Studies Showing the Toxicity of Aluminum in Vaccines

This video is a brief excerpt in which Christopher Shaw, a researcher, discusses his findings in regards to studying the effects of aluminum from adjuvants:

Answers to Common Misconceptions Regarding the Toxicity of Aluminum Adjuvants in Vaccines
This is a chapter in the book "Vaccines and Autoimmunity"
"This chapter presents answers to the most common misconceptions regarding the safety of aluminium (Al) compounds in vaccines by providing an overview of what is currently known about Al adjuvants, in particular, and their modes of action and mechanisms of potential toxicity. It gives a brief overview of the crucial role of Al in a variety of neurological disorders and then elaborates on the unresolved controversy about Al adjuvant safety. Al adjuvants exert their immunostimulatory effect through many different actions, which impinge on both the innate and adaptive immune systems. Some of the actions are activation of the NLRP3 inflammasome pathway, and protection of antigens, resulting in prolonged delivery. The risks associated with vaccine-derived Al are threefold: it can persist in the body, it can trigger pathological immunological responses, and it can make its way into the central nervous system (CNS)."

Aluminum Hydroxide Injections Lead to Motor Deficits and Motor Neuron Degeneration
J Inorg Biochem 2009 Nov;103(11):1555-62. Epub 2009 Aug 20"Gulf War Syndrome is a multi-system disorder afflicting many veterans of Western armies in the 1990-1991 Gulf War. A number of those afflicted may show neurological deficits including various cognitive dysfunctions and motor neuron disease, the latter expression virtually indistinguishable from classical amyotrophic lateral sclerosis (ALS) except for the age of onset...Possible causes of GWS include several of the adjuvants in the anthrax vaccine and others. The most likely culprit appears to be aluminum hydroxide...Aluminum-treated mice showed significantly increased apoptosis of motor neurons and increases in reactive astrocytes and microglial proliferation within the spinal cord and cortex...The demonstrated neurotoxicity of aluminum hydroxide and its relative ubiquity as an adjuvant suggest that greater scrutiny by the scientific community is warranted."

Reviewing the association between aluminum adjuvants in the vaccines and autism spectrum disorder
 “The manuscript reviews the association between aluminum adjuvants (AlAd) in vaccines and autism spectrum disorder (ASD). Aluminum (Al) is neurotoxic. Infants who have received AlAd in vaccines show a higher rate of ASD. The behavior of mice changes with Al injection. Patients suffering from ASD have higher concentrations of Al in their brains. Thus, AlAd is an etiologic factor in ASD. Immune efficacy led to the use of the AlAd in vaccines; however, the safety of those who are vaccinated with such vaccines has not been considered. The mechanisms of action of AlAd and the pharmacodynamics of injected AlAd used in vaccines are not well-characterized. The association between aluminum adjuvants in the vaccines and autism spectrum disorder is suggested by multiple lines of evidence.”

Aluminum in the central nervous system (CNS): toxicity in humans and animals, vaccine adjuvants, and autoimmunity.
Immunol Res. 2013 Jul;56(2-3):304-16
"We have examined the neurotoxicity of aluminum in humans and animals under various conditions, following different routes of administration, and provide an overview of the various associated disease states. The literature demonstrates clearly negative impacts of aluminum on the nervous system across the age span. In adults, aluminum exposure can lead to apparently age-related neurological deficits resembling Alzheimer's and has been linked to this disease and to the Guamanian variant, ALS-PDC. Similar outcomes have been found in animal models. In addition, injection of aluminum adjuvants in an attempt to model Gulf War syndrome and associated neurological deficits leads to an ALS phenotype in young male mice. In young children, a highly significant correlation exists between the number of pediatric aluminum-adjuvanted vaccines administered and the rate of autism spectrum disorders. Many of the features of aluminum-induced neurotoxicity may arise, in part, from autoimmune reactions, as part of the ASIA syndrome."

