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Recognizing and Treating Adverse Effects of Vaccines in People
Victor Huber
April 26, 2017
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
Adaptive Immunity
• Acquired Immunity
• Specificity (clearance)
• Memory develops against pathogen
• Antibody• Goal of vaccination
Figure 1-20Antibody Response to Vaccination
Neutralization of Viral Particles by Antibodies
Janeway et al., Immunobiology, 2001
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
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
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
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
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
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
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
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
• 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
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)
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)
Resistance to Vaccination
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
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
• 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?
• 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?
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
The effects of the flawed Wakefield report will be felt for decades
• Public perception of vaccines has been compromised (retracted Feb 2, 2010)
Questions/Discussion