > 10 years! d) Hepatitis B series! e) Meningococcal C vaccine!

3 a) Tetanus booster with acellular pertussis last Td was 3 years ago! b) Intra-nasal Influenza vaccine! c) Pneumococcal vaccine booster originally given at age 65! d) Zoster vaccine without checking antibodies! e) Zoster vaccine only if no prior shingles and with documented positive varicella Ab! Pertussis vaccine revisited! Varicella Zoster Vaccine! Influenza & Pneumonia vaccines! Hepatitis B, Measles, Mumps, Rubella! Human Papilloma Virus vaccine! Tdap for Adults!

4 CDC, ACIP 2006

5 Ward JL et al. NEJM, 2005;353(13) Incidence decreased by 70% to 80% between 1995 and 2001! Mortality decreased by 66%: 0.41 to 0.14 per million persons! Benefit clear in persons < 50 yrs! Benefit in all racial and ethnic groups! Immunization program against varicella led to fewer deaths! Nguyen, NEJM 2005; 352: !

6 315 (1.6%) cases 642 cases (3.3%) 61.1 RRR 27 (8.6%) cases PHN No zoster cases had vaccine virus detectable in lesions 80 (12.5%) cases PHN 66.5 RRR No serious difference in group side effects Kimberlin DW. NEJM, 2007;356 Simberkoff S, Ann Intern Med 2010; 152: 545

7 National survey of primary care MDs! 72% response: 301 GIM and 297 FM! 49% stock and deliver in their office! 36% refer to purchase and bring back! 33% refer to a pharmacy for shot! 88% recommend HZV; 41% strongly! 45% aware Medicare part D covers! Reimbursement issues 12% stopped! Hurley L, et al. Ann Intern Med 2010; 152: !

8 British study of 20,486 patients with MI and 19,063 cases of stroke! No increase in risk of MI or stroke after vaccination against the flu, pneumococcal disease and tetanus! There was an increased risk in the 3 days after a systemic respiratory infection RR = 4.95 (4.43 a 5.53)! Smeeth, NEJM, 2004; 351: ! Monto AS, et al. NEJM, 2009;361. Persons 50 years of age and older! Residents of chronic care facilities! Chronic cardiopulmonary disorders! Chronic metabolic diseases, renal dysfunction, hemoglobinopathies, or immunosuppression requiring regular medical follow up! Women who will be in 2nd or 3rd trimester of pregnancy!

9 Pooled data, 18 cohorts from to ! 713,872 person-seasons of observations! 58% vaccinated; mean age 73; 43% men! High-risk conditions more prevalent by among vaccinated (56% vs 46%)! 27% (OR= 0.73; ) reduction in hospitalizations (all but 1 season)! 48% (OR=0.52; ) reduction in risk of death present in all seasons! 1 death prevented for every 302 flu shots!! Evidence that flu vaccine for HCW helps patients: 17% vs. 10% mortality in study of SNF in Scotland! NHIS Survey in 2000 of 1651 health care workers: 38% vaccinated in previous yr! Decline in GBS cases from 0.17 to 0.04 per 100,000 coincided with stepped up food safety interventions and 28% decline in campylobacter infections! 65% adults >65 vaccinated, 50% for Latinos and Blacks, more if MD contact! Automatic orders work!

10 April 21, 2009: CDC confirms 2 in CA! Segments from previous swine influenza viruses! June 11, 2009: 30,000 cases across 74 countries! WHO issues phase 6 alert = official pandemic is now over!! Risk factors for invasive disease! Age >65 or <2 years! People with chronic illness! Crowding, PPIʼs! Antecedent respiratory infection and recent antibiotic! Smokers! African Americans and American!!Indians! All persons older than 65 y Chronic cardiovascular disease Chronic pulmonary disease Diabetes mellitus Cirrhosis, Alcoholism, CSF leaks Functional or anatomic asplenia HIV infection Immunocompromised persons (cancers, ESRD, transplants) MMWR 1997; 46:1-24 (RR-8)

