2009 08 15 vaccines, adverse reactions, and the florida law

43
Vaccine, Adverse Reactions, and the Florida Law David Berger, MD, FAAP Board Certified Pediatrician Medical Director Wholistic Pediatrics Tampa, FL (813) 960-3415 www.wholisticpeds.com University of South Florida Marshall Center August 15, 2009

Upload: drdavid999

Post on 30-May-2015

1.759 views

Category:

Health & Medicine


2 download

DESCRIPTION

This lecture was given at the University of South Florida Marshall Student Center

TRANSCRIPT

Page 1: 2009 08 15 Vaccines, Adverse Reactions, and the Florida Law

Vaccine, Adverse Reactions, and the Florida Law

David Berger, MD, FAAPBoard Certified Pediatrician

Medical DirectorWholistic Pediatrics

Tampa, FL (813) 960-3415

www.wholisticpeds.com

University of South FloridaMarshall CenterAugust 15, 2009

Page 2: 2009 08 15 Vaccines, Adverse Reactions, and the Florida Law

Discover Magazine, 3/14/07

Page 3: 2009 08 15 Vaccines, Adverse Reactions, and the Florida Law

IMMUNIZATIONS

I am not suggesting that we abandon the use of vaccines

I am concerned about the growing number of chronically ill children

There are more children with learning disabilities and hyperinflammatory/ autoimmune disorders then there has ever been in the history of medicine.

Page 4: 2009 08 15 Vaccines, Adverse Reactions, and the Florida Law

Concerns about Vaccines Are we unnaturally stressing underdeveloped immune

systems beyond their capabilities in our effort to keep the children from becoming ill?

There are inadequate safety studies that have looked beyond the immediate period after vaccination.

Are we giving too many vaccines too early in life or over a short time span?

We do not have a clear understanding of the effects of some of the vaccine components such as Thimerosal, aluminum, formaldehyde, and human fetal tissue. Nor do we understand how they interact with atypical immune systems and toxins that people are more commonly being exposed to.

Page 5: 2009 08 15 Vaccines, Adverse Reactions, and the Florida Law

“The developing fetus and young children are thought to be disproportionately affected by mercury exposure, because many aspects of development, particularly brain maturation, can be disturbed by the presence of mercury. Minimizing mercury exposure is, therefore, essential to optimal child health…..Mercury in all of its forms is toxic to the fetus and children, and efforts should be made to reduce exposure to the extent possible to pregnant women and children as well as the general population.”

MERCURYStatement:Pediatrics 2001 Jul, American Academy of Pediatrics:

Committee on Environmental Health.

Page 6: 2009 08 15 Vaccines, Adverse Reactions, and the Florida Law

Mercury/Thimerosal

Typical Mercury Exposure for 2 month old infant prior to 2001:

Hep B 12.5 mcg EthylmercuryDTaP 25 mcg EthylmercuryHib 25 mcg Ethylmercury------------------------------Total 62.5 mcg Ethylmercury

Total “safe” dose for 10 pound (2 month old) baby by EPA standards: 0.5 mcg. The average 2 month old received ~120x the EPA limit

Page 7: 2009 08 15 Vaccines, Adverse Reactions, and the Florida Law

Mercury/Thimerosal

By 6 months of age, a fully vaccinated infant would have received:– 3 DTP 75 mcg ethylmercury– 3 Hib 75 mcg ethylmercury– 3 Hep B 37.5 mcg ethylmercury

------------------------------------------------

Total 187.5 mcg ethylmercury

1999 FDA Center for Biologics Evaluation and Research

Page 8: 2009 08 15 Vaccines, Adverse Reactions, and the Florida Law

2008-08 www.vaccinesafety.edu

Page 9: 2009 08 15 Vaccines, Adverse Reactions, and the Florida Law

Type Name Manufacturer mcg mercuryDTaP Tripedia Sanofi Pasteur ≤0.3DT No Name (single) Sanofi Pasteur

≤0.3DT No Name (multi ) Sanofi Pasteur 25 Td No Name Mass Public Health 8.3Td Decavac Sanofi Pasteur ≤0.3TT No Name Sanofi Pasteur 25Hep A/B Twinrix GlaxoSmithKline ≤1Influenza Afluria multi dose CSL 24.5Influenza Fluzone –Full dose for 3y)Sanofi Pasteur 25Influenza Fluzone – ½ dose < 3y/o) Sanofi Pasteur 25Influenza Fluvirin Novartis 25Influenza Fluvirin (Prsv Free) Novartis ≤1Influenza Fluarix GlaxoSmithKline ≤1Influenza FluLaval ID Biomedical 25Jap Enceph. JE-VAX Osaka Univ. 17.5 -35Meningococus Menomune (multidose) Sanofi Pasteur 25

Updated full table maintained in “Vaccine” Section at www.wholisticpeds.comPrevious tables dating back to 2000 are also presented.

