Adult Immunization: What's New in 2008

Adult Immunization: What's New in 2008 Michael F. Para, MD Division of Infectious Diseases Incidence Incidence*of Invasive Hib Disease, 1990-2004 Vaccine 25 20 15 10 5 0 1990 1992 1994 1996 1998 2000 2002 2004 Year *Rate per 100,000 children <5 years of age Vaccine-Preventable Diseases Number of Cases Maximum (year) in 2005 Tetanus 524 (1954) 27 Diphtheria 2,041 (1954) 0 Pertussis 62,786 (1955) 22,739 Measles 763,094 (1958) 66 Mumps 152,209 (1968) 314 Rubella 57,686 (1969) 11 Invasive Pneumococcal Disease by Age and Year Children <5 Years, 1998-2003 Cases/100,000 population 250 200 150 100 50 0 Age group 1 yr <1 yr 2 yrs 3 yrs 4 yrs Vaccine Year Source: Active Bacterial Core Surveillance/EIP Network 1998 1999 2000 2001 2002 2003 1

Vaccine Preventable Diseases (VPDs) in Adults VPD's kill hundreds of times more adults than children every year in the U.S.! Burden of Illness on Hospitals 114,000 Influenza admissions 15,000 Hepatitis admissions More than 40,000 deaths per year: 20-40,000 from pneumonia and influenza 5,000 from hepatitis B Adult immunization coverage levels are generally low Strengthening Adult Immunization: A Call to Action, Partnership for Prevention, 2005 Vaccine Information Statements New or Revised Since August 2006 New Human papillomavirus Zoster Rotavirus Revised DTaP Hepatitis B Varicella Meningococcal Influenza (TIV and LAIV) Influenza Vaccine 2

Impact of Influenza Hospitalization Rates By Age Age Group 0-11 mos 1-2 yrs 3-4 yrs 5-14 yrs 15-44 yrs 45-64 yrs >65 yrs Rate** 496-1038 186 86 41 23-25 13-23 125-228 (90% of deaths) * Data from several studies 1972-1995, ** Hospitalizations per 100,000 population More than 200,000 influenza-related hospitalizations/yr 36,000 influenza-associated deaths each influenza season Influenza Vaccines 70%-90% effective among healthy persons <65 30%-40% effective among frail elderly persons 50%-60% effective in preventing hospitalization 80% effective in preventing death Influenza Vaccines Trivalent (H3N2, H1N1, B) 2008-2009 Inactivated subunit (TIV) - Intramuscular Duration of immunity for inactivated influenza vaccine is considered to be 1 year or less Live attenuated vaccine (LAIV) - Intranasal Duration of immunity for LAIV is uncertain, transmission rare Inactivated Influenza Vaccine Recommendations All persons 50 years of age or older, Oct to March Children 6-59 months of age Persons >6 months of age with chronic illness Pulmonary (e.g., emphysema, asthma) Cardiovascular (e.g., CHF) Metabolic (e.g., diabetes) Renal dysfunction Hemoglobinopathy Immunosuppression, including HIV infection Conditions compromising respiratory function or handling of secretions or increasing risk of aspiration 3

Inactivated Influenza Vaccine Recommendations Pregnant women (or will be during flu season) Residents of long-term care facilities Persons 6 months to 18 yrs of age on chronic ASA Influenza Vaccine Recommendations International travelers Persons in institutional setting dorm, prison Anyone who wants to reduce the likelihood of becoming ill from influenza Influenza Vaccine Recommendations Healthcare providers, including home care Only 42% HCP were vaccinated in 2004 Employees of long-term care facilities Household contacts of high-risk persons Providers of essential community services Live Attenuated Influenza Vaccine (LAIV) 25% Reduction of febrile URI, lost work days Approved only for healthy persons 2-49 years of age Healthcare providers Persons in close contact with high-risk groups LAIV should not be administered to HCP working with severely immunosuppressed persons Persons who want to reduce their risk of influenza Not in pregnancy or immunocompromised state 4

