Preventing Infections

Transcription

1 Preventing Infections Adult Vaccines: Update 2017 Thomas M File, Jr MD MSc MACP FIDSA FCCP Chair, Infectious Disease Division Summa Health, Akron, Ohio; Professor of Internal Medicine, Chair of Infectious Disease Section, Master Teacher Northeast Ohio Medical University, Rootstown, Ohio

2 Objectives Review new developments in adult vaccines Focus on Influenza and pneumococcal vaccines Additional comments: Zoster, Tdap, HPV, Meningococcal B

3 Vaccine evaluation center

4 Threats to Vaccines Falling rates Success of past vaccines olack of awareness of disease that is prevented Effects of anti-vacccine movement ofear, mistrust, ignorance GA Poland 2011

5 Adult Immunization Coverage, US **Influenza Estimates MMWR. Feb 5, Healthy People 2020 Objectives on Immunization and Infectious Disease.

6 Consequences of lapses of immunization: Outbreaks Ohio ( ) oin 2010, there were 964 cases of pertussis reported by Columbus and Franklin Counties. Most cases reported in 25 years. oin 2014, there have been 377 cases of measles (10 hospitalized) since March. oin 2014, there have been 460 cases of mumps (many linked to OSU) since Jan. California (2010) 9,143 cases of pertussis (including ten infant deaths) were reported throughout California. Most cases reported in 63 years. Measles outbreak source

7 Burden of Vaccine-Adult Preventable Disease in the US Disease Influenza Invasive pneumococcal disease Hepatitis B Human papillomavirus Pertussis Zoster Annual Burden of Disease, United States 200,000 hospitalizations; 36,000 deaths (> 90% in older adults) 44,000 cases, 4500 deaths (higher rates of both in older adults and persons with comorbidities) 51,000 infections (95% adults); deaths; 1.25 million with chronic HBV infection 6.2 million new infections (>4000 women die in US annually;? Male deaths) 10,454 cases reported in 2007 (3152 adults) Severe illness in infants; often transmitted by older child or adult 1 million cases; risk for shingles and postherpetic neuralgia increases with age

8 It is September and you are evaluating a 65 year old male, smoker, who has chronic lung and heart disease. Your nurse asks if he would like to receive the influenza vaccine but he declines because last time I received the vaccine I developed the flu shortly afterwards. What is your most appropriate response? A. Tell him all vaccines have life-threatening adverse effects which are common. B. In order to convince him, tell him there are no side effects of the vaccine C. Since you want him to feel satisfied with your patient-doctor relationship, you pleasantly accept his response. D. Strongly recommend the vaccine stating it cannot transmit infection and the risk of disease is high in his case. E. Tell him that if he refuses the vaccine you will no longer 0% 0% 0% 0% 0% participate in his care. 10 A. B. C. D. E.

9 Need to improve Vaccine Uptake Clear and unambiguous message to public, patients, providers o High benefit/risk ratio o SAFE Low rates lead to outbreaks and death Anti-vaccine movement is harmful to public health GA Poland 2011

10 National Foundation for Infecgious Diseases. Surveys of consumers and physicians 2010 Physician-Patient Miscommunication

11 The Communications Breakdown Recommendation You need to get this vaccine. OR I want you to get this vaccine. Vaccine- Motivated Patient Not a Recommendation Do you want this vaccine? OR Think about getting the vaccine. Vaccine- Ambivalent Patient

12 Vaccines: Very high benefit/risk ratio All vaccines have possible side effects, most mild, rarely severe The risk of disease far outweighs the risk of vaccine MESSAGE: Vaccines Effective Need Clear, Unambiguous message Safe Need to recommend

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15 2016/17 U.S. Influenza Vaccine Composition oa/california/7/2009 (H1N1) Changed for 2017/18: A/Michigan/45/2015 o A/Hong Kong/2014) ob/brisbane/60/2008-like virus; Victoria strain) ob/phuket/3073/2013-like virus (Quadrivalent). Similar to last year (Yamagata Strain) 15