Behavioral abnormalities in young female mice following administration of aluminum adjuvants and the human papillomavirus (HPV) vaccine Gardasil.
Vaccine. 2016 Jan 8. pii: S0264-410X(16)00016-5
"Vaccine adjuvants and vaccines may induce autoimmune and inflammatory manifestations in susceptible individuals. To date most human vaccine trials utilize aluminum (Al) adjuvants as placebos despite much evidence showing that Al in vaccine-relevant exposures can be toxic to humans and animals. We sought to evaluate the effects of Al adjuvant and the HPV vaccine Gardasil versus the true placebo on behavioral and inflammatory parameters in young female mice... Al-injected mice showed a significantly decreased preference for the new arm in the Y maze test (p=0.03), indicating short-term memory impairment. Moreover, anti-HPV antibodies from the sera of Gardasil and Gardasil+Pt-injected mice showed cross-reactivity with the mouse brain protein extract. Immunohistochemistry analysis revealed microglial activation in the CA1 area of the hippocampus of Gardasil-injected mice compared to the control. It appears that Gardasil via its Al adjuvant and HPV antigens has the ability to trigger neuroinflammation and autoimmune reactions, further leading to behavioral changes."

Are there negative CNS impacts of aluminum adjuvants used in vaccines and immunotherapy?Immunotherapy. 2014;6(10):1055-71
"In spite of a common view that aluminum (Al) salts are inert and therefore harmless as vaccine adjuvants or in immunotherapy, the reality is quite different. In the following article we briefly review the literature on Al neurotoxicity and the use of Al salts as vaccine adjuvants and consider not only direct toxic actions on the nervous system, but also the potential impact for triggering autoimmunity. Autoimmune and inflammatory responses affecting the CNS appear to underlie some forms of neurological disease, including developmental disorders. Al has been demonstrated to impact the CNS at every level, including by changing gene expression. These outcomes should raise concerns about the increasing use of Al salts as vaccine adjuvants and for the application as more general immune stimulants."
 
On vaccine's adjuvants and autoimmunity: Current evidence and future perspectives.
Autoimmun Rev. 2015 Oct;14(10):880-8
"Adjuvants are compounds incorporated into vaccines to enhance immunogenicity and the development of these molecules has become an expanding field of research in the last decades. Adding an adjuvant to a vaccine antigen leads to several advantages, including dose sparing and the induction of a more rapid, broader and strong immune response. Several of these molecules have been approved, including aluminium salts, oil-in-water emulsions (MF59, AS03 and AF03), virosomes and AS04. Adjuvants have recently been implicated in the new syndrome named "ASIA-Autoimmune/inflammatory Syndrome Induced by Adjuvants", which describes an umbrella of clinical conditions including post-vaccination adverse reactions. Recent studies implicate a web of mechanisms in the development of vaccine adjuvant-induced autoimmune diseases, in particular, in those associated with aluminium-based compounds. Fewer and unsystematised data are instead available about other adjuvants, despite recent evidence indicating that vaccines with different adjuvants may also cause specific autoimmune adverse reactions possible towards different pathogenic mechanisms. This topic is of importance as the specific mechanism of action of each single adjuvant may have different effects on the course of different diseases. Herein, we review the current evidence about the mechanism of action of currently employed adjuvants and discuss the mechanisms by which such components may trigger autoimmunity."

Aluminum-induced entropy in biological systems: implications for neurological disease.
J Toxicol. 2014;2014:491316
"Humans are increasingly exposed to Al from food, water, medicinals, vaccines, and cosmetics, as well as from industrial occupational exposure. Al disrupts biological self-ordering, energy transduction, and signaling systems, thus increasing biosemiotic entropy. Beginning with the biophysics of water, disruption progresses through the macromolecules that are crucial to living processes (DNAs, RNAs, proteoglycans, and proteins). It injures cells, circuits, and subsystems and can cause catastrophic failures ending in death. Al forms toxic complexes with other elements, such as fluorine, and interacts negatively with mercury, lead, and glyphosate. Al negatively impacts the central nervous system in all species that have been studied, including humans. Because of the global impacts of Al on water dynamics and biosemiotic systems, CNS disorders in humans are sensitive indicators of the Al toxicants to which we are being exposed."