Vaccines that Still Contain Mercury

Page 10: 2009 08 15 Vaccines, Adverse Reactions, and the Florida Law

Total toxicityAutism rates

On average, for each 1000 lb of environmentally released mercury, there was a 43% increase in the rate of special education services and a 61% increase in the rate of autism.Palmer et al. Health & Place 12 (2006) 203–209

Proximity to point sources of environmental mercury release as a predictor of

autism prevalence. Palmer et al. Health & Place 2008

Page 11: 2009 08 15 Vaccines, Adverse Reactions, and the Florida Law

Mercury levels in Certain Fish Species (PPM) (EPA 2006; http://www.cfsan.fda.gov/~frf/sea-mehg.html)MACKEREL KING 0.730

SHARK 0.988

SWORDFISH 0.976

TILEFISH (Gulf of Mexico) 1.450

BASS (SALTWATER, BLACK, STRIPED)3 0.219

BASS CHILEAN 0.386

BLUEFISH 0.337

CARP 0.14

GROUPER (ALL SPECIES) 0.465

HALIBUT 0.252

LOBSTER (NORTHERN/AMERICAN) 0.310

MACKEREL SPANISH (Gulf of Mexico) 0.454

MARLIN * 0.485

ORANGE ROUGHY 0.554

SNAPPER 0.189

TUNA (CANNED, ALBACORE) 0.353

TUNA(FRESH/FROZEN, ALL) 0.383

TUNA (FRESH/FROZEN,ALBACORE) 0.357

TUNA (FRESH/FROZEN, BIGEYE) 0.639

TUNA (FRESH/FROZEN, SKIPJACK) 0.205

TUNA (FRESH/FROZEN, YELLOWFIN) 0.325

TUNA (FRESH/FROZEN, Species Unknown) 0.414

Page 12: 2009 08 15 Vaccines, Adverse Reactions, and the Florida Law

Dental Amalgams as a source of MercuryHarris 2008, University of Sydney, “Migration of mercury from

dental amalgam through human teeth”: Most importantly the detection of Hg in areas of the tooth that once contained an active bloodstream and in calculus indicates that both exposure pathways should be considered as significant.

Austin 2008, Swinburne University of Technology, Melbourne, “An epidemiological analysis of the ‘autism as mercury poisoning’ hypothesis”: to examine the autism as mercury poisoning hypothesis, this paper reviews the existing scientific literature within the context of established epidemiological criteria and finds that the evidence for a causal relationship is compelling. Exposure to mercury (via vaccines and maternal dental amalgam) in utero and during infant years is confirmed; ….. given the severity, devastating lifelong impact and extremely high prevalence of autism, it would be negligent to continue to expose pregnant and nursing mothers and infant children to any amount of avoidable mercury.

Page 13: 2009 08 15 Vaccines, Adverse Reactions, and the Florida Law

Amalgam dental fillings and hearing lossInt J Audiol. 2008 Dec;47(12):770-6, Rothwell JA, Boyd PJ. Audiology Department,

General Hospital, St. Helier, Jersey, Channel Islands.

In this study we investigated the effects of amalgam dental fillings on auditory

thresholds. Participants (n=39) were non-smoking women age 40 to 45.

Regression and correlation analyses were performed between auditory thresholds,

measured from 0.25 to 16 kHz, and the number/surface area of dental fillings,

using the ASHA criteria for ototoxic change as a reference for comparison. No

significant correlation (p>0.05) was found between composite (non-amalgam)

filling or drilling data and auditory thresholds. However, there was a significant

positive linear correlation between amalgam filling data and auditory thresholds at

8, 11.2, 12.5, 14, and 16 kHz. The strongest association (r=0.587, n=39, p<.001,

r(2)=0.345) was at 14 kHz, where each additional amalgam filling was associated

with a 2.4 dB decline in hearing threshold (95% confidence interval [CI], 1.3-3.5

dB). The results suggest an association between more amalgam fillings and poorer thresholds at higher frequencies, which could contribute to presbyacusis in developed countries. This provides further argument for the use of amalgams to be phased out where suitable alternatives exist.

Page 14: 2009 08 15 Vaccines, Adverse Reactions, and the Florida Law

Children with Autism are Prone to Decreased Ability to Detoxify

Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with autism.James SJ, Cutler P, Melnyk S, Jernigan S, Janak L, Gaylor DW, Neubrander JA.

Department of Pediatrics, University of Arkansas for Medical Sciences

Am J Clin Nutr. 2004 Dec;80(6):1611-7

BACKGROUND: Autism is a complex neurodevelopmental disorder that usually presents in early childhood and that is thought to be influenced by genetic and environmental factors. Although abnormal metabolism of methionine and homocysteine has been associated with other neurologic diseases, these pathways have not been evaluated in persons with autism. OBJECTIVE: The purpose of this study was to evaluate plasma concentrations of metabolites in the methionine transmethylation and transsulfuration pathways in children diagnosed with autism. DESIGN: Plasma concentrations of methionine, S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH), adenosine, homocysteine, cystathionine, cysteine, and oxidized and reduced glutathione were measured in 20 children with autism and in 33 control children. On the basis of the abnormal metabolic profile, a targeted nutritional intervention trial with folinic acid, betaine, and methylcobalamin was initiated in a subset of the autistic children. RESULTS: Relative to the control children, the children with autism had significantly lower baseline plasma concentrations of methionine, SAM, homocysteine, cystathionine, cysteine, and total glutathione and significantly higher concentrations of SAH, adenosine, and oxidized glutathione. This metabolic profile is consistent with impaired capacity for methylation (significantly lower ratio of SAM to SAH) and increased oxidative stress (significantly lower redox ratio of reduced glutathione to oxidized

glutathione) in children with autism. The intervention trial was effective in normalizing the metabolic imbalance in the autistic children. CONCLUSIONS : An increased vulnerability to oxidative stress and a decreased capacity for methylation may contribute to the development and clinical manifestation of autism.