LAIV Adverse Reactions Significantly increased rate of cough, coryza, nasal congestion, sore throat, chills No increase in fever No serious adverse reactions have been identified LAIV Storage and Handling Tdap Vaccine Must be stored at <5 F (-15 C ) until just before use May be stored in a refrigerator and stored at 35-46 F for up to 60 hours before use Thawed vaccine cannot be refrozen Influenza Antiviral Use, 2008-2009 Neither amantadine nor rimantadine should be used for treatment or chemoprophylaxis of influenza A infections during influenza season Oseltamivir or zanamivir should be prescribed if an antiviral drug is indicated for the treatment of influenza Source: MMWR 2007;56 (RR-6) Tetanus and Diphtheria Vaccines and Immunity in Adults Tetanus and Diphtheria Toxoid (Td) Formalin-inactivated toxins 3-4 doses induces protective antibody in nearly everyone Protection for at least 10 years Many adults do not receive vaccine every decade Half of adults over 20 yo lack protective Ab levels 5

Cases Reported Pertussis by Age Group 1990-2005 30000 25000 20000 15000 10000 5000 >18 yrs 11-18 yrs <11 yrs 0 1990 1993 1996 1999 2002 2005 Year Use of Tdap (Adacel) Among Adults Single dose of Adacel to replace a single dose of Td May be given at an interval less than 10 years since receipt of last tetanus toxoid-containing vaccine Special emphasis on adults with close contact with infants (e.g., childcare and healthcare personnel (HCP), and parents) HCP with direct patient contact especially with infants <1 year, should receive a single dose of Adacel as soon as feasible. Other HCP should receive a dose of Tdap to replace the next scheduled Td. Source: MMWR 2006;55(RR-17) Tetanus, Diphtheria, Acellular Pertussis Vaccines for Adults Tdap preferred to Td to provide protection against pertussis Adacel (Sanofi) Only Tdap brand approved for adults Single dose Approved for persons 11 through 64 yrs Approved only for a single booster dose in persons who have received a full series of pediatric DTaP or DTP Boostrix (GlaxoSmithKline) Approved for persons 10 through 18 years of age Meningococcal Disease Among Young Adults, United States, 1998-1999 18-23 years old 1.4 / 100,000 18-23 years old not college student 1.4 / 100,000 Freshmen 1.9 / 100,000 Freshmen in dorm 5.1 / 100,000 Bruce et al, JAMA 2001;286;688-93 6

Meningococcal Vaccines Composed of 4 capsular polysaccharides from serogroups A, C, Y, & W-135 (note no group B) Two available meningococcal vaccines: Menomune - Menactra - polysaccaride - MPSV4 polysacccharide conjugated to diphtheria toxoid MCV4 Documented utility in controlling outbreaks Menactra - preferred for persons 11-55 years old Menomune - only for persons at increased risk of N. meningiditis infection who are 2-10 years or >55 years of age, or if MCV4 is not available Hepatitis A and B Vaccines Recommendations for the Use of Meningococcal Vaccines Menactra for children ages 11-18 Menactra (or MPSV4) for all college freshmen living in dormitories Risk Factors for Hepatitis B Household 3% Other 23% Multiple sex partners 24% Menactra (or MPSV4) for adults with meningococcal risk Terminal complement deficiencies Anatomic or functional asplenia Research/clinical lab personnel with exposure Travelers to countries with known hyperendemic or epidemic meningococcal disease Military recruits HIV infection Sex contact 13% MSM 17% IDU 20% CDC Sentinel Sites. 2001 data. 7

Hepatitis B Vaccine Recombinant DNA HB surface antigen vaccine Protective antibody levels develop in >90% Immunologic memory develops following vaccination Antibody level declines following successful vaccination Anamnestic response upon exposure (antibody level increases quickly) Routine vaccination through age 18 years Hepatitis B Vaccine Adult Candidates Lifestyle factors Heterosexual with>1 partner past year, recently acquired STD Men who have sex with men Commercial sex workers Injection drug users Environmental situations Household members and sex partners of HBs antigen carrier Household members of adoptees from hep B endemic areas Hepatitis B Vaccine Adult Candidates All health-care workers with body fluid exposure including Staff /clients in institutions for the developmentally disabled Special patient groups Persons receiving hemodialysis Recipients of certain blood products Alaska Natives, Pacific Islanders Persons who travel to HBV-endemic areas Postvaccination Serologic Testing Not routinely recommended following vaccination of infants, children, adolescents, or most adults Recommended for: Hemodialysis patients Immunocompromised persons Sex partners of persons with chronic HBV infection Certain healthcare personnel who have contact with patients or blood and are at ongoing risk for injuries with sharp instruments or needles should be tested for antibody after vaccination Routine revaccination (boosters) are not recommmended 8

