This blog is a way of sharing the information and resources that have helped me to recover my son Roo from an Autism Spectrum Disorder. What I have learned is to view our symptoms as the results of underlying biological cause, which can be identified and healed. I say "our symptoms" because I also have a neuro-immune disorder called Myalgic Encephalomyelitis.

And, of course, I am not a doctor (although I have been known to impersonate one while doing imaginative play with my son)- this is just our story and information that has been helpful or interesting to us. I hope it is helpful and interesting to you!


Monday, March 17, 2014

Studies Supporting a Link Between Vaccinations and Diseases and Disorders Other Than ASD

Certain vaccines increase susceptibility to other contagious diseases:

Live Attenuated Influenza Vaccine Enhances Colonization of Streptococcus pneumoniae and Staphylococcus aureus in Mice
18 February 2014 mBio vol. 5no. 1 e01040-13
"Community interactions at mucosal surfaces between viruses, like influenza virus, and respiratory bacterial pathogens are important contributors toward pathogenesis of bacterial disease. What has not been considered is the natural extension of these interactions to live attenuated immunizations, and in particular, live attenuated influenza vaccines (LAIVs). Using a mouse-adapted LAIV against influenza A (H3N2) virus carrying the same mutations as the human FluMist vaccine, we find that LAIV vaccination reverses normal bacterial clearance from the nasopharynx and significantly increases bacterial carriage densities of the clinically important bacterial pathogens Streptococcus pneumoniae (serotypes 19F and 7F) and Staphylococcus aureus (strains Newman and Wright) within the upper respiratory tract of mice. Vaccination with LAIV also resulted in 2- to 5-fold increases in mean durations of bacterial carriage."

Dosing schedule of pneumococcal vaccine linked with increased risk of getting multiresistant strain
JAMA, 2010; (304)10:1099
"Infants who received heptavalent pneumococcal conjugate vaccination at 2, 4, and 11 months were more likely than unvaccinated controls to have nasopharyngeal (in the nasal passages and upper part of the throat behind the nose) acquisition of pneumococcal serotype 19A, a leading cause of respiratory pneumococcal disease, according to a new study."

ANTIPHOSPHOLIPID SYNDROME (Hughes Syndrome)

When APS (Hughes syndrome) met the autoimmune/inflammatory syndrome induced by adjuvants (ASIA)
Lupus  June  2012 vol.21 no. 7 711-714
(I highly recommend reading this article in it's entirety.  It's not long and it discusses many of the mechanisms involved how vaccination affects the immune system)
"Autoimmune diseases have been reported to associate or to follow a diverse list of vaccinations.  This is not surprising since autoimmune diseases are known to be caused by infections. –  On the one hand, one can assume that vaccine may lead to autoimmunity via the infection agent ingredient being recombinant, weakened, or synthetic. Such mechanisms as molecular mimicry and polyclonal activation may be involved. Yet, recently a new syndrome was defined: ASIA (autoimmune syndrome induced by adjuvants), eluding to the important role of the adjuvant ingredients in the vaccine. This syndrome encompasses all the auto-reactive conditions associated with vaccines, but also those emerging following silicone implants which ruptured and invaded neighboring tissues. In addition, the syndrome may include clinical conditions such as the Gulf syndrome chronic fatigue syndrome and the sick building syndrome. The common denominator to all of the above clinical circumstances is the existence of an adjuvant which chronically stimulates the immune system."

"Several case reports showed the possibility of triggering antiphospholipid syndrome following tetanus vaccination"

"Tarjan et al found that repeated influenza vaccination in clinically stable SLE patients with low disease activity may result in increased production of anti-β2GPI antibodies, and therefore may increase the risk of thrombotic manifestations."

"Although there are rare cases of elevated levels of circulating anti-β2GPI Abs upon post-vaccination, one has to keep in mind that the memory cells are waiting for a second hit. This may come in time, by molecular mimicry or non-specifically by bystander activation or by adjuvant triggering, the common denominator of most vaccines during lifetime, and induce the development of the clinical picture of APS in genetically susceptible individuals. Therefore, these all strengthen the importance of ASIA and should be kept in mind during clinical work and research."


APNEA

Risk Factors for Developing Apnea After Immunization in the Neonatal Intensive Care Unit
PEDIATRICS Vol. 121 No. 3 March 1, 2008 pp. 463 -469 
"For infants in the NICU without apnea during the 24 hours immediately before immunization, younger age, smaller size, and more severe illness at birth are important predictors of post immunization apnea."

ASTHMA AND ALLERGY

Effects of diphtheria-tetanus-pertussis or tetanus vaccination on allergies and allergy-related respiratory symptoms among children and adolescents in the United States.
Hurwitz EL, et al. J Manipulative Physiol Ther. 2000.
"The odds of having a history of asthma was twice as great among vaccinated subjects than among unvaccinated subjects (adjusted odds ratio, 2.00; 95% confidence interval, 0.59 to 6.74). The odds of having had any allergy-related respiratory symptom in the past 12 months was 63% greater among vaccinated subjects than unvaccinated subjects (adjusted odds ratio, 1.63; 95% confidence interval, 1.05 to 2.54). The associations between vaccination and subsequent allergies and symptoms were greatest among children aged 5 through 10 years.

DTP or tetanus vaccination appears to increase the risk of allergies and related respiratory symptoms in children and adolescents. Although it is unlikely that these results are entirely because of any sources of bias, the small number of unvaccinated subjects and the study design limit our ability to make firm causal inferences about the true magnitude of effect."


Delay in diphtheria, pertussis, tetanus vaccination is associated with a reduced risk of childhood asthma
J Allergy Clin Immunol. 2008 Mar;121(3):626-31
"Early childhood immunizations have been viewed as promoters of asthma development by stimulating a T(H)2-type immune response or decreasing microbial pressure, which shifts the balance between T(H)1 and T(H)2 immunity...  Among 11, 531 children who received at least 4 doses of DPT, the risk of asthma was reduced to (1/2) in children whose first dose of DPT was delayed by more than 2 months. The likelihood of asthma in children with delays in all 3 doses was 0.39 (95% CI, 0.18-0.86)... 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."

Effects of Diphtheria-Pertussis-Tetanus or Tetanus Vaccination on Allergies and Allergy-Related Respiratory Symptoms Among Children and Adolescents in the United States
J Manipulative Physiol Ther.  2000 Feb;23(2):81-90.
"The odds of having a history of asthma was twice as great among vaccinated subjects than among unvaccinated subjects (adjusted odds ratio, 2.00; 95% confidence interval, 0.59 to 6.74). The odds of having had any allergy-related respiratory symptom in the past 12 months was 63% greater among vaccinated subjects than unvaccinated subjects (adjusted odds ratio, 1.63; 95% confidence interval, 1.05 to 2.54). The associations between vaccination and subsequent allergies and symptoms were greatest among children aged 5 through 10 years."

Is infant immunization a risk factor for childhood asthma or allergy?
Epidemiology. 1997 Nov;8(6):678-80.
"The Christchurch Health and Development Study comprises 1,265 children born in 1977. The 23 children who received no diphtheria/pertussis/tetanus (DPT) and polio immunizations had no recorded asthma episodes or consultations for asthma or other allergic illness before age 10 years; in the immunized children, 23.1% had asthma episodes, 22.5% asthma consultations, and 30.0% consultations for other allergic illness. Similar differences were observed at ages 5 and 16 years. These findings do not appear to be due to differential use of health services (although this possibility cannot be excluded) or con-founding by ethnicity, socioeconomic status, parental atopy, or parental smoking."


