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Routine Vaccination of Adults Against Infectious Diseases: Where We Are And Where We’re Going

Routine Vaccination of Adults Against Infectious Diseases: Where We Are And Where We’re Going. Ken Zangwill, M.D. UCLA Center for Vaccine Research Harbor-UCLA Medical Center Professor of Pediatrics David Geffen School of Medicine at UCLA.

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Routine Vaccination of Adults Against Infectious Diseases: Where We Are And Where We’re Going

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  1. Routine Vaccination of Adults Against Infectious Diseases:Where We Are And Where We’re Going Ken Zangwill, M.D. UCLA Center for Vaccine Research Harbor-UCLA Medical Center Professor of Pediatrics David Geffen School of Medicine at UCLA

  2. Impact of Routine Pediatric Immunization in the United States Annual Max in Pre-Vaccine Era2003%Change Diphtheria 175,885 1 -99.99% Measles 503,282 42 -99.99% Mumps 152,209 197 -99.87% Pertussis 147,271 8,483 -94.24% Polio (paralytic) 16,316 0 -100.00% Rubella 47,745 7 -99.99% Cong. rubella synd. 823 0 -100.00% Tetanus 1,314 14 -98.93% H. influenzaetype b and 20,000 213 -98.94% type unknown ( < 5 yrs)

  3. ADULT VACCINATION:

  4. New Vaccines for Adults: Changes Afoot… • NOW: • Human papillomavirus vaccine • Pertussis vaccine • Meningococcal vaccine • Zoster vaccine • LATER: • Herpes simplex virus vaccine • Human papillomavirus type 16,18 (Cervarix)

  5. www.gfmer.ch/Books/ Cervical_cancer_modules/

  6. Human Papillomavirus Infection • >100 epitheliotropic types (45-50 in humans) • High risk (16, 18, 31, 33, 35, 39, 45, 51, 52, others) • Most common STD: 6.2 million new infections/year • 9,710 cases cervical cancer w/ 3,700 deaths (2006) • 1 million new cases of genital warts • 2nd leading cause womens’ cancer death in developing countries 1. CDC, 2004. 2. Cates W Jr, et al: Sex Transm Dis. 1999; 26(suppl): S2–S7. 3. Weinstock H, et al: Perspect Sex Reprod Health. 2004;36:6–10. 4. Burk RD, et al: J Infect Dis. 1996;174:679–689. 5.Bauer HM, et al:JAMA. 1991;265:472–477.

  7. HPV Point Prevalence in Sexually Active Women 14-59 years • 14-19 years: 40% • 20-24 years: 49% • 25-29 years: 28% • 30-39 years: 27% • 40-49 years: 24% • 50-59 years: 20% • Overall: 40% • High Risk HPV: 15% • Low Risk HPV: 18% • 30-50% in men Dunne E F, et al. JAMA 2007; 297:813

  8. Sexual Activity in High School Students Grunbaum J A, et al: MMWR 2004; 53 (SS-2): 1-96. Mosher et al: 2005; Vital & Health Statistics, No 362

  9. HPV Vaccines • Gardasil • Types 16, 18, 6, 11 • Merck • Cervarix • Types 16, 18 • GSK

  10. HPV Vaccine • Contain no DNA, is non-infectious, and • induces high titers of neutralizing antibodies

  11. HPV Vaccine Efficacy: Gardasil • Very high per-protocol efficacy against • CIN 1, 2/3, adenoca in situ, genital warts, vulvar and vaginal intraepithelial neoplasia • Up to 5 years F/U so far • No data on cervical cancer • No efficacy if HPV (+) pre-vaccination • No efficacy for non-vaccine-containing serotypes • Minimal protection against persistent infection (89%) • Data for males are pending

  12. Gardasil • IM at 0, 2, 6 months for females 9-26y • 11-12 years of age targeted; catch-up encouraged • May be given with other vaccines • OK to give if immunocompromised or lactating, avoid in pregnant women • Cervical cancer screening recommendations have not changed

  13. Ongoing HPV Vaccine Issues • Duration of protection? • Post-licensure impact and safety • Geographic serotype variation and replacement? • Efficacy against vulvar, anal, penile and oral CA? • Lengthening of Pap screening interval? • Acceptance by providers and/or families? • Requires multiple doses and refrigeration – problematic for developing countries • Efficacy in men

  14. AAP images

  15. 18.8 fold 15.5 fold Reports of Pertussis in the U.S. 2004 1990-1993 1994-1996 1997-2000 2001-2003 9000 8000 7000 6000 Average Numberof Cases / Year 5000 4000 3000 2000 1000 0 <1 yr 1-4 yrs 5-9 yrs 10-19 yrs 20+ yrs Age Group Güriş et al. Clin Infect Dis. 1999;28:1230-1237. MMWR. 2002;51:73-76, 2001;50(53):1-108, 2002;51(53):1-84, 2003;52(54):1-85

  16. Pertussis Clinical Features in Individuals > 10 Years Also may lead to seizures, encephalopathy, pneumonia/aspiration, rib fracture, hernias, lost productivity, missed school/work days Rothstein E. Peds Inf Dis JMay 2005 Suppl.

