Wendy Rosenthal, Pharm.D.

Transcription

1 Wendy Rosenthal, Pharm.D.

2 Basics of vaccine use Influenza vaccine Herpes Zoster vaccine HPV vaccine

3 True or False? Vaccines are among the greatest achievements of biomedical science & public health.

4 Since widespread use of vaccines, the annual number of cases has fallen by: >99% for diphtheria, measles, poliomyelitis, rubella, smallpox & Haemophilus influenzae type B >90% for pertussis, tetanus & mumps >80% for hepatitis A & B & varicella 34% for pneumococcal disease JAMA 2007;298(18):

5 In addition, associated mortality has decreased by: >99% for diseases with vaccines before 1980, as well as H. influenzae type B >80% for hepatitis A & B & varicella 25% for pneumococcal disease JAMA 2007;298(18):

6 Basics of Immunity

7 Active immunity produced by vaccine Immunity and immunologic memory similar to natural infection but without risk of disease Epidemiology and Prevention of Vaccine-Preventable Diseases 9th ed

8 Live attenuated Weakened form of the original Must replicate in body to be effective Generally require one dose Severe reactions possible Examples: measles, varicella, intranasal influenza Epidemiology and Prevention of Vaccine-Preventable Diseases 9th ed

9 Inactivated Composed for whole viruses or bacteria or fractions Cannot replicate Generally require more than one dose Antibody titer diminishes over time Examples: pneumococcal, HPV, influenza Epidemiology and Prevention of Vaccine-Preventable Diseases 9th ed

10 Vaccine Adverse Reactions Local Pain, swelling, redness at injection site Usually mild & self-limited Systemic Fever, malaise, headache Live attenuated vaccines: may produce mild symptoms after incubation period of 7 21 days Allergy Due to vaccine components

11 True or False? There is an inverse relationship between the levels of vaccinepreventable diseases & safety concerns.

12 Contraindications & Precautions Condition Live Inactivated Allergy to component C C Severe illness P P Pregnancy C V Immunosuppression C V C=contraindication P=precaution V= vaccinate if indicated

13 Vaccine Manufacturer Vaccine* Patient Vaccine* Provider s Office Distributor Vaccine* *Vaccine is transported in a refrigerated or frozen state, as appropriate (refrigerator F (2-8 C); freezer 5 F (-15 C) or colder), using an insulated container or a refrigerated truck.

14 Maintain freezer temperature at 5 F (-15 C) or colder Maintain refrigerator temperature at 3546 F (2-8 C) *MMR may be stored in either the freezer or refrigerator MMR* Varicella Herpes Zoster DTaP, DT, Td Tdap, Hib, Hepatitis A, Hepatitis B, HPV, Influenza (TIV & CAIV-T) IPV, MMR* Meningococcal Pneumoccal (PPV & PCV)

15 Intramuscular Injection (IM) Tetanus, Diphtheria with Pertussis Hepatitis A Hepatitis B Human papillomavirus Influenza, trivalent inactivated Meningococcal, conjugated Subcutaneous Injection (subq) Meningococcal, polysaccharide Measles, mumps, rubella Varicella Herpes Zoster IM or subq Pneumococcal polysaccharide Intranasal Cold-adapted Influenza Vaccine-Trivalent

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18 Spreads by contact with infected respiratory droplets Incubation period: 1 5 days Adults are infectious for 1 day prior & 5 days following symptom onset Symptoms Sudden onset of fever, muscle aches, headache, malaise, nonproductive cough, sore throat & rhinitis Symptoms resolve in 3-7 days; cough & malaise may persist for > 2 weeks

19 Influenza viral pneumonia Exacerbate underlying medical conditions such as pulmonary & cardiac disease Secondary bacterial pneumonia, sinusitis or otitis

20 Almost 16 million cases per year in the U.S. among people <20 years of age About 4.5 million per year in the U.S. among the elderly Influenza-related pulmonary and circulatory deaths : average 36,000 Rates of death/100, aged 0 49 years 7.5 aged years 98.3 aged 65 years JAMA. 2003;289:

21 Single-stranded Three Moderate to severe illness All age groups Subtypes determined by surface antigens: hemagglutinin & neuraminidase Type B strains Type A RNA virus Milder diseases Primarily affects children Type C Rarely reported in humans

22 Antigenic Occur only in type A Drastic changes in hemagglutinin or neuraminidase Responsible for epidemics & pandemics Antigenic Shift Drifts Occur in all three types Minor change in surface antigens May result in epidemic

23 What was the name & date of the last major antigenic shift? Sydney in Hoboken in Hong Kong in

24 Contains surface proteins of virus strains Most likely to circulate in the coming winter Generally two type A and one type B Epidemiological data reviewed and strains chosen 6 9 months before distribution

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26 vaccine vaccine A/Solomon Islands/3/2006 (H1N1) like virus A/Wisconsin/67/2005 (H3N2) -like virus B/Malaysia/2506/2004 -like virus A/Brisbane/59/2007 (H1N1)-like virus A/Brisbane/10/2007 (H3N2)-like virus B/Florida/4/2006-like virus

27 Trivalent Fluzone (Sanofi Pasteur) Approved for > 18 years of age FluLaval (GlaxoSmithKline) Approved for > 4 years of age Fluarix (GlaxoSmithKline) Approved for > 6 mo of age Fluvirin (Chiron) Inactivated Vaccines (TIV): Approved for > 18 years of age Afluria (CSL Limited) Approved for > 18 years of age Cold-adapted Influenza Vaccine Trivalent : FluMist (MedImmune) Approved for 2 to 49 years of age

28 Inactivated influenza vaccine 70 90% effective among healthy persons <65 yo 30 40% effective among frail elderly 50 60% effective in preventing hospitalization 80% effective in preventing death Cold-adapted influenza vaccine-trivalent 87% effective in pediatric population Among healthy adults, 18 37% fewer days of healthcare provider visits

29 True or False? I got the flu vaccine last year so I don t need it this year.

30 Persons at Increased Risk for Complications Persons aged 50 years Residents of nursing homes and chronic-care facilities Adults with chronic heart or lung disorders, including asthma Adults with: Chronic metabolic disease (e.g., diabetes) Renal dysfunction Hemoglobinopathies Immunosuppression (e.g., HIV)

31 Persons Adults with conditions that can compromise respiratory function or the handling of secretions or that can increase the risk for aspiration at Increased Risk for Complications Cognitive disorders Spinal cord injuries Seizure disorders Other neuromuscular disorders Women who will be pregnant during the influenza season MMWR. 2007

32 Persons Who Can Transmit the Virus to Those at High Risk Health care workers Employees of chronic-care facilities or residences for persons in groups at high risk Persons providing home care to persons in groups at high risk Household members (including children) of persons at high risk Household contacts and out-of-home caretakers of children aged <2 years MMWR. 2007

33 True or False? Annual influenza immunization reduces the risk of CV events in patients with CV disease.

34 Healthy Individuals 2 49 Years of Age Who wish to decrease their risk of influenza Who are in close contact with persons at high risk for influenza-related complications

35 Influenza vaccination as personal protection versus Immunization for the greater public good

36 Which of the following statements is true regarding the peak month for influenza? There has been great variability over the past 30 years Peak most commonly occurs in February Can peak as late as April & May

37 Inactivated vaccine Staggered administration based on need High risk/health care workers can get as early as Sept, Oct or Nov is ideal Nursing homes October or later Healthy November or later Cold-adapted trivalent Starting in October

38 Inactivated Dose: 0.50 ml IM injection in deltoid Cold-adapted Trivalent Dose: 0.5 ml intranasally Half dose to each nostril No need to inhale No need to repeat if sneezing or coughing occur

39 Soreness at injection site Fever, malaise, myalgia Immediate allergic reaction Sneezing or cough (intranasal)

40 Inactivated vaccine Egg allergy History of anaphylactic reaction to components of the vaccine Cold-adapted trivalent vaccine Egg allergy History of anaphylactic reaction to components of the vaccine Aged <2 years or >50 years Persons with chronic diseases Pregnant women

41 True or False? You can contract influenza from the IM vaccine.

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43 Varicella Zoster Virus (VZV) Varicella (Chicken Pox) Herpes Zoster (Shingles)

44 Reactivation of dormant varicella zoster virus Likelihood for reactivation related to: Age Immune status

45 90% of U.S. population has serologic evidence of varicella 50% of persons who live to age 85 will develop herpes zoster More than 500,000 cases occur yearly in U.S.