Aluminum Vaccine Adjuvants- Are They Safe?
Current Medicinal Chemistry, vol.18: 17 pp 2630-2637
"Experimental research, however, clearly shows that aluminum adjuvants have a potential to induce serious immunological disorders in humans. In particular, aluminum in adjuvant form carries a risk for autoimmunity, long-term brain inflammation and associated neurological complications and may thus have profound and widespread adverse health consequences. In our opinion, the possibility that vaccine benefits may have been overrated and the risk of potential adverse effects underestimated, has not been rigorously evaluated in the medical and scientific community."

Hypersensitivity Reactions to Vaccine Components
Dermatitis. 2005;16(3):115-120. 

"FDA regulations limit the aluminum content of an individual dose of a vaccine to 0.85 mg of elemental aluminum.[7] The diminutive level of aluminum needed in vaccines to induce serious toxicities is evidenced by the undetectable changes in the normal plasma concentration of aluminum (5 µg/L) after intramuscular administration of an aluminum-containing vaccine. Aluminum allergy has been reported to be associated with an axillary rash[3] and with hand dermatitis.  The more typical route of sensitization, however, is via the absorption of aluminum through hyposensitization injections and vaccines."

Do aluminum vaccine adjuvants contribute to the rising prevalence of autism?
J Inorg Biochem. 2011 Nov;105(11):1489-99

"Aluminum (Al), the most commonly used vaccine adjuvant, is a demonstrated neurotoxin and a strong immune stimulator. Hence, adjuvant Al has the potential to induce neuroimmune disorders. When assessing adjuvant toxicity in children, two key points ought to be considered: (i) children should not be viewed as "small adults" as their unique physiology makes them much more vulnerable to toxic insults; and (ii) if exposure to Al from only few vaccines can lead to cognitive impairment and autoimmunity in adults, is it unreasonable to question whether the current pediatric schedules, often containing 18 Al adjuvanted vaccines, are safe for children? By applying Hill's criteria for establishing causality between exposure and outcome we investigated whether exposure to Al from vaccines could be contributing to the rise in ASD prevalence in the Western world. Our results show that: (i) children from countries with the highest ASD prevalence appear to have the highest exposure to Al from vaccines; (ii) the increase in exposure to Al adjuvants significantly correlates with the increase in ASD prevalence in the United States observed over the last two decades; and (iii) a significant correlation exists between the amounts of Al administered to preschool children and the current prevalence of ASD in seven Western countries, particularly at 3-4 months of age. The application of the Hill's criteria to these data indicates that the correlation between Al in vaccines and ASD may be causal. Because children represent a fraction of the population most at risk for complications following exposure to Al, a more rigorous evaluation of Al adjuvant safety seems warranted."

Empirical Data Confirm Autism Symptoms Related to Aluminum and Acetaminophen Exposure
Entropy 2012, 14(11), 2227-2253

"Our results provide strong evidence supporting a link between autism and the aluminum in vaccines. A literature review showing toxicity of aluminum in human physiology offers further support... Using standard log-likelihood ratio techniques, we identify several signs and symptoms that are significantly more prevalent in vaccine reports after 2000, including cellulitis, seizure, depression, fatigue, pain and death, which are also significantly associated with aluminum-containing vaccines. We propose that children with the autism diagnosis are especially vulnerable to toxic metals such as aluminum and mercury due to insufficient serum sulfate and glutathione. A strong correlation between autism and the MMR (Measles, Mumps, Rubella) vaccine is also observed, which may be partially explained via an increased sensitivity to acetaminophen administered to control fever."

