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Vaccination Update

Vaccination Update American College of Physicians, 2007 Missouri Chapter Meeting September 27, Tan Tar A Resort, Osage Beach, MO Gordon Christensen, M.D., F.A.C.P. University of Missouri-Columbia 573-882-3107 Points to be Covered: Vaccination Primer New adult vaccines:

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Vaccination Update

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  1. Vaccination Update American College of Physicians, 2007 Missouri Chapter Meeting September 27, Tan Tar A Resort, Osage Beach, MO Gordon Christensen, M.D., F.A.C.P. University of Missouri-Columbia 573-882-3107

  2. Points to be Covered: • Vaccination Primer • New adult vaccines: • Varicella (“Shingles”) • Human Papillomavirus (HPV) • Routine adult vaccines: • Pneumococcal • Influenza • Hepatitis A • Hepatitis B • MMR • Meningococcal

  3. Active immunization: Durable immunity Primary immune response with: B-cell proliferation Antibody production T-cell sensitization Passive immunization Transient immunity Antibody infusion Background

  4. TRUE Contraindications to Vaccination • Severe hypersensitivity reaction • Anaphylaxis • Vaccine specific – avoid vaccine • Eggs – avoid: measles, mumps, influenza, & yellow fever • Neomycin & streptomycin – avoid MMR • Severe reaction to past vaccine, seen with: • Cholera, Typhoid, and Plague vaccines • History of post-vaccine encephalopathy from past vaccines • Live vaccines • Immunocompromised patients (IP) • Household members of IP – avoid oral polio (but not MMR) • Pregnant women

  5. FALSE Contraindications to Vaccination • Current or recent mild illness, with or without fever • Current or recent antimicrobial therapy • Previous mild to moderate reaction after any vaccination, such as: • Local tenderness • Redness • Swelling • Fever < 40.5°C • Family history of adverse reaction to immunization No post-vaccination contraindications for athletics or alcohol

  6. Vaccination Requirements for PROVIDERS • Follow instructions • Maintain administration records • Report adverse events • Provide vaccine information brochures for patients, available from: CDC National Center for Immunization and Respiratory Disease website @: www.cdc.gov/nip

  7. Schedule Problems • Off schedule? – Do not restart series, just pick-up where left off and continue • Multiple vaccines? – Can usually co-administer vaccines, such as: • Pneumococcal and influenza & travel vaccines Exceptions: • Live virus vaccines: delay one for a month to avoid possible impaired immune response to either agent • Immune globulins should not be given with live virus vaccines (exceptions: inactivated virus vaccines, oral polio, and yellow fever)

  8. For Healthy Adults: q 10 yrs q year

  9. For Adults with Health Problems: 1 dose 1-2 doses 2 doses 3 doses 1 or more doses

  10. New Adult Vaccines Zoster for adults (“Shingles” vaccine) Human Papillomavirus Also: New intranasal influenza vaccine New meningococcal conjugate vaccine New hepatitis A & B combined vaccine (New conjugate pneumococcal vaccine)

  11. Varicella (“Chickenpox” ) Vaccine: Varivax® • Live, attenuated, virus vaccine, US license in 1995 • Contraindicated in pregnancy & immunocompromised • For children (>12 mos) & adults, particularly adult: • Health care workers • Primary school teachers & day care workers • Institutional residents and employees • Military personnel • Non-pregnant women of child bearing age • International travelers • 2 dose adult schedule: 0 & 4-8 weeks – No booster

  12. Varicella (“Shingles” ) Vaccine: Zostavax® • Zostavax® has 14 times more virus than in Varivax® • Licensed 2006 for >59 y/o to prevent shingles • Clinical study: • 38,000 adults, 60-80 y/o, followed median of 3+ years • Vaccine group: • 51% fewer episodes of shingles • Duration reduced from 24 to 21 days • 66% less post-herpetic neuralgia • Efficacy highest for 60-69 @ 64% • Efficacy declines with age, 18% for >80 y/o

  13. Varicella (“Shingles” ) Vaccine: Zostavax® • Administer as a single dose • Contraindicated for: • Anaphylactic reaction to gelatin or neomycin, • Immunodeficiency states including: • leukemia, lymphomas, neoplasms affecting the bone marrow or lymphatic system • AIDS • active untreated tuberculosis. • immunosuppressive therapy including high-dose corticosteroids • women who are or may be pregnant • Average wholesale price: $190

