Vaccines and Childhood Illnesses: Beyond Thimerosal

1. Vaccines and Childhood Illnesses: Beyond Thimerosal disclosure: no financial conflicts David Ayoub, MD Springfield, Illinois August 5th, 2009 raypoke@mac.com

2. Aluminum MSDS Ingestion: Chronic ingestion of aluminum may cause Aluminum Related Bone Disease or aluminum-induced Osteomalacia with fracturing Osteodystrophy, microcytic anemia, weakness, fatigue, visual and auditory hallucinations, memory loss, speech and language impairment (dysarthria, stuttering, stammering, anomia, hypofluency, aphasia and  eventually, mutism), epileptic seizures (focal or grand mal), motor disturbance (tremors, myoclonic jerks, ataxia, convulsions, asterixis, motor apraxia, muscle fatigue), and dementia (personality changes, altered mood, depression, diminished alertness, lethargy, 'clouding of the sensorium', intellectual deterioration, obtundation, coma), and altered EEG. http://www.sciencelab.com/xMSDS-Aluminum-9922844

3. “Now the presentations we heard yesterday clearly demonstrate that there are huge gaps in our information about what we know about the toxicology of aluminum. I would like to just reiterate what Neal Halsey said, the differences between adults and infants, there appears to be practically no[t] even animal data never mind human data.” May 11th - 12th, 2000

4. published 1928 Dr Charles T Betts What is aluminum? • 3rd most abundant element • food, water, air, soil, medicine • ~8% of earth’s crust • no biological role • a poison

5. “All salts of aluminum are poisonous when injected subcutaneously or intravenously” Dr. Victor Vaughn, Toxicologist, University of Michigan before US Federal Trade Commission Hearings on aluminum, 1927

6. Adjuvant “agents that act nonspecifically to increase the specific immune response to an antigen” Dictionary of Immunology

7. (How) do aluminium adjuvants work? Brewer JM. Immunol Lett. 2006 15;102(1):10-5. The aluminium compounds, originally identified as adjuvants over 70 years ago, remain unique in their widespread application to human vaccines. Given this history, it is surprising that the physicochemical interactions between aluminium compounds and antigens are relatively poorly understood. This has clearly been a contributing factor to vaccine failures, for example, through inappropriate selection of aluminium species or buffers. Similarly, the mechanism(s) of action of aluminium adjuvants are relatively unstudied, although it appears that these agents fail to fit within the current principles underlying activation of the immune response. This review aims to examine recent developments in our understanding of the physicochemical and biological aspects of research into aluminium adjuvants

8. Aluminum Salts Adjuvants aluminum hydroxide aluminum phosphate aluminum sulfate aluminum hydroxyphosphate sulfate

10. Number of administered vaccines containing aluminum increased after Thimerosal reduced (by 18 months age) aluminum-containing shots mercury-containing shots source: David Ayoub, MD, Prairie Collaborative, Inc

11. DTaP Infanrix 625 micrograms Hep B Engerix 250 micrograms HiB PedVax 225 micrograms Pediarix 850 micrograms Prevnar 125 micrograms DTaP Daptacel 330 micrograms DTaP Tripedia 170 micrograms HepB HiB Comvax 225 micrograms HepB Recombivax 500 micrograms Hep A Havrix 250 micrograms HepA-B Twinrix 450 micrograms Aluminum content of some vaccines

13. Aluminum Exposure Safety Limits

14. TITLE 21--FOOD AND DRUGS CHAPTER I--FOOD AND DRUG ADMINISTRATION DEPARTMENT OF HEALTH AND HUMAN SERVICES SUBCHAPTER F--BIOLOGICS PART 610 -- GENERAL BIOLOGICAL PRODUCTS STANDARDS Sec. 610.15 Constituent materials. (a) Ingredients, preservatives, diluents, adjuvants.An adjuvant shall not be introduced into a product unless there is satisfactory evidence that it does not affect adversely the safety or potency of the product. The amount of aluminum in the recommended individual dose of a biological product shall not exceed: (1) 0.85 milligrams if determined by assay; (2) 1.14 milligrams if determined by calculation on the basis of the amount of aluminum compound added; or (3) 1.25 milligrams determined by assay provided that data demonstrating that the amount of aluminum used is safe and necessary to produce the intended effect are submitted to and approved by the Director, Center for Biologics Evaluation and Research or the Director, Center for Drug Evaluation and Research (see mailing addresses in 600.2 of this chapter).