A comparison of temporal trends in United States Autism Prevalence to trends in suspected environmental factors
Environ Health. 2014 Sep 5;13(1):73
"Among the suspected toxins surveyed, polybrominated diphenyl ethers, aluminum adjuvants, and the herbicide glyphosate have increasing trends that correlate positively to the rise in autism... Diagnosed autism prevalence has risen dramatically in the U.S over the last several decades and continued to trend upward as of birth year 2005. The increase is mainly real and has occurred mostly since the late 1980s. In contrast, children's exposure to most of the top ten toxic compounds has remained flat or decreased over this same time frame. Environmental factors with increasing temporal trends can help suggest hypotheses for drivers of autism that merit further investigation."
(aluminum adjuvants are components of many vaccines)

Pruritic nodules and aluminium allergy arise after vaccinations or treatments for allergies
Medical News December 14, 2010
"(T)here are now reports of pruritic nodules and aluminium allergy arising after vaccinations or treatments for allergies... A study of whooping cough vaccinations in Gothenburg a few years ago showed that almost one per cent of the children developed pruritic nodules in the area of the vaccination. Three out of four of the children who had a reaction with nodules also developed an allergy to aluminium... There are a number of possible explanations as to why aluminium allergy has become more common. There is new technology for identifying the allergy, the type of aluminium compounds used in vaccines and other treatments may have changed, and the number of vaccinations has increased with the increase in international travel."

Aluminum adjuvant linked to gulf war illness induces motor neuron death in mice
Neuromolecular Med. 2007;9(1):83-100
"Associated with some cases of GWI are increased incidences of amyotrophic lateral sclerosis and other neurological disorders. Whereas many environmental factors have been linked to GWI, the role of the anthrax vaccine has come under increasing scrutiny... Aluminum-treated groups also showed significant motor neuron loss (35%) and increased numbers of astrocytes (350%) in the lumbar spinal cord. The findings suggest a possible role for the aluminum adjuvant in some neurological features associated with GWI and possibly an additional role for the combination of adjuvants."

Mechanisms of Aluminum Adjuvant Toxicity And Autoimmunity in Pediatric Populations
Lupus February 2012 vol. 21 no. 2 223-230
"Immune challenges during early development, including those vaccine-induced, can lead to permanent detrimental alterations of the brain and immune function. Experimental evidence also shows that simultaneous administration of as little as two to three immune adjuvants can overcome genetic resistance to autoimmunity. In some developed countries, by the time children are 4 to 6 years old, they will have received a total of 126 antigenic compounds along with high amounts of aluminum (Al) adjuvants through routine vaccinations. According to the US Food and Drug Administration, safety assessments for vaccines have often not included appropriate toxicity studies because vaccines have not been viewed as inherently toxic. Taken together, these observations raise plausible concerns about the overall safety of current childhood vaccination programs. When assessing adjuvant toxicity in children, several key points ought to be considered: (i) infants and children should not be viewed as “small adults” with regard to toxicological risk as their unique physiology makes them much more vulnerable to toxic insults; (ii) in adult humans Al vaccine adjuvants have been linked to a variety of serious autoimmune and inflammatory conditions (i.e., “ASIA”), yet children are regularly exposed to much higher amounts of Al from vaccines than adults; (iii) it is often assumed that peripheral immune responses do not affect brain function. However, it is now clearly established that there is a bidirectional neuro-immune cross-talk that plays crucial roles in immunoregulation as well as brain function. In turn, perturbations of the neuro-immune axis have been demonstrated in many autoimmune diseases encompassed in “ASIA” and are thought to be driven by a hyperactive immune response; and (iv) the same components of the neuro-immune axis that play key roles in brain development and immune function are heavily targeted by Al adjuvants. In summary, research evidence shows that increasing concerns about current vaccination practices may indeed be warranted. Because children may be most at risk of vaccine-induced complications, a rigorous evaluation of the vaccine-related adverse health impacts in the pediatric population is urgently needed."

