Vaccinations for Adult and Adolescent Women Eliseo J. Pérez-Stable, MD Professor of Medicine DGIM, Department of Medicine University of California, San Francisco July 3, 2013 Declaration of full disclosure: No conflict of interest Vaccines Available in the US 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 Effect of Full Use of Adult Immunizations Deaths/yr. Efficacy Use Prev Deaths/yr Influenza 36,000 70% 65% 18,000 Pneumonia 40,000 60% 60% 20,000 HBV 6,000 90% 30% 4,000 Tetanus-D < 25 99% 64% < 15 MMR < 30 95% varies < 30 Trends in Vaccine-Preventable Diseases Post Vaccine Measles and Rubella: 99.9% reduction (66 cases total and 1 case CRS in 2006) Tetanus: 93% reduction Pertussis: 92% reduction (recent increase) Hepatitis A: 87% reduction Acute HBV: 80% reduction Invasive pneumococcal disease: 34% cases and 25% mortality reduction Varicella: 85% reduction Roush SW, et al. JAMA 2007; 298: 2155-63
Vaccination Coverage in US Adults by Age Groups, 2011 HPV: 29.5% women 19-26 y Td or TDaP past 10 years: 64.5% (19-49 y), 63.9% (50-64 y), 54.4% ( 65 y) Hepatitis A: 12.5% (19-49 y) and 20.1% for those who travel outside US HBV: 35.9% (19-49 y) Pneumococcal: 20.1% (19-64 y), 62.3% ( 65 y) Varicella: 15.8% 60 y Health Care Staff: TDaP 26.8% and HBV 63.8% CDC, MMWR 2013; 62: 66-72 26 year old woman, immigrant from Guatemala with no records; says she got usual shots. What would you do? 1. Order tests for rubella, measles, and varicella antibodies before immunizing 2. Obtain detailed clinical history of possible childhood infections 3. Offer vaccines without tests given that immunization rate is low 4. Obtain medical record documentation or immunization card 5. Ask about possible social contacts before giving live viral vaccines 10 45 year old woman traveling to South Africa in May for 3 months and asks about need for vaccines. Besides advising her to check the CDC web site, are any of the following NOT needed? 1. Tetanus booster if more than 10 years from last dose 2. Influenza vaccine 3. Hepatitis A vaccine in two doses if not previously given or one dose if > 10 years 4. Hepatitis B series 5. Meningococcal C vaccine 10 70 year old man with diabetes and hypertension for routine visit. Which of the following do you recommend? 1. Tetanus booster with acellular pertussis last Td was 3 years ago 2. Intra-nasal Influenza vaccine 3. Pneumococcal vaccine booster originally given at age 65 4. Zoster vaccine without checking antibodies 5. Zoster vaccine only if no prior shingles and with documented positive varicella Ab 10
Summary of Presentation Pertussis vaccine revisited Varicella Zoster Vaccine Influenza & Pneumonia vaccines Hepatitis A and B Measles, Mumps, Rubella Human Papilloma Virus vaccine New Information from Today Pertussis vaccine for 65 y + Varicella Zoster Vaccine at 50? Pneumonia vaccine for asthma Pneumococcal conjugate vaccine for selected adults Hepatitis B vaccine for persons with diabetes Human Papilloma Virus vaccine 2 doses may be good enough Pertussis not just for children anymore Pertussis Tdap for Adults
