recognizing and treating adverse effects of vaccines in...
TRANSCRIPT
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Recognizing and Treating Adverse Effects of Vaccines in People
Victor Huber
April 26, 2017
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Outline of Talk
I. Desired effects of vaccines
II. General signs of adverse effects
III. More severe adverse effects
IV. Vaccine-specific adverse effects
V. Treatment of adverse effects
VI. Resistance to vaccination/controversies
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Adaptive Immunity
• Acquired Immunity
• Specificity (clearance)
• Memory develops against pathogen
• Antibody• Goal of vaccination
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Figure 1-20Antibody Response to Vaccination
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Neutralization of Viral Particles by Antibodies
Janeway et al., Immunobiology, 2001
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Treatment vs. Prevention
• Treatment (antibiotics):- Benefit immediately and directly observed
• Prevention (vaccine):- Benefit not immediately apparent
http://ispectrummagazine.com/wp/wp-content/uploads/2016/10/antibiotics-daily-sun.png, Accessed April 25, 2017http://vaccines.procon.org/files/1-vaccines-images/vaccine_syringe_vials.jpg, Accessed April 25, 2017
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Vaccine Design
• Immunogenicity- Try to mimic natural infection, without illness- Live, attenuated (less common, more immunogenic)- Inactivated (more common, less immunogenic)
• Minimize antigens to include most protective portions- Split vaccines- Subunit vaccines- Recombinant protein vaccines
• Less like pathogen- Must provide additional stimulation- Adjuvants
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Vaccine-Preventable Diseases
• Smallpox (Edward Jenner)
• Vaccine developed in 1700’s (Milkmaids = cowpox)
• Officially eradicated in 1979
• Vaccine no longer administered on a routine basis
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Vaccine-Preventable Diseases
~14 different vaccines (0-18 years of age)
http://pediatrics.aappublications.org/content/pediatrics/131/2/397/F1.large.jpg, Accessed April 25, 2017
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Types of Vaccines
• Live, attenuated (closest to natural infection)
• Inactivated vaccines (whole pathogen-to-subunit)- Protein or polysaccharide
• Conjugate vaccines- Polysaccharide linked to protein
• Recombinant protein
• Adjuvants
http://tools.thermofisher.com/content/sfs/prodImages/high/77161-Imject-Alum.jpg, Accessed April 25, 2017http://news.wisc.edu/newsphotos/images/influenza_virus_Kawaoka04.jpg, Accessed April 25, 2017http://photos.the-scientist.com/legacyArticleImages/2011/05/Bacteria.jpg, Accessed April 25, 2017
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General signs of adverse effects
• Pain at injection site
• Low-grade fever
• Swelling at injection site
• Most are minor and self-limiting
http://2rdnmg1qbg403gumla1v9i2h.wpengine.netdna-cdn.com/wp-content/uploads/sites/3/2014/01/14-HHB-050-Fever-Infographic.jpghttps://www.cdc.gov/vaccines/vac-gen/side-effects.htm, accessed 04/25/2017
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More severe adverse effects
• Wide range
• Dizziness/fainting• Fever greater than 105⁰ F• Seizures • Anaphylaxis or anaphylactic shock• Neurological complications (encephalopathy)• Guillain-Barre Syndrome (GBS)
• Many of the most severe adverse effects are vaccine-specific
https://consumeraffairs.global.ssl.fastly.net/files/news/epipen.jpg accessed 04/25/2017https://www.cdc.gov/vaccines/vac-gen/side-effects.htm accessed 04/25/2017
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Vaccine-specific examples
• Rotavirus vaccine• Intussusception: bowel blockage that can require surgery• Can occur in absence of vaccination, but vaccine is known to
increase risk
• Influenza vaccine• GBS• Increased incidence of 1 or 2 additional cases per million
people vaccinated• 1976 vaccine campaign
http://healthimpactnews.com/wp-content/uploads/sites/2/2014/10/President_Ford_receives_a_swine_flu_inoculation-900x550.jpghttps://www.cdc.gov/vaccines/vac-gen/side-effects.htmaccessed 04/25/2017
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• Adjuvant-free (1968)
• Multi-dose vials contain thimerosal• Most single-dose vials do not• LAIV does not
• System for reporting adverse events • Vaccine Adverse Event Reporting System (VAERS) = CDC and FDA• Vaccine Safety Datalink (VSD)
