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A 25 Gauge View of Prevention: Adult Vaccinations

A 25 Gauge View of Prevention: Adult Vaccinations. Shobhina Chheda, M.D., M.P.H Laurel Romer, M.D. Primary Care Conference September 14, 2005. Learning Objectives. Understand epidemiology of vaccine preventable diseases. Review recommendations for common adult vaccinations.

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A 25 Gauge View of Prevention: Adult Vaccinations

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  1. A 25 Gauge View of Prevention: Adult Vaccinations Shobhina Chheda, M.D., M.P.H Laurel Romer, M.D. Primary Care Conference September 14, 2005

  2. Learning Objectives • Understand epidemiology of vaccine preventable diseases. • Review recommendations for common adult vaccinations. • Offer vaccination to appropriate patients. • Answer patient questions regarding upcoming vaccines.

  3. Influenza • Epidemiology • Hospitalizations (From 1979/80 to 2000/01) • 54,000 to 430,000 per epidemic • 226,000 influenza-related hospitalizations/year • 63% of these among patients > 65 years old • Deaths • 19,000 per season from 1976-1990 • 36,000 per season from 1990-1999 MMWR 13 June 2005;54:1-40.

  4. Influenza • Virus characteristics • Influenza A • Envelope glycoproteins/Hemagglutinins 1,2,3/ Neuraminidases 1,2 • Antigenic shift (epidemics/pandemics) • Antigenic drift (localized outbreaks) • Influenza B • Antigenic drift

  5. Influenza • Vaccine Characteristics • Changes yearly to approximate currently circulating strains of Influenza A/B • Trivalent inactivated influenza vaccine • intramuscular • Trivalent live-attenuated, cold-adapted influenza vaccine • Intranasal • Protection conferred by induction of antibodies (mainly against the hemagglutinin)

  6. Influenza • Vaccine Efficacy • Greater reduction in serologically confirmed cases than in clinical influenza • Healthy adults ages 14-65 years: • 68% reduction in serologically confirmed influenza • 48% reduction with intranasal vaccine • 24% reduction in clinical influenza • 13% reduction with intranasal vaccine Demichelli V, et al. Cochrane Database Syst Rev 2001; CD001269.

  7. Influenza • Vaccine efficacy • Elderly • > 90% of influenza-related deaths occur among those > age 60

  8. Influenza • Vaccine Recommendations for 2005-2006 • Persons age > 65 with comorbid conditions • Residents of long-term care facilities • Persons aged 2-64 with comorbid conditions • Persons age > 65 without comorbid conditions • Children age 6-23 months • Pregnant women • Health-care personnel who provide direct patient care • Household contacts and out-of-home caregivers of children < 6 months CDC

  9. Pneumococcus • Epidemiology • Illness • 150,000 - 570,000 cases per year • 36% of community-acquired pneumonias in adults • Deaths • 6,000–12,000 per year • Case-fatality rate 5%-7%, higher in elderly • Risk highest in • Older adults • Any age with certain underlying chronic diseases CDC/Fishbein

  10. Pneumococcus • Vaccine characteristics • First used in 1945 • First vaccine developed from a capsular polysaccharide • 23-valent formulation created in 1983 (PPV23) • Intramuscular injection

  11. Pneumococcus • Efficacy: Cochrane database • Review of all RCT from 1/66 to 6/03 • Combined results fail to show PPV is effective in preventing pneumonia (OR 0.77) or death (OR 0.90) • Review of all case-control studies for same interval • Combined results show significant efficacy in preventing invasive pneumococcal disease (OR 0.47), corresponding to an efficacy of 53% Dear KB, et al. Cochrane Database Syst Rev;3: 2005.

  12. Pneumococcus • Recommendations for use • Adults age 65 or older • Persons age >2 • with chronic disease (similar to influenza) • No spleen • Compromised immunity (HIV, malignancy, chronic renal disease, organ transplant, chemotherapy) • Second dose of vaccine if patient received vaccine > 5 years previously and was < 65 MMWR 2003;52:965 MMWR 2002;51:931

  13. Hepatitis B • Incidence • In endemic areas, ~70% of adult population positive for prior infection • 8-15% with chronic Hep B • Globally • 2 billion with evidence of prior Hep B infection • 350 million chronic carriers • 1 million deaths annually due to cirrhosis/hepatocellular carcinoma Poland GA and Jacobson RM. NEJM;351(27):2004.

