VHC Network MILVAX Refresher Update

Non-IgE Mediated Vaccine Reactions 2012 Updates
Renata J. M. Engler, MD, FAAAAI, FACAI
AAAAI 2013 San Antonio, TX
4804 Workshop: 25 Feb 2013 @ 4:45-6:00 PM
Non-IgE-Mediated
Adverse Reactions to Vaccines
Renata J. M. Engler, MD, FACP, FAAAAI, FACAAI
Director, Vaccine Healthcare Centers Network
Division of MILVAX/ US Army Public Health Command
Walter Reed National Military Medical Center
Professor of Medicine/Pediatrics, Allergy-Immunology
Uniformed Services University of the Health Sciences
Bethesda, MD
Learning Objectives
Participants will be able to . . .
• Discuss non-IgE mediated adverse reactions to vaccines and their
management
• Describe the 2011 Institute of Medicine findings on causality of adverse
event-vaccine pairs reviewed including a new approach to categorizing
evidence and classifying level of evidence for or against a causal
association.
• Understand the importance of live virus vaccines and their risk to some
but not all immunodeficient patients.
Conflict of Interest, Financial Disclosures and Disclaimers
Financial: None
Research: grants through NIH/CDMRP
Legal Consult/Expert Witness: None
Organizational: Army Medical Department
Gifts: None
Other: None
National Faculty Education Initiative Training Updates
• Training completed 2012 Dec 29: www.acme-nfei.org
Disclaimer: The views expressed in this presentation are
those of the author and do not reflect the official policy of the
Army/Navy/Air Force Medical Departments, Department of the
Army/Navy/Air Force, Department of Defense, U.S.
Government, or other federal agencies.
Vaccines & 21st Century
Evolving Standards & Knowledge
• Prescription drugs
– Diversity of responses seen post-marketing
– Vaccines as “orphan prescription drugs”
– Apply standards for prescribing any drug to vaccines
• Safe and effective: population to individual
– FDA & Public Health/CDC perspectives
– Operational medicine perspective
– Provider perspective
– Patient/Individual vaccinee perspective
• Need: improved life cycle safety surveillance
– Understanding gender, racial/ethnic/genetic differences
– Evidence-based practice improvements
Knowledge Gaps & Unmet Needs
Beyond Epidemiology and FDA Guided Studies
“Undermining the public trust . . “
1st: “inadequate ongoing, credible education
of the public and health professions
concerning the known and unknown benefits
and risks of vaccines.”
2nd: grossly insufficient investment in
research on the safety of immunization.
Adverse Event Following Immunization
AEFI – International “VAERS”
Side Effect
Versus
“Serious or
Impacting”
Adverse
Reaction
Impact Criteria?
Level of Pain?
Quality of Life?
2009 Newsweek Report
By Dr. Louis Z. Cooper, Heidi Larson and Dr.
Samuel L. Katz | Newsweek Feb 23, 2009
Duration?
Recurrence?
http://www.newsweek.com/id/185986
From the desk of RJM Engler, MD: 2013
1
Non-IgE Mediated Vaccine Reactions 2012 Updates
Adverse Events Following
Immunization (AEFI)
Many Items to Consider for
Complex Reactions
Vaccinology/Immunology &
Personalized Medicine
2012 NIH Jordan Report
Cause or Coincidence?
www.niaid.nih.gov/topics/vaccines/Pages/Jordan2012.aspx
The Xs & Y of Immune
Response to Viral Vaccines
Lancet 2010; 10:338-349.
Sex Differences in Response to Both
Childhood and Adult
Virus Vaccines
YFV Vaccination Induces
TLR-Interferon Signaling F>M
Genes expressed in women (pink), men (blue), or
both (white) 2–10 days after YFV17D vaccination
TIV/LAIV: influenza vaccines
MMR: measles, mumps, and rubella.
HAV: Hepatitis A; HBV: Hepatitis B.
Klein SL et al. The Xs and Y of immune responses to
viral vaccines. Lancet 2010; 10:338-49.
17DV, BERNA-YF, RKI-YF, ARILVAX, YFVAX, AP-YF, 17DD, 17D: yellow fever.
RA27/3: rubella; Schwarz : measles.