16 INFLUENZA VACCINE-Importance oinfluenza may lead to many complications in adults secondary pneumonia exacerbation of underlying disease(i.e., chronic lung or heart disease) ohigh Risk patients: > 65; Chronic Conditions: Pulmonary (including asthma), CV (except hypertension), Renal, Liver, Hematologic, Neurologic, smokers; Immunosuppression (including HIV); Residents of chronic care facilities; Pregnancy; Children < 19 on aspirin; Obesity oinfluenza virus changes antigens over time; patients may therefore, not be immune because of prior exposure oefficacy Depends on: 1. Immunogenicity; 2. Serotype match Recently varied 20-60% pending patient type ocan be given at SAME time as pneumococcal vaccine

17 Influenza Vaccine Abundant Choices for the Clinician IIV4, Standard Dose o Fluarix ( 3 y.o.) o Flulaval ( 3 y.o.) o Fluzone ( 6 months) IIV4, Standard Dose, Intradermal o Fluzone Intradermal (18-64 y.o.) cciiv4, Standard Dose o Flucelvax ( 4 y.o.) IIV3, Standard Dose o Afluria ( 9 y.o.) o Fluvirin ( 4 y.o.) aiiv3, Standard Dose o Fluad ( 65 y.o.) IIV3, High Dose o Fluzone High-Dose ( 65 y.o.) RIV3 o Flublok ( 18 y.o.) LAIV4** o FluMist (2 to 49 y.o.) *MMWR. 2016; 65(5):1-54. Fluarix and Flulaval (GlaxoSmithKline); Fluzone, Fluzone Intradermal, Fluzone High-Dose (Sanofi Pasteur); Flucelvax, Afluria, Fluvirin, Fluad (Seqirus); Flublok (Protein Sciences); FluMist (MedImmune). **Flumist, while approved by the FDA, is not CDC recommended or available on the market for the season. IIV inactive influenza vacc; cciiv cell culture IIV; aiiv adjuvanted IIV; RIV recombivant IIV

18 Case Exercise 1 Which vaccine for: A 67-year-old man with type 2 diabetes mellitus and no history of egg allergy? A. IIV3, standard B. IIV3 high-dose (Fluzone High- Dose) C. IIV4, intradermal (Fluzone Intradermal) D. cciiv4 (Flucelvax)

19 Influenza Vaccine Regular Dose IIV3 or IIV4: Killed, injectable 6 months and older Trivalent (IIV3) or Quadrivalent (IIV4) FDA-indicated ages may vary by manufacturer: Practically speaking, these vaccines are for anyone who doesn t have a contraindication to influenza vaccine IIV4 Intradermal (Fluzone Intradermal) FDA approval for years Manufacturer-supplied injection device (includes needle) 90% smaller needle; 9 mcg of each antigen (compared to 15 mcg of standard dose in IIV4) Quadrivalent IIV, Inactivated Influenza vaccine Fluzone Intradermal Quadrivalent (Influenza Vaccine) Prescribing Information. Sanofi Pasteur Inc., Swiftwater, PA. June 2016.

20 Influenza Vaccine High Dose IIV3, high-dose (Fluzone High-Dose) Contains 60 mcg each of the 3 influenza antigens (compared to 15 mcg each for regular IIV3) oslightly higher rate of MILD reactions Indications: Patients 65 years. Clinical trial had shown high-dose vaccine was 24.2% more effective in preventing influenza in adults 65 than the standard vaccine. NEW STUDY (CDC March 2017): High Dose associated with 38% reduction in mortality Fluzone High-Dose (Influenza Vaccine) Prescribing Information. Sanofi Pasteur Inc. Swiftwater, PA. June DiazGranados CA, et al. N Engl J Med. 2014;371: ; 2.

21 Influenza Vaccine Adjuvanted Vaccine aiiv3, adjuvanted vaccine (Fluad ) Trivalent inactivated influenza vaccine plus a proprietary adjuvant that is proposed to recruit immune cells at the site of injection and enhance antigen uptake oresults in potentially greater immunogenic response in elderly patients Indication: Patients 65 years. Clinical trials show non-inferiority with IIV3 based on seroconversion and geometric mean titers ono data yet available that demonstrate decrease in influenza disease Fluad (influenza vaccine, adjuvanted) Prescribing Information. Sequiris, Inc., Holly Springs, NC. March 2016.