  14. Hepatitis B • Viral source • Blood or blood-derived body fluids • Transmission • Percutaneous, mucosal • Sex, injection drug use, mother-child, health care • 100x more infectious than HIV

  15. Hepatitis B • Vaccine characteristics • First generation HBV vaccine was plasma derived • Current vaccines are recombinant HBV • Schedule: 3 doses, intramuscular injection • 0, 1-2 months, 4-6 months • Combined form with Hepatitis A • Safety • Soreness at injection site (25%) • Fever, malaise, headache, myalgia, joint pain (1-3%)

  16. Hepatitis B • Efficacy • After completing the 3 dose course of vaccine • 90% of adults have protective serum antibody concentrations • 95% of infants, children and adolescents Mast E, et al. In: Vaccines, 2004. 299-337.

  17. Hepatitis B • Vaccine recommendations • All infants • Catch-up vaccination • Pregnant women • Homosexual/bisexual men • Multiple sexual partners (4 or more/lifetime) • Household contacts of patients with Hep B • Injection drug users • Healthcare workers • Patients on hemodialysis (recipients of frequent transfusion) • Patients with chronic illness • Immunocompromised patients

  18. Hepatitis A • Significant decrease in incidence with vaccine • Most occurs in community wide epidemics • Higher disease incidence in West and Southwest • Highest incidence in children ages 5-14 • Children – reservoir

  19. Hepatitis A • Transmission: Fecal-oral • 70% children asymptomatic or nonspecific symptoms • > 70% adults have jaundice • Liver failure rare • Chronic infection doesn’t occur

  20. Hepatitis A and Hurricane Katrina • No transmission from contaminated water in US since 1980’s • No outbreak seen in other recent hurricane/floods • < 10 cases of hepatitis A in New Orleans in past 3 months CDC

  21. Hepatitis A • Inactivated vaccine • 2 brands licensed for children>2 and adults • Different pediatric and adult formulations

  22. Hepatitis A • 2 doses – 6 months apart • 97% immunogenic with first dose • 100% with second dose- long term immunity • No severe/adverse reactions • Side effects • Soreness/tenderness –50% • Headache-15% • Malaise-7%

  23. Hepatitis A • Not routine pediatric immunization • Adult recommendations • Certain international travelers • Men who have sex with men • Illicit drug users • Chronic liver disease • Persons receiving clotting factor concentrates • Persons working with laboratory HAV • Not routinely recommended for healthcare workers

  24. Combined Hepatitis A and B vaccine • FDA approved for > age 18 • Immunogencity/safety similar to single antigen vaccines • Schedule 0, 1, 6 months (same as Hep B) • Total 3 injections instead of 5

  25. Meningococcal disease • 1,400-2,800 cases/yr • Rate 0.5-1.1/100,000 • College freshman* • 1.9/100,000 • Living in dorms 5.1/100,000 • Leading cause of bacterial meningitis • Dramatic reductions of Strep Pneumoniae and HIB meningitis from universal vaccination of children *Bruce et al. JAMA 2001 286:688-93

  26. Meningococcal disease • Three clinical forms • Meningitis (49%) • Bacteremia (33%) • Pneumonia (9%) • High case- fatality ratio (10-14%) • High morbidity • 11-19% of survivors have sequelae • Transmission: direct contact with large droplet respiratory secretions • 5-10% carries bacteria

  27. Meningococcal disease • Disease caused by 5 serogroups worldwide • A, B, C, Y W-135 • United States • B, C, Y • Serogroup B (no vaccine available) • > 50% cases in age <1 • < 25% cases age >11

  28. Meningococcal vaccines • MCPV4 – licensed 1981 • Polysaccharide vaccine • Mature B-lymphocyte response, no T-cell stimulation • Not long lasting, no amnestic response • MCV4 – licensed 2005 for ages 11-55 • Polysaccharide protein conjugate vaccine • T-cell dependent immune response • Longer lasting and stronger amnestic response

  29. Meningococcal disease:MCV4 use • Universal vaccination • Ages 11-12 • Adolescents at age 15 if not previously vaccinated • Groups at elevated risk • College freshman in dorms • Military recruits • Certain microbiologists • Certain travelers • Asplenia/Terminal complement component deficiencies • Single dose IM

  30. Meningococcal disease:MCV4 use (continued) • Adverse reactions • Mild injection site pain and tenderness • Brief fever 5% • Severe allergic reaction (<0.1/100,000) • Neurological reaction (<0.1/100,000)

  31. Meningococcal disease:MPSV4 use • Groups at elevated risk ages 2-10; >55 • Groups at elevated risk if MSV4 not available • No longer recommended for routine vaccination • Single dose IM • Adverse reactions similar to MCV4

  32. Pertussis: Secular Trends • Incidence • 1940 (Prior to vaccination): 150 cases /100,000 • 1960: 8 cases/100,000 • 1980-90: 1 cases/100,000 (2,900 cases/yr) • 2003: 11,647 cases Only disease for which universal immunization is recommended that incidence is on the rise !