Alum-Containing Vaccines Increase Total and Food Allergen-Specific IgE, and Cow's Milk Oral Desensitization Increases Bosd4 IgG4 While Peanut Avoidance Increases Arah2 IgE: The Complexity of Today's Child with Food Allergy.
"From ages 8 to 12 months, our patient’s total IgE decreased from 61.4 to 44.1; peanut decreased from 13.6 to 11.2, and cow’s milk decreased from 3.84 to 2. She then received 12-month vaccines. Three weeks later, her IgE sharply increased from 44.1 to 75.6; her peanut IgE increased from 11.2 to 16.5, and her milk IgE increased from 2 to 5.06. She then avoided alum-containing vaccines and, by age 16 months, her IgE decreased to 51; her peanut decreased to 13.7, and her milk decreased 1.54."

For more on this study read here.

Kinetics of asthma- and allergy-associated immune response gene expression in peripheral blood mononuclear cells from vaccinated infants after in vitro re-stimulation with vaccine antigen.
Vaccine. 2008 Mar 25;26(14):1725-30.
"The global expression of immune response genes in infants after vaccination and their role in asthma and allergy is not clearly understood. Pharmacogenomics is ideally suited to study the involved cellular responses, since the expression of thousands of genes can be assessed simultaneously. Here, array technology was used to assess the expression kinetics of immune response genes with association to asthma and allergy in peripheral blood mononuclear cells (PBMC) of five healthy infants after vaccination with Infanrix-Polio+Hib. At 12h after in vitro re-stimulation of the PBMC with pertussis toxin (PT) antigen, 14 immune response pathways, 33 allergy-related and 66 asthma-related genes were found activated."

Reported pertussis infection and risk of atopy in 8- to 12-yr-old vaccinated and non-vaccinated children
Pediatric Allergy and Immunology Volume 19, Issue 1, pages 46–52, February 2008
"Pertussis infection has been suspected to be a potential causal factor in the development of atopic disease because of the effect of pertussis immunization on specific IgE antibodies. Although several studies found a positive association between pertussis infection and atopic disorders, this relationship has not yet been studied in a population stratified by vaccination status. To assess the association between pertussis infection and atopic disorders in pertussis-unvaccinated children and in pertussis-vaccinated children. Using data from a previously conducted study on the relationship between the diphtheria-tetanus-pertussis-(inactivated) poliomyelitis vaccination in the first year of life and atopic disorders, the study population of 1872 8–12 yr old was divided into children pertussis-unvaccinated and children pertussis-vaccinated in the first year of life. Within each group, the association between pertussis infection and atopic disorders (both as reported by the parents) was assessed. In the unvaccinated group, there were no significant associations between pertussis infection and atopic disorders. In the vaccinated group, all associations between pertussis infection and atopic disorders were positive, the associations with asthma [odds ratio (OR) = 2.24, 95% confidence interval (CI95%): 1.36–3.70], hay fever (OR = 2.35, CI95%: 1.46–3.77) and food allergy (OR = 2.68, CI95%: 1.48–4.85) being significant. There was a positive association between pertussis infection and atopic disorders in the pertussis vaccinated group only. From the present study, it cannot be concluded whether this association is causal or due to reverse causation."

Mercury induces inflammatory mediator release from human mast cells
Journal of Neuroinflammation 2010, 7:20
"Mercury is known to be neurotoxic, but its effects on the immune system are less well known. Mast cells are involved in allergic reactions, but also in innate and acquired immunity, as well as in inflammation. Many patients with Autism Spectrum Disorders (ASD) have "allergic" symptoms; moreover, the prevalence of ASD in patients with mastocytosis, characterized by numerous hyperactive mast cells in most tissues, is 10-fold higher than the general population suggesting mast cell involvement. We, therefore, investigated the effect of mercuric chloride (HgCl2) on human mast cell activation... HgCl2 stimulates VEGF and IL-6 release from human mast cells. This phenomenon could disrupt the blood-brain-barrier and permit brain inflammation. As a result, the findings of the present study provide a biological mechanism for how low levels of mercury may contribute to ASD pathogenesis."

Infection of human B lymphocytes with MMR vaccine induces IgE class switching.
Clin Immunol. 2001 Sep;100(3):355-61.
"Circulating immunoglobulin E (IgE) is one of the characteristics of human allergic diseases including allergic asthma. We recently showed that infection of human B cells with rhinovirus or measles virus could lead to the initial steps of IgE class switching. Since many viral vaccines are live viruses, we speculated that live virus vaccines may also induce IgE class switching in human B cells. To examine this possibility, we selected the commonly used live attenuated measles mumps rubella (MMR) vaccine. Here, we show that infection of a human IgM(+) B cell line with MMR resulted in the expression of germline epsilon transcript. In addition, infection of freshly prepared human PBLs with this vaccine resulted in the expression of mature IgE mRNA transcript. Our data suggest that a potential side effect of vaccination with live attenuated viruses may be an increase in the expression of IgE."

AUTO-IMMUNITY

Vaccines and autoimmunity
Nature Reviews Rheumatology 5, 648-652 (November 2009)
" Like other drugs, vaccines can cause adverse events, but unlike conventional medicines, which are prescribed to people who are ill, vaccines are administered to healthy individuals, thus increasing the concern over adverse reactions. Most side effects attributed to vaccines are mild, acute and transient; however, rare reactions such as hypersensitivity, induction of infection, and autoimmunity do occur and can be severe and even fatal. The rarity and subacute presentation of post-vaccination autoimmune phenomena means that ascertaining causality between these events can be difficult. Moreover, the latency period between vaccination and autoimmunity ranges from days to years. In this article, on the basis of published evidence and our own experience, we discuss the various aspects of the causal and temporal interactions between vaccines and autoimmune phenomena, as well as the possible mechanisms by which different components of vaccines might induce autoimmunity."

Self-Organized Criticality Theory of Autoimmunity
PLoS ONE 4(12): e8382. doi:10.1371/journal.pone.0008382
"Systemic autoimmunity appears to be the inevitable consequence of over-stimulating the host's immune ‘system’ by repeated immunization with antigen, to the levels that surpass system's self-organized criticality."

On vaccine's adjuvants and autoimmunity: Current evidence and future perspectives.
Autoimmun Rev. 2015 Oct;14(10):880-8
"In 2011 a new syndrome termed 'ASIA Autoimmune/Inflammatory Syndrome Induced by Adjuvants' was defined pointing to summarize for the first time the spectrum of immune-mediated diseases triggered by an adjuvant stimulus such as chronic exposure to silicone, tetramethylpentadecane, pristane, aluminum and other adjuvants, as well as infectious components, that also may have an adjuvant effect. All these environmental factors have been found to induce autoimmunity by themselves both in animal models and in humans: for instance, silicone was associated with siliconosis, aluminum hydroxide with post-vaccination phenomena and macrophagic myofasciitis syndrome. Several mechanisms have been hypothesized to be involved in the onset of adjuvant-induced autoimmunity; a genetic favorable background plays a key role in the appearance on such vaccine-related diseases and also justifies the rarity of these phenomena. This paper will focus on protean facets which are part of ASIA, focusing on the roles and mechanisms of action of different adjuvants which lead to the autoimmune/inflammatory response. The data herein illustrate the critical role of environmental factors in the induction of autoimmunity."

Infection, vaccines and other environmental triggers of autoimmunity.
Autoimmunity. 2005 May;38(3):235-45.
"Many environmental factors are known to affect the immune system and may play a role as triggers of the autoimmune mosaic.Infections: bacterial, viral and parasitic infections are known to induce and exacerbate autoimmune diseases, mainly by the mechanism of molecular mimicry. Vaccines, in several reports were found to be temporally followed by a new onset of autoimmune diseases. The same mechanisms that act in infectious invasion of the host, apply equally to the host response to vaccination. It has been accepted for diphtheria and tetanus toxoid, polio and measles vaccines and GBS. Also this theory has been accepted for MMR vaccination and development of autoimmune thrombocytopenia, MS has been associated with HBV vaccination."