Hepatitis B vaccine induces apoptotic death in Hepa1-6 cells.
Apoptosis. 2012 May;17(5):516-27
"Vaccines can have adverse side-effects, and these are predominantly associated with the inclusion of chemical additives such as aluminum hydroxide adjuvant. The objective of this study was to establish an in vitro model system amenable to mechanistic investigations of cytotoxicity induced by hepatitis B vaccine, and to investigate the mechanisms of vaccine-induced cell death. The mouse liver hepatoma cell line Hepa1-6 was treated with two doses of adjuvanted (aluminium hydroxide) hepatitis B vaccine... Hepatitis B vaccine exposure increased cell apoptosis as detected by flow cytometry and TUNEL assay. Vaccine exposure was accompanied by significant increases in the levels of activated caspase 3, a key effector caspase in the apoptosis cascade. We conclude that exposure of Hepa1-6 cells to a low dose of adjuvanted hepatitis B vaccine leads to loss of mitochondrial integrity, apoptosis induction, and cell death, apoptosis effect was observed also in C2C12 mouse myoblast cell line after treated with low dose of vaccine (0.3, 0.1, 0.05 μg/ml). In addition In vivo apoptotic effect of hepatitis B vaccine was observed in mouse liver."

Inhibition by aluminum hydroxide of the voltage-dependent closure of the mitochondrial channel, VDAC  Biochim Biophys Acta. 1989 Apr 25;991(1):68-78.

"Micromolar quantities of aluminum have been found (Dill et al. (1987) J. Membrane Biol. 99, 187-196) to reduce the voltage dependence of the mitochondrial outer membrane channel, VDAC, from Neurospora crassa. In the present study, various metallic and organic ions were tested for possible aluminum-like effect, and only the trivalent metals exhibited a similar ability to reduce the channels voltage dependence... While providing new insight into the nature of VDAC's sensor, these results also indicate that aluminum-cell interaction may result from the presence of AI(OH)3 in solution in addition to the widely accepted AI3+-mediated interactions. While the [AI3+] is vanishingly low at neutral pH, the trihydroxide is the major form and should be considered as an important candidate for aluminum-induced cellular effects."

Aluminium overload after 5 years in skin biopsy following post-vaccination with subcutaneous pseudolymphoma
J Trace Elem Med Biol. 2012 Oct;26(4):291-3
"Aluminium hydroxide is used as an effective adjuvant in a wide range of vaccines for enhancing immune response to the antigen. The pathogenic role of aluminium hydroxide is now recognized by the presence of chronic fatigue syndrome, macrophagic myofasciitis and subcutaneous pseudolymphoma, linked to intramuscular injection of aluminium hydroxide-containing vaccines. The aim of this study is to verify if the subcutaneous pseudolymphoma observed in this patient in the site of vaccine injection is linked to an aluminium overload. Many years after vaccination, a subcutaneous nodule was discovered in a 45-year-old woman with subcutaneous pseudolymphoma. In skin biopsy at the injection site for vaccines, aluminium (Al) deposits are assessed by Morin stain and quantification of Al is performed by Zeeman Electrothermal Atomic Absorption Spectrophotometry. Morin stain shows Al deposits in the macrophages, and Al assays (in μg/g, dry weight) were 768.10±18 for the patient compared with the two control patients, 5.61±0.59 and 9.13±0.057. Given the pathology of this patient and the high Al concentration in skin biopsy, the authors wish to draw attention when using the Al salts known to be particularly effective as adjuvants in single or repeated vaccinations. The possible release of Al may induce other pathologies ascribed to the well-known toxicity of this metal."

Highly delayed systemic translocation of aluminum-based adjuvant in CD1 mice following intramuscular injections.
J Inorg Biochem. 2015 Jul 22. 
"Concerns regarding vaccine safety have emerged following reports of potential adverse events in both humans and animals. In the present study, alum, alum-containing vaccine and alum adjuvant tagged with fluorescent nanodiamonds were used to evaluate i) the persistence time at the injection site, ii) the translocation of alum from the injection site to lymphoid organs, and iii) the behavior of adult CD1 mice following intramuscular injection of alum (400μgAl/kg). Results showed for the first time a strikingly delayed systemic translocation of adjuvant particles. Alum-induced granuloma remained for a very long time in the injected muscle despite progressive shrinkage from day 45 to day 270...This study confirms the striking biopersistence of alum. It points out an unexpectedly delayed diffusion of the adjuvant in lymph nodes and spleen of CD1 mice, and suggests the importance of mouse strain, route of administration, and doses, for future studies focusing on the potential toxic effects of aluminum-based adjuvants."