  14. Varicella (“Shingles” ) Vaccine: Zostavax® • The Advisory Committee on Immunization Practices voted in October 25, 2006 that: “A single dose of zoster vaccine [i.e. Zostavax] is recommended for adults 60 years of age and older whether or not they report a prior episode of herpes zoster. Persons with chronic medical conditions may be vaccinated unless a contraindication or precaution exists for their condition.” • This recommendation was tentatively set for publication in CDC Morbidity and Mortality Weekly Report for June 2007, but this did not happen. It is still under review by the CDC and the Department of Health & Human Services.

  15. Human Papillomavirus (HPV) Double stranded DNA virus – more than 100 types • 60 types  cutaneous infection  skin warts • 40 types mucosal & genital infection • Genital, laryngeal, rectal warts & cervical abnormalities • No cross protection between types • Certain types PROMOTE (virus infection is necessary but not sufficient to cause) 99+% of cervical cancer • Type 16 causes 50%; Types 16 + 18 cause 70% • Type 16 causes 10% of HPV genital infection in ♀s • Causes squamous cell & adenocarcinoma • Types 6 & 11  90% of anogenital warts

  16. Human Papillomavirus (HPV) • Risk Factors for infections: • Number of sex partners • Age < 25y • Most common STD in the US: • 20 million in US, 6 million new annual infections • 75% of new infections in 15-24 y/o • 80% of sexually active women infected by 50 y/o • 20% of men infected • Causes 90% anal cancer, 40% of vulvar/vaginal/penile cancer, & 12% oral & pharyngeal cancer

  17. Human PapillomaVirus (HPV) Vaccine • Quadrivalent Vaccine • L1 major capsid protein, propagated in yeast • Self assembles into virus-like-particles • Vaccine includes types 6, 11, 16, & 18 • 99.5% of vaccinees develop antibody to all 4 types • Efficacy: • 100% prevention of cervical precancer by types 16 & 18 • 99% prevention of vaccine type genital warts • HPV vaccine released in 2006 • Routine vaccination recommended in 2007

  18. Human PapillomaVirus (HPV) Vaccine • For all women <27 y/o • Best if given to before sexual debut • Can begin at age 9 y/o, recommended for 11-12 y/o • Sexually active women should still be vaccinated • Women with genital warts and abnormal PAP can be vaccinated • Not recommended for men • Complete series: 3 doses: 0, +2 months, +4 months • Cost: $120 per dose, $360 for the 3 dose series • Not for pregnant women – if pregnancy develops during vaccination series, then delay completion of series until after delivery

  19. Routine Adult Vaccines • MMR • Tetanus, Diphtheria, & Pertussis • Meningococcal Influenza Pneumococcal Hepatitis A Hepatitis B

  20. Influenza: 3 Types • Influenza A • moderate to severe illness • epidemic & pandemic • all ages • humans & animals (horse, avian & swine) • Influenza B • Milder disease • Children & seniors • Humans only • Influenza C • Pigs, rare in humans & no epidemics

  21. HA - Hemaglutinin • Binds virus to cells • Antigenic types: H1-H15 Influenza A Virus • NA - Neuraminidase • Promotes viral entry into cells • Antigenic types: N1-9

  22. Influenza Vaccine • Two types • Trivalent inactivated vaccine (1940s) • Trivalent attenuated vaccine (2003) • Vaccinate in October & November • Recommended composition of influenza virus for both vaccines for use in the 2007-2008 northern hemisphere influenza season: • A/Solomon Islands/3/2006 (H1N1)-like virus • A/Wisconsin/67/2005 (H3N2)-like virus • B/Malaysia/2506/2004-like virus

  23. Inactivated Influenza Vaccine When the antigenic match between vaccine and circulating virus is close, prevents • <65: prevents 70-90% • >65: prevents only 30-40% of clinical illness, BUT: • Prevents hospitalization in 50-60% • Prevents death in 80%