HPV4: Human papillomavirus #6,/11/16/18.
HSV-2 gD: Herpes virus type 2.
HDCV and PCEC: rabies.
Dryvax: smallpox.
Edmonston-Zagreb: measles.
Adverse Events & Anthrax Vaccine
Symptoms not Relieved by Meds, Cannot Perform
J Occup Environ Med 2003;45:222-33.
•
•
•
•
•
•
•
•
•
•
•
Muscle aches
416 Male – 185 Female 2.0% - 3.0%
Fatigue
1.2% - 2%
Headache
1.4% - 0.5%
Joint ache
1.4% - 1.4%
Loss of appetite
0.2% - 0.5%
Nausea and vomiting
0.6% - 1.4%
Fever
1.1% - 4.5%
Chills
0.3% - 0.8%
Diarrhea
0.3% - 0.8%
Shortness of breath
0.3% - 0.2%
Itching over entire body
0.5% - 0.6%
TAMC Anthrax Vaccine Study 601 HCW’s: Severity “4”
From the desk of RJM Engler, MD: 2013
(A). Ingenuity pathways
analysis of innate immunity
genes identified as being
important predictors of
adaptive responses to YFV
17D and the changes in
expression specific to
study participants who
were women (B) and men
(C). In the pathway
analysis, node colours
indicate changes of gene
expression (purple=2–18fold upregulation; green= –
downregulation; white=no
significant change from
baseline) between day 0
and 7 in women (n=11) and
men (n=5).
Klein SL et al. The Xs and Y of immune responses to viral vaccines. Lancet 2010; 10:338-49.
Gender Difference in Immune
Responses and Side Effect Severity
Gender
More important determinant of
immune response than dose or age
groups
Arch Intern Med 2004; 164:266-2272
Geometric Mean Titers: 18-49 Years
Reduced dose influenza vaccine
in impacting side effects for women
Local reactions
Impacting systemic side effects
Geometric Mean Titers: 50-64 Years
Clinical Relevance
Individuals with Complaints of More
Severe, Impacting FLU-like
Symptoms after Influenza Vaccine:
Should dose be lowered?
2
Non-IgE Mediated Vaccine Reactions 2012 Updates
An Expanding Platform of
Challenges in Immunization
• Updates and Highlights
– TdaP/Td: New vaccine information sheet 24Jan12
• Tdap: Fever over 102 F (about 1 in 100 adolescents and 1 in 250
adults), Headache (1 in 300), nausea, vomiting, diarrhea, stomach
ache (up to 3 in 100 adolescents and 1 in 100 adults)
• Dose after 20 weeks pregnancy, elderly in contact with infants
• NEW: with each pregnancy even if less than 3 years apart!
• Risk of repeated TdaP every few years with new guidelines
– Influenza vaccine ingredients:
Oculo-respiratory Syndrome
2000 Canadian Case Definition of ORS
• At least one of the following symptoms: bilateral conjunctivitis, respiratory
problem (chest tightness, difficulty breathing, wheezing), and oropharyngeal
edema, or any combination of these conditions within 24 hours of receiving the
vaccine. Exclusions: URI prior to or after immunization.
http://www.collectionscanada.gc.ca/webarchives/20071222064231/http://www.phac-aspc.gc.ca/publicat/ccdrrmtc/01vol27/dr2710ea.html
• Attack Rate of 3.4% (95% CI 2.4-4.4%)
• Evolved case definition to 2 symptoms for
specificity
Age-group distribution (years) of ORS cases for 20002001 to 2003-2004 influenza seasons (n=3264)
• FluMist: egg, MSG, gentamicin, gelatin, arginine
• Fluzone: egg, formaldehyde, gelatin, thimerosal (multi-dose),
latex(single)
– Afluria: egg, neomycin, polymyxin B, thimerosal (multi-dose vials)
2 Deaths/males: age 72
(day 54) and age 66 (day
8) – insufficient evidence
to determine causality?
Females
affected more
than males
(2x)
• Influenza vaccines
• Oculorespiratory syndrome: not anaphylaxis
Canadian Influenza Vaccines
Oculorespiratory Syndrome
Symptoms in Primary & Revaccinated
Smallpox Vaccine Recipients
Randomized crossover DBPC trial (vaccine-placebo 7 days apart): Recurrence Rates?