Autoimmune hazards of hepatitis B vaccine
Autoimmun Rev. 2005 Feb;4(2):96-100
"According to Hippocratic tradition, the safety level of a preventive medicine must be very high, as it is aimed at protecting people against diseases that they may not contract. This paper points out that information on the safety of hepatitis B vaccine (HBV) is biased as compared to classical requirements of evidence-based medicine (EBM), as exemplified by a documented selectivity in the presentation or even publication of available clinical or epidemiological data. Then, a review is made of data suggesting that HBV is remarkable by the frequency, the severity and the variety of its complications, some of them probably related to a mechanism of molecular mimicry leading to demyelinating diseases, and the others reproducing the spectrum of non-hepatic manifestations of natural hepatitis B. To be explained, this unusual spectrum of toxicity requires additional investigations based upon complete release of available data."

Acquired autoimmunity after viral vaccination is caused by molecular mimicry and antigen complimentarity in the presence of an immunologic adjuvant and specific HLA patterns
Med Hypotheses.  2008; 70(2): 346-8
"Acquired autoimmunity syndromes occur after viral vaccinations. Molecular mimicry is involved in these phenomena as is the necessity for the presence of two chemically complimentary antigens and an immunologic adjuvant. The HLA pattern of the host is also an important factor. The example used to explain these phenomena is demyelinating disease that follows hepatitis B vaccination...  Why more than one type of autoimmune disease occurs is explained by the fact that specific autoimmune T-cells have been shown to develop clones that attack multiple human tissues."

Anti-NMDA receptor encephalitis after TdaP–IPV booster vaccination: cause or coincidence?
J Neurol (2011) 258:500–501
"The onset of prodromal symptoms shortly after the immunization is intriguing and suggests the vaccination as a possible trigger of anti-NMDA receptor encephalitis."

"ASIA" Autoimmune/Inflammatory Syndrome Induced by Adjuvants
J Autoimmun. 2011 Feb;36(1):4-8. Epub 2010 Aug 13.
(adjuvants are vaccine ingredients meant to provoke an immune response)
"In recent years, four conditions: siliconosis, the Gulf war syndrome (GWS), the macrophagic myofasciitis syndrome (MMF) and post-vaccination phenomena were linked with previous exposure to an adjuvant. Furthermore, these four diseases share a similar complex of signs and symptoms which further support a common denominator.Thus, we review herein the current data regarding the role of adjuvants in the pathogenesis of immune mediated diseases as well as the amassed data regarding each of these four conditions. Relating to the current knowledge we would like to suggest to include these comparable conditions under a common syndrome entitled ASIA, “Autoimmune (Auto-inflammatory) Syndrome Induced by Adjuvants”.

The spectrum of ASIA: ‘Autoimmune (Auto-inflammatory) Syndrome induced by Adjuvants’
Lupus February 2012 vol. 21 no. 2 118-120
"A Saudi Sheikh, who suffered at the age of 27 from joints pains, rash and serological evidence of anti-Ro antibodies, was diagnosed with probable systemic lupus erythematosus (SLE) at that time. He was treated with Plaquenil for a year, but as no signs of SLE were apparent, treatment was stopped and he remained disease free for the next 12 years. At the age of 39 years, 2 weeks after immunization with the flu vaccine, his disease reemerged. This time he presented with severe arthritis and pericarditis.

This patient’s story illustrates the acceleration of an autoimmune or immune-mediated condition following exposure to external stimuli. During the past year a new syndrome was introduced and termed ASIA, ‘Autoimmune (Auto-inflammatory) Syndrome induced by Adjuvants’. The use of medical adjuvants has become common practice and substances such as aluminum adjuvant are added to most human and animal vaccines. The adjuvant effect has been recognized for years, and is broadly utilized to enhance desired antigen-specific immune responses. This effect is accomplished via mechanisms that impinge on both the innate and adaptive immune systems. Formerly, adjuvants were thought to pose little or no independent threat. Alas, studies of animal models and humans demonstrated the ability of some of them to inflict autoimmunity and immune-mediated diseases by themselves."


ASIA: A New Way to Put the Puzzle Together
The Rheumatologist, June 2011
"The worldwide prevalence of autoimmune and auto-inflammatory diseases is determined by the interplay of genetic and environmental factors. The latter factors include infections, toxins, drugs, and others agents that can be linked by the occurrence of immune-mediated diseases as well as the nature of the clinical manifestations and their severity. The mechanisms by which these environmental factors trigger autoimmunity are diverse but, as a group, they may incorporate an adjuvant effect. An adjuvant is a substance that enhances the activation of the immune system, both the innate and the adoptive ones.  For years, adjuvants have been used by physicians and scientists to boost a desirable immune response, either in experimental models or during medical interventions, most classically, immunization.. 

 Despite their ability to boost immune responses, in the past, adjuvants were generally considered to be inert materials that posed little or no independent threat to the host. Alas, animal studies as well as reports of human diseases have clearly demonstrated the ability of adjuvants to inflict diseases by themselves.."

Autoimmunity induced by adjuvant hydrocarbon oil components of vaccine
Biomedicine and Pharmacotherapy, Volume 58, Issue 5, June 2004, Pages 325–337
"We have reported that a single intraperitoneal injection of the adjuvant oils pristane, IFA or squalene induces lupus-related autoantibodies to nRNP/Sm and -Su in non-autoimmune BALB/c mice. Induction of these autoantibodies appeared to be associated with the hydrocarbon’s ability to induce IL-12, IL-6, and TNF-α, suggesting a relationship with hydrocarbon’s adjuvanticity. Whether this is relevant in human vaccination is a difficult issue due to the complex effects of vaccines and the fact that immunotoxicological effects vary depending on species, route, dose, and duration of administration. Nevertheless, the potential of adjuvant hydrocarbon oils to induce autoimmunity has implications in the use of oil adjuvants in human and veterinary vaccines as well as basic research."

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."

Vaccination and autoimmunity- "vaccinosis": a dangerous liaison?
J Autoimmun 2000 Feb;14(1):1-10
"A heated debate is going on regarding the causality between vaccines, such as measles and anti-hepatitis B virus (HBV), and multiple sclerosis (MS). Brain antibodies as well as clinical symptoms have been found in patients vaccinated against those diseases. Other autoimmune illnesses have been associated with vaccinations. Tetanus toxoid, influenza vaccines, polio vaccine, and others, have been related to phenomena ranging from autoantibodies production to full-blown illness (such as rheumatoid arthritis (RA)). Conflicting data exists regarding also the connection between autism and vaccination with measles vaccine. So far only one controlled study of an experimental animal model has been published, in which the possible causal relation between vaccines and autoimmune findings has been examined: in healthy puppies immunized with a variety of commonly given vaccines, a variety of autoantibodies have been documented but no frank autoimmune illness was recorded. The findings could also represent a polyclonal activation (adjuvant reaction). The mechanism (or mechanisms) of autoimmune reactions following immunization has not yet been elucidated. One of the possibilities is molecular mimicry; when a structural similarity exists between some viral antigen (or other component of the vaccine) and a self-antigen. This similarity may be the trigger to the autoimmune reaction."

Risk of Immune Thrombocytopenic Purpura After Measles-Mumps-Rubella Immunization in Children
PEDIATRICS Vol. 121 No. 3 March 1, 2008 pp. e687 -e692
"Measles-mumps-rubella vaccine that is given in the second year of life is associated with an increased risk of immune thrombocytopenia purpura."