Page 15: 2009 08 15 Vaccines, Adverse Reactions, and the Florida Law

Neurotoxicity of Thimerosal in Human Brain Cells is Associated with Glutathione

Depletion:

Protective Effect of Cysteine or Glutathione Supplementation

Neurotoxicology. 2005 Jan;26(1):1-8

S. Jill James, William Slikker, Elizabeth New, Stefanie Jernigan, Stepan Melnyk

Department of PediatricsUniversity of Arkansas for Medical Sciences

Little Rock, AR

Page 16: 2009 08 15 Vaccines, Adverse Reactions, and the Florida Law

0 2.5 5 10 20

VIABILITY OF GLIOBLASTOMA AND NEUROBLASTOMA CELLS WITH INCREASING

DOSE OF THIMEROSAL

0.0

0.1

0.2

0.3

0.4

0.5

0.0

0.2

0.4

0.6

0.8

1.0

1.2

Via

bilit

y (M

TT

OD

) Glioblastoma Cells Neuroblastoma Cells (48 hr Exposure) (3 hr Exposure)

0 2.5 5 10 20 0 2.5 5 10 20

M Thimerosal M Thimerosal

Page 17: 2009 08 15 Vaccines, Adverse Reactions, and the Florida Law

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

Control Thimerosal +GSH + Cystine +NAC + Methionine

O.D

. (V

iab

ility

)

Viability of Glioblastoma cells exposed to 15 M Thimerasol in the presence of GSH-ester,

Cystine, N-acetylcysteine (NAC), or Methionine

Page 18: 2009 08 15 Vaccines, Adverse Reactions, and the Florida Law

Heavy Metal ExposuresAfter exposure to mercury, the length of time to be

eliminated varies for different organs:

Blood and Hair: 4-6 months Non Central Nervous System organs: several years Brain: 20 years(Boyd Haley, PhD, University of Kentucky, Dept of

Chemistry)

Lead typically deposits into brain and bone. After exposure to lead, within several months the blood and urine levels will be normal even if the lead is still in the bone and brain (Clarkson, 2002)

Page 19: 2009 08 15 Vaccines, Adverse Reactions, and the Florida Law

Some Children with Autism Do Not Clear MercuryMercury in first-cut baby hair of children with autism versus

typically-developing children J. B. Adams;  J. Romdalvik;  K. E. Levine; Lin-Wen Hu (Arizona State University)Toxicological & Environmental Chemistry, May 2, 2008

Children with autism were examined to determine amounts of mercury (Hg) in their baby hair and the factors that might affect Hg body burden. US children with autism (n = 78) and matched controls (n = 31) born between 1988 and 1999 were studied. Hg in first-cut baby hair was determined using cold vapor atomic fluorescence spectrometry (CVAFS). Twenty samples were split and also measured with Neutron Activation Analysis (NAA). Logistic regression analysis showed that

compared to children with higher levels of mercury (above 0.55 mcg g-1), children with lower levels of mercury in their hair (below 0.55 mcg g-1) were 2.5-fold more likely to manifest with autism. Children with autism had similar mercury exposure as controls from maternal seafood and maternal dental amalgams. Children with autism also had 2.5-fold higher incidence of oral antibiotic use during their first 18 months of life. Their mothers were possibly more likely to use oral antibiotics during pregnancy or nursing. The amount of Hg in the baby hair of children with autism showed a significant correlation with the number of

maternal dental amalgams. The lower level of Hg in the baby hair of children with autism indicates an altered metabolism of Hg, and may be due to a decreased ability to excrete Hg. This is consistent with usage of higher amounts of oral antibiotics, which are known to inhibit Hg excretion in rats due to alteration of gut flora, and may exert a similar effect in humans. Higher usage of oral antibiotics in infancy may also partially explain the high incidence of chronic gastrointestinal problems seen in individuals with autism.

Page 20: 2009 08 15 Vaccines, Adverse Reactions, and the Florida Law

Heavy Metals Accumulate in Children with Autism

Austin (2008), Swinburne University of Technology, Melbourne, “An investigation of porphyrinuria in Australian children with autism.”: Two recent studies, from France (Nataf et al., 2006) and the United States (Geier & Geier, 2007), identified atypical urinary porphyrin profiles in children with an autism spectrum disorder (ASD). These profiles serve as an indirect measure of environmental toxicity generally, and mercury (Hg) toxicity specifically, with the latter being a variable proposed as a causal mechanism of ASD (Bernard et al., 2001; Mutter et al., 2005). To examine whether this phenomenon occurred in a sample of Australian children with ASD, an analysis of urinary porphyrin profiles was conducted. A consistent trend in abnormal porphyrin levels was evidenced when data was compared with those previously reported in the literature. The results are suggestive of environmental toxic exposure impairing heme synthesis. Three independent studies from three continents have now demonstrated that porphyrinuria is concomitant with ASD, and that Hg may be a likely xenobiotic to produce porphyrin profiles of this nature.

Page 21: 2009 08 15 Vaccines, Adverse Reactions, and the Florida Law

Mitochondria, Vaccines and Autism

The case of Hannah Polling:

“According to the concession report, this case involved a toddler who was developing normally until 18 months of age. Several days after the 18 month shots her development began to decline to the point that she eventually displayed many features of autism. Doctors also discovered that the child had a mitochondrial disorder (a disorder of metabolism that makes a child pre-disposed to developmental and medical problems). The court decided that there was enough evidence to show that the vaccines may have aggravated the mitochondrial disorder and triggered problems consistent with autistic-like behavior.”