• 2 FLU Vaccines used
• Risk difference in ORS symptoms 24 hours after receiving vaccine vs placebo
• Recurrence 34% (21-47%)
Fluviral S/F 34% (21-47%)
Deoxycholate
• Virus-splitting acid
• Used in vaccines linked to
febrile seizures in Australia
and Canadian ORS
• Manufacturing changes
linked with reductions in ORS
(A) Percentage
With Indicated
Vaxigrip 15% (2-28%)
Rate 2x higher in patients with ORS in 2000/revaccinated
vs not revaccinated vs ORS in 2001 not in 2000
Symptom
And
(B) Mean Number
of Clinic Visits
Etiology Identified?
Vaccine Production with
Deoxycholate –
Linked to Febrile Seizures
& ORS:
AEFI Prevented Through
Vaccine Modifications!
At Which
Symptom
Was Reported
Cytokine Response to Smallpox Vaccine • JID 2010:201 (15 April) • 1183-1191
New Onset Systemic Symptoms
Following Smallpox (SPX) Immunization
Host
Cytokine Patterns Associated with
Adverse Events after Smallpox Immunization
Pattern of 4 cytokines (108
cytokines and chemokines
measured pre/post 1st SPX)
• Discriminated between patients
with and without Adverse
Events (fever, adenopathy,
rash):
Many Unmet Needs
Personalized Medicine
Issues within the
Immunization Clinical
Mission
Targeting Safety,
Efficacy &
Acceptability
Evidence Based
Practice
Improvements &
Enhance Adverse
Events Reporting
ICAM-1-CD54
G-CSF
Eotaxin
TIMP-2
Kinetics of Serum Cytokines after
Primary or Repeat Vaccination with
the Smallpox Vaccine
J Infect Dis. 2010; 201:1183-1191
IFN- , TNF- , IP-10, MIG, IL-6, etc.
TIMP-2: Natural inhibitors of the matrix metalloproteinases
- a group of peptidases involved in degradation of the
extracellular matrix and with ability to directly suppress the
proliferation of endothelial cells and of quiescent tissues in
response to angiogenic factors.
McKinney et al. Cytokine Expression Patterns Associated with Systemic AEs following Smallpox Immunization J Infect Dis.2006;194:444–53
From the desk of RJM Engler, MD: 2013
3
Non-IgE Mediated Vaccine Reactions 2012 Updates
Myocarditis After
Smallpox Vaccine
Data Source
N=
Associated with Eosinophilic
Hypersensitivity Myocarditis
# Cases
Percent %
Cases: 1 in
Historical Data1
New York - 1947
~6,000,000
1
0.00002%
~50,000
Finland 1877-1879
60,000
10
0.02%
~5,000
CDC-Dryvax ®-2004 (Epi)
40,449
21
0.05%
~2,000
DoD-Dryvax 2004 ®- (Epi)
~1,200,000
140
0.01%
~10,000
Helle (Finland) 1974
234
8
3.4%
~30
Ahlborg (Sweden) 1963
286
3
1.0%
~100
Acambis FDA Data2003-4
All Studies
Prospective Studies1
15 punctures
Acambis-Dryvax®-All1
868
3
0.35%
~289
Acambis-ACAM2000®-All1
2983
7
0.23%
~426
1
Data Source: FDA-CBER Meeting Website 2007 May 17 on website at
www.fda.gov/ohrms/dockets/AC/07/briefing/2007-4292B2-02.pdf
Initial Evidence of Increased Risk for
Febrile Seizures: MMRV vs MMR+V
• Measles-mumps-rubella plus varicella: MMRV
– MMRV combination vaccine to morbidity of shot #s
• ACIP preferential recommendation MMRV over MMR+V
• Post-licensure Safety Surveillance Studies
– Vaccine Safety Data Link (VSD): confirmatory study
• Demonstrated ~2 fold increased risk of febrile seizures (12-23
months) when MMRV in a single injection versus in 2 shots
− MMWR Morb Mortal Wkly Rep. 2008 Mar 14;57(10):258-60.
