In the previous post we discussed the relations between vaccines with Al as adjuvant and diseases. Such relations include those of simple co-appearance (vaccine and disease happen in the same individual but one does not necessarily cause the other), and causation, (i.e. the vaccine causes the disease). Such reactions to vaccines are considered quite rare and not impinging on the general safety of vaccines.
The problems with vaccine-derived Al include the facts that:
1. Al can persist in the body for a long time after vaccination (up to years for Macrophagic Myofasciitis - described further down),
2. Al can trigger immunologic diseases and
3. Al can make its way into the central nervous system (CNS) where it can drive further dangerous immuno-inflammatory and excitotoxic processes (! here could be found the link between Al-vaccine and autoimmune reaction, neurogedeneration and behavioral dysfunctions).
1. Al is engulfed into macrophages (immune system white blood cells) and can remain there for a long time and transported inside them throughout the organism.
2. Al can trigger immune responses, in predisposed people. For an adjuvant disease to develop, genetic susceptibilities or co-exposure to other environmental factors are needed. Therefore, adjuvant effect appears in subjects who are genetically susceptible OR in those who are subject to another trigger, such as in co-exposure to more than one adjuvant (or repetitive vaccines). These individuals show an adverse reaction to Al-vaccines and it seems that for these people aluminium acts as an antigen –an intruder to be fought against. Several receivers of vaccines (as many as 1% of all vaccinated people) retain a memory of exposure to aluminium from, for example, childhood vaccination, and show delayed hyper-sensitivity (a form of allergy) to subsequent exposures: i.e. these recipients are sensitized to aluminium. This hyper-sensitivity together with an aluminium overload through repetitive vaccination can lead to an adverse reaction: the immune system fights against the antigen Al contained in the vaccine as well as against all significant body stores of it, an autoimmune reaction.
3. Al has been found in CNS and it is now clear that it can cross the protective blood-brain barrier causing neurological damages. Alum is potentially highly neurotoxic, but it is used at such concentrations that are considered by the industry and regulatory agencies an acceptable compromise between acting as adjuvant and being toxic. The potential toxicity of alum depends by its capacity to remain localized at injection points or dispersing and accumulating in distant tissues. Al is present as aggregates of minuscule (nano-sized, 1/1,000,000 mm) particles in the vaccines and these minuscule particles were believed to remain at the shot site and outside o the cell membranes. However some cells of the immune system take up these alum particles and transport them to distant sites through the lymphatic system and into blood, spleen, and can even penetrate the brain, although at a very low rate in normal conditions. However, continuous doses of Al may become dangerously unsafe, especially in case of overimmunization or of an immature or altered blood brain barrier, like the one of babies or aging people.
While scientists and doctors have known about the property of aluminium of facilitating the immune response for at least 80 years, they still do not fully understand the mechanism of this functioning! The challenge would seem to try to balance the Al facilitating effect with the risk of it remaining in the organism and triggering an inflammatory reaction, the fighting response of the immune system. Some scientists believe that a subject’s sensitivity to Al should probably be detected before submitting him/her to a vaccine containing Al. Or else, less dangerous adjuvants could be experimented.
Similar to the case of Al, a causative relationship between an adjuvant (but not from a vaccine) and a particular group of symptoms has been reported for a completely different scenario. A significant link has been documented frequently in recent years between breast implants and a collection of conditions, some of which are autoimmune reactions: systemic sclerosis, systemic lupus erythematosus, rheumatoid arthritis and fibromyalgia, chronic fatigue, impaired cognition, depression, dry eyes, dry mouth, skin abnormalities, paresthesia, swollen and tender axillary glands, unexplained fever, hair loss, headache and morning stiffness. The term “the adjuvant disease” or siliconosis was given in the early 1990s to these silicone-induced autoimmune phenomena.
ASIA, a new syndrome1? The manifestations of post-vaccination reactions and siliconosis are now recognized by scientists to be similar to other recently described conditions called Gulf War Syndrome (GWS) and Macrophagic Myofasciitis syndrome (MMF).
GWS showed up in veterans of Gulf War presenting similar symptoms as discussed above: fatigue, muscle pain, cognitive problems, memory problems, neurological problems, rashes and diarrhea. During the Gulf War, the vaccination plan included the anthrax vaccine, administered in a six-shot regimen and adjuvated by aluminium hydroxide and squalene.
MMF presents with a lesion containing aluminium salts at the site of an intramuscular injection, and with systemic symptoms of muscle and joint pain which are the effects of an inflammatory reaction to alum from 3 months to 10 years after injection.
Thus 2 years ago, these four conditions, post- vaccinations autoimmune reactions, siliconosis, GWS and MMF, carrying common systemic symptoms were linked to the exposure to an adjuvant and defined by a group of researchers under the same umbrella of ASIA, Autoimmune or auto-inflammatory Syndrome Induced by Adjuvants.
The mechanisms by which ASIA symptoms are triggered are unknown, however the adjuvant (Al in the case of vaccines, GWS and MMF) is researched as the possible culprit.