Critical analysis of reference studies on the toxicokinetics of aluminum-based adjuvants
"We reviewed the three toxicokinetic reference studies commonly used to suggest that aluminum (Al)-based adjuvants are innocuous. A single experimental study was carried out using isotopic 26Al (Flarend et al., Vaccine, 1997). This study used aluminum salts resembling those used in vaccines but ignored adjuvant uptake by cells that was not fully documented at the time. It was conducted over a short period of time (28days) and used only two rabbits per adjuvant. At the endpoint, Al elimination in the urine accounted for 6% for Al hydroxide and 22% for Al phosphate, both results being incompatible with rapid elimination of vaccine-derived Al in urine. Two theoretical studies have evaluated the potential risk of vaccine Al in infants, by reference to an oral "minimal risk level" (MRL) extrapolated from animal studies. Keith et al. (Vaccine, 2002) used a high MRL (2mg/kg/d), an erroneous model of 100% immediate absorption of vaccine Al, and did not consider renal and blood-brain barrier immaturity. Mitkus et al. (Vaccine, 2011) only considered solubilized Al, with erroneous calculations of absorption duration. Systemic Al particle diffusion and neuro-inflammatory potential were omitted. The MRL they used was both inappropriate (oral Al vs. injected adjuvant) and still too high (1mg/kg/d) regarding recent animal studies. Both paucity and serious weaknesses of reference studies strongly suggest that novel experimental studies of Al adjuvants toxicokinetics should be performed on the long-term, including both neonatal and adult exposures, to ensure their safety and restore population confidence in Al-containing vaccines. "

Inflammation and Autophagy: A Convergent Point between Autism Spectrum Disorder (ASD)-Related Genetic and Environmental Factors: Focus on Aluminum Adjuvants
"Among various environmental factors causing risk for ASD, aluminum (Al)-containing vaccines injected during critical periods have received special attention and triggered relevant scientific questions. The aim of this review is to discuss the current knowledge on the role of early inflammation, immune and autophagy dysfunction in ASD as well as preclinical studies which question Al adjuvant impacts on brain and immune maturation. We highlight the most recent breakthroughs and the lack of epidemiological, pharmacokinetic and pharmacodynamic data constituting a "scientific gap". We propose additional research, such as genetic studies that could contribute to identify populations at genetic risk, improving diagnosis, and potentially the development of new therapeutic tools. "

[Aluminum as an adjuvant in vaccines and post-vaccine reactions]
"Vaccines adsorbed onto aluminium salts are a more frequent cause of local post-vaccinal reactions than plain vaccines. 5-10% those vaccinated can develop a nodule lasting several weeks at the injection site. In some rare cases the nodules may become inflammatory and even turn into an aseptic abscess. The nodules persisting more than 6 weeks may indicate development of aluminium hypersensitivity. Finally aluminium adjuvant immunogens induce the production of IgE antibodies. "

Sixty-four children with persistent itching nodules and contact allergy to aluminium after vaccination with aluminium-adsorbed vaccines-prognosis and outcome after booster vaccination
"Sixty-four children with itching nodules following vaccination with diphtheria-tetanus-pertussis (DTP) vaccines currently used in Sweden (Infanrix® and Pentavac®) were spontaneously reported to the authors from 1999 and followed for up to 12 years. The median duration of itching was 5 years in the 44 children who were free or almost free from symptoms at the latest follow-up. Typical findings were a long interval between vaccination and onset of symptoms (months or years) and intensified itching during intercurrent infections. Contact allergy to aluminium was demonstrated in 60/63 children (95 %). Neither the incidence nor differences between the two vaccines can be estimated from this study, but vaccine-induced itching nodules are probably more common than hitherto realised. The median interval between onset of symptoms and diagnosis was 8 months in a region where nurses were educated to recognise the condition compared to 2 years in other regions. Booster vaccination with DTP-polio was postponed or declined by 15/40 families in fear for new problems. Out of 25 children who received a booster dose, only two had new itching nodules. "