Management of Nonresponse to Hepatitis B Vaccine Complete a second series of three doses Should be given on the usual schedule of 0, 1 and 6 months Retest 1-2 months after completing the second series No further dosing if no response but check HbsAg If exposed to HBV treat as nonresponder with prophylaxis Twinrix Combination hepatitis B (adult dose) and hepatitis A vaccine (pediatric dose) 3-dose series at 0, 1, 6-12 months Approved for persons over 18 years of age Can be used interchangeably with monovalent hepatitis B and hepatitis A vaccine Recommendations for the Routine Use of Hepatitis A Vaccine Travelers to endemic areas Men who have sex with men Illegal drug users Persons with certain occupational risks (lab) Persons with chronic liver disease including HCV and clotting factor disorders All children at 1 year Twinrix Accelerated Schedule Doses at 0, 7, 21-30 days and booster dose at 12 months Approved only for persons over 18 years old The first THREE doses of the newly- licensed Twinrix schedule provide equivalent protection to The first dose in the standard, single antigen adult hepatitis A vaccine series The first two doses in the standard adult hepatitis B vaccine series 9

Human Papillomavirus (HPV) Nonenveloped double-stranded DNA virus >100 HPV types identified 60 types cause cutaneous lesions 30 40 infect anogenital mucosa 15 20 oncogenic (high risk) types include 16, 18, 31, 33, 35, 39, 45, 51, 52 HPV 16 (54%) and 18 (13%) cervical CA Nononcogenic (low risk) types include 6, 11, 40, 42, 43, 44, 54 HPV 6 and 11 most often ass d with external anogenital warts. High Risk HPV Infection Is A Necessary Cause of Cervical Cancer Infection with oncogenic HPV type is the most important risk factor in cervical cancer etiology. Analysis of 922 cervical cancer specimens from women in 22 countries showed a prevalence of HPV DNA of 99.7%. Most common HPV types found in cervical cancer were 16, 18, 31, 33 and 45. Two thirds of cervical cancer had types 16 and 18. 1. Walboomers JM, Jacobs MV, Manos MM, et al. J Pathol. 1999;189:12 19. 2. Clifford GM, Smith JS, Plummer M, Muñoz N, Franceschi S. Br J Cancer. 2003;88:63 73. Lesions Associated With Low- and High- Risk Genital HPV Types Natural History of HPV Infection and Potential Progression to Cervical Cancer 0 1 Year 0 5 Years 1 20 Years Initial HPV Infection all types Continuing Infection 30% CIN 1 CIN 2/3 40% 5-12% 10% Invasive Cervical Cancer Not all CIN 2/3 Comes from CIN 1 Genital Warts 60% 40% of CIN 2 32% of CIN 3 Cleared HPV Infection Cervical cell abnormalities of low risk types usually resolve and do not lead to cancer 1. Pinto AP, Crum CP. Clin Obstet Gynecol. 2000;43:352 362. 10

Estimated Annual Burden of HPV- Related Diagnoses in the United States 9,710 new cases of cervical cancer 1 3,700 deaths estimated in 2006 1 330,000 new cases of high-grade cervical dysplasia (CIN 2/3) 2 1.4 million new cases of low-grade cervical dysplasia (CIN 1) 2 1 million new cases of genital warts 3 6.2 million new HPV infections/yr in US Mental health burden maybe even more significant 1. ACS. Cancer Facts and Figures 2006. 2. Schiffman M. Findings to date from the ASCUS-LSIL Triage Study. Arch Pathol Lab Med. 2003;127:9463. 2. Fleischer AB, et al Condylomata acuminata (genital warts):patient demographics and treating physicians. Sex Transm Dis. 2001;28:643 647. HPV/Cervical Cancer Vaccine Quadrivalent HPV 6/11/16/18 L1 virus-like particle (VLP) vaccine VLPs are produced in Saccharomyces cerevisiae. The L1 proteins self-assemble into VLPs. Purified VLPs are adsorbed on aluminum-containing adjuvant. The adjuvant is amorphous aluminum hydroxyphosphate sulfate (225 μg per dose). Each 0.5-mL dose contains HPV Types 6/11/16/18 (20/40/40/20 μg L1 protein, respectively). Estimated, % Cancer Types, Other Than Cervical Cancer, Attributable to HPV Estimated percentage of cancer cases attributable to HPV 100 80 60 40 20 0 70 50 50 50 Anal Vulvar Vaginal Penile Oropharyngeal Cancer Type González Intxaurraga MA et al. Acta Dermatovenerol. 2002;11:1 8. 20 Natural History of HPV Infection: Surrogate Markers for Cervical Cancer Initial HPV Infection CIN = cervical intraepithelial neoplasia. AIS = adenocarcinoma in situ. 0 1 Year 0 5 Years 1 20 Years Continuing Infection CIN 1 Cleared HPV Infection Adapted from Pinto AP et al. Clin Obstet Gynecol. 2000;43:352 362. CIN 2/3 or AIS Invasive Cervical Cancer Primary efficacy objective of quadrivalent HPV vaccine program: Demonstrate prevention of HPV 16/18 related CIN 2/3 + AIS 11