Update: recommendations from the Advisory Committee on
Immunization Practices (ACIP) with update in 2009
– ACIP removes previous preference recommendation
• Provider must make benefit-risk information available to enable
choice of MMR+V versus MMRV
− Complex risk communication in a setting of limited time
Neurologic Immune Inflammatory Reactions
Recurrent Guillain-Barré Syndrome Following Vaccination
• GBS: acute polyradiculopathy, probably autoimmune
– Reported as a rare but serious vaccine adverse event
– ACIP recommends no influenza vaccine to individuals with a prior
history of GBS within 6 weeks of a prior FLU vaccine IF not at higher
risk of severe complications from influenza illness
• Northern California Kaiser Study Clin Infect Dis 2012;54(6):800–4
– 1995-2006: hospital discharge diagnoses, neurology reviewed GBS
– 550 cases of GBS over 33 million person-years, 6 with recurrence
• 989 vaccines given to 279 of these individuals with 405 TIV vaccine
doses given to 107 individuals with prior Dx of GBS
• 18 had GBS with 6 weeks following FLU vaccine – 2 revaccinated
without recurrence
– Limitations of study: selection bias so at greatest risk for recurrence
were not revaccinated?
http://cid.oxfordjournals.org/content/54/6/800
From the desk of RJM Engler, MD: 2013
Antibiotic
Anti-inflammatory
Amphotericin B
Ampicillin
Chloramphenicol
Penicillin
Tetracycline
Streptomycin
Cephalosporin
Sulfonamide
Sulfadiazine
Sulfisoxazole
Anticonvulsant
Phenindione
Phenytoin
Carbamazepine
Antituberculous
Isoniazid
Para-aminosalicylic acid
Indomethacin
Oxyphenbutazone
Phenylbutazone
Diuretic
Acetazolamide
Chlorthalidone
Hydrochlorothiazide
Spironolactone
Other
Amitriptyline
Methyldopa
Sulfonylurea
Tetanus toxoid
Dobutamine
Digoxin
Captopril and enalapril
Others To Consider
Vaccinia, vaccines?
Other drugs?
Parvovirus B19
Other viruses?
Barton M, et al. Eosinophilic
myocarditis temporally associated
with conjugate meningococcal C
and hepatitis B vaccines in children.
Pediatr Infect Dis J. 2008; 27:831-5.
Can J Cardiol. 2006 December; 22(14): 1233–1237.
Inactivated Trivalent Influenza Vaccine
and Pneumococcal Vaccine (PCV13)
• Febrile Seizures
– Occur in 2-5% of all children: generally benign outcome
– INCREASED RATE in children, especially 12-23 months, compared
with those who received vaccines separately
– ACTUAL RISK: 1 additional seizure in every 2225 children vaccinated
– WHAT IS RISK of delaying one vaccine at well –baby visits?
• Why Vaccinate with FLU Vaccine? MMWR Sep 16, 2011
– 2010-11: 115 children in US died from influenza
– 50% of deaths occurred in children < 5 years of age
• 17/74 (23%) had been vaccinated with TIV
• Why Vaccinate with Pneumococcal Vaccine?
– Pneumococcal disease: 1 million deaths annually worldwide (<5 yrs)
– 13% of all infections in children, major cause of pneumonia
– Rates of disease reduced in all ages with vaccine: 20% pneumonia
Autoimmune Responses
Influenza Vaccine? (Lupus. 2012;21(2):175-83.)