  33. Pertussis: Why the increase? • Increase in reporting vs. actual disease • True burden is at least 10x > reported • Waning immunity • Less passive Ab transmitted to newborns • Decreased herd immunity • Aging cohort • ? Under-vaccination in childhood

  34. Pertussis: Important to internists? • Number of cases high in adults • Rate, morbidity and mortality higher in < age 1 • Adults are source of infection for children • 80% secondary attack rate • Wisconsin with high number of cases

  35. Pertussis Children • Catarrhal stage 1-2 weeks • Paroxysmal cough stage 1-6 weeks • Convalescent stage weeks-months

  36. Pertussis Adults • Accounts for 7% of all cough illnesses per year • Mild disease • No phases • Persistent cough >21d • Often not diagnosed/treated until after maximum transmission

  37. Pertussis • Aerobic gram negative rod • Attaches to cilia • Local tissue damage • Decreased ability to clear secretions • Challenging to diagnose • Gold standard-culture (Low sensitivity) • PCR (Sensitivity highly age dependent) • DFA (now rarely used) • Serology (not practical)

  38. Pertussis: Vaccine • Acellular (DTaP) • Licensed 1996 for primary series • Replaced whole- cell vaccine for children • More effective and fewer side effects • Purified subunit vaccine • Varies between 2 and 4 subunit components

  39. Immunogenicity and Safety Study • Prospective, randomized, double blinded trial comparing safety and efficacy of dT and DTaP • 4480 participants enrolled • Ages 11-64 Results: • Elicited robust immune responses to all antigens • No differences observed in side effects in 2 vaccines groups Pinchicherio et al. JAMA 2005:293(24) 3003

  40. Immunogenicity and Safety Study • Prospective, randomized, double blinded trial comparing safety and efficacy of dT and DTaP • 4480 participants enrolled • Ages 11-64 • 39 US centers • Results • Elicited robust immune responses to all antigens Pinchicherio et al. JAMA 2005:293(24) 3003

  41. Pertussis: Bottom line • DTaP – 2 vaccines licensed 2005 by FDA • Adcel* ages 11 to 65 • Boostrix ages 11-19 • ACIP recommendations/most cost effective • Ages 11-12 give DTaP instead of dT • Ages 11-18 give DTaP even if dT given • 5 year interval recommended * Used in JAMA study

  42. Pertussis: Bottom line (cont.) Watch for ACIP recommendations for older adults • Universal (using DTaP instead of dT for all) vs. “High risk-groups” (health care workers, those in contact with infants) • Economic issue

  43. Hurricane Katrina: Evacuees in crowded settings • Influenza -all > 6 months • < 8 years old need 2 doses • Hepatitis A -all > 6 months • Varicella, MMR, dT (DTaP) , meningococcal, pneumococcus • Usual recommendations

  44. Hurricane Katrina • Evacuees not in crowded settings • Usual recommendations • Responders • dT and Hepatitis B

  45. Varicella • Vaccine recommendations • Who: • Age >18 lacking history of chicken pox or documentation of prior vaccination • Schedule: • 2 doses • 0, 4-8 weeks • Characteristics: • Oka/Merck VZV vaccine – 1350 plaque-forming units • IM injection

  46. Varicella Zoster • Epidemiology • Prevalence • 15% of the population • Incidence • 74 per 100,000 age < 10 • 300 per 100,000 age 35-44 • 1200 per 100,000 age >75 Donahue JG, et al. Arch Intern Med 1995;155: 1605-1609.

  47. Varicella Zoster • Epidemiology • Incidence and severity increase with advancing age • Half of those who develop zoster are > 60 years old • 36.6% of those > 60 have persistent pain > 1 year • 47.5% of those > 70 have persistent pain > 1 year De Moragas JM and Kierland RR. AMA Arch Derm 1957;75:193-196.

  48. Varicella Zoster • Clinical Features • Unilateral radicular pain and vesicular rash usually limited to a single dermatome • Results from reactivation of latent VZV within the sensory ganglia

  49. Varicella Zoster • Vaccine administration: • Live attenuated VZV vaccine • 18,700 to 60,000 plaque-forming units of virus • (1350 p-f units in VZV vaccine for children) • Higher dosage necessary to elicit a significant increase in cell-mediated immunity to VZV among older adults • One subcutaneous injection

  50. Varicella Zoster • Efficacy • Recent Randomized Controlled Trial in NEJM: • 38,546 adults age 60 or older • Administered adult VZV vaccine • Primary endpoint: burden of illness due to herpes zoster (incidence, severity and duration of pain) • Secondary endpoint: incidence of postherpetic neuralgia Oxman MN, et al. NEJM;352(22):2271-2284.

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