  17. Source Locale Years % of Cough Illness Nennig et al. San Francisco 1994-1995 12 Strebel et al. Minn.—St. Paul 1995-1996 13 Jackson et al. Seattle 1983-1987 15 Jansen et al. San Diego 1993-1994 17 Wright et al. Nashville 1992-1994 21 Mink et al. Los Angeles 1986-1989 26 Rosenthal et al. Chicago 1993-1994 26 Pertussis as a Cause of Prolonged Cough Illness in Adolescents and Adults Senzilet LD et al. Clin Infect Dis 2001;32:1691

  18. Acellular Pertussis Vaccines (Tdap) • Two vaccines licensed in 2005: • Boostrix®: GlaxoSmithKline, 3 Ags, 10-18y • Adacel®: sanofi pasteur, 4 Ags, 11-64y • Licensure based on immunogenicity compared to infants • Efficacious • Role: to prevent morbidity and transmission

  19. Acellular Pertussis Vaccines (Tdap) • Tdap should replace the initial Td at 11-12 yrs • Give to adolescents 11-18y who received Td >5 yrs ago • Wound management: 5 year interval from last Td encouraged, but shorter intervals “may be used” • May give with Menactra, Hep B or influenza vaccine • Data only for Adacel and w/ influenza and hep B • Provisional recs for adults: • Use Tdap for booster immunization if >10 yrs since Td • Vaccinate adults with close contact w/ infants <12m of age • Pregnancy not a contraindication to Tdap

  20. AAP

  21. Neiserria meningitidis • The bug: • US invasive disease caused by serogroups B, C, Y, and W-135 • NP colonizer, 3-4d incubation, followed by abrupt disease onset • The challenge: • Can spread in epidemic fashion among healthy individuals • Fatality rate 9%-12%; up to 40% in meningococcemia • 60% symptomatic for <24 hrs prior to hospitalization • High emotional impact

  22. Age- and Gender-Specific Rates of Meningococcal Disease in the U.S. 6 Male Female 5 4 Incidence per 100,000 Population 3 2 1 0 0-4 5-9 10-14 15-19 20-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-79 80-84 ≥ 85 Age (years) Rosenstein NE, et al. J InfectDis. 1999;180:1894-901.

  23. Rates of Meningococcal Disease in U.S. College Students, 9/1/98 - 6/30/99 Rates/Groups # Cases Population 100,000 All 18-23 year olds 304 22,070,535 1.4 College Students 90 14,897,268 0.6 Undergraduates 87 12,771,228 0.7 Freshmen Students 40 2,285,001 1.9 Dormitory Residents 45 2,085,618 2.3 Freshmen Living in Dormitories 27 591,587 5.1 MMWR. 2000;49(RR-7);1-20; Bruce MG et al. JAMA. 2001;286:688-693.

  24. Meningococcal Polysaccharide Vaccine (Menomune) • Sanofi pasteur product licensed since 1981 for those >2 years of age • One dose, given SQ • Includes serogroups A, C, Y and W135 • Indicated for travelers, occupational exposure, college students in dormitories, immune compromised persons, military recruits, those with deficiencies in late complement components (C3, C5-C9) • 85% to 93% effective, very safe

  25. Meningococcal Conjugate Vaccine (Menactra) • Sanofi pasteur product licensed since 1/2005 for 11-55y • Includes serogroups A, C, Y and W135 • One dose, given IM • Similar in construct to Hib and pneumococcal conjugate vaccines using diphtheria protein carrier • Safe and immunogenic (with Td or typhoid) • No efficacy data • Recommended to target 11-18 year olds

  26. Serogroup C Meningococcal Disease, England and Wales, Cumulative Cases Ages 15 to 17y 150 1998/99 Immunization with serogroup C conjugate vaccine in 15- 17-year-olds began on Nov 1, 1999 100 Number of Cases 1999/00 50 2000/01 0 1 5 10 15 20 25 30 35 40 45 50 Week Number (total from mid-year) hpa.org.uk/infections/topics_az/meningo/graph_meni-groupC.htm

  27. Meningococcal Conjugate Vaccine: Issues • No controlled efficacy data • Duration of immune response unknown • Not cost-effective if routinely given to entire age range • Herd immunity effects? • Licensure pending for children <10 years of age • Does not include serogroup B • Guillain-Barré?