Aluminum is the most widely distributed metal in our environment plus it is the most common adjuvant used in human and animal vaccine. A suggestion to this link is given by animal (mice, fish, sheep) studies and observations in which chronic exposure to aluminum is associated with behavioral, neuropathological and neurochemical changes.
Al is widely used in animal vaccines. In veterinary applications the safety of alum as an adjuvant is being questioned at present: a new syndrome was recently described affecting up to 50–70% of farmed sheep flocks and up to 100% of animals within a flock or salmons in a farm. The symptoms are severe neurobehavioural impacts like restlessness, compulsive wool biting, weakness, muscle tremors, loss of response to stimuli, tetraplegia, diseases of the liver and peritoneum, circulatory disease and kidney disease, stupor, coma and death. Scientists believe that these reactions depend on the persistence of Al in the central nervous system AND on the chronic hyperstimulation of the immune system which would facilitate the production of autoantibodies (antibodies against own healthy cells) leading to autoimmune disease. A similar explanation to the hypersensitivity reactions of certain humans.
1 A syndrome is defined as “a collection of signs and symptoms that often occur together in the same individuals. Its characteristics may be induced by a number of different primary causes that give rise to the same clinical manifestations”.
Agmon-Levin N, Paz Z, Israeli E, Shoenfeld Y. 2009 Vaccines and autoimmunity. Nat
Agmon-Levin, N, GRV Hughes and Y Shoenfeld 2012. The spectrum of ASIA: 'Autoimmune (Auto-inflammatory) Syndrome induced by Adjuvants Lupus 21: 118
Barthelow Classen J, Classen JB 2014 Review of Vaccine Induced Immune Overload and the Resulting Epidemics ofType 1 Diabetes and Metabolic Syndrome, Emphasis on Explaining the Recent Accelerations in the Risk of Prediabetes and other Immune Mediated Diseases, J Mol Genet Med S1:02
Belmonte, M., Greg Allen, Andrea Beckel-Mitchener, Lisa M. Boulanger, Ruth A. Carper, and Sara J. Webb 2004 (Autism and Abnormal Development of Brain Connectivity. The Journal of Neuroscience, 20 October 2004, 24(42): 9228-9231
Bernsen RM, Nagelkerke NJ, Thijs C, van der Wouden JC. 2008 Reported pertussis infection and risk of atopy in 8- to 12-yr-old vaccinated and non-vaccinated children. Pediatr Allergy Immunol. 19(1): 46-52.
Biasi D, Carletto A, Caramaschi P, Frigo A, Pacor ML, Bezzi D, Bambara LM. Rheumatological manifestations following hepatitis B vaccination. 1994. A report of 2 clinical cases (article in Italian). Recenti Prog Med 85:438-440.
Biasi D, De Sandre G, Bambara LM, Carletto A, Caramaschi P, Zanoni G, Tridente G. 1993 A new case of reactive arthritis after hepatitis B vaccination. Clin Exp Rheumatol 11:215.
Shaw, C.A., Y. Li, L. Tomljenovic 2013. Administration of aluminium to neonatal mice in vaccine-relevant amounts is associated with adverse long term neurological outcomes. Journal of Inorganic Biochemistry
Couette, M., Marie-Françoise Boisse, Patrick Maison, Pierre Brugieres, Pierre Cesaro, Xavier Chevalier, Romain K. Gherardi, Anne-Catherine Bachoud-Levi, François-Jérôme Authier 2009 Long-term persistence of vaccine-derived aluminum hydroxide is associated with chronic cognitive dysfunction, Journal of Inorganic Biochemistry 103, 1571–1578
Europan Hospital, 2012. Silicone gel breast implants and connective tissue and autoimmune disease risk , http://www.european-hospital.com/en/article/9384-Silicone_gel_breast_implants_and_connective_tissue_and_autoimmune_disease_risk.html
Exley C, Siesjo P, Erikssson H. 2010 The immunobiology of aluminium adjuvants: how do they really work? Trends Immunol. 31:103–9.
Finielz P, Lam-Kam-Sang LF. 1998 Systemic lupus erythematosus and thrombocytopenic purpura in two members of the same family. Nephrol Dial Transplant 13:2420-2421.
Fisher SG, Weber L, Carbone M. 1999 Cancer risk associated with simian virus 40 contaminated polio vaccine. Anticancer Res. 19(3B):2173-80.
Gherardi RK and FJ Authier 2012 Macrophagic myofasciitis: characterization and pathophysiology, Lupus 21: 184
Gross K. Combe C, Kruger K, Schattenkirschner M. 1995 Arthritis after hepatitis B vaccination. Report of three cases. Scand J Rheumatol 24:50-52.
Guiseriz J. 1996 Systemic lupus erythematosus following hepatitis B vaccine. Nephron, 74:441.
Haschulla E, Houvenagel E, Mingui A, Vincent G, Laine A. 1990. Reactive arthritis after hepatitis B vaccination. J Rheumatol 17:1250-1251.