22 Case Exercise 2 Which vaccine for: A 19-year-old with history of severe allergic reaction (i.e., respiratory distress) to eggs? A. IIV4, standard B. aiiv3 (Fluad) C. RIV3 (Flublok) D. No vaccine/refer to specialist

23 Influenza Vaccine in Egg Allergies Cell-Cultured and Recombinant Vaccines cciiv4 (Flucelvax Quadrivalent) o In place of chicken eggs, uses animal cells (Canine Kidney) as host (reference strain obtained from virus originally grown in eggs); quadrivalent o Approved for ages 4 years RIV3 (Flublok ) o Recombinant vaccine egg-free hemagglutinin influenza vaccine produced by recombinant DNA technology using a baculovirus (a virus that infects insects) that produces virus-like particles, hemagglutinin (vaccine of choice for true egg allergy) o Approved for ages >18; only 16-week shelf-life; trivalent Adverse events similar to other inactive vaccines Flucelvax Quadrivalent (influenza vaccine) Prescribing Information. Sequiris, Inc., Holly Springs, NC. April Flublok (influenza vaccine) Prescribing Information. Protein Sciences Corp., Meriden, CT. September 2016.

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25 Influenza and Pregnancy Pregnant woman at high risk for severe complications and death o Cellular immune response diminished Maternal influenza associated with increased (Zaman et al. NEJM 2008) o Maternal hospitalization o Fetal malformation o Other illnesses Prevention is best approach Newborns are at high risk for severe complications o Several reports of 2 nd MRSA infection o No approved vaccine for infants < 6 months of age o All care givers need to be free from possible transmission to this vulnerable population

26 Benefits/Obligations of Influenza vaccine for Healthcare providers As HCW we all have an obligation to protect our patients o Transmission may occur without illness May be asymptomatic carriers Infectious prior to onset of symptoms o Studies show reduced transmission after vaccination Protection form acute illness ofor H1N1 greatest morbidity and mortality is in healthy individuals aged Protection of family members (especially if very young or with medical conditions) Mandatory immunization of all HCW being implemented at SUMMA

27 77% of Influenza asymptomatic Flu Watch Study 1 ocourse of influenza over 5 cohorts ( ) oserology; PCR; Weekly assessment for RTI Findings o77 % appeared to asymptomatic oonly 17% of PCR-confrimed infection sought medical attention A large number of well individuals in the community make a substantial contribution to transmission Hayward et al. Lancet Resp Med. 2014; 2: ; Horby Lancet Resp Med. 2014; 2: 430

28 INFLUENZA VACCINE Reduction in Hospitalizations for Cardiac disease and Strokes (Nichols et a. NEJM 348, April 3, 2003) Observational studies of large cohorts (140,000; 146,000), AND 99-00, 3 HMOs, age 65 Vaccination against influenza associated with reduction in hospitalization for : o Cardiac disease (19% both seasons) o Cerebrovascular disease (16%; 23%) o Pneumonia and Influenza (32%; 29%) o All cause Death (48%; 50%) Possible mechanisms: infection cause alterations in clotting factors, platelet aggregation, amount of inflammatory- response cytokines which enhance thrombosis Lower risk of Cardiovascular complications (JAMA. 2013;310(16): )

29 Influenza Nuts and Bolts 1 Vaccination season: Soon as available to ~April oinfluenza season unpredictable-can start Oct oimmunity will last for almost all patients (no concern for waning immunity for most)) olate season vaccination important and underutilized olaiv can be safely used in MOST healthcare settings as alternative to TIV 2 Egg allergy NO LONGER contraindication 3 oanaphylaxis is EXCEEDINGLY rare [<10 documented cases] oflublok if concern ook to give egg-based if not history of severe anaphylaxis If vaccinated, should be observed ~30 minutes in office 1. Centers for Disease Control and Prevention. Inactivated Influenza Vaccine Available at: 2. Talbot TR, et al. Infect Control Hosp Epidemiol. 2010;31:

30 Case Exercise 3 A 66-year-old man with COPD who has not received any immunization in the past 15 years. What do you recommend today? A. Influenza vaccine B. Pneumococcal vaccine C. Zoster vaccine D. A and B only E. A, B, and C

31 Centers for Disease Control and Prevention Active Bacterial Core Surveillance Report, Emerging Infections Program Network, Streptococcus pneumoniae, Accessed February 3, Pneumococcal Diseases causes more deaths per year in US than Breast Cancer or Prostate Cancer Xu. Et al. Deaths: Prelimanary data for Natl Vital Stat Rep. 2009; 58: 1-51

32 Pneumococcal Vaccines-adults 90 known serotypes of S. pneumoniae Pneumococcal polysaccharide vaccine (PPSV23) Inactive vaccine; contains 23 serotypes which account for majority (75-80%) of clinical disease. Approved for use in adults of any age;? Efficacy for pneumonia Pneumococcal conjugate vaccine (PCV13) approved for use in adults age 50 and older Inactive vaccine, conjugated with diptheria CRM 197 protein); 13 serotypes which account for approx 45-50% of invasive disease Approval from FDA announced December 30, 2011 for adults 50 years and older Previously approved and recommended for use in children CDC s Advisory Committee on Immunization Practices (ACIP) recommends use for patients who are immunocompromised

33 Strategies for sequential use of Conjugate and Polysaccharide vaccine use in adults Conjugate vaccine more immunogenicity (higher antibody levels) and can have booster effect o 13 serogroups (accounts for approx 50% of invasive cases of pneumococcal disease Polysaccharide vaccine less immunogenecity and NO booster effect (may have hyporesponsiveness) o But has 23 serogroups (accounts for approx 89% of invasive cases) Give Conjugate first followed by polysaccharide for potentially optimal effect If polysaccharide given initially wait one year to administer the conjugate vaccine (reduce? Hyporesponsiveness)

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35 Source: Designed by National Foundation for Infectious Disease based on CDC recommendations;

36 CDC Recommendations 2015 for aged > 65

37 Which Vaccine(s) 24 year with asthma has not previously received any pneumococcal vaccine A. Conjugate 13 B. Conjugate 13 followed by Polysaccharide 23 one year later C. Polysaccharide 23 D. Pneumococcal vaccine not indicated

38 Which Vaccine(s) 24 year with asthma has not previously received any pneumococcal vaccine PPSV23 now; PCV age 65 followed by PPSV 6-12 months later

39 Which Vaccine(s) 28 year old woman with HIV infection received one dose PPSV23 a year ago. A. Conjugate 13 B. Conjugate 13 followed by Polysaccharide 23 one year later C. Conjugate 13 followed by Polysaccharide 23 4 years later D. Polysaccharide 23

40 Patient Scenario 28 year old woman with HIV infection received one dose PPSV23 a year ago. One dose PCV now (> one year since PPSV); 2 nd dose PPSV23 age 32 (> 5 years since PCV); 3 rd dose PPSV age 65

41 Which Vaccine(s) 66 year old male, CHF, received PPSV23 age 55 A. Conjugate 13 B. Conjugate 13 followed by Polysaccharide 23 one year later C. Conjugate 13 followed by Polysaccharide 23 4 years later D. Polysaccharide 23

42 Patient Scenarios 66 year old male received PPSV23 age 55 One dose PCV13 now followed by PPSV 23 in one year Another one: 68 year old who received PPSV23 age 66???

43 ACIP Tdap Recommendations Specific Priority Groups Pregnant women at weeks' gestation oat EACH PREGNANCY! Adults, regardless of age, who are in close contact with infants younger than age 12 months (e.g., parents, grandparents, or childcare providers) Healthcare Providers

44 Zoster Vaccine (Zostavax ) olive vaccine Not for pregnancy, immunocompromised oapproved for the prevention of herpes zoster (shingles) in persons aged 50 years and older. (CDC 60) osingle SC injection within 30 minutes of reconstitution In 38,000 patient study, reduced the incidence of shingles by 51% in persons aged 60 years and older (less effective in older patients) Incidence of postherpetic neuralgia less by 39%.

