U.S. Tetanus Diptheria Pertussis Measles Mumps Rubella Varicella Meningococcus Pneumococcus 2/17/2015

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1 Katherine Julian, MD Professor of Clinical Medicine, UCSF February 11, 2015 Vaccines Generally Available in the U.S. Tetanus Diptheria Pertussis Measles Mumps Rubella Varicella Meningococcus Pneumococcus Human Papillomavirus Influenza Hepatitis B Hepatitis A Haemophilus influenzae type B Rotovirus Inactivated polio Rabies Typhoid Yellow fever Japanese encephalitis Vaccines Generally Available in the U.S. Tetanus Diptheria Pertussis Measles Mumps Rubella Varicella Meningococcus Pneumococcus Human Papillomavirus Influenza Hepatitis B Hepatitis A Haemophilus influenzae type B Rotovirus Inactivated polio Rabies Typhoid Yellow fever Japanese encephalitis 1

2 Vaccines for Special Populations Plague Tularemia Smallpox Anthrax Botulism Tuberculosis BCG Adenovirus Key Website Centers for Disease Control and Prevention Vaccines Approved by Federal Drug Administration (FDA) Recommended by the Advisory Committee on Immunization Practices (ACIP) MMWR, Feb 5,

3 Measles Measles Resurgence Measles Resurgence Of the 52 initial cases reported to CDC 28 (55%) were unvaccinated 17 (31%) had unknown vaccination status Extremely contagious Transmitted by aerosolized droplets 9 out of 10 susceptible people with close contact to measles will develop measles Measles Resurgence 2000: Considered eliminated in the US 2014: 23 outbreaks, >600 infected Most cases in unvaccinated people who were infected in other countries Most affected: England, France, Germany, India, and the Philippines accessed June 3,

4 Measles Resurgence Morbillivirus, enveloped RNA virus with 1 serotype Acute viral illness, incubation period 7 21 days Symptoms: high fever, cough, runny nose and conjunctivitis Measles Resurgence Pathognomonic enanthema: Koplik spots on the inner cheeks of mouth 14 days after exposure: rash Infectious 4 days before rash to 4 days after accessed 6/3/14 accessed 6/3/14 Measles Complications Common: ear infections, pneumonia 1/1000 acute encephalitis 1/1000 children infected will die from respiratory and neurologic complications years after infection: rare subacute sclerosing panencephalitis (SSPE) CNS degenerative disease with behavioral/intellectual deterioration and seizures Measles Prevention MMR vaccine Covers measles, mumps, rubella Given X 2: ages months and 4 6 years 1 dose 93% effective; 2 doses 97% effective Live vaccine 4

5 Measles Recommendations MMR Adults born before 1957: immune Children: 2 doses, mo and 4 6 years Post high school students who are not immune: 2 doses at least 28 days apart Adults born during/after 1957 who are not immune need at least one dose International travelers who are not immune: 2 doses at least 28 days apart Infants 6 11 months travelling internationally : 1 dose Influenza (Flu) Symptoms: fever, chills, fatigue, headache, sore throat, cough Spread: droplets Complications: sinus infections, pneumonia or worsening of chronic medical conditions 5

6 Influenza (Flu) 3 Main Types A, B, (C) Surface proteins of influenza A (HA, NA) create virus serotypes H1N1 H2N2, etc Why Get the Flu Vaccine? , CDC estimates influenza vaccine prevented: 7.2 million illnesses 90,000 hospitalizations <50% of people age >6 mo vaccinated Reed C, et al. MMWR, Dec 12, 2014;63(49) Who Should be Vaccinated for Flu? All people older than 6 months Unless there is a contraindication Influenza Vaccine Strains for Flu Season Trivalent vaccine A/California/7/2009 (H1N1 like) A/Texas/50/2012 (H3N2 like) not a good match this year B/Massachusetts/2/2012 like For quadrivalent vaccine 2 A strains and 2 B strains B/Brisbane/60/2008 same as last year 6

7 Seasonal Influenza Vaccine Types Inactivated influenza vaccine (IIV) Given by injection IIV3 (Trivalent) IIV4 (Quadrivalent) Recombinant hemagglutinin influenza vaccine (RIV) Trivalent formulation RIV3 Live attenuated influenza vaccine (LAIV) Quadrivalent Seasonal Influenza Vaccine Inactivated influenza vaccine (IIV) Approved for all > 6 months Given as an injection Live attenuated influenza vaccine (LAIV) Same strains as IIV Intra nasal vaccine; cold adapted, temp sensitive Runny nose, congestion, headache, wheezing Approved in the U.S. for healthy 2 49 year olds Seasonal Influenza Vaccine The Evidence In children, several studies suggest better efficacy of LAIV compared to IIV LAIV recommended for healthy children 2 8 yrs In adults, studies suggest better efficacy of IIV 7