• Autoimmune Inflammatory Rheumatic Disease (AIRD)
– Prospective cohort study with 6 months follow-up: 218 patients AIRD
• 50 vaccinated with seasonal FLU, 6 with H1N1, 104 with both
• 58 non-vaccinated controls
– Healthy controls: 41 subjects (9 seasonal FLU, 3 H1N1, 18 both)
• Outcome Measures: Autoantibodies
– ANA, ENA, aCL IgG/IgM, anti-beta2-glycoprotein
• Antinuclear antibody (ANA), anti-extractable nuclear antigen (anti-ENA),
anticardiolipin (aCL) IgG/IgM antibodies, anti-beta 2-glycoprotein I (anti-β2GPI)]
– Baseline, 1 (AIRD only) and 6 month post vaccine
• Results
– Transient changes in autoantibody production in AIRD & controls
– Small subset: tendency toward anti-ENA development (ANA+ pts)
– H1N1 – aCL induction in some
4
Non-IgE Mediated Vaccine Reactions 2012 Updates
Adverse Events Following
12 & 18 Months Vaccinations
• Population-based, self-controlled case series
– 271,495 12-month vaccinations
– 184,312 18-month vaccinations
• Relative incidence of ER visits or hospital admissions
– Consecutive one day intervals following vaccination
– Compared to control period 20-28 days later
– Post-hoc analysis: reasons for ER visits, average acuity score for 12month vaccines. NOTE: No increase in hospitalizations seen
• Results
– 4-12 days post 12 months vaccines, RR incidence: 1.33 (1.29-1.38)
• 1 excess event during risk interval every 168 children vaccinated
– 10-12 days post 18-month vaccines: RRI 1.25 (1.17-1.33)
• 1 excess event for every 730 children vaccinated
• Future Studies: Risk Factors and/or Prevention?
PLoS One. 2011;6(12):e27897. @ www.ncbi.nlm.nih.gov/pubmed/22174753
Defining Vaccine Injury:
Evidence of Causality?
• 2008 Table of Reportable Events Following Vaccination
– Based on independent review of existing evidence
• http://vaers.hhs.gov/resources/VAERS_Table_of_Reportable_Eve
nts_Following_Vaccination.pdf
– Defines events that are compensable without dispute under the
Vaccine Injury Compensation Program (VICP)
• 2011 Institute of Medicine (IOM) Report
– 12000 peer-reviewed articles considered; 158 vaccine AE pairs
• Goal: Updated scientific basis for review and adjudication of
claims of vaccine injury by the VICP
– Lesson learned: “some issues simply cannot be resolved with
currently available epidemiologic data, excellent as some of the
collections and studies are.” www.iom.edu/Reports/2011/AdverseEffects-of-Vaccines-Evidence-and-Causality.aspx
– Outcomes: 134 “insufficient evidence to accept or refute a causal
relationship”; 24 consensus for or against causal association
2011 Institute of Medicine
IOM Report Summary - 1
Adverse Effects of Vaccines: Evidence & Causality
Evidence Supports Causal Relationship
• Consensus Report: August 25, 2011
– www.iom.edu/Reports/2011/Adverse-Effects-of-Vaccines-Evidence-and-Causality.aspx - New
Categories of Causation Agreed on!
• Reviewed 8 of 12 covered vaccines: varicella zoster, influenza (not H1N1), hepatitis B,
HPV, MMR, Hepatitis A, meningococcal, tetanus-containing vaccines (aP)
• Evidence convincingly supports a causal relationship
– Example: paralytic polio and oral polio vaccine
• Evidence favors acceptance of a causal relationship
– Evidence is strong and generally suggestive, although not firm enough to be
described as convincing or established.
• Evidence is inadequate to accept or reject a causal relationship
– The evidence is not reasonably convincing either in support of or against
causality; evidence that is sparse, conflicting, of weak quality, or merely
suggestive— whether toward or away from causality —falls into this category.
Where there is no evidence meeting the standards described above, the
committee also uses this causal conclusion.
• Evidence favors rejection of a causal relationship
– The evidence is strong and generally convincing, and suggests there is no causal
relationship.