Dr Robert Sears, Author of “The Vaccine Book: Making the right decision for your child”

Page 22: 2009 08 15 Vaccines, Adverse Reactions, and the Florida Law

Mitochondrial Dysfunction and Autism

Evidence of Mitochondrial Dysfunction in Autism and Implications for TreatmentDaniel A. Rossignol, J. Jeffrey Bradstreet, International Child Development Resource Center 

 

Abstract: Classical mitochondrial diseases occur in a subset of individuals with autism and are usually

caused by genetic anomalies or mitochondrial respiratory pathway deficits. However, in many cases of autism, there is evidence of mitochondrial dysfunction (MtD) without the classic features associated with mitochondrial disease. MtD appears to be more common in autism and presents with less severe signs and symptoms. It is not associated with discernable mitochondrial pathology in

muscle biopsy specimens despite objective evidence of lowered mitochondrial functioning. Exposure to environmental toxins is the likely etiology for MtD in autism. This dysfunction then contributes to a number of diagnostic symptoms and comorbidities observed in autism including: cognitive impairment, language deficits, abnormal energy metabolism, chronic gastrointestinal problems, abnormalities in fatty acid oxidation, and increased oxidative stress. MtD and oxidative stress may also explain the high

male to female ratio found in autism due to increased male vulnerability to these dysfunctions. Biomarkers for mitochondrial dysfunction have been identified, but seem widely under-utilized despite available therapeutic interventions. Nutritional supplementation to decrease oxidative stress along with factors to improve reduced glutathione, as well as hyperbaric oxygen therapy (HBOT) represent supported and rationale approaches. The underlying pathophysiology and autistic symptoms of affected individuals would be expected to either improve or cease worsening once effective treatment for MtD is implemented.

Page 23: 2009 08 15 Vaccines, Adverse Reactions, and the Florida Law

Mercury Inhibits Mitochondrial Energy MetabolismAt environmental doses, dietary methylmercury inhibits mitochondrial energy

metabolism in skeletal muscles of the zebra fish Cambier S, Bénard G, Mesmer-Dudons N, Gonzalez P, Rossignol R, Brèthes D, Bourdineaud JP.

Int J Biochem Cell Biol. 2008 Aug 13

The neurotoxic compound methylmercury (MeHg) is a commonly encountered pollutant in the environment, and

constitutes a hazard for human health through fish eating. To study the impact of MeHg on mitochondrial structure and function, we contaminated the model fish species Danio rerio with food containing 13mug of MeHg per gram, an environmentally relevant dose. Mitochondria from contaminated zebrafish muscles presented structural abnormalities under electron microscopy observation. In permeabilized muscle fibers, we observed, a strong inhibition of both state 3 mitochondrial respiration and functionally isolated maximal cytochrome c oxidase (COX) activity after 49 days of MeHg exposure. However, the state 4 respiratory

rate remained essentially unchanged. This suggested a defect at the level of ATP synthesis. Accordingly, we measured a dramatic decrease in the rate of ATP release by skinned muscle fibers using either pyruvate and malate or succinate as respiratory substrates. However, the amount and the assembly of the ATP synthase were identical in both control and contaminated muscle mitochondrial fractions. This suggests that MeHg induced a decoupling of mitochondrial oxidative phosphorylation in the skeletal muscle of zebrafish. Western blot analysis showed a 30% decrease of COX subunit IV levels, a 50% increase of ATP synthase subunit alpha, and a 40% increase of the succinate dehydrogenase Fe/S protein subunit in the contaminated

muscles. This was confirmed by the analysis of gene expression levels, using RT-PCR. Our study provides a basis for further analysis of the deleterious effect of MeHg on fish health via mitochondrial impairment.

Page 24: 2009 08 15 Vaccines, Adverse Reactions, and the Florida Law

Vaccines can Induce Th2 weighted Immunity

McDonald et al(2008), University of Manitoba

J Allergy Clin Immunol. 2008 Mar;121(3):626-31

“Many early childhood vaccinations have been viewed as promoters of asthma development by stimulating a Th2-type immune response, shifting the cytokine balance” (Johnston, et al, 2002)

“At birth the newborn immune system has a limited ability to produce Th1 cytokines but levels increase over the period of the next 6 months” (Marodi, 2002)

CONCLUSION: We found a negative association between delay in administration of the first dose of whole-cell DPT immunization in childhood and the development of asthma; the association was greater with delays in all of the first 3 doses. The mechanism for this phenomenon requires further research.

Delay in diphtheria, pertussis, tetanus vaccination is associated with a reduced risk of childhood asthma

Page 25: 2009 08 15 Vaccines, Adverse Reactions, and the Florida Law

Vaccine Induced Autoimmunity(Cohen&Shoenfeld, Tel Aviv University, Journal of Autoimmunity, 1996)

Page 26: 2009 08 15 Vaccines, Adverse Reactions, and the Florida Law

Vaccination-induced systemic autoimmunity in farmed Atlantic salmonKoppang EO, Bjerkås I, Haugarvoll E, Chan EK, Szabo NJ, Ono N, Akikusa B, Jirillo E, Poppe TT, Sveier H, Tørud B, SatohDepartment of Basic Sciences and Aquatic Medicine, Norwegian School of Veterinary Science, Oslo, Norway.