Efficacy Against HPV 6/11/16/18-Related Lesions PPE-Combined Population; subjects were naïve to HPV Types 6, 11, 16, and/or 18 Combined Analysis End Point: HPV 6/11/16/18-related CIN or AIS GARDASIL Cases n=7,858 4 Placebo Cases n=7,861 83 Vaccine Efficacy 95% 95% CI 87 99 Herpes Zoster - Shingles End Point: HPV 6/11/16/18-related GARDASI L Cases* n=7,897 Placebo Cases* n=7,899 Vaccine Efficacy 95% CI Genital warts 1 91 99% 94 100 The efficacy of GARDASIL against HPV 6-, 11-, 16-, and 18- related. VIN 1 or VaIN 1 was 100%. classic patches of localized clustered vesicular lesions Human Papillomavirus Vaccine Recommendations 3 dose series, given IM, at 0, 2 months, and 6 months minimum intervals:dose 1-2: 4 weeks, dose 2-3: 12 weeks Indicated females aged 9 to 26 years for the prevention of cervical CA, precancerous lesions, and genital warts caused by HPV types 6, 11, 16, 18 regardless of HPV hx Duration of efficacy has been demonstrated for up to 4 years and studies continue. Vaccination with HPV vaccine does not protect against diseases from non-vaccine HPV types. Does not substitute for routine cervical cancer screening. Is not intended to be used for treatment of active genital warts; cervical cancer; CIN, VIN, or VaIN. Establishment of VZV Latency in Sensory-Nerve Ganglia Virus establishes latency in dorsal root sensory ganglion and reactivates and tracks down the sensory nerve of the dermatome. Kimberlin D and Whitley R. N Engl J Med 2007;356:1338-1343 12

Rate per 1,000 person-years* (95% CI) Zoster Incidence 16 14 12 10 8 6 4 2 0 Age (years) Cases (N=9,152) 1.1 1.4 0 14 397 15 29 527 2.0 30 39 600 2.9 40 49 1,213 4.6 50 59 1,989 6.9 60 69 1,778 9.5 70 79 1,692 10.9 Estimated million cases/yr in US, with lifetime incidence of > 30%, 50% of those surviving to age 85 will have had it 80 956 Zoster Complications- Zoster Ophthalmicus Presents with pain and rash over distribution of 1st division of trigeminal nerve, red eye, decreased vision, eye pain. Lesions can involve eyelid, but conjunctivitis, iritis, dendriform ulcers on cornea (noted on fluorescein exam) and rarely retinal necrosis are seen Ophthalmologic consultation is important if the diagnosis is serious consideration. 30% 50% of patients with this experience visual morbidity 1 1. Pavan-Langston D. In: Watson CPN, Gershon AA, eds. Herpes Zoster and Postherpetic Neuralgia, 2nd Revised and Enlarged Edition. Vol 11. Amsterdam, The Netherlands: Elsevier Science B.V.;2001:119 129. Risk Factors for Herpes Zoster History of chickenpox Advancing age and waning cellular immunity VZV-specific immunity declines with age After bout of zoster, zoster immunity goes up Second bout of zoster uncommon (1-5%) Decreased zoster immunity may also be due to immunosuppressive illness or medications Approximately 1% of HIV patients get zoster a yr Recurrences in HIV are common Gnann JW, Whitley RJ. N Engl J Med. 2002;347:340 346. Complications of Zoster Ophthalmic Visual impairment Ptosis Cutaneous Scarring Bacterial superinfection Neurologic Postherpetic neuralgia (PHN) Loss of sensation Allodynia Cranial nerve palsies (Bell s) Motor nerve palsies Encephalitis, stroke Visceral (very rare) Pneumonia Oxman MN. In: Arvin AM, Gershon AA, eds. Varicella-Zoster Virus, Virology and Clinical Management. Cambridge Press; 2000:246 275. 13

