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 Basics of Immunity

6 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 9 th ed

7 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 9 th ed

8 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 9 th ed

9 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

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

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

12 Vaccine Manufacturer Vaccine* Distributor Vaccine* Provider s Office Vaccine* Patient *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.

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

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16 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

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

18 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 years 7.5 aged years 98.3 aged 65 years JAMA. 2003;289:

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

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

21 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

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

23 Trivalent Inactivated Vaccines (TIV): Fluzone (Sanofi Pasteur) Approved for > 6 mo of age Fluvirin (Chiron) Approved for > 4 years of age Fluarix (GlaxoSmithKline) Approved for > 18 years of age FluLaval (GlaxoSmithKline) 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

24 Which of the following impacts the effectiveness of the influenza vaccine? 1. Age of the recipient 2. Race of the recipient 3. Geographic location of the recipient

25 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

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

27 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) Adults with conditions that can compromise respiratory function Cognitive disorders Spinal cord injuries Seizure disorders Other neuromuscular disorders Women who will be pregnant during the influenza season MMWR. 2008

28 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. 2008

29 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

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

31 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

32 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

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

34 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

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

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

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

39 90% of U.S. population has serologic evidence of varicella 50% of persons who live to age 85 will develop herpes zoster Estimated 1 million cases occur yearly in U.S.

40 Is there a gender difference in the incidence of zoster? 1. Yes, the incidence is higher among males 2. Yes, the incidence is higher among females 3. No, the incidence is equal

41 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

42 Based on pain research, which of the following is correct? 1. Labor pain > HZ pain 2. HZ pain > labor pain 3. HZ pain = labor pain

43 Serious complications Postherpetic neuralgia (PHN) 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

44 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

45 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 Patients need not be asked about history of varicella or have varicella immunity determined by serologic testing

46 What is the potency of Zostavax compared to Varivax? 1. Zostavax > Varivax 2. Zostavax < Varivax 3. Zostavax = Varivax

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

48 Which of the following is a contraindication for Zostavaz? 1. Contact with young children 2. Pregnancy 3. Age > 95yo

49 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

50 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;

51 Only about 2% of eligible people have been vaccinated against zoster If everyone in the U.S. who was eligible was vaccinated: Reduce number of new cases of shingles every year by at least 280,000 Reduce number of new cases of PHN by more than 46,000

52 Duration of protection? At what age should the vaccine be administered?

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54 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

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

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

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

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

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

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

61 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

62 What % of women tested positive for HPV DNA within 12 months of intercourse with FIRST male sex partner? 1. 5% 2. 13% 3. 28% 4. 42%

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

64 1 million new cases annually; two thirds in women Present in 15% of general population Transmitted during vaginal or anal sex with infected partner May appear within several weeks, months or years after sex or not at all Occur predominantly at sites of friction Penis, scrotum, vulva, vagina, cervix, perineum & perianal area

65 Condylomata acuminata Cauliflower-like appearance Skin colored or pink Smooth papules Dome-shaped Skin colored Flat papules Slightly raised, smooth surface Skin colored More common on internal structures Keratotic warts Resemble common warts

66 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%

67 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

68 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

69 According to ACIP, who is the target population to receive Gardasil? 1. Females 9 10 yo 2. Females yo 3. Females yo

70 HPV vaccine is a prophylactic vaccine Individuals infected with 1 or more vaccine-related HPV types prior to vaccination will achieve protection from the remaining vaccine HPV types

71 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

72 Conclusions from pivotal trials Vaccine was well tolerated 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

73 As of , 9700 adverse events reported since approval 94% classified as nonserious 6% classified as severe Vasovagal syncope High baseline risk among target population 15 waiting period following administration Contraindicated for persons with history of immediate hypersensitivity to yeast or any vaccine components

74 Once a female has received the complete Gardasil vaccine series, how often should she receive PAP smears? 1. PAP smears are no longer necessary 2. Yearly according to guidelines 3. Yearly until age 30

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

76 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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78 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:

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

80 As of August 2008

81 In the typical American household, which family member has the most accurate & up-to-date immunization record on file? 1. The parents 2. The children 3. The pets

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