Pertussis Vaccine Original - whole cell vaccine consisting of killed organisms Acellular vaccine contains purified, detoxified antigens Childhood DTaP: diptheria toxoid, tetanus toxoid, and acellular pertussis Adult/adolescent Td and Tdap: tetanus + reduced dose diptheria +/- reduced dose pertussis antigens Tetanus and Diphtheria Toxoid + Acellular Pertussis Vaccine (Tdap) Available as of June 2005 Replace Td with Tdap in adolescents at age 11-12 or give as single dose by 18 y Tdap should replace Td in adults 18-64 y as a one-time dose as part of primary series or as routine booster Administer to adults caring for children <1 year and all staff with direct patient contact at any age May be done at any time CDC, Updated recommendations MMWR 2011; 60:13 Pertussis Vaccine What s the Evidence? 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) Varicella Zoster Virus Vaccine Prevention of Chicken Pox Disease and Mortality Vaccine to Prevent Shingles and Neuralgia
Varicella Mortality 1990-2001 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 A Vaccine for Zoster Pathogenesis- Varicella >90% in U.S. serologic + Sensory nerves to Dorsal Root Ganglia Cell Mediated Immunity Reactivation Incidence >75yrs: 2-3/1000 yrs Lifetime risk 10-20% PHN pain > 30 days Nguyen, NEJM 2005; 352: 450-458 Zoster Adult Immunization Live attenuated Oka/Merck Zoster Vaccine 20-60K cfu (1350 cfu in varicella vaccine) RCT n=38,546 healthy >60 years old, VZI + (Zoster shot) (placebo) 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 NEJM 352;22 June 2, 2005 66.5 RRR No serious difference in group side effects Varicella Zoster Vaccine Frozen for storage, administered immediately after reconstitution Cost of vaccine is $150-$200 Decrease in pain burden by 61% Vaccinate 17 people to prevent 1 case of zoster $3,330 Vaccinate 31 to prevent 1 case of post-herpetic neuralgia $6,405 Adverse events sub-study: local 16% vs. 48%; no hospitalization or death differences at 3.4 years Kimberlin DW. NEJM, 2007;356 Simberkoff S, Ann Intern Med 2010; 152: 545
Barriers to Use of Zoster Vaccine 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; 152:555-560 Varicella Zoster Vaccine Vaccinate once at age 60 No need to check for evidence of varicella immunity FDA approved VZV for adults at age 50, but CDC is not recommending If high coverage with childhood varicella vaccine, what happens to Zoster? Patients with previous shingles Adult Vaccines Did Not Precipitate Acute Cardiac Events or Strokes Influenza and Pneumonia Seasonal Flu H1N1 Pneumococcal Vaccine 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: 2611-2618
Seasonal Influenza Vaccine: The Evidence to Support Use RCT of 1952 healthy adults age 18-49 during 2007-2008 of Inactivated vs. live attenuated vaccine Absolute efficacy of inactivated vaccine was 73% Absolute efficacy of the live vaccine was 51% Monto AS, et al. NEJM, 2009;361. Influenza Vaccine Priority Recommendations 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 Universal Immunization Recommended Seasonal Flu Vaccine for All Persons Effectiveness of Influenza Vaccine (Nichol KL, et al. NEJM 2007; 357:1373-81) Pooled data, 18 cohorts from 1990-91 to 1999-2000 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; 0.68-0.77) reduction in hospitalizations (all but 1 season) 48% (OR=0.52; 0.50-0.55) reduction in risk of death present in all seasons 1 death prevented for every 302 flu shots!