Over half of the salmon consumed globally are farm-raised. The introduction of oil-adjuvanted vaccines into salmon aquaculture made large-scale production feasible by preventing infections. The vaccines that are

given i.p. contain oil adjuvant such as mineral oil. However, in rodents, a single I.P. injection of adjuvant hydrocarbon oil induces lupus-like systemic autoimmune syndrome, characterized by autoantibodies, immune complex glomerulonephritis, and arthritis. In the present study, whether the farmed salmon that received oil-adjuvanted vaccine

have autoimmune syndrome similar to adjuvant oil-injected rodents was examined . Sera and tissues were collected from vaccinated or unvaccinated Atlantic salmon (experimental, seven farms) and wild salmon. Autoantibodies (immunofluorescence, ELISA, and immunoprecipitation) and IgM levels (ELISA) in sera were measured. Kidneys

and livers were examined for pathology. Autoantibodies were common in vaccinated fish vs unvaccinated controls and they reacted with salmon cells/Ags in addition to their reactivity with mammalian Ags. Diffuse nuclear/cytoplasmic staining was common in immunofluorescence but some had more specific patterns. Serum total IgM levels were also increased in vaccinated fish; however, the fold increase of autoantibodies was much more than that of total IgM. Sera from vaccinated fish immunoprecipitated ferritin and approximately 50% also reacted with other unique proteins.

Thrombosis and granulomatous inflammation in liver, and immune-complex glomerulonephritis were common in vaccinated fish. Autoimmunity similar to the mouse model of adjuvant oil-induced lupus is common in vaccinated farmed Atlantic salmon. This may have a significant impact on production loss, disease of previously unknown etiology, and future strategies of vaccines and salmon farming.

Page 27: 2009 08 15 Vaccines, Adverse Reactions, and the Florida Law

Hepatitis B vaccine and the risk of CNS inflammatory demyelination in childhood

Yann Mikaeloff, MD, PhD, Guillaume Caridade, MSc, Samy Suissa, PhD and Marc Tardieu, MD, Ph

FromAssistance Publique-Hôpitaux de Paris and Division of Clinical Epidemiology (S.S.), McGill University and Royal Victoria Hospital, Montreal, Canada.

Background: The risk of CNS inflammatory demyelination associated with hepatitis B (HB) vaccine is debated, with studies reporting conflicting findings.

Methods: We conducted a population-based case-control study where the cases were children with a first episode of acute CNS inflammatory demyelination in France (1994–2003). Each case was matched on age, sex, and geographic location to up to 12 controls, randomly selected from the general population.

Information on vaccinations was confirmed by a copy of the vaccination certificate. The odds ratios (ORs) of CNS inflammatory demyelination associated with HB vaccination were estimated using conditional logistic regression.

Results: The rates of HB vaccination in the 3 years before the index date were 24.4% for the 349 cases and 27.3% for their 2,941 matched controls. HB vaccination within this period was not associated with an increase in the rate of CNS inflammatory demyelination (adjusted OR, 0.74; 0.54–1.02), neither >3 years nor as a function of the number of injections or brand type. When the analysis was restricted to subjects compliant with vaccination, HB vaccine exposure >3 years before index date was associated with an increased trend (1.50; 0.93–2.43), essentially from the Engerix B vaccine (1.74; 1.03–2.95). The OR was particularly elevated for this brand in patients with confirmed multiple sclerosis (2.77; 1.23–6.24).

Conclusions: Hepatitis B vaccination does not generally increase the risk of CNS inflammatory demyelination in childhood. However, the Engerix B vaccine appears to increase this risk, particularly for confirmed multiple sclerosis, in the longer term. Our results require confirmation in future studies

Page 28: 2009 08 15 Vaccines, Adverse Reactions, and the Florida Law

Mercury Induced AutoimmunityIL-12 Down-Regulates Autoantibody Production in Mercury-Induced Autoimmunity

Lee M. Bagenstose, Padmini Salgame2 and Marc Monestier2

Department of Microbiology and Immunology, Temple University School of Medicine, Philadelphia, PA

In genetically susceptible H-2s mice, subtoxic doses of mercuric chloride (HgCl2)induce a complex autoimmune syndrome characterized by the production of anti-nucleolar

IgG Abs, lymphoproliferation, increased serum levels of IgG1 and IgE Abs, and renal Ig deposits. Mercury-induced

autoimmunity in H-2s mice provides a useful model for chemically related autoimmunity in humans. The increase in serum IgG1 and IgE, which are under IL-4 control, suggests a role for the Th2 subset in this syndrome. The IL-12 cytokine induces T cell proliferation and IFN- production and is necessary for differentiation of naive T cells into the Th1 subset. To gain an understanding of T cell control in this syndrome and, in particular, Th1/Th2 regulation, we assessed the effect of IL-12 administration in mercury-induced autoimmunity. Groups of A.SW mice (H-2s) received HgCl2 plus IL-12, HgCl2 alone, or IL-12 alone. IL-12 treatment resulted in a dramatic reduction

of the anti-nucleolar Ab titers. IL-12 also inhibited the HgCl2-induced serum IgG1 increase, but, in contrast, did not significantly affect IgE induction in this model. This observation may be related to our unexpected finding that IL-12 further potentiated the HgCl2-triggered IL-4 induction in this model. The levels of renal Ig deposits were similar in mice receiving HgCl2 alone or HgCl2 plus IL-12. Our results indicate that IL-12 can down-regulate the autoimmune component of this experimental syndrome and that the various manifestations of mercury-induced autoimmunity are independently regulated.