  24. Inactivated Influenza Vaccine Annual vaccination indicated for: • Chronic pulmonary disease & cardiovascular disease • Chronic metabolic disease (diabetes & renal failure) • Immunosuppression & HIV • Aspiration risk (dementia, spinal cord injury, seizure) • Pregnancy • Health care workers & long-term-care-facility residents • Household members of people at risk • On demand

  25. Live-Attenuated Influenza Vaccine • Not for immunocompromised • Temperature sensitive, cold-adapted, lives only in nasopharynx • 87% effective in children - 27% reduction in otitis • FluMist (MedImmune) • For 5-49 y/o healthy patients • Intranasal administration, half in each nares • Will test positive for Influenza A & B for several weeks after vaccination with rapid tests

  26. Pneumococcal Vaccine • > 90 capsular serotypes known • Capsular polysaccharide vaccine • 14 valent licensed in 1977 • 23 valent licensed in 1983 • Active against 88% of bacteremic pneumococcal pneumonia • Cross-reactive for an additional 8% of bacteremic disease • Prevents 60-70% of invasive disease • Does not prevent pneumococcal pneumonia • For adults, not effective in children < 2 y/o

  27. Pneumococcal Vaccine • All >64 y/o • Chronic pulmonary disease (except asthma) • Chronic cardiovascular disease • Diabetes mellitus • Chronic liver disease • Chronic renal failure & nephrotic syndrome • Asplenia – functional or anatomical (pre-surgery) • Immunosuppression & HIV • Neoplasia: leukemia, lymphoma, multiple myeloma • Cochlear implants (pre-placement) • Special populations: Native Americans & long-term-care-facility residents

  28. Pneumococcal Revaccination • After 5 years for : • Chronic renal failure & nephrotic syndrome • Asplenia – functional or anatomical • Immunosuppression & HIV • Neoplasia: leukemia, lymphoma, multiple myeloma • For >65 y/o if: • Vaccinated >5 years ago & • <65 when first vaccinated

  29. Conjugate Pneumococcal Vaccine • Licensed for children (<2 y/o) in 2000 • 7 valent capsular polysaccharide linked to nontoxic diptheria toxin (AKA “CRM197”) • Active versus childhood: bacteremia (86%), meningitis (83%), & otitis media (65%) • Efficacy: • Reduce invasive disease by serotypes by 97% • Reduce all invasive disease by 89% • Reduce severe pneumonia by 73% • Reduce otitis media by 7% & tympanoplasty by 20%

  30. Hepatitis A Vaccine • Inactivated, whole cell vaccine • 95% of adults develop protective antibody in 4 weeks • 100% seroconvert after two doses • Indicated for: • Travelers to areas of high hepatitis A endemicity • Men who have Sex with Men (MSM) & IV Drug abusers • Patients with chronic liver disease • Patients who receive clotting factors • Administer: • 2 dose schedule: 0 & +6-18 months • Single dose provides ~ 1 year immunity

  31. Hepatitis B Vaccine • HBsAg recombinant vaccine from yeast • Two vaccines – in adult & child formulations • After 3 doses, >90% of adults are sero-positive • >40 y/o: 90% respond • >60 y/o: 75% respond • Some patients (hemodialysis) may require larger & more doses to develop a response • Prevents 80-100% clinical hepatitis

  32. Hepatitis B Vaccine Indications • On demand • All adults at risk: • People who work or live in areas with high endemicity for Hepatitis B • Health-care workers • Occupational & recreational blood exposure • Travelers to areas of high hepatitis A endemicity • Sexual exposure: sex partner of hepatitis B patient, promiscuous sex (STD clinic patients), & MSM

  33. Hepatitis B Vaccine Schedule • Usual: • 0 & 1 month: 50-60% protection • + 6 month: full protection • Accelerated: • 0,1& 2 months OR 0,1& 3 weeks: good protection • + 12 month for full protection • Confirmatory serologic testing not recommended for healthy adults ~ is recommended for hemodialysis patients & health care workers with blood exposure • No booster needed

  34. Hepatitis A&B Combined Vaccine • Hepatitis A/B (Twinrix®), approved in 2001 • 0 & 1 month: • adequate against A • 50-60% protection against B • Repeat @ 6 months for full protection • 0,1& 3 weeks (accelerated schedule): • good protection • Repeat @ 12 months for full protection NO: Hepatitis C or E vaccine