46 Symptoms Sharp, stabbing pain & tenderness along the nerve Lesions appear 3 5 days later Papules vesicles pustules Heal in 7 10 days Present on only one side of the body Contagious until dry crusts appear: 5 10 days Pain can occur during the prodrome and/or eruptive phase

47 Based on pain research, which of the following is correct? Labor pain > HZ pain HZ pain > labor pain HZ pain = labor pain

48 Serious Postherpetic neuralgia (PHN) complications 90% pain-free 1 month after acute attack; 95% pain-free at 3 months & 97% pain-free after 12 months Incidence & duration directly correlate with patient age Difficult to treat Scarring, bacterial superinfection, cranial and motor neuron palsies, pneumonia, encephalitis, visual impairment, hearing loss

49 Live, attenuated varicella-zoster virus Indication: prevention of HZ in individuals 60 and older Stimulates the patient s immune system to reestablish memory cells Dose: 0.65 ml subq

50 Advisory Committee On Immunization Practices (ACIP) recommendations Routinely administer to all people 60 years of age and older This includes those who have had a previous episode of the disease

51 What is the potency of Zostavax compared to Varivax? Zostavax > Varivax 3. Zostavax < Varivax 4. Zostavax = Varivax 2.

52 Must be kept frozen at -15º C (+5º F) Reconstitute straight from freezer and use immediately Adverse effects: injection site reactions

53 History of anaphylactic reaction to gelatin, neomycin, or other component of the vaccine Immunodeficiency (leukemia, lymphomas, other bone marrow or lymphatic neoplasms, HIV) Immunosuppressive therapy Active, untreated tuberculosis Pregnancy

54 Efficacy Efficacy with respect to incidence of zoster was 63.9% among those yo compared with 37.6% in those 70 years and older Reduced incidence of postherpetic neuralgia by 67% Duration of time patients experienced pain was significantly lower in those who received the vaccine N Engl J Med 2005:352;

55 Duration of protection? Degree of efficacy in the very old? At what age should the vaccine be administered?

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57 DNA tumor virus Skin virus About 40 genital types 15 to 18 of these associated with cancer Sexually transmitted disease Intercourse Genital, oral & skin to skin contact

58 True or False? The use of condoms will prevent all HPV transmission.

59 Cervical dysplasia and cancer Genital warts Anogenital cancers (vulvar, penile, vaginal) Head & neck cancers (esophagus, pharynx)

60 HPV Types Manifestations Low-grade cervical changes High-Risk Types 16, 18, High-grade cervical changes 31, and 45 Cervical cancer Anogenital and other cancers Benign low-grade cervical changes Types 6 and 11 Low-Risk Condylomata acuminata (Genital warts)

61 HPV Normal Cervix Infection HPV- Progression Precancer Infected Clearance Cervix Regression Mild Cytologic and/or Histologic Abnormalities Invasion Cervical Cancer

62 HPV 80 90% of infections resolve in 2 years Average duration of infection 9 13 months Unclear if eradicated or latent HPV clearance persistence 10 20% of infections persist Major risk factor for cancer Clearance & persistence are age related

63 Increasing age Infection with multiple HPV types Immunosuppression Oral contraceptive use > 5 years Smoking HIV Coinfection with other sexually transmitted diseases

64 6.2 million new cases of sexually transmitted HPV occur in the U.S. each year 20 million people in the U.S. currently have a detectable genital HPV infection 50% of sexually active men and women acquire genital HPV infection at some point in their lives $1.6 billion in direct annual medical costs for treating symptoms of genital HPV infection

65 The American Cancer Society estimates in 2007 for the United States: 11,150 new cases of cervical carcinoma with 3670 deaths 4650 new cases of anal cancers with 690 deaths 1280 new cases of penile cancers with 290 deaths 34,360 new cases of oral & pharyngeal cancers with 7550 deaths

66 What % of women tested positive for HPV DNA within 12 months of intercourse with FIRST male sex partner? 5% 3. 13% 4. 28% 5. 42% 2.