Page 29: 2009 08 15 Vaccines, Adverse Reactions, and the Florida Law

Children with Autism are prone to autoimmunityPrevalence of serum antibodies to caudate nucleus in autistic children

Vijendra K. Singh , and Wyatt H. RivasDepartment of Biology, Biotechnology Center Building, Utah State University

Neuroscience Letters, October 2003

Autism may involve autoimmunity to brain. We studied regional distribution of antibodies to rat caudate nucleus, cerebral cortex, cerebellum, brain stem and hippocampus. The study included 30 normal and 68 autistic children. Antibodies were assayed by immunoblotting. Autistic children, but not normal children, had antibodies to caudate nucleus (49% positive sera), cerebral cortex (18% positive sera) and cerebellum (9% positive sera). Brain stem and hippocampus were negative. Antibodies to caudate nucleus were directed towards three proteins having 160, 115 and 49 kD molecular weights. Since a significant number of autistic children had antibodies to caudate nucleus, we propose that an autoimmune reaction to this brain region may cause neurological impairments in autistic children. Thus, the caudate nucleus might be involved in the neurobiology of autism.

Page 30: 2009 08 15 Vaccines, Adverse Reactions, and the Florida Law

Children with Autism are prone to autoimmunityAbnormal Measles-Mumps-Rubella Antibodies and CNS Autoimmunity in Children with Autism

Vijendra K. Singh, Sheren X. Lin, Elizabeth Newell, Courtney NelsonDepartment of Biology and Biotechnology Center, Utah State University, Logan, Utah, USAJournal of Biomedical Science 9:4:2002, 359-364.

Autoimmunity to the central nervous system (CNS), especially to myelin basic protein (MBP), may play a causal role in autism, a neurodevelopmental disorder. Because many autistic children harbor elevated levels of measles antibodies, we

conducted a serological study of measles-mumps-rubella (MMR) and MBP autoantibodies. Using serum samples of 125 autistic children and 92 control children, antibodies were assayed by ELISA or immunoblotting methods.

ELISA analysis showed a significant increase in the level of MMR antibodies in autistic children. Immunoblotting analysis revealed the presence of an unusual MMR antibody in 75 of 125 (60%) autistic sera but not in control sera. This antibody specifically detected a protein of 73-75 kD of MMR. This protein band, as analyzed with monoclonal antibodies, was immunopositive for measles hemagglutinin (HA) protein but

not for measles nucleoprotein and rubella or mumps viral proteins. Thus the MMR antibody in autistic sera detected measles HA protein, which is unique to the measles subunit of the vaccine. Furthermore, over 90% of MMR antibody-positive autistic sera were also positive for MBP autoantibodies, suggesting a strong association between MMR and CNS autoimmunity in autism. Stemming from this evidence, we suggest that an inappropriate antibody response to MMR, specifically the measles component thereof, might be related to pathogenesis of autism

Page 31: 2009 08 15 Vaccines, Adverse Reactions, and the Florida Law

Children with Autism are prone to autoimmunitySerum autoantibodies to brain in Landau-Kleffner variant, autism, and other neurologic

disorders.Connolly AM, Chez MG, Pestronk A, Arnold ST, Mehta S, Deuel RK.Departments of Neurology and Pediatrics, Washington University, St. Louis Children's Hospital J Pediatr. 1999 May;134(5):607-13.

OBJECTIVE: Etiologically unexplained disorders of language and social development have often been reported to improve in patients treated with immune-modulating regimens. Here we determined the frequency of autoantibodies to brain among such children. DESIGN: We collected sera from a cohort of children with (1) pure Landau-Kleffner syndrome (n = 2), (2) Landau-Kleffner syndrome variant (LKSV, n = 11), and (3) autistic spectrum disorder (ASD, n = 11). None had received immune-modulating treatment before the serum sample was obtained. Control sera (n = 71) were from 29 healthy children, 22 with non-neurologic illnesses (NNIs), and 20 children with other neurologic disorders (ONDs). We identified brain autoantibodies by immunostaining of human temporal cortex and antinuclear autoantibodies using commercially available kits. RESULTS: IgG anti-brain autoantibodies were present in 45% of sera from children with LKSV, 27% with ASD, and 10% with ONDs compared with 2% from healthy children and control children with NNIs. IgM autoantibodies were present in 36% of sera from children with ASD, 9% with LKSV, and 15% with ONDs compared with 0% of control sera. Labeling studies identified one antigenic target to be endothelial cells. Antinuclear antibodies with titers >/=1:80 were more common in children with ASD and control

children with ONDs. CONCLUSION: Children with LKSV and ASD have a greater frequency of serum antibodies to brain endothelial cells and to nuclei than children with NNIs or healthy children. The presence of these antibodies raises the possibility that autoimmunity plays a role in the pathogenesis of language and social developmental abnormalities in a subset of children with these disorders.

Page 32: 2009 08 15 Vaccines, Adverse Reactions, and the Florida Law

Children with Autism are prone to autoimmunityAntibrain antibodies in children with autism and their unaffected siblings.Singer HS, Morris CM, Williams PN, Yoon DY, Hong JJ, Zimmerman AW.

 

Department of Neurology, Johns Hopkins University School of Medicine,

J Neuroimmunol. 2006 Sep;178(1-2):149-55.

Serum autoantibodies to human brain, identified by ELISA and Western

immunoblotting, were evaluated in 29 children with autism spectrum disorder (22 with autistic disorder), 9 non-autistic siblings and 13 controls . More autistic subjects than controls had bands at 100 kDa in caudate, putamen and prefrontal cortex (p<0.01) as well as larger peak heights of bands at 73 kDa in the cerebellum and cingulate gyrus. Both autistic disorder subjects and their matched non-autistic siblings had denser bands (peak height and/or area under the curve) at 73 kDa in the cerebellum and cingulate gyrus

than did controls (p<0.01). Results suggest that children with autistic disorder and their siblings exhibit differences compared to controls in autoimmune reactivity to specific epitopes located in distinct brain regions.