8 Who Should NOT Get the Live Attenuated Influenza Vaccine? Outside recommended age ranges (<2yrs or >49yrs) Chronic medical conditions including asthma Pregnant women Highly immunosuppressed Contact with highly immunosuppressed High Dose IIV3 Vaccine 12/09 FDA licensed Fluzone High Dose for >65 yrs Contains 60µg of hemagglutinin per strain virus vs. 15 µg in regular IIV 31,989 people Randomized to high dose vs. standard dose High dose = 1.4 % confirmed influenza Standard dose = 1.9% confirmed influenza Relative efficacy 24.2% DiazGranados CA et al. NEJM, 2014;371(1) Intradermal Influenza Vaccine Fluzone intradermal vaccine approved by FDA in May 2011 Developed in hopes of conserving vaccine supply Needle one tenth of standard length Contains 9 mcg hemagglutinin per strain versus standard 15 mcg Dose is 0.1 ml versus standard 0.5 ml Approved ages years Local reactions are more common Allergic to Eggs? IIV and LAIV made with propagation of virus in embryonated eggs Recombinant Influenza Vaccine Trivalent (RIV3) FluBok Egg free vaccine Approved ages Inactivated trivalent vaccine (cciiv3) Flucelvax Canine kidney cell culture derived NOT egg free since initial seed virus passaged in eggs Approved >18 yrs ACIP recs: mild egg allergy can get RIV3 or IIV/ccIIV3 with additional safety precautions. Severe egg allergy: give RIV3 if yrs 8

9 Pertussis Not Just for Kids Whooping cough bacteria 27,000 cases in ,880 pertussis cases and 14 infant deaths in 2012 Many cases among preadolescents Classic Sx First 7 10 days: runny nose, low grade fever, mild cough Lasts 6 10 weeks: severe cough, post cough vomiting and inspiratory whoop Complications: bleeding in brain, pneumonia, brain damage, death ACIP. MMWR, 2013;62 Cornia PB, et al. JAMA, 2010;304(8) Pertussis Not Just for Kids Residual immunity from prior vaccination may modify the clinical presentation Among adults, prolonged cough may be the only manifestation of pertussis 13 32% of adolescents/adults with cough >6 days have serologic evidence of infection with pertussis ACIP. MMWR, 2013;62 Cornia PB, et al. JAMA, 2010;304(8) 9

10 Pertussis Not Just for Kids Highly contagious to home contacts Adults may act as reservoirs of the disease to vulnerable populations Majority of deaths in infants <2 months Immunity for pertussis wanes after childhood vaccination Pertussis Vaccine Vaccine contains purified, detoxified pertussis antigens Childhood DTaP: diptheria toxoid, tetanus toxoid, and acellular pertussis (full dose) Adult/adolescent Td and Tdap: tetanus toxoid (full dose) and reduced dose diptheria toxoid +/ reduced dose acellular pertussis antigens Adacel: age Boostrix: >10 years Hewlett EL et al. NEJM, 2005;35:12 Pertussis Vaccine How Effective? 2781 subjects aged randomized to reduced dose of acellular pertussis vaccine or hepatitis A placebo Followed for 2.5 years Based on primary pertussis definition (cough and positive culture/pcr), vaccine 92% effective Tdap Recommendations Adolescents: give Tdap instead of Td at routine year visit Adults >19 years: Tdap regardless of interval since last tetanus (if never had Tdap) Older Adults: recommended for all >65 yo Health care workers with patient contact Ward JL et al. NEJM, 2005;353(13) 10

11 Tdap Recommendations If pregnant woman Administer Tdap during EACH pregnancy (27 36 weeks) If not give immediately postpartum Adolescents and adults with close contact with an infant aged <12 months should receive a single dose of Tdap if they have not received Tdap previously JAMA 2014: 48 pregnant women no adverse outcomes and babies with larger immune response when mother vaccinated in 3 rd trimester Munoz FM, et al. JAMA, 2014;311(17) Pneumococcus Background Gram + bacteria Over 90 serotypes Settles in the upper respiratory tract Ear infections, sinus infections, pneumonia, blood stream infections, meningitis Causes 40,000 deaths annually in the U.S. Mainly transmitted by direct contact with respiratory secretions (ex: household) Pneumococcus Background Risk factors for invasive disease Age >65 or <2 years People with chronic illness, immunocompromised Crowding, antacids Antecedent respiratory infection and recent antibiotic Smokers 11

