Wendy Rosenthal, Pharm.D.

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

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):

 Basics of Immunity

 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

 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

 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

 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

Contraindications & Precautions C=contraindication P=precaution V= vaccinate if indicated VCImmunosuppression VCPregnancy PP Severe illness CC Allergy to component InactivatedLiveCondition

VaccineManufacturer Vaccine* Distributor Vaccine* Provider’sOffice Vaccine* Patient * *Vaccine is transported in a refrigerated or frozen state, as appropriate (refrigerator 35° - 46°F (2° - 8°C); freezer 5° F (-15°C) or colder), using an insulated container or a refrigerated truck.

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

 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  1990–1999: average 36,000  Rates of death/100, –0.6 aged 0–49 years 7.5 aged 50–64 years 98.3 aged ≥65 years JAMA. 2003;289:179–86.

 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

 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

 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

vaccine  A/Solomon Islands/3/2006 (H1N1)– like virus  A/Wisconsin/67/2005 (H3N2) -like virus  B/Malaysia/2506/ like virus 2008 – 2009 vaccine  A/Brisbane/59/2007 (H1N1)-like virus  A/Brisbane/10/2007 (H3N2)-like virus  B/Florida/4/2006-like virus

 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

 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

 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)

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

 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

 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

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

Which of the following statements is true regarding the peak month for influenza? 1. There has been great variability over the past 30 years 2. Peak most commonly occurs in February 3. Can peak as late as April & May

 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

 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

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

 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 50 years  Persons with chronic diseases  Pregnant women

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

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

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

 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.

 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

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

 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

 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

 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

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

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

 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

 Efficacy  Efficacy with respect to incidence of zoster was 63.9% among those 60 – 69 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;

 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

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

NormalCervix HPV-InfectedCervix Progression Regression Precancer CervicalCancer Invasion HPV Mild Cytologic and/or Histologic Abnormalities Infection Clearance

 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

 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

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%

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

 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%

 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

 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

 Advisory Committee On Immunization Practices (ACIP) recommendations  Routinely administer to all girls when they are 11 – 12 years old  Immunize females 13 – 26 who have not previously received the vaccine  At their discretion, physicians could vaccinate girls as young as 9

 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

 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

 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

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

 90,000 Americans die of vaccine- preventable 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:

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

As of August 2007

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