  28. Meningococcal Conjugate Vaccine: Guillain-Barré Syndrome • Since early 2005 introduction, 15 GBS cases among 11-19 year-olds w/in 6 wks of vaccine • Relative rate of 1.78 (95% CI = 1.02–2.85) • Excess risk: 1.25 (CI = 0.058–5.99)/million doses • No cases reported since Sep 2006 • History of GBS a relative contraindication to

  29. Children 6-59m ≥50 y Persons <18y on ASA Pregnant women >6m w/ high-risk conditions and their contacts Immunosuppressed >6m w/ condition that compromises respiratory fcn or handling of secretions Residents of long-term facilities Healthcare personnel Contacts of children <59m and adults >50y ACIP Influenza Vaccine Recommendations (2007-8) CDC. MMWR July 13, 2007

  30. “How’m I Doin?” * * * * * * CDC. MMWR Morb Mortal Wkly Rep. 2005;54(30);749

  31. Available Influenza Vaccines • Trivalent inactivated vaccine (intramuscular) • Trivalent live attenuated cold-adapted vaccine (intranasal)

  32. Comparing TIV and FluMist

  33. Comparing TIV and FluMist CDC. MMWR July 13, 2007

  34. Avian Influenza StrainsKnown to Infect Humans • H5: HPAIV, current human cases, high pathogenicity • H7: HPAIV, human outbreaks, generally mild disease • H9: Some documented human cases, generally mild disease • H10: Two cases in Egypt

  35. Is a Flu Pandemic Imminent? Webby RJ and Webster RG. Science 2003;302:1519

  36. Webster RG, Gorvorkova EA. N Engl J Med. 2006;355(21):2174

  37. Major Flyways of Migratory Birds msn.com

  38. Azerbaijan: 8 cases Cambodia: 7 cases China: 25 cases Djibouti: 1 case Egypt: 37 cases Indonesia: 102 cases Iraq: 3 cases Lao PDR: 2 cases Nigeria: 1 case Thailand: 25 cases Turkey: 12 cases Vietnam: 95 cases 318 Human H5N1 Cases As of 7/2007, Case Fatality 60% Probable human-to-human transmission, but NOT sustained. WHO 2007. Accessed: 11 Jul 2007.

  39. Ongoing Efforts for Pandemic Flu Vaccine Development One vaccine licensed Health care workers ± 1st responders, chronic disease, persons 6-23m or >65 years Accelerate cell-culture-based vaccine technology Develop novel vaccine approaches Evaluate dose-sparing strategies, especially adjuvants Broaden the use of live, attenuated vaccine approaches

  40. Bird flu hits DISNEYLAND!

  41. 7th cervical 1st sacral

  42. Zoster: Summary • Primary infection (varicella); most prevalent in children • VZV targets epithelial cells, neurons, T-lymphocytes • Cell-mediated immunity (CMI) limits disease • VZV becomes latent in sensory nerve ganglia • CMI wanes over time, permitting reactivation manifesting as herpes zoster

  43. Dermal Hypo- or hyper-pigmentation Scarring Bacterial infection Central Nervous System Aseptic meningitis (up to 40%) Encephalitis (0.2%-0.5%) Transverse myelitis Delayed contralateral hemiparesis Granulomatous cerebral angiitis Guillain-Barre Syndrome Post-herpetic neuralgia Peripheral Neuropathies Cranial Neuropathies Ocular Dendritic keratitis Anterior uveitis Iridocyclitis with glaucoma Panophthalmitis Lid scarring Bone Osteonecrosis maxilla or mandible Disseminated visceral Zoster: Complications Gilden d H, et al: New Engl J Med 2000; 342: 635 Shaikh S: Am Fam Physician 2002;66:1723

  44. Post-Herpetic Neuralgia • PHN is a chronic neuropathic pain syndrome that persists or recurs in dermatome(s) affected by zoster

  45. Zoster Vaccine • Randomized, DB, PC trial of 38,546 non-immunocompromised adults ≥60 y w/ median 3.1y F/U Oxman MN et al. New Engl J Med 2005;352:2271.

  46. Herpes Zoster Vaccine • Vaccine boosts cell-mediated immunity • One SQ dose indicated for prevention of herpes zoster in persons >60 yrs • Not indicated for treatment of herpes zoster or PHN • Duration of protection unknown • Use in persons with a previous history of zoster has not been studied • No known transmission of vaccine virus to close contacts

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