15. "The amount of 15 mg of alum or 0.85 mg aluminum per dose was selected empirically from data that demonstrated that this amount of aluminum enhanced the antigenicity and effectiveness of the vaccine (Joan May, FDA/CBER, personal communication)." from NW Baylor, W Egan and Paul Richman, FDA, CBER; VACCINE; 20 (2002), S18-23 FDA limits NOT based upon safety data!

16. Aluminum Exposure Defined 2 methods: acute toxicity: 1) maximum blood levels chronic toxicity: 2) weight adjusted total exposures 250 -1225 µg aluminum in shot blood volume 50 - 250 µg/kg

17. Aluminum blood levels

18. K/DOQI Clinical Practice Guidelines for Bone Metabolism and Disease in Children With Chronic Kidney Disease 12.2.b Baseline levels of serum aluminum should be <20 µg/L. (OPINION) 12.2.c If levels of serum aluminum are between 20-60 µg/L, a search for and elimination of all sources of aluminum should be performed. (OPINION) 12.3 A deferoxamine (DFO) test should be performed if there are elevated serum aluminum levels (60-200 µg/L) or clinical signs and symptoms of aluminum toxicity

19. potential aluminum blood levels post vaccine newborn: 250 μg/ 250ml blood = 1,000 μg/L 2 month infant*:1225 μg/ 340ml blood = 3,603 μg/L adult:1225 μg/ 5L blood = 245 μg/L *70cc/kg blood volume

20. weight adjusted exposure

21. “Research indicates that patients with impaired kidney function, including premature neonates, who receive parenteral levels of aluminum at greater than 4 to 5 mcg/kg/day accumulate aluminum at levels associated with central nervous system and bone toxicity. Tissue loading may occur at even lower rates of administration.” from: http://www.fda.gov/cder/foi/appletter/2004/19626scs019ltr.pdf

22. “....I5 and 30 mcg/kg/day of aluminum from TPN solutions. This amount resulted in tissue loading with aluminum but not in clearly associated disease. Thus, this rate of aluminum administration could be defined as unsafe. Finally,.....60 mcg/kg/d of aluminum (32). This rate could be considered toxic.” Gordon Klein, et al 1991

23. Finally,.....60 mcg/kg/d of aluminum (32). This rate could be considered toxic.” Gordon Klein, et al 1991

24. Calculating the dose of aluminum exposure 9-11 y/o: 23-55 kg (50-120 lbs) 225 µg/shot x 3 shots= 675 µg total 4-10 µg/kg per shot (12-30 µg/kg total) Calculating the potential peak blood level 9-11 y/o: 1.6-3.9 L blood volume* 58-140 µg/L potential blood aluminum *blood volume (70 cc/kg)

25. 27-64 µg/kg on day of vaccines > 800 µg/L blood level

26. MRL note: This is a smaller dose than children now receive vaccine formula breast milk MRL violation with just 2 vaccines!