Page 33: 2009 08 15 Vaccines, Adverse Reactions, and the Florida Law

Thimerosal Induces Autistic Symptoms in Mice prone to Autoimmune diseases

Neurotoxic effects of postnatal thimerosal are mouse strain dependent.

Hornig M, Chian D, Lipkin WI.

Jerome L and Dawn Greene Infectious Disease Laboratory, Department of Epidemiology, Mailman School of Public Health, Columbia University

Mol Psychiatry. 2004 Sep;9(9):833-45

The developing brain is uniquely susceptible to the neurotoxic hazard posed by mercurials. Host differences in maturation, metabolism, nutrition, sex, and autoimmunity influence outcomes. How population-based variability affects the safety of the ethylmercury-containing vaccine preservative, thimerosal, is unknown. Reported increases in the prevalence of autism, a highly heritable neuropsychiatric condition, are intensifying public focus on environmental exposures such as thimerosal. Immune profiles and family history in autism are

frequently consistent with autoimmunity. We hypothesized that autoimmune propensity influences outcomes in mice following thimerosal challenges that mimic routine childhood immunizations. Autoimmune disease-sensitive SJL/J mice showed growth delay; reduced locomotion; exaggerated response to novelty; and densely packed, hyperchromic hippocampal neurons with altered glutamate receptors and transporters. Strains resistant to autoimmunity, C57BL/6J and BALB/cJ, were not susceptible. These findings implicate genetic influences and provide a model for investigating thimerosal-related neurotoxicity.

Page 34: 2009 08 15 Vaccines, Adverse Reactions, and the Florida Law

9x increase in Special Education Services in Children who received Hepatitis B Vaccine

Hepatitis B triple series vaccine and developmental disability in US children aged 1-9 years

Carolyn Gallagher ; Melody Goodman

Graduate Program in Public Health, Stony Brook University Medical Center, Health Sciences Center, New York, USA

Toxicological & Environmental Chemistry, Volume 90, Issue 5, Sept. 2008, pages 997 - 1008

This study investigated the association between vaccination with the Hepatitis B triple series vaccine prior to 2000 and developmental disability in children aged 1-9 years (n = 1824), proxied by parental report that their child receives early intervention or special education services (EIS). National Health and Nutrition Examination Survey 1999-2000 data were analyzed and adjusted for survey design by Taylor Linearization using SAS version 9.1 software, with SAS callable SUDAAN version 9.0.1. The odds of receiving EIS were approximately nine times as great for vaccinated boys (n = 46) as for unvaccinated boys (n

= 7), after adjustment for confounders. This study found statistically significant evidence to suggest that boys in United States who were vaccinated with the triple series Hepatitis B vaccine, during the time period in which vaccines were manufactured with thimerosal, were more susceptible to developmental disability than were unvaccinated boys.

Page 35: 2009 08 15 Vaccines, Adverse Reactions, and the Florida Law

Proposed 2010 Florida Legislation Call for a standardized, transparent informed consent system as follows:

A parent/patient should: Have the right to know the ingredients of the vaccine(s) to be administered. Have sufficient time to inform and educate themselves by weighing the risks

and benefits of vaccinating, not vaccinating or implementing an alternate vaccine schedule.

Render proper, written, legal consent PRIOR to the administration of any vaccine.

Have protection from action being taken against them if a child were to contract a disease that may have been prevented by a vaccine. (*Note: the practitioner should also be protected by law regardless of whether the family is choosing to follow the recommended or an alternative plan.  The provider should not be liable for a vaccine reaction or if the child were to contract a vaccine-preventable disease if the parent chose not to vaccinate.)

Page 36: 2009 08 15 Vaccines, Adverse Reactions, and the Florida Law

Requirement for Daycare/School EntryVaccines that are “required”: polio, DTaP, Hep B, MMR, Hib,

Chicken pox

Other vaccines are “recommended” by the CDC and Florida DOH, but not “required”

In order to enroll a child in school or daycare, the child must have commenced a schedule to complete vaccines, it is not required that the child is up to date. But a medical practitioner must sign off using a temporary medical exemption, updating the form as additional vaccines are given.

There is no set schedule that must be followed to “catch up” the child.

Page 37: 2009 08 15 Vaccines, Adverse Reactions, and the Florida Law

Religious ExemptionThere is clear wording in the Florida Statute as to

who can claim a religious exemption. As I am not a member of the clergy, it would be inappropriate for me to comment on who can qualify for this exemption. For a better understanding as to what the law says about the Religious Exemption, detailed information, including the actual wording of the statute and the Florida Supreme Court's 1998 ruling on the statute, can be found at www.know-vaccines.org.

Page 38: 2009 08 15 Vaccines, Adverse Reactions, and the Florida Law

My Personal Recommendations Regarding Vaccines

Unless there are certain circumstances (mom Hep B+, early day-care), consider waiting until at least 6 months old before giving any vaccine.

Do not give more then 1 new vaccine at a time so if there is a reaction, it will be easier to figure out what it was to.

Consider giving more than 1 vaccine at a time for 3rd and subsequent doses for a particular vaccine, if there were no negative reactions to the first 2 doses.