Vaccination may be associated with autoimmune disease
IMAJ 2004: 6: July: 430-432

CANCER

Peripheral T-cell lymphoma at the injection site of influenza vaccination
IJDVL Year : 2014 | Volume : 80 | Issue : 6 | Page : 526-529
"Pseudolymphomas or B-cell lymphoma at the vaccination site have been reported by several authors. However, onset of cutaneous T-cell lymphoma with cytotoxic features is a rare complication of vaccination. We report a 27-year-old man who developed a nodule and ulcer that arose at the site of injection of influenza vaccine. The neoplastic cells reacted positively for CD56, CD3, CD2, perforin, and granzyme B, but negatively for CD4, CD8, CD10, CD19, CD30, CD34, CD79, and betaF1. Molecular studies showed T-cell receptor γ (TCR-γ) chain monoclonal rearrangement. A diagnosis of peripheral T-cell lymphoma, not otherwise specified (NOS) was established. The patient had high fever, progressive liver dysfunction and a rapid fatal evolution."

CARDIAC DISEASE

Myocarditis, Pericarditis, and Dilated Cardiomyopathy after Smallpox Vaccination among Civilians in the United States, January–October 2003
Clin Infect Dis. (2008) 46(Supplement 3): S242-S250. 
"We conducted surveillance to describe and determine the frequency of myocarditis and/or pericarditis (myo/pericarditis) among civilians vaccinated during the US smallpox vaccination program between January and October 2003. We developed surveillance case definitions for myocarditis, pericarditis, and dilated cardiomyopathy after smallpox vaccination. We identified 21 myo/pericarditis cases among 37,901 vaccinees (5.5 per 10,000); 18 (86%) were revacinees, 14 (67%) were women, and the median age was 48 years (range, 25–70 years). The median time from vaccination to onset of symptoms was 11 days (range, 2–42 days). Myo/pericarditis severity was mild, with no fatalities, although 9 patients (43%) were hospitalized. Three additional vaccinees were found to have dilated cardiomyopathy, recognized within 3 months after vaccination. We describe an association between smallpox vaccination, using the US vaccinia strain, and myo/pericarditis among civilians."

Eosinophilic-lymphocytic myocarditis after smallpox vaccination
"Smallpox vaccination was historically the most effective defence measure against wild smallpox virus. The risk of myopericarditis after vaccination might limit this option. We report a case of biopsy-proven eosinophilic-lymphocytic myocarditis diagnosed in vivo with histological evidence for eosinophil-mediated cardiac myocyte necrosis shortly after smallpox vaccination. Furthermore, we report a beneficial haemodynamic response to high-dose corticosteroids. A better understanding of the aberrant immune mechanism of myocyte injury after smallpox vaccination might improve the risk/benefit assessment for people considering smallpox vaccination and better smallpox vaccines in the future."

Myocarditis: the unexpected return of smallpox vaccine adverse events
"Immunisations are among the best ways to control infectious diseases, but their use requires balancing risks and benefits. The decision to use vaccines needs to take account of the changing interaction over time between the vaccine coverage within a population, the incidence of the disease targeted, and the frequency and severity of adverse events attributed to the vaccine (figure). This evolution was well illustrated by the discontinuation of routine smallpox vaccination in the USA and UK in 1971 when the risk of adverse events after vaccination outweighed that from imported smallpox, well before global eradication of smallpox was completed."

Acute Myocarditis Associated With Tetanus Vaccination
Mayo Clinic Proceedings Volume 78, Issue 11, Pages 1431–1433, November 2003
"To the Editor: Millions of people undergo vaccination each year; thus, it is perhaps not surprising that a fraction develop adverse effects because of immunologic responses to the target antigen and to other nonspecific antigens contained within the vaccine. These immunologic reactions can result in aberrations in systemic physiology or direct injury to tissues and organs...  Hypersensitivity myocarditis should be considered when new ECG changes occur in association with acute-onset chest pain, mildly elevated cardiac enzyme levels, and eosinophilia due to drugs and vaccination."

Myocarditis after triple immunisation
Arch Dis Child 1986;61:403-405
"We describe a 3 month old infant who developed myocarditis several hours after diphtheria, tetanus, and pertussis vaccination. The time of occurrence of symptoms, the clinical course, and the negative virological studies suggest a possible cardiogenic adverse reaction to the vaccine."

Acute fulminant myocarditis after diphtheria, polio, and tetanus vaccination
Asian Cardiovasc Thorac Ann. 2006 Dec;14(6):e111-2.
"We report an infant case of acute fulminant myocarditis which occurred after administration of a diphtheria, polio, and tetanus vaccination. Fever and dyspnea developed after the vaccination. Extracorporeal membrane oxygenation was used for intractable cardiogenic shock. The patient survived the extracorporeal support, but poor ventricular contractility recurred 2 months later and she died while waiting for heart transplantation."

CHANGES IN THE STRUCTURE AND FUNCTION OF THE BRAIN

Influence of pediatric vaccines on amygdala growth and opioid ligand bonding in rhesus macaque infants: A pilot study
Acta Neurobiol Exp 2010, 70: 147-164
"These results suggest that maturational changes in amygdala volume and the binding capacity of [
11C]DPN in the amygdala was significantly altered in infant macaques receiving the vaccine schedule. The macaque infant is a relevant animal model in which to investigate specific environmental exposures and structural/functional neuroimaging during neurodevelopment."


CHRONIC FATIGUE SYNDROME/FIBROMYALGIA

Chronic fatigue syndrome with autoantibodies- the result of an augmented adjuvant effect of hepatitis-B vaccine and silicone implant
Autommine Rev.  2008 Oct;8(1):52-5
"CFS etiology is multi-factorial commonly triggered by infectious agents. Vaccines, induce an immune response similarly to infections, and may trigger just like infections autoimmune diseases, CFS and fibromyalgia. Furthermore vaccines contain an adjuvant which enhances their immune stimulation...  Vaccines have been reported to precede CFS mainly following exposure to multiple vaccinations (e.g. the Gulf war syndrome), or as an adverse response to the vaccine adjuvant (e.g. the macrophagic myofasciitis syndrome)...  To the best of our knowledge this is the first case of combined adverse effect to vaccine and silicone. Vaccine safety in individuals with silicone implants requires further studies."

Infection, vaccination, and autoantibodies in chronic fatigue syndrome, cause or coincidence?
Ann N Y Acad Sci. 2009 Sep;1173:600-9
"Similarly, vaccination is depicted as playing an important role in CFS onset. Recently, a case report pointed toward a causal association between silicone breast linkage, hepatitis B virus vaccination, and CFS onset in a previous healthy woman. Such findings suggest that there is a likely deregulation of the immune system influenced by specific agents (infections, vaccination, and products, such as silicone). Evidence suggests that CFS is a complex disease in which several risk factors might interact to cause its full expression."

DEATH/MISCARRIAGE

Infant Mortality Rates Regressed Against Number of Vaccine Doses Routinely Given:  is there a biochemical or synergistic toxicity?
Hum Exp Toxicol, 2011 Sept;30(9):1420-1428
This study  found a statistically significant positive correlation between the number of vaccine doses routinely given in a country and the IMR (infant mortality rate) of that country- meaning the more vaccine doses given, the HIGHER- not lower- the IMR. This study looked at the US and the 33 nations that have lower IMRs.

Comparison of VAERS Fetal-Loss Reports During Three Consecutive Influenza Seasons: was there a synergistic fetal toxicity associated with the two-vaccine 2009/2010 Season?
Hum Exp Toxicolvol. 32 no. 5 464-475
"Thus, a synergistic fetal toxicity likely resulted from the administration of both the pandemic (A-H1N1) and seasonal influenza vaccines during the 2009/2010 season."