[Aluminium allergy and granulomas induced by vaccinations for children]
"Vaccination with aluminium-adsorbed vaccines can induce aluminium allergy with persistent itching subcutaneous nodules at the injection site - vaccination granulomas. In this article we give an overview of childhood aluminium-adsorbed vaccines available in Denmark. Through literature studies we examine the incidence, the symptoms and the prognosis for the vaccination granulomas and the allergy. Finally we discuss the status in Denmark. "

Macrophagic Myofasciitis
Macrophagic Myofasciitis Associated with Vaccine-Derived Aluminum
Med J Aust 2005; 183(3): 145-146
"Macrophagic myofasciitis is characterised by sheets of macrophages in striated muscle, a few lymphocytes and inconspicuous muscle fibre damage. It is due to aluminium contained in vaccines, and is localised to the inoculation site. We report the first Australian case, detected incidentally when investigating a raised serum creatine kinase level."

Macrophagic Myofasciitis Lesions Assess Long-Term Persistence of Vaccine-Derived Aluminum Hydroxide in Muscle
Brain 2001 Sep;124(Pt 9):1821-31
"We conclude that the MMF lesion is secondary to intramuscular injection of aluminium hydroxide-containing vaccines, shows both long-term persistence of aluminium hydroxide and an ongoing local immune reaction, and is detected in patients with systemic symptoms which appeared subsequently to vaccination."

Gulf war illness, post-HPV vaccination syndrome, and Macrophagic Myofasciitis. Similar disabling conditions possibly linked to vaccine-induced autoimmune dysautonomia
"post-HPV vaccination syndrome, Macrophagic Myofasciitis, and gulf war illness analogy suggests that some vaccines or multiple vaccinations in a very short period of time may induce, in susceptible individuals, chronic pain, fatigue and dyscognition. Vaccine-induced autoimmune dysautonomia is hypothesized as the common pathogenetic mechanism for this symptom cluster. Further research on the presence of small fiber neuropathy, adrenergic receptor antibodies, and abnormal autonomic function tests in the three syndromes under discussion may help to elucidate this hypothesis."

[Lessons from macrophagic myofasciitis: towards definition of a vaccine adjuvant-related syndrome]
"Macrophagic myofasciitis is characterized by a stereotyped and immunologically active lesion at deltoid muscle biopsy. Electron microscopy, microanalytical studies, experimental procedures, and an epidemiological study recently demonstrated that the lesion is due to persistence for years at site of injection of an aluminum adjuvant used in vaccines against hepatitis B virus, hepatitis A virus, and tetanus toxoid. Aluminum hydroxide is known to potently stimulate the immune system and to shift immune responses towards a Th-2 profile...  the WHO recommended an epidemiological survey, currently conducted by the French agency AFSSAPS, aimed at substantiating the possible link between the focal macrophagic myofasciitis lesion (or previous immunization with aluminium-containing vaccines) and systemic symptoms...  Multiple vaccinations performed over a short period of time in the Persian gulf area have been recognized as the main risk factor for Gulf War syndrome. Moreover, the war vaccine against anthrax, which is administered in a 6-shot regimen and seems to be crucially involved, is adjuvanted by aluminium hydroxide and, possibly, squalene, another Th-2 adjuvant. If safety concerns about long-term effects of aluminium hydroxide are confirmed it will become mandatory to propose novel and alternative vaccine adjuvants to rescue vaccine-based strategies and the enormous benefit for public health they provide worldwide. "