67 Pap Tests for cervical cancer & precancerous changes in the cervix Begin testing within 3 years of onset of sexual activity or by age 21 HPV test DNA test Indicated in women > 30 yo with mild Pap test abnormalities No screening test available for men

68 1 million new cases annually; two thirds in women Present in 15% of general population Transmitted during vaginal or anal sex with infected partner

69 Can spontaneously disappear without treatment May remain unchanged or increase in size and/or number Treatment options Provider applied topical medications Patient applied topical medications Freezing, laser and surgical excision Recurrence rates of 30-40%

70 Indication: Approved for use in females aged 9 to 26 for prevention of the diseases caused by HPV types 6,11,16 & 18: Cervical cancer Genital warts And the following precancerous or dysplastic lesions: Cervical adenocarcinoma in situ (AIS) Cervical intraepithelial neoplasia (CIN) grade 2 & 3 Vulvar intraepithelial neoplasia (VIN) grade 2 & 3 Vaginal intraepithelial neoplasia (VaIN) grade 2 & 3 Cervical intraepithelial neoplasia (CIN) grade 1

71 HPV types 16 & 18 account for 70% of all cervical cancers HPV types 31,33,35,39,45,51,52,56,58,&59 account for an additional 20% Gardasil provides cross-protection reducing incidence for precursor lesions by 38% 45% protection with types 31 &45

72 Advisory Committee On Immunization Practices (ACIP) recommendations Routinely administer to all girls when they are years old Immunize females who have not previously received the vaccine At their discretion, physicians could vaccinate girls as young as 9

73 True or False? HPV vaccine can be used to treat cervical cancer and/or genital warts.

74 Administration Given as 3 separate IM injections over 6 months 1st dose: at elected date 2nd dose: 2 months after 1st dose 3rd dose: 6 months after 1st dose Available in single-dose vial or prefilled syringe No dilution or reconstitution necessary

75 Conclusions Vaccine was well tolerated from pivotal trials No differences between its ADRs and the placebo Most common complaints: pain at injection site & headache There was complete protection against persistent HPV types 16 & 18 infection and associated cervical lesions in the fully vaccinated cohort Obstet Gynecol 2006;107:18-27 Lancet Oncol 2005;6:271-8

76 Pain, swelling & erythema at injection site No serious reactions have been reported Contraindicated for persons with history of immediate hypersensitivity to yeast or any vaccine components

77 True or False? Once a female has received the complete Gardasil vaccine series she no longer needs routine PAP smears.

78 How long does the vaccine last? Will it require a booster? Should males be vaccinated?

79 In the pipeline Designed to prevent HPV types 16 & 18 (bivalent vaccine) No effect on genital warts Has been shown to be effective in women up to age 55 years 3 doses: 0 / 1 month / 6 months

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81 90,000 Americans die of vaccinepreventable infections every year Most visited health care providers in the year preceding their deaths but were not vaccinated Influenza and pneumonia are the fifth leading cause of death for Americans 65 Most American adults are inadequately vaccinated Am J Health Syst Pharm 2003;60:

82 Advocate Motivating people to be vaccinated Screen for needed vaccines and refer Facilitator Hosting others who vaccinate Immunizer Administering vaccines

83 As of August 2007

84 In the typical American household, which family member has the most accurate & up-to-date immunization record on file? 2. The parents 3. The children 4. The pets

85 Centers for Disease Control National Immunization Program Immunization Institute for Vaccine Safety Immunization Action Coalition Gateway

86 Partners National for Immunization Coalition for Adult Immunization National Network for Immunization Information Allied Vaccine Group

87 Subscribe to MMWR for delivery at Sign up for CDC s live satellite and webcast immunization update every August Obtain copies of latest immunization recommendations Pink Book - Epidemiology and Prevention of Vaccine-Preventable Diseases 9th ed, 1/06.

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