Simultaneous sudden infant death syndrome
J Forensic Leg Med. 2007 Feb;14(2):87-91
"The case(s): Twin girls (3.5-month-old) were found dead by their mother in their crib, both in supine position. The infants were identical twins and delivered at a hospital by cesarean section. Both infants were healthy and did not have any serious medical history. Two days prior to the incident, the twins had received the second dose of oral polio, DPT and the first dose of hepatitis B vaccines and they had fever on the first day of the vaccination and been given teaspoonful of acetaminophen. Death scene investigation, judicial investigation, parental assessment, macroscopic and microscopic autopsy findings and the toxicological analysis did not yield any specific cause of death. The case(s) were referred to a supreme board composed of multidisciplinary medical professionals at the Institute of Forensic Medicine, Ministry of Justice, in Istanbul. The Board decided that the available data was consistent with SIDS."

The introduction of diphtheria-tetanus-pertussis vaccine and child mortality in rural Guinea-Bissau: an observational study.
Int J Epidemiol. 2004 Apr;33(2):374-80.
"In low-income countries with high mortality, DTP as the last vaccine received may be associated with slightly increased mortality. Since the pattern was inversed for BCG, the effect is unlikely to be due to higher-risk children having received vaccination. The role of DTP in high mortality areas needs to be clarified."
"The sequence of routine immunisations may be important for childhood mortality. Three doses of diphtheria–tetanus–pertussis vaccine (DTP) should be given at 6, 10, and 14 weeks and measles vaccine (MV) at 9 months of age. The sequence is not always respected. We examined in-hospital mortality of children having received DTP with or after measles vaccine... The case fatality was increased for children who had received DTP with or after measles vaccine compared with children who had received measles vaccine as the most recent vaccine, the ratio being 2.53 (1.37–4.67) and 1.77 (0.92–3.41) in the two periods, respectively. The combined estimate was 2.10 (1.34–3.28). These results were not explained by differences in nutritional status, number of doses of DTP or discharge policy. Administration of DTP with, or after MV, may reduce the beneficial effect of MV."

DIABETES

Discontinuation of BCG Vaccination Precedes Significant Drop in Type 2 Diabetes in Japanese Children.  Role of Inflammation and Cortisol Activity as a Cause of Type 2 Diabetes
The Open Endocrinology Journal, 2008, 2, 1-4
"The incidence of type 2 diabetes dropped by over 50% in children from Tokyo following
discontinuation of BCG immunization, the relative risk reached 2.78 (95% confidence interval 1.03 - 7.480). This drop appears to be more significant given the epidemic of type 2 diabetes in children around the world. The increased secretion of cortisol following immunization is thought to result in metabolic syndrome and type 2 diabetes."


The timing of immunization affects the development of diabetes in rodents
Autoimmunity. 1996;24(3):137-45.
"Animal studies have demonstrated the timing and content of human vaccines can affect the development of diabetes. Clinical trials of new human vaccines are not designed and generally not powered to detect an effect of immunization on the development of IDDM. These animal toxicology studies indicate that the effect of vaccines on human insulin dependent diabetes needs to be examined."

Clustering of cases of insulin dependent diabetes (IDDM) occurring three years after hemophilus influenza B (HiB) immunization support causal relationship between immunization and IDDM.
Autoimmunity. 2002 Jul;35(4):247-53.
"The difference in cumulative incidence between those receiving 4 doses and those receiving 0 doses is 54 cases of IDDM/100,000 (P = 0.026) at 7 years, (relative risk = 1.26). Most of the extra cases of IDDM appeared in statistically significant clusters that occurred in periods starting approximately 38 months after immunization and lasting approximately 6-8 months. Immunization with pediatric vaccines increased the risk of insulin diabetes in NOD mice."

Clustering of Cases of IDDM 2 to 4 Years after Hepatitis B Immunization is Consistent with Clustering after Infections and Progression to IDDM in Autoantibody Positive Individuals 
The Open Pediatric Medicine Journal, 2008, 2, 1-6

The following are comments that are part of expert congressional testimony regarding vaccine policy and safety, submitted by J. Barthelow Classen, M.D., M.B.A.
"Our research has focused on the effect of vaccines on insulin dependent diabetes (diabetes) , an autoimmune disease. An autoimmune disease is a condition where a person's immune system destroys their own tissue. The effect of vaccines on the development of diabetes are expected to reflect the effect of vaccines on other autoimmune diseases. Vaccines are immune stimulants and would thus be expected to increase the risk of autoimmune disease. We found that the incidence of diabetes rose 60% in New Zealand following a massive hepatitis B immunization program (1). The CDC initiated a study to verify our findings. Their preliminary data has been published and shows hepatitis B immunization when given starting after 8 weeks of age is associated with a 90% increase in the risk of diabetes (2), supporting our findings...  Currently we are attempting to collect additional data on the hepatitis B vaccine as well as data on other vaccines. Our data shows the hemophilus vaccine is likely to cause diabetes (4) and we have confirmed a rise in diabetes in the US (5) and UK (6) following the introduction of the hemophilus vaccine."

Vaccines and type 1 diabetes (IDDM), data supports a causal relation
BMJ 1999;318:1487 (letter)
"Human data linking vaccines to an increased risk of diabetes was presented at the meeting.[4] Our data was presented that administering the hepatitis B vaccine starting after 2 months of life was associated with an increased risk of IDDM in New Zealand, relative risk 1.6. A CDC study[5]
found hepatitis B immunization starting after 2 months of life was associated with an increased risk of IDDM, odds ratio 1.9, thus supporting our data. The preliminary data from our study in Finland showing the hemophilus vaccine is associated with an increased risk of diabetes[3] was also presented. Several studies linking BCG vaccination after 1 month of life to the development of diabetes was also presented."


Association between type 1 diabetes and Haemophilus influenzae type b vaccination: birth cohort study
BMJ 1999;318:1169
"The results are disturbing. The rise in IDDM, just one potentialadverse effect exceeds the potential benefit of the vaccine, which has been estimated to prevent 7 deaths and 7 to 26 cases of severe disability per 100,000 children immunized (1). Even the difference between the groups receiving 4 and 1 dose exceeds the mean expected benefit. Temporal changes in the incidence of IDDM do not explain the differences since there were an extra 31 cases of IDDM/100,000 children in the age 5 to 10 and the incidence of IDDM in this group had been stable for about 10 years prior to this (2). Furthermore sharp rises in IDDM have been recorded in the US (3) and the UK (4) following the introduction of the Hemophilus vaccine."

Difficulties in assessing the relationship, if any, between mumps vaccination and diabetes mellitus in childhood.
Vaccine. 2000 Dec 8;19(9-10):1018-25.
"This paper considers the hypothesis that mumps vaccine may be an environmental factor for childhood diabetes and the difficulties assessing the available information about this. A review was undertaken of the published literature about mumps or mumps vaccine and diabetes mellitus in childhood. There has been considerable speculation about the role of wild mumps virus and mumps vaccine in the onset of childhood diabetes. Available data about this is incomplete and difficult to interpret partly as several factors are thought to be involved in the development of childhood diabetes. Well-designed and long-term studies about the use of mumps vaccine and incidence of childhood diabetes could be done. The general approach used in this paper could be applied to study the health effects of other vaccines."

GUILLAIN-BARRE SYNDROME

Immunologic studies of rabies vaccination‐induced Guillain‐Barré syndrome
Neurology March 1988 vol. 38 no. 3 375
"Patients with Guillain-Barré syndrome (GBS) induced by rabies vaccines prepared from either suckling mouse brain (SMB) or mature sheep brain (Semple vaccine) and patients with sporadic, idiopathic GBS were studied for antibody to myelin basic protein (MBP), P2 protein, and Schwann cells. Sera from all four Semple vaccine- and one of five SMB vaccine-induced GBS patients, but none of the sporadic GBS patients, had antibody to MBP. Sera from Semple vaccinees also had antibody to fixed, transformed Schwann cells, but similar amounts of antibody were found in sera from Semple vaccinees with CNS complications and with minor non-neurologic complications, suggesting that this antibody was not specifically linked to the development of polyneuritis. None of the sera had detectable antibody to P2 protein. We conclude that patients with GBS constitute a heterogeneous population and that different target antigens may serve as a focus for this presumed autoimmune disease."