Evidence Convincingly Supports a Causal Relationship
• Varicella Vaccine:
– Disseminated varicella infection rash after vaccination
– Disseminated varicella infection with subsequent infection resulting in
pneumonia, meningitis, or hepatitis in individuals with demonstrated
immunodeficiencies
– Vaccine strain viral reactivation (appearance of chickenpox rash
months to years after vaccination
– Vaccine strain viral reactivation with subsequent infection resulting in
meningitis or encephalitis (inflammation of the brain)
• MMR Vaccine
– Linked to disease called measles inclusion body encephalitis
• In very rare cases, can affect people whose immune systems are
compromised and usually occurs within a year of acute infection or
vaccination
IOM Report Summary – 2
IOM Report Summary – 1
Evidence Supports Causal Relationship
Evidence Favors Causal Relationship
Evidence Convincingly Supports a Causal Relationship
• MMR Vaccine
– Linked to disease called measles inclusion body encephalitis
• In very rare cases, can affect people whose immune systems are
compromised and usually occurs within a year of acute infection or
vaccination
– Linked to febrile seizures
• Generally benign and hold no long term consequences
• NOTE: enhanced risk when MMRV used versus MMR & V
• 6 Vaccines Linked to Anaphylaxis
– MMR, varicella zoster, influenza, hepatitis B, meningococcal,
tetanus-containing vaccines
• Injection of Vaccine, Independent of Antigen Involved
– Syncope (risk of fall complications described)
– Deltoid bursitis (frozen shoulder): shoulder pain, loss of motion
From the desk of RJM Engler, MD: 2013
Evidence Favors Acceptance of a Causal Relationship
(Evidence favors acceptance of 4 vaccine AEFI: strong and
generally suggestive but not firm enough to be convincing)
• HPV vaccine and anaphylaxis
• MMR vaccine and Transient Arthralgia (temporary joint
pain) in female adults
• MMR vaccine and transient arthralgia in children
• Certain trivalent influenza vaccines used in Canada in
some recent years and mild/temporary oculorespiratory
syndrome
– Conjunctivitis, facial swelling, upper respiratory symptoms including
cough and wheezing
5
Non-IgE Mediated Vaccine Reactions 2012 Updates
Human Statue of Liberty 1918
18,000 men preparing for war
at Camp Dodge, Iowa
IOM Report Summary – 1
Evidence Favors Rejection of a Causal Relationship
Base to Shoulder: 150 feet
Right Arm: 340 feet
Widest part of arm holding torch:
12 1/2 feet
Right thumb: 35 feet
Thickest part of body: 29 feet
Left hand length: 30 feet
Face: 60 feet - Nose: 21 feet
Longest spike of head piece: 70 feet
Torch and flame combined: 980 feet
Number of men in:
Flame of torch: 12,000
Torch: 2,800
Right arm: 1,200
Body, head & balance of
figure only: 2,000
Evidence Favors Rejection of a Causal Relationship
• MMR vaccine and
– Autism
– Type 1 diabetes
• DTaP vaccine and
– Type 1 diabetes
• Inactivated influenza vaccine
– Bell’s palsy (weakness of facial nerve)
• Inactivated influenza vaccine
– Exacerbation of asthma or reactive airway disease episodes in
children and adults
TEAMWORK & COMMUNICATION
www.VHCinfo.org/www.vaccines.mil
Clinical Consultations 24/7: 1-866-210-6469
Questions?
Countermeasure Injury
Compensation Program (CICP)
• Health Resources and Services Administration
– HRSA houses CICP: created by PERP Act
• PERP: Public Readiness & Emergency Preparedness Act
• PERP Act (http://www.hrsa.gov/countermeasurescomp/)
Vaccine Healthcare Centers Network
Supporting Quality Immunization Healthcare
Building Trust Through Improved Understanding of
Biodiversity in Vaccine Responses
CICP Coverage
Populations and Countermeasures
• Coverage: Secretarial declaration specifies . . .
– Categories of threats or conditions for which countermeasures are
recommended.
– The time period of liability protections are in effect
– The population of individuals protected
– The geographic areas for which the protections are in effect.
• Countermeasures currently covered include vaccines,
antibiotics or devices used to protect against the following:
– Influenza (pandemic, not seasonal)
• Seasonal influenza vaccines covered by VICP
– Anthrax
Filing deadline: Within 1 year of vaccination
– Botulism
If a possibility, FILE as placeholder!
– Smallpox
Contact or refer patients to the
– Acute Radiation
Vaccine Healthcare Centers Network
From the desk of RJM Engler, MD: 2013
– Provides compensation to individuals for serious physical injuries or
deaths from pandemic, epidemic, or security countermeasures
• Identified in declarations issued by Secretary of HHS
• Pursuant to section 319F-3(b) of the Public Health Service Act
− PHS Act 42 (U.S.C.247d-6d)
– Provides broad liability protections to cover
• Manufacture and testing
• Development and distribution
• Use of designated covered countermeasures
• Vaccine Injury Compensation Program (VICP): distinct
Immunization Tool Kit (7th Edition)
The VHCN offers four ways for military healthcare
professionals to view and receive the comprehensive
immunization information included in the Tool Kit:
1. Order a Printed Tool Kit
• The Tool Kit is a pocket-sized immunization
reference book
• Printed, bound for flexibility in what you carry,
laminated (can spill coffee on it): ideal for use in the
field.