Hertz-Picciotto, I., Hye-Youn Park, Miroslav Dostal, Anton Kocan, Tomas Trnovec and Radim Sram 2008 Prenatal Exposures to Persistent and Non-Persistent Organic Compounds and Effects on Immune System Development, Basic & Clinical Pharmacology & Toxicology, 102, 146–154
Hurwitz EL, Morgenstern H. 2000 Effects of diphtheria-tetanus-pertussis or tetanus vaccination on allergies and allergy-related respiratory symptoms among children and adolescents in the United States. J Manipulative Physiol Ther. 23(2):81-90.
Israeli E, Agmon-Levin N, Blank M, Shoenfeld Y. 2009 Adjuvants and autoimmunity.
Kawahara M (2005) Effects of aluminum on the nervous system and its possible link with neurodegenerative diseases. J Alzheimers Dis 8: 171-182.
Khan, Z. Christophe Combadière, François-Jérôme Authier, Valérie Itier, François Lux,
Christopher Exley, Meriem Mahrouf-Yorgov, Xavier Decrouy, Philippe Moretto, Olivier Tillement, Romain K Gherardi† and Josette Cadusseau 2013 Slow CCL2-dependent translocation of biopersistent particles from muscle to brain, BMC Medicine 11:99
Kawahara M, Kato-Negishi M (2011) Link between Aluminum and the Pathogenesis of Alzheimer’s Disease: The Integration of the Aluminum and Amyloid Cascade Hypotheses. Int J Alzheimers Dis 2011: 276393.
Kelly H. 2006. Evidence for a causal association between oral polio vaccine and transverse myelitis: A case history and review of the Literature. J Paediatr Child Health., 42(4):155-9.
Kool M, Soullié T, van Nimwegen M, Willart MA, Muskens F, Jung S, Hoogsteden HC, Hammad H, Lambrecht BN: Alum adjuvant boosts adaptive immunity by inducing uric acid and activating inflammatory dendritic cells. J Exp Med 2008, 205:869–882.
Luján, L., Marta Pérez, Eider Salazar, Neila Álvarez, Marina Gimeno, Pedro Pinczowski, Silvia Irusta, Jesús Santamaría, et al. 2013 Autoimmune/autoinflammatory syndrome induced by adjuvants (ASIA syndrome) in commercial Immunologic Research, 55,1-3, 2013
Masahiro Kawahara and Midori Kato-Negishi 2011 Link between Aluminum and the Pathogenesis of Alzheimer's Disease: The Integration of the Aluminum and Amyloid Cascade Hypotheses Int J Alzheimers Dis.
Melendez, L., Diana dos Santos, Luna Polido, Mariel Lopes Mendes, Silvia Sella, Luiz Querino Caldas and Emmanoel Silva-Filho, 2013, Aluminium and Other Metals May Pose a Risk to Children with Autism Spectrum Disorder: Biochemical and Behavioural Impairments Clin Exp Pharmacol, 3:1
Meroni, PL 2011. Autoimmune or auto-inflammatory syndrome induced by adjuvants (ASIA): Old truths and a new syndrome? Journal of Autoimmunity 36
Rev Rheumatol 5:648e52.
Orbach H1, Tanay A. 2009 Vaccines as a trigger for myopathies. Lupus. 18(13):1213-6.
Rodella LF, Ricci F, Borsani E, Stacchiotti A, Foglio E, et al. (2008) Aluminium exposure induces Alzheimer’s disease-like histopathological alterations in mouse brain. Histol Histopathol 23: 433-439.
Exley, C., Louise Swarbrick, Rhomain K. Gherardi, Francois-Jérôme Authier 2008 A role for the body burden of aluminium in vaccine-associated macrophagic myofasciitis and chronic fatigue syndrome. Medical Hypothesis
Rogerson SJ. Nye FJ. 1990 Hepatitis B vaccine associated with erythema nodosum and polyarthritis. BMJ 301:345.
RxList, the internet Drug Index, 2014, http://www.rxlist.com/flulaval-drug.htm
Shaw CA, Petrik MSJ 2009 Aluminum hydroxide injections lead to motor deficits and motor neuron degeneration. J Inorg Biochem, 103:1555–1562.
Shaw, CA, Tomljenovic, L. Aluminium in the central nervous system (CNS): toxicity in humans and animals, vaccine adjuvants, and autoimmunity. Immunol. Res.
Shoenfeld Y, Agmon-Levin N. 2011 'ASIA' - autoimmune/inflammatory syndrome induced by adjuvants. J Autoimmun. 36(1):4-8. doi: 10.1016/j.jaut.2010.07.003.
Shoenfeld, Y, Agmon Levine, N 2011 ASIA: A New Way to Put the Puzzle Together,The Rheumatologist
Tomljenovic, L., Shaw, C.A. 2011 Do aluminium vaccine adjuvants contribute to the rising prevalence of autism?. Jouranl of Inorganic Biocemistry, 105, 1489-1499
Tudela P, Marti S, Bonanl J. 1992 Systemic lupus erythematosus and vaccination against hepatitis B. Nephron 62:236.
Yokel RA, Allen DD, Meyer JJ (1994) Studies of aluminum neurobehavioral toxicity in the intact mammal. Cell Mol Neurobiol 14: 791-808.
Wikipedia 2014, Thiomersal, http://en.wikipedia.org/wiki/Thiomersal