12 2 Pneumovax Vaccines Polysaccharide Vaccine (PPSV23) Conjugate Vaccine Prevnar13 (PCV13) Pneumovax Polysaccharide Vaccine (PPSV23) 23 purified capsular polysaccharide antigens Represent at least 85 90% of the serotypes that cause invasive pneumococcal infections Immune response is not long lived Doesn t decrease pneumonia rates Retrospective cohort 47K people >65 yrs Decreased invasive disease by ~1/2 (HR 0.56) Jackson LA. NEJM, 2003;348:18. Pneumovax Polysaccharide Vaccine PPSV23 Recommendations Age >65 People >2 years old** with chronic illness Chronic cardiovascular disease Chronic pulmonary disease including ASTHMA Chronic liver disease, alcoholics Diabetes Immunocompromising conditions Smokers People aged 2 64 living in environments in which the risk for invasive pneumococcal disease is increased Pneumococcal 13 Valent Conjugate Vaccine for Adults (PCV13) Prevnar13 Connects the bacteria particle to a carrier protein Longer antibody duration FDA data comparing PPSV23 vs. PCV13 Antibodies for PCV13 equal or higher in adults yrs Adults 50 59yrs given PPSV23 first had lower antibody titers when given PCV13 booster compared to those given PCV13 for 2 doses ACIP. MMWR, 2012; 61(40). 12

13 Pneumococcal 13 Valent Conjugate Vaccine (PCV13) Recommendations Age >65 years Age years AND Immunocompromising conditions HIV, Chronic kidney failure, malignancy, transplant Absent spleen CSF leaks Cochlear implants Pneumococcal 13 Valent Conjugate Vaccine (PCV13) Recommendations Age >65 years CAPiTA Trial 85K subjects in Netherlands >65 yrs PCV13 vs. placebo 46% fewer vaccine type pneumococcal pneumonias 75% fewer vaccine type invasive pneumococcal disease MMWR, Sept 19, 2014;63(37):822-5 Pneumovax Head to Head Pneumovax Booster Rules PPSV23 23 serotypes 12 serotypes in common with PCV13 Prevents invasive dz but NOT pneumonia Antibodies not longlasting 2013: 38% of invasive dz caused by serotypes unique to PPSV23 PCV13 13 serotypes Prevents invasive disease AND pneumonia Better immune response and longer lasting Should be given first If PCV13 indicated, try to give it first Ideal time between PCV13 dose and PPSV23 dose 1 year (minimum 8 weeks) PCV13 only given once Max # of PPSV23 doses=3 Chronic conditions 1 dose Booster every 5 years X 2 but can stop earlier if 1 booster given after age 65 years 13

14 Case 53 yo man presents complaining of burning sensation over left chest. Nothing abnormal is seen on examination of the skin. 3 days later, a rash appears. Diagnosis? Varicella (Shingles/Zoster) Zoster Vaccine Chicken pox virus After chickenpox infection, the virus goes dormant and settles in the sensory nerves Decline in immunity with advanced age predisposes to reactivation of this virus (shingles/zoster) Zoster develops in 30% of people over a lifetime Pain persisting >120 days = Post herpetic neuralgia Seen in 13 40%; increases with advanced age Live attenuated virus vaccine Older adults need greater amount of live attenuated virus to produce a boost in their immunity Zoster vaccine contains more plaque forming units/dose than the chickenpox vaccine Vaccine boosts older adults waning immunity to prevent reactivation of varicella Kimberlin DW, et al. NEJM, 2007;356(13). 14

15 Varicella Zoster Vaccine The Evidence 38,546 adults Randomized to zoster vaccine vs. placebo Primary endpoint: burden of illness due to zoster Incidence, severity of pain, duration of pain Secondary endpoint: incidence of post herpetic neuralgia (pain >120 days) Varicella Zoster Vaccine The Evidence Results: followed median 3.12 years Incidence of zoster reduced by 51.3% Incidence of post herpetic neuralgia decreased by 66.5% Burden of illness due to zoster decreased by 61.1% Higher efficacy ages Oxman MN et al. NEJM, 2005;352(22) Oxman MN et al. NEJM, 2005;352(22) Tseng HF et al. JAMA, 2011;305(2) Varicella Zoster Vaccine Licensed in March 2011 for adults > 50 years 22K adults years followed 1 year Zostavax vs. placebo decreased risk of zoster by 69.8% ACIP: recommended for >60 years due to vaccine production shortages No need to determine if immune to chickenpox Varicella Zoster Vaccine Contraindications h/o anaphylaxis to gelatin, neomycin Immunodeficiency or immunosuppressive therapy OK if healthy HIV patient with CD4>200 Pregnant women (for varicella vaccine) Pts with active (untreated) TB Schmader et al, Clin Infect Dis 2012;54 15