2. Download the Tool Kit (pdf format)
• The Tool Kit is a pocket-sized immunization
reference book
3. View Tool Kit as a book online
4. Access Immunization Took Kit Online
• Access for links to online information & resources
6
Non-IgE Mediated Vaccine Reactions 2012 Updates
Viewing the Tool Kit on an iPhone
iPAD, Other Apps Coming Soon
1. On the iPhone, go to the Apple Store and search for PDF Reader Lite.
2. Install the PDF Reader application on your iPhone
3. Go to www.vhcinfo.org using Safari on your iPhone and click on Tool Kit on the
main menu.
4. Click on “Download Tool Kit (pdf). Item # 2
5. When the main page of the Tool Kit appears, touch the screen on the iPhone
once. In the top corner you will see “Open in Adobe Reader”, tap this and the
Tool Kit will now be viewable in Adobe Reader.
6. Any time you open the Adobe Reader application on your iPhone, you will be
able to access the Tool Kit.
Growing Complexity with
Challenges to Competency
Sustainment in the Force
Managing Vaccines as
Prescription Drugs
Supporting Balanced Benefit-Risk
Assessments for
Medical Exemptions
Users will not need Wi-Fi or internet connection to view the Tool
Kit once it is saved to Adobe Reader. Use the tools available
with the Adobe Reader application to search or bookmark pages
in the Tool Kit for quick and easy access.
COMING SOON: Apps for iPod, android, etc.
www.vhcinfo.org/education.asp?page=toolkit&title=Toolkit
UNCLASSIFIED
38 of x
Alternate Vaccination Schedule
Outcomes of Immunizations in Infancy & Childhood
• Pediatrics 2011 (online 3 Oct 2011): Hit the News
JAMA. 2007;298(18):2155-2163
– Dempsey AF et al. Pediatrics 2011;128:848-856.
Arch Pediatr Adolesc Med. 2005;159(12):1136-1144.
Vaccination with 7 of the 12 routinely recommended childhood
vaccines prevents an estimated
33 000 deaths and 14 million cases of disease in every
birth cohort,
saves $10 billion in direct costs in each birth cohort,
and saves society an additional
$33 billion in costs that include
disability and lost productivity.
UNCLASSIFIED
Preferences Among Parents of Young Children
• http://www.foxnews.com/health/2011/11/29/many-parents-request-delays-in-vaccineschedule/
• Results of Survey (748 parents responded, 61%)
– 13% of parents reported alternative vaccine schedules
– 53% refused certain vaccines and/or delayed some vaccines until the
child was older (55%)
– 17% reported refusing all vaccines: factors associated
• Not having a regular health care provider
• Nonblack race
– Large proportion of alternative schedule vaccinators followed initial
recommendations
– 28% thought delaying vaccine was safer & 22% disagreed with experts
39 of x
International Focus
Immunization Safety Importance
• Brighton Collaboration
Adverse Reaction Rates to Smallpox
Vaccine (per Million)
– http://www.who.int/vaccines-documents/DocsPDF05/815.pdf
Estimates reviewed: Military Medicine 2000; 165:4:287
• Encephalitis:
0.2-8 with 0 in healthy revaccinees
– Lower rates related to age/re-vaccinees
• Vaccinia necrosum:
1-4 per million
• Eczema vaccinatum:
2-15 with highest in Israel
Defense Force (IDF) experience (91-96)
• Generalized vaccinia:
2-30 (highest in Puerto
Rico experience 1967-68)
• E multiforme:
3-24 (Puerto Rico )
• Inadvertent inoculation:
2-13
• Secondary infection:
6 (in IDF experience)
US Total 46 per million
From the desk of RJM Engler, MD: 2013
7
– www.brightoncollaboration.org/internet/en/index.html
– Adverse Events Following Immunization (AEFI) Case
Definitions
• http://brightoncollaboration.org/internet/en/index/definition___guid
elines.-MainContentPar-0005DownloadFile.tmp/Case_Definition_Format_Template.pdf
• World Health Organization (WHO)
– http://www.who.int/immunization_safety/en/
– Immunization Safety Priority Project
– Vaccine safety and quality
• WHO Causality Assessment Clinical Guidelines
Non-IgE Mediated Vaccine Reactions 2012 Updates
2009-2010 Influenza Vaccine
Safety Network
•
•
•
•
•
•
•
•
•
Vaccine Adverse Event Reporting System (VAERS)
Real Time Immunization Monitoring Systems (RTIMS)
Vaccine Safety Datalink (VSD),
Department of Defense (DoD) Defense Medical
Surveillance System (DMSS)
Post-Licensure Rapid Immunization Safety Monitoring
(PRISM),
Indian Health Service (IHS),
Department of Veteran Affairs (VA),
Centers for Medicaid and Medicare Services (CMS), and
CDC’s EIP.