27. retention excretion urine tissue blood/lymph transferrin ferritin brain bone spleen/liver myocardium endocrine syringe dissolved by alpha-hydroxycarboxylic acids citrate malate lactate interstitial fluid

30. Gardasil’s aluminum adjuvant may be solubilized faster and thus peak serum aluminum levels may appear higher and sooner than with other adjuvants Solubilization of aluminum-containing adjuvants by constituents of interstitial fluid. Seeber SJ, White JL, Hem SL. J Parenter Sci Technol. 1991 May-Jun;45(3):156-9. Department of Industrial and Physical Pharmacy, Purdue University, West Lafayette, Indiania. The solubilization of three commercially available aluminum-containing adjuvants by citrate anion was studied. Amorphous aluminum hydroxyphosphate and boehmite were both solubilized, however, amorphous aluminum hydroxyphosphate dissolved significantly faster than boehmite. The results suggest that citrate and other alpha-hydroxy carboxylate anions in the interstitial fluid are able to solubilize and thereby facilitate the excretion of aluminum from aluminum-containing adjuvants which are administered by intramuscular injection. The results also suggest that the release of antigen following administration may be significantly more rapid from an amorphous aluminum hydroxyphosphate-adjuvanted vaccine in comparison to a boehmite-adjuvanted vaccine.

31. blood levels of aluminum after Hep B vaccine in adults on dialysis: significant blood levels achieved with inter-individual variability toxic n=17 baseline

32. In viva absorption of aluminium-containing vaccine adjuvants using 26Al RE Flarend SL Hem, JL White. et al. Vaccine 1997:15(12-13);1314-18. so where is the rest of the aluminum? 78-95% retained in 1 month!

33. Evidence of aluminum loading in infants receiving intravenous therapy. Sedman AB, Klein GL, Merritt RJ, Miller NL, Weber KO, Gill WL, Anand H, Alfrey AC.N Engl J Med. 1985 May 23;312(21):1337-43. Premies average 78% of aluminum still retained in 5 infants exposed for at least 2 weeks (range 60-95%) less than vaccine exposure

35. aluminum hydroxide in young adult mice • 50 μg/kg per dose x 2 shots • 100 μg/kg fully vaccinated infants: 50-250 μg/kg Gardasil: 27-64μg/kg

36. Behavioral effects of aluminum • 50% reduction in strength/endurance (wire-mesh hanging) • 138% increase in anxiety(open-field testing) • increase memory errors (water maze; ns) • 20% hair loss at injection site

37. histopathology • spinal cord: • 255% increase in apoptosis in spinal cord neurons • 35% reduction in motor neurons in cord • 350% increase astrocytes • motor cortex neurons • 192% increase in apoptosis

38. Morin stain for aluminum

39. myelin mitochondria microsomes synapses

41. Are their similarities between aluminum toxicity and neurodevelopmental disorders? ..............................................47 cases • renal insufficiency • oral phosphate binders • contaminated dialysate • oral antacids • TPN • infant formula • normal renal function • aluminum containing vaccines and MMF • antacids/TPN/formula .............34 cases ................................................4 cases 85 cases

42. Progressive encephalopathy in children with chronic renal insufficiency in infancy. Rotundo A, Nevins TE, Lipton M, Lockman LA, Mauer SM, Michael AF. Kidney Int. 1982 Mar;21(3):486-91. n=20

43. ASD and Aluminum Toxicity • seizures • myoclonus • hypotonia • motor development • autonomic/cholinergic dysfunction • mitochondrial dysfunction • oxidative stress • ADD/ADHD • iron deficiency and anemia • calcium homeostasis • bone metabolism/microcephaly • melatonin, seratonin and sleep disorders • neuropathology • immune dysfunction • systemic infections/ bacterial binding/immunity

44. A Random Case Survey David Ayoub, MD Anju Usman, MD October 10, 2007 Fall DAN! Think Tank Aluminum in Autism Spectrum Disorders

46. Aluminum in Hair • Iron: 10.5% above upper limits • Manganese: 13.2% above upper limits mean 12.9 µg/g 76.3% upper limits normal n-38

47. Urinary Provocative ChallengeIV Ca-EDTA • n-34, profile with the highest metals recorded if multiple done

48. post IV Ca EDTA challenge measuring urinary metals

49. Aluminum in Urine random vs EDTA vs other agents* mean 410 mean 177.0 97% 0-31 0-21 18 13.9 10.0 n-4 n-10 n-4 n-10 n-34 * DMSA, DMPS, glutathione