11 Only one-time re-vaccination at 5 years recommended for:!! no spleen - functional or anatomical!! chronic kidney disease!! immune suppressed conditions!! chemotherapy with cancer drugs! Persons at age 65 years if first dose was given 5 years before! Otherwise--Re-vaccination not needed!! Randomized trials showed no decrease in death or bacteremia; 50% decrease in pneumonia! Case control studies--60% to 70% protective efficacy for bacteremia! CDC cohort analysis: 57% (95% CI= 45%-66%) protection, sustained over time! Vaccine cost effective: saves money and lives even after including future costs! Used for infants in the US since 2000! Cases of drug resistant Strep Pneumo invasive disease decreased (cases /100,000)!!!!!!1999!!2004! Penicillin resistant! 6.3!! 2.7! Muliple Abx resistant! 4.1!! 1.7!! Decline of 50% among adults 65 years and older! NEJM 2006;354:

12 2 billion persons with hepatitis B! 350 million chronic carriers! 1 million deaths per year! HBV vaccination programs have been implemented in > 100 countries! Reduction of chronic infections and liver cancer! Most of chronic infections are acquired as children!

13 Antibody (HBsAb) levels decline to undetectable by 6 yrs in up to 50%! Initial non-responders re-vaccinated with one more dose 15% to 25% respond!!three more doses 50% to 75% respond! No documented case of symptomatic hepatitis in vaccine recipient with initial antibody response! Long incubation of HBV allows triggering T cell memory! Boosters are not routinely recommended! Have you ever seen a case?!

14 Use combined MMR vaccine in most people! Born after 1957 limited exposure! Documentation of vaccine receipt; Clinical diagnosis of disease documented or Serologic evidence of immunity! Health care workers a priority! Non-infectious clinical syndromes! No evidence for autism association!

15 Prevention of warts, persistent HPV infection, and HGSIL lesions! Lag time to detect efficacy in prevention of cervical cancer will be 10 to 20 years! CIN 2 or CIN 3: about 40% progress to cervical cancer! Near 100% effective at decreasing HGSIL of cervix in published trials! HPV 16/18 include about 70% of oncogenic HPV types but varies by country! HPV 16/18 + 6/11 vaccine! 12,167 and 5455 women age y; 3 years follow up! Per-protocol analysis = no viral evidence of infection by month 7! CIN grade 2 or 3 or cancer Efficacy = 98% (86 to 100)! Intention to treat efficacy = 44% (26 58) or 34% (15 to 49)! Efficacy for all CIN 2/3 or cancer was only 17% (1 to 31) or 20% (8 to 31)!

16 Duration of immunity unknown q 5 or 10 years? Long term efficacy?! Acceptability by parents?! Reassurance regarding safe sex?! Cover more oncogenic types?! Alter routine Pap screening?! Global Application?! Women aged yrs, randomized, placebo-controlled, double-blind study with no h/o genital warts or cervical disease! 3817 women received quadrivalent HPV vaccine vs. placebo 3 doses! Outcome=disease/infection related to HPV 6, 11, 16, 18! Efficacy 90.5%, but ITT efficacy: 30.9%! Munoz N, et al. Lancet, 2009;373! HPV linked to penile/anal warts, penile/anal/head/neck cancers! HPV prevalence in men 20-70%! Men with h/o more sexual partners associated with 7X risk of cervical cancer in their women partners! In one study, males age y, vaccine 90% efficacious to prevent external genital lesions for HPV!

17 Are effective: 5% to 20% absolute increase in 33 of 41 RCT! Immunization rate: 42% vs. 27%! Influenza, pneumococcal, tetanus! All ages--children do better! Academic > private or public clinic! Telephone is most effective, costly! Mailed postcards and auto-dials OK! CDC Travel Advisory!! National Immunization Program! National Vaccine Program Office! Immunization Action Coalition!