Pathophysiology of PHN atrophy Recommended Oral Antiviral Therapy for Herpes Zoster in Immunocompetent Adults Acyclovir 800 mg every 4 hrs (5 times/d) for 7-10 days cost $35 Famciclovir (Famvir) 500 mg every 8 hrs (3 times/d) 7 days cost $180 fibrosis Valcyclovir (Valtrex) 1000 mg every 8 hrs (3 times/d) 7 days cost $180 If started within 72 hrs of onset, treatment speeds healing by three days. Reduces some complications but post-herpetic neuralgia not consistently helped. Duration of Zoster-Associated Pain According to Age ZOSTAVAX Indications and Usage [Zoster Vaccine Live (Oka/Merck)] ZOSTAVAX is a lyophilized is the Oka/Merck strain of the live attentuated VZV. Each dose has about 19,400 viruses Varivax (chickenpox vaccine) has about 1300. Based on large study (38,546 subjects) of shingles prevention in VA system ZOSTAVAX is indicated for the prevention of herpes zoster (shingles) in individuals 60 years of age and older. The benefit of ZOSTAVAX in the prevention of postherpetic neuralgia can be primarily attributed to the effect of the vaccine on the prevention of zoster. PHN also worse when more severe rash, sensory abnormalities and pain acutely 14

Number of zoster cases Prevention of Shingles in Zoster Vaccine Study 700 600 500 400 300 200 642 51% (95% CI: 44%, 58%) 315 64% (95% CI: 56%, 71%) 334 41% (95% CI: 28%, 52%) 100 156 18% 122 (95% CI: 29%, 48%) 0 47 37 Incidence rate 11.1 5.4 10.8 3.9 11.4 6.7 12. 9.9 of zoster per 1,000 personyears Overall 60 69 70 79 2 80 Age (years) 261 Placebo ZOSTAVA X Effect of Zoster Vaccine on Cumulative Incidence of Postherpetic Neuralgia and Herpes Zoster Postherpetic Neuralgia Oxman M et al. N Engl J Med 2005;352:2271-2284 Herpes Zoster Postherpetic Neuralgia (pain after 90 days) in the Shingles Prevention Study % of Zoster Cases with Postherpetic Neuralgia 50 40 Cases of PHN Cases Cases of HZ Cases 30 26% (95% CI: 69%, 68%) 20 39% 55% 25.5 (95% CI: 18%, 76%) (95% CI: 7%, 59%) 5% 17.2 18.9 10 12.5 (95% CI: 107%, 56%) 8.6 6.9 6.6 7.7 0 80 27 23 8 45 12 12 7 642 315 334 122 261 156 47 37 Overall 60 69 70 79 80 Age (years) *Zoster-associated pain rated as 3 on a 10-pt scale and occurring or persisting at least 90 days after rash onset. Age-adjusted estimate based on the age strata (60-69 and 70 years of age) at randomization. Placebo ZOSTAVAX Dosage and Administration Advisory Committee on Immunization Practices (ACIP) recommended single dose of Zostavax for persons aged >60 years with a history of varicella. MMWR 12/1/06 Zostavax is indicated for the prevention of herpes zoster (shingles) in persons 60 years of age and older. Can give to person with hx of zoster.?? Need 15

Dosage and Administration Zostavax is administered as single subcutaneous dose. Reconstitution from frozen virus vaccine, give immediately Discard vaccine if not used in 30 min. Do not re-freeze. Helpful Website http://www.cdc.gov/vaccines Health & Safety Topics: Vaccines and Immunizations Publications & Products: MMWR (January 5, 2007) MMWR (October 13, 2006) 16