Influenza Vaccine Points Flu vaccine for Health Care Workers helps patients: 17% vs. 10% mortality in study of SNF in Scotland Survey in 2011-12 of 2348 health care workers: 66.9% vaccinated (86% MDs) 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 Influenza A H1N1 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! Pneumococcus - Background Risk factors for invasive disease Age >65 or <2 years People with chronic illness Crowding Chronic use of Proton Pump Inhibitors Antecedent respiratory infection and recent antibiotic Smokers African Americans and American Indians Pneumococcal Vaccine Indications All persons older than 65 y 50 y? Chronic cardiovascular disease Chronic pulmonary disease + asthma Diabetes mellitus, smokers Cirrhosis, Alcoholism, CSF leaks Functional or anatomic asplenia HIV infection Immunocompromised persons MMWR1997; 46:1-24 (RR-8)
Pneumococcal vaccine Re- Vaccination: CDC 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! Efficacy of Pneumococcal Vaccine 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 Pneumococcal Conjugate Vaccine 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;354:1455-63 Recommendation of Pneumococcal Conjugate (PCV13) Vaccine in Adults More immunogenic, 3X more expensive PCV13 first, followed by PPSV23 8 weeks later If already received PPSV23, give PCV13 1 yr later; boost once at 5 years if given < 65 y Conditions: CSF leak, cochlear implant Sickle cell disease, asplenia HIVn infection, chronic renal failure, nephrotic syndrome, leukemia, lymphoma, Hodgkin disease, myeloma, solid organ transplant, iatrogenic immunosuppression CDC, MMWR 2012; 61: 8116-19
Global Burden of Illness of Hepatitis B Hepatitis Vaccines Prevention of Acute and Chronic Hepatitis and Cancer! 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 Hepatitis B Vaccination 2006: 13,200 acute cases, 1460 hospitalized, 47 deaths; 2007: 1815 deaths from chronic HBV Adults target sexually active, health care workers, injection drug users, ESRD, diabetes < 60 y Needle exchange programs are effective Immunity = >10 U/ml anti-hbs Check post-vaccination serology 1-2 m after series in selected patients Universal vaccination is the goal HBV Vaccination Protection 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
Hepatitis A Vaccination Only 19.7% of adults 19 to 49 years with chronic liver conditions have received 2 doses of hepatitis A vaccine Target: Injection drug users Patients with chronic liver disease Travelers to high/intermediate risk areas in LMIC Household contacts adoptees Measles, Mumps, Rubella Have you ever seen a case? Status of MMR Diseases in 2006 Measles 55 cases; no deaths Global: 242,000 deaths; 68% reduction from 2000 Mumps 6584 cases; no deaths Rubella 11 cases; no deaths; 1 CRS Measles, Mumps, Rubella Vaccine 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
Human Papilloma Virus Vaccine Cancer Prevention at its Best? Human Papilloma Virus HPV causes cervical cancer (90%+) 50% of adults are infected with HPV 13,000 cases of cervical cancer per year in the US; 3700 deaths High burden of disease in low and middle income countries HPV is not curable or treatable $2 billion dollars to prevent up to 7000 cases of cervical cancer if vaccine is 100% effective HPV Vaccine Efficacy 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 Vaccine Recommendations by CDC/ACIP and the ACS All girls at age 9 to 11 years or as adolescents (CDC) All Women 18 to 26 years (not ACS) Give before onset of sexual activity Not to be administered during pregnancy Boys at age 11-12; 13-26 if not done Adverse effects: minor local reactions, low-grade fever, fainting Cost is about $360 it is covered
HPV Vaccine Phase 3 Trials: Futures I and II HPV 16/18 + 6/11 vaccine 12,167 and 5455 women age 15-26 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) HPV Vaccine Questions Duration of immunity unknown Acceptability by parents? Reassurance regarding safe sex? Cover more oncogenic types? Alter routine Pap screening? Global Application? 21% of women age 18-26 had received HPV in 2010 HPV Vaccine In Older Women Women aged 24-45 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 Immunogenicity of 2 Doses of HPV Vaccine in Adolescents Mean Ab levels to HPV-16 and 18 830 women randomized; girls 9-13 y to either 2 or 3 doses; women 16-26 y received 3 doses Outcome = geometric mean titer of Ab; non-inferiority up to 36 months No significant difference in GMT Dobson S, et al. JAMA 2013; 309: 1793-1802
Patient Reminders for Immunizations 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 Immunization Information Resources CDC Travel Advisory http://www.cdc.gov/travel/diseases.htm National Immunization Program http://www.cdc.gov/nip/ National Vaccine Program Office http://www.cdc.gov/od/nvpo/ Immunization Action Coalition http://www.immunize.org/