45 Zoster Vaccine (Zostavax ) Most common questions owhat if no history of chicken pox? OK to give owhat if past zoster? Give after resolution of past episode; no specific time interval recommended ois it covered by Medicare Covered by Part D not Part B. Insurance payment varies by plan. To be covered by ACA oshould I receive if around pregnant or immunosuppressed persons? YES--not transmitted

46 Zoster: Special Consideration Simultaneous administration of pneumococcal vaccine o One study showed the average titer against varicella zoster virus (VZV) was lower in persons who received zoster and PPSV at the same visit compared to persons who received these vaccines 4 weeks apart o However, a large study was subsequently conducted that showed that zoster vaccine was equally effective at preventing herpes zoster whether it was administered simultaneously with PPSV or 4 weeks earlier o CDC continues to recommend that HZV and PPSV be administered at the same visit if the person is eligible for both vaccines. vaccination.htm&ei=lkhcvdgnm47soat46ogqag&usg=afqjcnfngswk1ajgj7j82ibja- 2GCnYATw&bvm=bv ,d.cGU (Mar 12, 2015)

47 NEW Zoster vaccine (Shingrix ): subunit recombinant, adjuvant Recombinant: VZV glycoprotein E (target of both humoral and cellular immune responses) with novel adjuvant High and sustained efficacy in clinical trials o ZOE-50: associated with a risk of herpes zoster that was 97.2% lower than that associated with placebo in age 50 and older. 1 o 2 nd trial (ZOE-70) for 70 + demonstrated 89% efficacy and reduced PHN. 2 o Pooled analysis: 91% efficacy against zoster; 89% against PHN 2 doses; AEs comparable. Recommended unanimously by ACIP advisory committee (approved by CDC 10/20/2017) 1. Lal H, et al. N Engl J Med. 2015;372: Cunningham AL, et al. N Engl J Med. 2016;375: Mar 12, 2015)

48 HPV Vaccine HPV 9-valent vaccine (Gardasil 9, Merck) The vaccine is indicated for females aged 9 to 26 years and males aged 9 to 21 (22-26 high risk) years, and for cancers caused by HPV types 6,11, 16, 18, 31, 33, 45, 52 and 58 and for the prevention of genital warts caused by HPV type 97% effective in preventing cervical, vulvar and vaginal cancers Last year CDC recommended reducing to 2 doses No apparent adverse effect if inadvertently given in pregnancy (Quad; Scheller et al. NEJM 2017; 376:1223)

49 Meningococcal Serogroup B Vaccines Group B not in the Quadrivalent (A,C,Y,W) High-risk individuals ocomplement deficiencies, oanatomic or functional asplenia, omicrobiologists routinely exposed to N. meningitidis isolates o serogroup B meningococcal disease outbreak 2 Vaccines: otrumenba 3 doses for high-risk; 2 doses* (6 months apart) healthy obexsero : 2 doses series * ACIP Oct 2016

50 28 y/o male had splenectomy after MVA. Which vaccines should be administered after the splenectomy? A. Pneumococcal B. Hemophilus influenzae B C. Meningococcal quadrivalent D.Menigococcal B E. All above 50 Summa Health Sample Preso

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52 28 y/o male had splenectomy after MVA. Which vaccines should be administered after the splenectomy? A. Pneumococcal A. PCV13; then PPSV23 > 8 weeks; PPSV23 in 5 years and at age 65 B. Hemophilus influenzae type B (Hib) A. If not previously received C. Meningococcal quadrivalent (ACWY) A. Menveo or Menactra (2 doses each, 2 months apart) D.Meningococcal B E. All above 52 Summa Health Sample Preso

53 The wars of the world: Saving lives through vaccination Without the safe and effective vaccines that we too often take for granted now, more than 300 million who lived full and rewarding lives during the 20th century would have died prematurely of a vaccinepreventable disease. Compare this with the 160 million estimated to have been killed in all wars combined during the same century. Stated another way, vaccines saved twice as many lives as were lost in war during the most destructive 100 years in human history. DW Kimberlin Inf Dis News. Aug 1, 2011