LUPUS

Ten cases of systemic lupus erythematosus related to hepatitis B vaccine
Lupus. 2009 Nov; 18(13): 1192-7
"Data from this case-series, and previously documented cases in the literature could only show a temporal relation between hepatitis B vaccination and the appearance of systemic lupus erythematosus. Systemic lupus erythematosus related to vaccine may differ from idiopathic systemic lupus erythematosus in its clinical presentation and may resemble drug-induced systemic lupus erythematosus. Thus, physicians should be alerted to this potential association, its possible long latency period and unique presentations, and be encouraged to report and analyze these cases."

MACROPHAGIC MYOFASCIITIS

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."

Postimmunization (Vaccination) Injection-Site Reactions: A Report of Four Cases and Review of the Literature
"Four patients each had a single subcutaneous nodule at the site of a previous vaccine injection; three after injection of diphtheria, tetanus, and pertussis vaccination and one after tetanus toxoid vaccination. Presentation was with a mass 4-22 months after vaccination at the site of injection. Histologically, three patients had a necrotizing granulomatus reaction with a surrounding infiltrate of lymphocytes, plasma cells, histiocytes, and associated fibrosis. The fourth patient demonstrated a lymphohistiocytic reaction with a predominance of histiocytic cells as well as associated plasma cells, fibroblasts, and fibrosis. The lymphoid infiltration in these reactions showed a predominance of T-lymphocytes over B-lymphocytes. Aluminum was demonstrated in necrotic foci, inflammatory stroma, and the granular cytoplasm of histiocytes with the aid of solochrome azurine and solochrome cyanine stains as well as by energy-dispersive x-ray microanalysis. The reactions are thought to be immunologic (hypersensitivity) reactions associated with the aluminum contents of the preparation."

[Lessons from macrophagic myofasciitis: towards definition of a vaccine adjuvant-related syndrome].
Rev Neurol (Paris). 2003 Feb;159(2):162-4.
"Macrophagic myofasciitis is a condition first reported in 1998.... The condition manifests by diffuse myalgias and chronic fatigue, forming a syndrome that meets both Center for Disease Control and Oxford criteria for the so-called chronic fatigue syndrome in about half of patients. One third of patients develop an autoimmune disease, such as multiple sclerosis. Even in the absence of overt autoimmune disease they commonly show subtle signs of chronic immune stimulation, and most of them are of the HLADRB1*01 group, a phenotype at risk to develop polymyalgia rheumatica and rheumatoid arthritis. 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. It is plausible that persistent systemic immune activation that fails to switch off represents the pathophysiologic basis of chronic fatigue syndrome associated with macrophagic myofasciitis, similarly to what happens in patients with post-infectious chronic fatigue and possibly idiopathic chronic fatigue syndrome. Therefore, 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. Interestingly, special emphasis has been put on Th-2 biased immune responses as a possible explanation of chronic fatigue and associated manifestations known as the Gulf war syndrome. Results concerning macrophagic myofasciitis may well open new avenues for etiologic investigation of this syndrome. Indeed, both type and structure of symptoms are strikingly similar in Gulf war veterans and patients with macrophagic myofasciitis. 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."

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 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."

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."

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."

AlOH3-adjuvanted vaccine-induced macrophagic myofasciitis in rats is influenced by the genetic background.
Neuromuscul Disord. 2006 May;16(5):347-52. Epub 2006 Apr 17.
"Macrophagic myofasciitis (MMF) is a specific histopathologic lesion involved in the persistence for years of aluminum hydroxide [Al(OH)(3)] at the site of previous intramuscular (i.m.) injection. In order to study mechanisms involved persistence of MMF lesions, we set up an experimental model of MMF-lesion in Sprague-Dawley and Lewis rat, by i.m. injections of 10 microL of an Al(OH)(3)-adjuvanted vaccine... A morphometric approach showed that Lewis rats with Th1-biased immunity had significantly smaller lesions than Sprague-Dawley rats with balanced Th1/Th2 immunity. Concluding, our results indicate that genetic determinatives of cytotoxic T-cell responses could interfere with the clearance process and condition the persistence of vaccine-induced MMF-lesions."

MITOCHONDRIAL DISEASE AND DYSFUNCTION

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."

MULTIPLE SCLEROSIS

Evolution of multiple sclerosis in France since the beginning of hepatitis B vaccination
Immunol Res. 2014; 60(2-3): 219–225.
"Since the implementation of the mass vaccination campaign against hepatitis B in France, the appearance of multiple sclerosis, sometimes occurring in the aftermath of vaccinations, led to the publication of epidemiological international studies. This was also justified by the sharp increase in the annual incidence of multiple sclerosis reported to the French health insurance in the mid-1990s. Almost 20 years later, a retrospective reflection can be sketched from these official data and also from the national pharmacovigilance agency. Statistical data from these latter sources seem to show a significant correlation between the number of hepatitis B vaccinations performed and the declaration to the pharmacovigilance of multiple sclerosis occurring between 1 and 2 years later. The application of the Hill’s criteria to these data indicates that the correlation between hepatitis B vaccine and multiple sclerosis may be causal."

Hepatitis B vaccine and the risk of CNS inflammatory demyelination in childhood
Neurology 2009 Mar 10;72(10):873-80
"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."

Recombinant hepatitis B vaccine and the risk of multiple sclerosis
Neurology 2004 Sept;63(5): 838-842
"These findings are consistent with the hypothesis that immunization with the recombinant hepatitis B vaccine is associated with an increased risk of MS, and challenge the idea that the relation between hepatitis B vaccination and risk of MS is well understood."

The potential role of subclinical Bordetella Pertussiscolonization in the etiology of multiple sclerosis
"It is established that (1) subclinical Bordetella pertussis colonization of the nasopharynx persists in highly vaccinated populations, and (2) B. pertussis toxin is a potent adjuvant that, when co-administered with neural antigens, induces neuropathology in experimental autoimmune encephalomyelitis, the principle animal model of multiple sclerosis. Building on these observations with supporting epidemiologic and biologic evidence, we propose that, contrary to conventional wisdom that subclinical pertussis infections are innocuous to hosts, B. pertussis colonization is an important cause of multiple sclerosis."

NARCOLEPSY

AS03 Adjuvanted AH1N1 Vaccine Associated with an Abrupt Increase in the Incidence of Childhood Narcolepsy in Finland
Published March 28, 2012
"Vaccination coverage in the cohort was 75%. Of the 67 confirmed cases of narcolepsy, 46 vaccinated and 7 unvaccinated were included in the primary analysis. The incidence of narcolepsy was 9.0 in the vaccinated as compared to 0.7/100,000 person years in the unvaccinated individuals, the rate ratio being 12.7 (95% confidence interval 6.1–30.8)...  Pandemrix vaccine contributed to the onset of narcolepsy among those 4 to 19 years old during the pandemic influenza in 2009–2010 in Finland. Further studies are needed to determine whether this observation exists in other populations and to elucidate potential underlying immunological mechanism. The role of the adjuvant in particular warrants further research before drawing conclusions about the use of adjuvanted pandemic vaccines in the future."

Increased Incidence and Clinical Picture of Childhood Narcoplepsy Following the 2009 H1N1 Pandemic Vaccination Campaign in Finland
Published March 28, 2012
"The average annual incidence among subjects under 17 years of age was 0.31 (0.12–0.51) per 100 000 inhabitants. In 2010, 54 children under age 17 were diagnosed with narcolepsy (5.3/100 000; 17-fold increase)...  A sudden increase in the incidence of abrupt childhood narcolepsy was observed in Finland in 2010. We consider it likely that Pandemrix vaccination contributed, perhaps together with other environmental factors, to this increase in genetically susceptible children."