Immunization 2012
New Framework for Evidence Based Guidelines
• Advisory Committee on Immunization Practices (ACIP)
– Expert advice/guidance to Director CDC and Secretary, HHS
– Basis of Evidence Based Recommendations:
• Grading of Recommendations, Assessment, Development,
Evaluation (GRADE)
− Balance of benefits and harms; Type of evidence
− Values and preferences of people affected
− Health economic analyses
• Category A: for all persons in an age- or risk-factor-based group
• Category B: “for individual clinical decision making and do not apply
to all members of an age- or risk-factor-based group, but in the
context of a clinician-patient interaction, where vaccination may be
found appropriate for a person”
• New: Balance Considering Not Just Quality of Evidence
Vaccine. 2011 Nov 15;29(49):9171-6. Epub 2011 Aug 11.
MMWR Report 2010 Jun
H1N1 Vaccine Safety Surveillance: Limitations
1. Misclassification of some cases, particularly in young
–
Impact: Underestimation of GBS cases
2. Inaccurate reporting of date of vaccination
–
Impact: Overestimation or underestimation of cases in risk window
3. Rate ratio relies on vaccination coverage estimates
–
–
BFRSS and NHFS data, not actual dose delivery – 2-3% diff
Impact: Underestimation of the rate ratio
4. Incomplete case ascertainment or reporting bias
–
Active case finding surveillance
5. None of vaccine monitoring systems currently in use,
including EIP, can fully account for other confounding
risk factors for GBS
–
Cannot prove causal relationship between vaccination & GBS
Vaccine Recommendations
GRADE Evidence Approach
• Evidence Tables To Summarize
– The benefits and harms
– The strengths and limitations of the body of evidence.
– ACIP unanimous vote to adopt GRADE approach: Oct 2010
• Quality of evidence for benefits & harms only 1 factor in developing
recommendations: balance with values, health economics
• New Evidence Framework Goals
– Enhance the ACIP's decision-making process by making it
• More transparent, consistent and systematic.
– Response to challenges and criticisms
– A move towards personalized/subpopulation-focused medicine?
Online Review of GRADE: http://www.cdc.gov/vaccines/recs/acip/GRADE/about.htm
Ahmed F, et al.; ACIP Evidence Based Recommendations Work Group (EBRWG). Methods
for developing evidence-based recommendations by the Advisory Committee on
Immunization Practices (ACIP) of the U.S. Centers for Disease Control and Prevention
(CDC). Vaccine. 2011 Nov 15;29(49):9171-6. Epub 2011 Aug 11.
New Framework for Development of
ACIP Guidelines for Vaccines
Vaccine. 2011 Nov 15;29(49):9171-6.
Advisory
Committee on
Immunization
Practices
From
Online Presentation
At
www.cdc.gov/vaccine
s/recs/acip/GRADE/d
ownloads/newframeworkrecs%20.pdf
Email: fahmed@cdc.gov
Category A: for all persons in an age- or risk-factor-based group
Category B: “for individual clinical decision making and do not apply to all members
of an age- or risk-factor-based group, but in the context of a clinician-patient
interaction, where vaccination may be found appropriate for a person”
From the desk of RJM Engler, MD: 2013
8