• Guillan-Barre Syndrome (GBS)• Neurological disorder that leads to muscle weakness/paralysis• Natural incidence is 3,000 to 6,000 cases per year
- 1-2 per 100,000 people per year (even without vaccines)• Associated with Campylobacter jejuni• 1976 vaccine campaign saw increase in GBS by 1 in 100,000 vaccinees
- Reason for this is unknown- Overall, 230 infected at Fort Dix, 13 severely, and 1 death
• During 2009 pandemic vaccine campaign- 122 million doses of vaccine, 61 GBS reports
Influenza Vaccine Safety
https://www.cdc.gov/flu/protect/vaccine/guillainbarre.htm, Accessed April 25, 2017
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Treatment of Adverse Effects
• Mild reactions• Often self-limiting
• More severe issues• Treat anaphylaxis• Surgery (intussusception)• Hospitalization• Muscle weakness (GBS)• Paralytic polio (oral polio vaccine, OPV)
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National Vaccine Injury Compensation Program (NVICP)
• National Childhood Vaccine Injury Act (NCVIA)• 1986• Reyes v. Wyeth caused threat to vaccine production
• 1974 case that held vaccine producer liable for child that developed polio after oral polio vaccine
• Vaccine did not have proper warnings
• NVICP offers no-fault alternative to litigation against vaccine companies
https://www.hrsa.gov/vaccinecompensation/index.html (accessed April 25, 2017)
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Resistance to Vaccination
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Link of Autism to Vaccination?
• Wakefield, et al., The Lancet 351:637 (1998).
• Autism linked to Measles, Mumps, Rubella (MMR) vaccine
• 8 children that developed autism within 1 month of MMR
• No control subjects included
• Led to controversy due to anti-vaccine sentiments
• Gerber and Offit, Clinical Infectious Diseases, 48:456, 2009• Editorial, Nature Medicine, 15:119, 2009
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Vaccinologist Response to Autism Controversy?
• MMR Vaccine does not induce autism
• Wakefield study found to be severely flawed (numerous controlled epidemiology studies)
• Gerber and Offit, Clinical Infectious Diseases, 48:456, 2009
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• MMR Vaccine does not induce autism
• Wakefield study found to be severely flawed (controlled epidemiology studies)
•Thimerosal
• Mercury-based anti-bacterial preservative (prevent contamination)• Used in multi-dose vaccines for >50 years • Immediate removal starting in 1999• Only certain influenza vaccines still contain thimerosal• MMR never contained thimerosal• Ethyl mercury (half-life = ~6 days), methyl mercury (half-life = ~45 days)
• Gerber and Offit, Clinical Infectious Diseases, 48:456, 2009; WHO and CDC statements on thimerosal (WWW)
Vaccinologist Response to Autism Controversy?
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• MMR Vaccine does not induce autism
• Wakefield study found to be severely flawed (controlled epidemiology studies)
•Thimerosal
• Mercury-based anti-bacterial preservative (prevent contamination) • Used in multi-dose vaccines for >50 years • Immediate removal starting in 1999• Only certain influenza vaccines still contain thimerosal• MMR never contained thimerosal• Ethyl mercury (half-life = ~6 days), methyl mercury (half-life = ~45 days)
• Too many vaccines
• Number of vaccines has increased, but vaccines are better formulated• 7 vaccines in 1980 = >3000 bacterial and viral proteins or polysaccharides• 15 vaccines today = <200 bacterial and viral proteins or polysaccharides
• Gerber and Offit, Clinical Infectious Diseases, 48:456, 2009
Vaccinologist Response to Autism Controversy?
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Public response to autism controversy
• MMR vaccination rates dropped in UK, and measles incidence escalated• Typically, people who refuse vaccines cluster together• Older diseases (measles) are re-emerging, and newer diseases
(pandemic influenza) may be more difficult to control• Vaccination against diseases we never see!!! • Mumps and measles outbreaks in the US• Children that have not received vaccines are at significant risk
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The effects of the flawed Wakefield report will be felt for decades
• Public perception of vaccines has been compromised (retracted Feb 2, 2010)
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Questions/Discussion