Swedish Medical Products Agency Publishes Report from a Case Inventory Study on Pandemrix Vaccination and Development of Narcolepsy with Cataplexy
Eurosurveillance vol.16, iss.26 30 June 2011
"Overall the incidence rate in those vaccinated was 4.2 versus 0.64 in unvaccinated per 100,000 person-years, respectively suggesting a relative risk of 6.6 (95% CI 3.1 -14.5) and an absolute risk of 3.6 (95% confidence interval 2.5 – 4.7) additional cases per 100,000 vaccinated cases or 1 case per 27,800 vaccinations (from 1 per 40,000 to 21,300 vaccination)."The actual study can be viewed here.

"A retrospective cohort study of vaccinated and non‐vaccinated children/adolescents followed subjects from the beginning of the pandemic period October 1st 2009 until the end of 2010; it revealed an almost seven‐fold higher incidence of narcolepsy with cataplexy in those vaccinated compared to those who were not vaccinated."

The above mentioned case inventory study can be seen here.

Risk of Narcolepsy in Children and Young People Receiving AS03 Adjuvanted Pandemic A/H1N1 2009 Influenza Vaccine: retrospective analysis
BMJ 2013;346:f794
"The increased risk of narcolepsy after vaccination with ASO3 adjuvanted pandemic A/H1N1 2009 vaccine indicates a causal association, consistent with findings from Finland. Because of variable delay in diagnosis, however, the risk might be overestimated by more rapid referral of vaccinated children."
Nature Genetics 46, 1274–1282 (2014)
"Febrile seizures represent a serious adverse event following measles, mumps and rubella (MMR) vaccination. We conducted a series of genome-wide association scans comparing children with MMR-related febrile seizures, children with febrile seizures unrelated to vaccination and controls with no history of febrile seizures. Two loci were distinctly associated with MMR-related febrile seizures, harboring the interferon-stimulated gene IFI44L (rs273259: P = 5.9 × 10−12 versus controls, P = 1.2 × 10−9 versus MMR-unrelated febrile seizures) and the measles virus receptorCD46 (rs1318653: P = 9.6 × 10−11 versus controls, P = 1.6 × 10−9 versus MMR-unrelated febrile seizures)."

Thimerosal exposure and increased risk for diagnosed tic disorder in the United States: a case-control study.
Interdiscip Toxicol. 2015 Jun;8(2):68-76.
"TD (Tic Disorder) cases were significantly more likely than controls to have received increased organic-Hg from TM-HepB administered within the first month-of-life (odds ratio (OR)=1.59, p

Vaccine Safety Datalink Project: A New Tool for Improving Vaccine Safety Monitoring in the United States
PEDIATRICS Vol. 99 No. 6 June 1, 1997 pp. 765 -773
"Preliminary design, data collection, and analytic capability of the Vaccine Safety Datalink project has been validated by replication of previous known associations between seizures and DTP and MMR vaccines."

J Clin Neurosci. 2008 Dec;15(12):1315-22.
" Post-infectious and post-immunisation encephalomyelitis make up about three-quarters of cases, where the timing of a febrile event is associated with the onset of neurological disease. Post-vaccination ADEM has been associated with several vaccines such as rabies, diphtheria-tetanus-polio, smallpox, measles, mumps, rubella, Japanese B encephalitis, pertussis, influenza, hepatitis B, and the Hog vaccine. We review ADEM with particular emphasis on vaccination as the precipitating factor. We performed a literature search using Medline (1976-2007) with search terms including "ADEM", "acute disseminated encephalomyelitis", "encephalomyelitis", "vaccination", and "immunisation". A patient presenting with bilateral optic neuropathies within 3 weeks of "inactivated" influenza vaccination followed by delayed onset of ADEM 3 months post-vaccination is described."

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."

Neuralgic Adverse Events Following Vaccination
Prog Health Sci 2012, v 2, no. 1
"Despite the assurances of the necessity and safety of vaccinations, there are more and more questions and doubts, which both physicians and parents are waiting to be clarified...A second part would be extensive neuro-immunological research confirming or excluding the relationship of vaccines with the reported adverse events (early, late/long-term) and chronic diseases whose upward trend has been observed in recent decades in children. It seems that it would be worthwhile to apply the precautionary principle-the ethical principle (from 1988) according to which if there is a probable, although poorly known, risk of adverse effects of new technology, it is better not to implement it rather than risk uncertain but potentially very harmful consequences."

Neurological Complications of Pertussis Inoculation
Archives of Disease in Childhood, 1974, 49, 46."We suggest, however, that in as many as a third of our patients there were contraindications to inoculation with pertussis vaccine, in that there was a previous history of fits, or family history of seizures in a first-degree relative; reaction to previous inoculation; recent intercurrent infection; or presumed neurodevelopmental defect. These findings are contrary to the experience of certain authorities. For example, Illingworth (1965) has claimed that he has never seen a complication from DPT inoculation in a child who has had previous convulsions. The differences between our two views may be due to differences in selection, and the conflict can only be resolved by a careful prospective study of the frequency and circumstances of possible complications. We recommend that pertussis vaccine is withheld from the groups of infants mentioned above, or administration postponed in those recently ill; this policy is unlikely to affect 'herd' immunity significantly. Finally, we urge the systematic reporting of reactions to all forms of inoculation to the Committee on Safety of Medicines, since we understand that few, if any, reactions to DPT inoculation are notified to the Committee. 

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."

Complex Regional Pain Syndrome Following Immunisation
Arch Dis Child archdischild-2011-301307Published Online First: 1 August 2012
"Here we present a case series of CRPS-1 following immunisation in adolescents, with either diphtheria-tetanus-acellular pertussis (1 case), or human papillomavirus vaccines (4 cases). Enhanced awareness of this syndrome and its potential to occur following immunisation in the paediatric population is vital to the prompt and effective management of this condition."

Can HPV immunisation cause ADEM?  Two case reports and literature review
Mult Scler May 2014 vol. 20 no. 6 762-763
"Recently, however, Schäffer et al. provided the first report regarding the onset of acute disseminated encephalomyelitis (ADEM) 23 days following HPV vaccination in a 15-year-old woman.2 Further reports provided similar observations,3,4 indicating a possible relationship between HPV vaccination and ADEM.  ADEM is an uncommon condition, usually preceded by an acute infection.5 In about 5% of ADEM cases, however, a precedent immunisation was described as the only risk factor.3"

Acute Disseminated Encephalomyelitis Onset: Evaluation Based on Vaccine Adverse Events Reporting Systems
PLOS One, October 16, 2013
"We retrieved 205 and 236 ADEM cases from the EVPM and VAERS databases, respectively, of which 404 were considered for epidemiological analysis following verification and causality assessment. Half of the patients had less than 18 years and with a slight male predominance. The time interval from vaccination to ADEM onset was 2-30 days in 61% of the cases. Vaccine against seasonal flu and human papilloma virus vaccine were those most frequently associated with ADEM, accounting for almost 30% of the total cases. Mean number of reports per year between 2005 and 2012 in VAERS database was 40±21.7, decreasing after 2010 mainly because of a reduction of reports associated with human papilloma virus and Diphtheria, Pertussis, Tetanus, Polio and Haemophilus Influentiae type B vaccines."