16 Varicella Zoster Vaccine Frozen for storage, administered immediately after reconstitution Cost of vaccine approx $150 Vaccinate 17 people to prevent 1 case of zoster Vaccinate 31 to prevent 1 case of postherpetic neuralgia Varicella Zoster Vaccine Remaining questions What happens in the future with childhood varicella vaccine? What is the efficacy of the vaccine in people who have had zoster? Kimberlin DW. NEJM, 2007;356 Yawn BP, et al. Mayo Clin Proc, 2011;86(2) 16

17 Human Papillomavirus (HPV) Background Virus causes genital warts, cervical cancer and anal cancer Sexually transmitted, over 200 types of HPV 40 million people currently infected with HPV 6.2 million new cases each year Most HPV infections self limited Lifetime cervical cancer risk 3.6% Human Papillomavirus (HPV) Vaccine Quadrivalent viral protein vaccine (Gardisil) Contains major virus protein from HPV types 6, 11 and 16, 18 Bivalent vaccine (Cevarix) contains proteins from types 16 and 18 Gardisil 9 approved 12/4/14 contains proteins from types 6, 11, 16, 18, 31, 33, 45, 52 and 58 Efficacy % in preventing infection of the virus types included in the vaccine Koutsky LA et al. NEJM, 2002;347(21) HPV Vaccine in Girls/Women 3 dose schedule (0, 1 2, 6 months) Little effect on HPV infections present prior to vaccination Approved for girls as young as 9; focus on yo Catch up vaccination for yo if not previously vaccinated h/o HPV NOT a contraindication to vaccination Side effects: low grade fever, local reactions, fainting Contraindicated in anyone with hypersensitivity to yeast or to the vaccine HPV Vaccine in Boys/Men HPV vaccine recommended for males yrs old; recommended years who have not been vaccinated Males may be vaccinated MSM recommended to be vaccinated through age 26 yrs Can be either HPV4 or HPV9 (approved for boys ages 9 15 only) 17

18 To Be Determined Will non vaccine viral strains emerge? What is the durability of the immunity? Meningococcus Background Gram neg bacteria (Neiserria meningitidis) Approximately 10% of adults carry N meningitidis in the nose/throat Rates of invasive disease cases/100,000 Meningitis Case fatality rates range 3 10% 13 subtypes of meningococci A: rare in U.S. B, C, Y: each cause approx 30% of meningococcal disease in the U.S. Meningococcal Vaccines Cover 4 types (A, C, W, W 135) Polysaccharide vaccine (MPSV4 Menomune) Antibody response is short lived (1 5 yrs) Not effective in age < 2; FDA approved for ages 2 10 and >55 Conjugate vaccine (Menactra, Menveo) Longer lasting antibodies Menactra now approved 9 months 55 years Manveo approved ages 2 55 Coming Soon? Meningococcal serogroup B vaccine Approved in Europe, Canada and now US Given to Princeton and UC Santa Barbara students following meningitis B outbreaks in

19 New Meningococcal Vaccines Trumemba Approved 10/29/14 Covers 4 different B strains Ages years 0, 2, 6 month IM schedule Bexsero Approved 1/23/15 Covers 3 different B strains Ages years 0, 1 month IM schedule Meningococcal Vaccine Recommendations Give conjugate vaccine to ages (ideally at 11 to 12 year old visit) Catch up at high school or college entry if not given at age Military recruits/travelers with increased risk Outbreak in NYC MSM, serogroup C Vaccine recommended fall 2012 based on HIV infection, neighborhood and behavioral risks Booster doses now routine for teenage vaccines Meningococcal Conjugate Vaccine Summary Table Risk Group Primary Series Booster Dose Age dose, preferred age Age 16, if primary dose age 11 or 12 Age 16 18, if primary dose age Also, 1 st year college No booster if primary students in dorms up to dose on/after age 16 age 21 Age 2 55 yrs with HIV, complement deficiency or functional/anatomic asplenia 2 doses, 2 months apart Every 5 years Age 2 55 yrs with prolonged increased risk of exposure 1 dose Age 2 6; after 3 years Age >7 yrs, after 5 years Take Home Points Don t forget Tdap boosters ages 11+ Pneumococcus conjugate vaccine for immunocompromised and > 65 years Zoster vaccine ages >60 (licensed for >50) Influenza vaccine everyone International travelers should be measles immune 19