  35. Measles • Prior to MMR, Measles nearly universal disease of childhood • Death in adults usually due to encephalitis • Causes subacute sclerosing pan-encephalitis – a persistent CNS infection leading to degenerative neurological disease • Worldwide still causes 30 million infections & 454K deaths • Atypical measles • 1963-67: 600-900K received killed measles vaccine (KV) • KMV sensitizes, but does not protect • With measles & KMV  polyserositis • Fever, pneumonia, pleural effusions, & edema • Atypical rash: maculopapular, petechial, urticarial, pupuric, & vesicular

  36. Mumps • Mumps in unvaccinated adults includes: • Commonly: orchitis & parotitis • Less commonly: meningitis & encephalitis • Rarely: pancreatitis, deafness, myocarditis, arthritis, & nephritis

  37. Rubella • AKA “German Measles” • In unvaccinated adults: • Arthralgias & arthritis • Encephalitis, frequently fatal • In pregnant woman  congenital rubella syndrome • Fetal death, spontaneous abortion, & prematurity • Cataracts • Heart defects • Deafness, microcephaly, & mental retardation • Bone lesions • Hepatomegaly & splenomegaly

  38. Measles/Mumps/Rubella (MMR) Vaccine • MMR vaccine includes live, attenuated measles, mumps, and rubella virus • Contraindicated for immunosuppressed: • Symptomatic HIV+ (asymptomatic OK) • Steroids (>20 mg/day) • Congenital immune deficiencies • Leukemia, lymphoma, advanced malignancy • Chemotherapy & radiation therapy • ProQuad incorporates live, attenuated Varicella into the vaccine for MMRV. Intended for children (12m – 12y)

  39. Measles/Mumps/Rubella (MMR) Vaccine • Born prior to 1957 considered measles & mumps immune • Adults born since 1956 should have at least one dose of the two dose series • One dose for women with either none or uncertain immunity • Do not vaccinate pregnant women or women who might become pregnant within 4 weeks of vaccination • Two doses indicated for: • Adults exposed to measles • Adults vaccinated with killed measles vaccine • Adult students • Health care workers without measles or mumps immunity • International travelers • No booster after 2 doses

  40. Tetanus, Diphtheria, & acellular Pertussis: Td/Tdap • Adult primary series: • 3 doses: 0, +4 weeks, +6-12 months • Booster with either Td or Tdap • Booster: primary series plus <10 years • <65? Vaccinate at least 1x with Tdap if not previously vaccinated • Pregnant? • >10 years since last boost? – vaccinate with Td in 2nd or 3rd trimester • <10 years since Td? – vaccinate with Tdap in immediate post-partum period

  41. Diphtheria, Tetanus, & Pertussis Formalin inactivated diphtheria toxin (toxoid) + Formaldehyde inactivated tetanospasmin (toxoid) +/- “Acellular” pertussis (purified subcomponents of Bordetella pertussis cells) Routine combined vaccination started in 1940s Td for adult booster DTaP replaced (1991) old DTP for children; Tdap for adults

  42. Tdap: Tetanus/Diptheria/acellular-Pertussis • Adolescent & Adult version of the “DPT” vaccine • ONE TIME vaccine in place of a “Td” booster for: • Adolescents & adults <65 y/o • Particularly adults with contact with infants <1 y/o • Particularly health-care workers with patient contact • Particularly post-partum women • Give if last Td boost >2 yr previous • Subsequent boosters with “Td” q 10 years • Pregnancy is not a contraindication to vaccination, vaccinate in a Pertussis outbreak

  43. Meningococcal Vaccine • No vaccine for group B, or groups L, X, & Z • Monovalent polysaccharide vaccine licensed in 1974 • Quadrivalent polysaccharide vaccine licensed in 1974 • Menactra®: quadrivalent, conjugate vaccine • Bound to diphtheria toxoid • Active against serotypes A,C,Y, & W135 • Licensed in 2005 • Intended for: • Children >11 • At risk adults (Travelers) • One dose vaccine, no booster needed

  44. Questions? CDC Resources • CDC Immunization Hotline: 800-232-2522 • CDC Info: 800-232-4636 • CDC website: www.cdc.gov/mmwr • CDC Division of Immunization: 404-639-8225

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