Wait at least 3 months in between live virus vaccines (M,M,R and Varicella). Consider delaying these until 2 years old unless high incidence in community.

Do not vaccinate when sick or until 2 weeks after illness resolved Do not vaccinate when there is signs of over-inflammation such as active wheeze,

eczema or allergy. Consider waiting until 2 years old, or not vaccinating at all, children who are high

risk, or with significant family history, of auto-immune or hyper-inflammatory conditions

Give vitamin C, zinc and Echinacea from 3 days before until 3 days after any vaccines, and vitamin A the day before, of and after (dosing according to “On the first signs of illness article” on the Medical Topics section at www.wholisticpeds.com

Get IgG titers before boosters in year prior to starting Kindergarten, only give vaccine if not immune at that time.

Page 39: 2009 08 15 Vaccines, Adverse Reactions, and the Florida Law

DAVID BERGER’S SUGGESTED ALTERNATIVE VACCINE SCHEDULE FOR THE STATE OF FLORIDA 

FAMILIES HAVE THE RIGHT TO FOLLOW THE STANDARD 2009 CDC IMMUNIZATION SCHEDULE.

MINIMAL TIME INTERVALS BETWEEN VACCINES SHOULD BE  ESTABLISHED BASED ON THE  2009 CDC CATCH-UP IMMUNIZATION SCHEDULE

http://www.cdc.gov/vaccines/recs/schedules/downloads/child/2009/09_catch-up_schedule_pr.pdf

 

STATE REQUIRED VACCINES:

         NAME                                                           Dose # Age to give

DTaP or no-Thimerosal Diphtheria-Tetanus 1 2-36 months

        (minimum of  1 month in between dose 1 and 2)

2 4-39 months

(minimum of 1 month in between dose 2 and 3)

  3 6-42 months

       (minimum of 6 months in between dose 3 and 4)                             

4 15-72 months

(minimum of 6 months in between dose 4 and 5)

*5 4-6 years

Tetanus-Diphtheria or Tdap (booster dose) 1  11-12 years

*per the CDC, the fifth dose is not necessary if the forth dose was administered at age 4 years or older, but at least 4 doses are needed before starting Kindergarten.

 

 

 

 

Page 40: 2009 08 15 Vaccines, Adverse Reactions, and the Florida Law

DAVID BERGER’S SUGGESTED ALTERNATIVE VACCINE SCHEDULE FOR THE STATE OF FLORIDA (cont)

 

 STATE REQUIRED VACCINES:

         NAME                                                           Dose # Age to give

Polio 1 2-36 months2 4-39 months

3 6-72 months**

  4* 8-10 years**

Must be a minimum of 4 weeks between each dose

*per the CDC, if the 3rd dose of Polio is given at 4 years or older, a 4th dose is not necessary, but at least 3 doses are needed before starting Kindergarten.

** consider getting IgG titer before giving this dose and exempting if titers indicate patient is protected

--------------------------------------------------------------------------------------------------------------------------

Varicella (Chicken Pox)

1 12-48 months

2 48-72 months**

Must be a minimum of 3 months between each dose

** consider getting IgG titer before giving this dose and exempting if titers indicate patient is protected

Page 41: 2009 08 15 Vaccines, Adverse Reactions, and the Florida Law

DAVID BERGER’S SUGGESTED ALTERNATIVE VACCINE SCHEDULE FOR THE STATE OF FLORIDA (cont) 

 STATE REQUIRED VACCINES:

         NAME                                                           Dose # Age to give

Measles/Mumps/Rubella*** 1* 12-48 months

2** 48-72 months

Mumps*** 1 12- 48 months

2 48-72 months

Rubella*** 1 12- 48 months

2 48-72 months

Measles*** 1 12 - 48 months

2 48-72 months

* if MMR Triple vaccine is the only vaccine available

** only if there are negative IgG titers for one or more components and MMR Triple Vaccine is only option available.

*** minimum of 1 months in between any 2 doses

check IgG titers for all children in the 12 months prior to starting Kindergarten form Measles, Mumps and Rubella. If not protected for one of the viruses and only MMR available, give MMR #2 at least 1 months after Triple or any of the single components given. If single virus available, give what is lacking, 1 month in between each vaccine

 

 

 

Page 42: 2009 08 15 Vaccines, Adverse Reactions, and the Florida Law

DAVID BERGER’S SUGGESTED ALTERNATIVE VACCINE SCHEDULE FOR THE STATE OF FLORIDA (cont)

  STATE RECOMMENDED VACCINES

NAME                                                   Dose # Age to give 

Hib*                   1                     15-18 months

(only 1 dose is recommended after 15 months old)

*Family can  also choose to follow the more standard recommendations of giving 3 doses prior to 15 months and 1 additional after 15 months as stated by the current CDC catch up schedule

---------------------------------------------------------------------------------------------------------------

Prevnar **                                               1                              (24-30 months)

(only 1 dose is recommended after 2 years old)

**Family can also choose to follow the more standard recommendations as stated in the  current CDC catch up schedule

---------------------------------------------------------------------------------------------------------------

Hep B ***                                           1                              11-13 years

                                                            2                              3 months after 1 st dose           

                                                            3                              3 months after 2nd dose       

***Family can also choose to follow the more standard recommendations as stated in the  current CDC catch up schedule

 

 

 

Page 43: 2009 08 15 Vaccines, Adverse Reactions, and the Florida Law

We Need More Research!

We Need More Research!

The Bottom Line:

----The Bottom Line----The Bottom Line----The Bottom Line----The Bottom Line---