Long-Term Follow-up of Cognitive Dysfunction in Patients with Aluminum Hydroxide-Induced Macrophagic Myofasciitis (MMF)
J. Inorg Biochem. 2011 Nov;105(11);1457-63
"Affected patients are middle-aged adults, mainly presenting with diffuse arthromyalgias, chronic fatigue, and cognitive dysfunction. Representative features of MMF-associated cognitive dysfunction (MACD) include (i) dysexecutive syndrome; (i) visual memory; (iii) left ear extinction at dichotic listening test. In present study we retrospectively evaluated the progression of MACD in 30 MMF patients. Most patients fulfilled criteria for non-amnestic/dysexecutive mild cognitive impairment, even if some cognitive deficits seemed unusually severe. MACD remained stable over time, although dysexecutive syndrome tended to worsen. Long-term follow-up of a subset of patients with 3 or 4 consecutive neuropsychological evaluations confirmed the stability of MACD with time, despite marked fluctuations."

Central Nervous System Disease in Patients with Macrophagic Myofasciitis
Brain 2001 May;124(pt 5):974-83
"Macrophagic myofasciitis (MMF), a condition newly recognized in France, is manifested by diffuse myalgias and characterized by highly specific myopathological alterations which have recently been shown to represent an unusually persistent local reaction to intramuscular injections of aluminium-containing vaccines. Among 92 MMF patients recognized so far, eight of them, which included the seven patients reported here, had a symptomatic demyelinating CNS disorder... (T)he association between MMF and multiple sclerosis-like disorders may give new insights into the controversial issues surrounding vaccinations and demyelinating CNS disorders. Deltoid muscle biopsy searching for myopathological alterations of MMF should be performed in multiple sclerosis patients with diffuse myalgias."

Macrophagic Myofasciitis: characterization and pathophysiology
Lupus 2012 Feb;21(2):184-9
"Although generally well tolerated, alum may occasionally cause disabling health problems in presumably susceptible individuals. A small proportion of vaccinated people present with delayed onset of diffuse myalgia, chronic fatigue and cognitive dysfunction, and exhibit very long-term persistence of alum-loaded macrophages at the site of previous intramuscular (i.m.) immunization, forming a granulomatous lesion called macrophagic myofasciitis (MMF). Clinical symptoms associated with MMF are paradigmatic of the recently delineated 'autoimmune/inflammatory syndrome induced by adjuvants' (ASIA). The stereotyped cognitive dysfunction is reminiscent of cognitive deficits described in foundry workers exposed to inhaled Al particles. Alum safety concerns will largely depend on whether the compound remains localized at the site of injection or diffuses and accumulates in distant organs. Animal experiments indicate that biopersistent nanomaterials taken up by monocyte-lineage cells in tissues, such as fluorescent alum surrogates, can first translocate to draining lymph nodes, and thereafter circulate in blood within phagocytes and reach the spleen, and, eventually, slowly accumulate in the brain."

 

Myalgia and chronic fatigue syndrome following immunization: macrophagic myofasciitis and animal studies support linkage to aluminum adjuvant persistency and diffusion in the immune system
"We present epidemiological, clinical and experimental evidence that ME/CFS constitutes a major type of adverse effect of vaccines, especially those containing poorly degradable particulate aluminum adjuvants....  Deltoid muscle biopsy performed to investigate myalgia typically yields macrophagic myofasciitis (MMF), a histological biomarker assessing longstanding persistency of aluminum agglomerates within innate immune cells at site of previous immunization...   Instead of being rapidly solubilized in the extracellular space, injected aluminum particles are quickly captured by immune cells and transported to distant organs and the brain where they elicit an inflammatory response and exert selective low dose long-term neurotoxicity. Clinical observations and experiments in sheep, a large animal like humans, confirmed both systemic diffusion and neurotoxic effects of aluminum adjuvants. Post-immunization ME/CFS represents the core manifestation of "autoimmune/inflammatory syndrome induced by adjuvants" (ASIA)."