PSEUDOLYMPHOMA

Vaccination-induced cutaneous pseudolymphoma
JAAD April 2005Volume 52, Issue 4, Pages 623–629
"Nine patients presenting with late-onset, chronic skin lesions occurring at the site of antihepatitis B (8 cases) and antihepatitis A (one case) vaccination were reported. Histopathologic and immunohistochemic studies, and molecular analysis of clonality of skin biopsy specimens, were performed. Furthermore, the presence of vaccine products was investigated in skin lesions by using histochemical, microanalytic, and electronic microscopy techniques. Aluminium deposits were evidenced in all cases by using histochemical staining in all cases, and by microanalysis and ultrastructural studies in one case. Associated manifestations were vitiligo (one case) and chronic fatigue with myalgia (two cases). Cutaneous lymphoid hyperplasia is a potential adverse effect of vaccinations including aluminium hydroxide as an adjuvant. Further prospective studies are warranted to evaluate the incidence of this complication in the immunized population."

[Late-onset vaccination-induced subcutaneous pseudolymphoma].
Ann Pathol. 2008 Apr;28(2):146-9.
"Persistent subcutaneous nodules arise on rare occasions at sites of injection of aluminium hydroxide-adsorbed vaccine. We report a case following a diphtheria, tetanus and pertussis vaccination. The late onset of the lesion, four years after the injection, led to an uncertain preoperative diagnosis. Histopathologic examination showed features of a subcutaneous pseudolymphoma. The demonstration of aluminium by Morin staining and atomic absorption spectrometry on a paraffin-embedded tissue probe supported the diagnosis of a vaccination-induced pseudolymphoma."

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."

Cutaneous B-cell Pseudolymphoma at the Site of Vaccination
Am J Dermatopathol. 2007 Dec;29(6):538-42.
"Pseudolymphomas are a rare complication of vaccination, presenting with dense lymphoid infiltrates and prominent follicular pattern. We report our observations on 4 patients with vaccination-induced B-cell pseudolymphoma (all females; age range 19 to 60 years; median: 34.5 years). Clinically 3 patients presented with subcutaneous nodules and 1 presented with a large, indurated, erythematous plaque. Necrotic areas surrounded by palisaded histiocytes were seen in 3 biopsies from 2 patients. A mixed-cell infiltrate with eosinophils and plasma cells was present in all cases. In addition, histiocytes with granular basophilic cytoplasm could be observed around the focal area of necrosis or within the inflammatory infiltrate. Two patients were treated with local radiotherapy and are alive and free of disease after 12 and 72 months, respectively. One of these two patients had a second pseudolymphoma on the contralateral arm after a new injection of vaccine. Cutaneous pseudolymphoma after vaccination should be distinguished histopathologically from low-grade cutaneous B-cell lymphomas (follicle center cell lymphoma, marginal zone lymphoma) and from other B-cell pseudolymphomas with prominent follicular pattern requiring different treatment (eg, Borrelia burgdorferi-induced lymphocytoma cutis)."
"Adverse reactions to vaccines are highly varied, ranging from mild local reactions to fatal outcomes. Cutaneous adverse events after exposure to aluminium-containing vaccines are usually benign, mostly consisting of mild transient reactions occurring at the site of injection. The development of painful and itching persistent aluminium induced subcutaneous nodules, extensive limb swelling, cold panniculitis or macrophagic myofasciitis is a rare event. (1) The observation of aluminium induced cutaneous B-cell lymphoid hyperplasia, showing prominent germinal centre formation in sites other than the vaccination injection sites is an exceedingly rare phenomenon. (2-4) Specific aluminium (Morin) stains, electronic microscopy, micro analysis and immunologic cutaneous provocation tests may permit to demonstrate the responsibility of aluminium hydroxide in such cutaneous reactions."

RHEUMATIC DISORDERS

Rheumatic disorders developed after hepatitis B vaccination
Rheumatology. vol 38(10): 978-983
"Hepatitis B vaccine might be followed by various rheumatic conditions and might trigger the onset of underlying inflammatory or autoimmune rheumatic diseases. However, a causal relationship between hepatitis B vaccination and the observed rheumatic manifestations cannot be easily established. Further epidemiological studies are needed to establish whether hepatitis B vaccination is associated or not with an incidence of rheumatic disorders higher than normal."

Autoimmune response following influenza vaccination in patients with autoimmune inflammatory rheumatic disease
Lupus. 2012 Feb;21(2):175-83
"We report that after the administration of seasonal/H1N1 vaccine there were mostly transient changes in autoantibody production in AIRD patients and in healthy participants. However, a small subset of patients, especially ANA-positive patients, had a tendency towards anti-ENA development. Although no convincing differences between the seasonal and H1N1 vaccines were observed, our results imply that there might be a slight tendency of the H1N1 vaccine towards aCL induction. Although seasonal and H1N1 vaccines are safe and effective, they also have the potential to induce autoantibodies in selected AIRD patients and healthy adults. Follow-up of such individuals is proposed and further research is needed."

SHAKEN BABY SYNDROME

Elevated blood histamine caused by vaccinations and Vitamin C deficiency may mimic the shaken baby syndrome.
Med Hypotheses. 2004;62(4):533-6.
"The findings of subdural hematoma and retinal hemorrhages in infants, without any documented history of major trauma, do not always indicate child abuse. A combination of ascorbate depletion and the injection of foreign proteins can cause a very high blood histamine level, leading to capillary fragility and venular bleeding. This can be prevented by the administration of vitamin C."

Reflections on “Shaken Baby Syndrome”: A Case Report
Jane M. Orient, M.D.
"The first witness called by the defense at the Yurko evidentiary hearing, Dr.Archie Kalokerinos of Australia, testified that vaccines can deplete vitamin C and precipitate scurvy. Kalokerinos had observed that aboriginal children had a very high mortality rate post vaccination—until he began administering a dose of vitamin C along with the vaccine.

Intracranial hemorrhage is surprisingly common in infants. An autopsy series of 50 nontraumatic deaths of infants of age up to 5 months showed fresh intradural hemorrhage in 36 cases (72 percent). An earlier study had documented intradural bleeding as a “constant feature” in premature infants.

One of the witnesses at the Yurko evidentiary hearing, Horace Gardner, M.D., testified that the peak age for alleged SBS is much later in Japan than in the United States, around 9 months compared to 2 months, coinciding with the respective timing of childhood vaccines [unpublished observations].

A medical review, with particular attention to vaccine history, should be done on all cases that have resulted in an investigation, prosecution, or conviction for SBS. But even before such a study can be done, the mere possibility of a vaccine connection demands vigilance and preventive measures. Inexpensive apnea monitors are technologically feasible and should be widely used. Based on the results reported by Kalokerinos, a dose of vitamin C with every vaccine is a reasonable precaution. Additionally, the vaccine schedule should be reviewed, as should the practice of giving multiple vaccines on one visit, or any vaccine to a child who is ill."

VACCINE-DERIVED DISEASES

Detection of measles vaccine in the throat of a vaccinated child.
Vaccine. 2002 Feb 22;20(11-12):1541-3.
"Measles vaccine is widely used, most often in association with mumps and rubella vaccines. We report here the case of a child presenting with fever 8 days after vaccination with a measles-mumps-rubella vaccine. Measles virus was isolated in a throat swab taken 4 days after fever onset. This virus was then further genetically characterised as a vaccine-type virus. Fever occurring subsequent to measles vaccination is related to the replication of the live attenuated vaccine virus. In the case presented here, the vaccine virus was isolated in the throat, showing that subcutaneous injection of an attenuated measles strain can result in respiratory excretion of this virus."

Polio programme: let us declare victory and move on
Indian J Med Ethics. 2012 Apr-Jun;9(2):114-7.
"It was hoped that following polio eradication, immunisation could be stopped. However the synthesis of polio virus in 2002, made eradication impossible. It is argued that getting poor countries to expend their scarce resources on an impossible dream over the last 10 years was unethical. Furthermore, while India has been polio-free for a year, there has been a huge increase in non-polio acute flaccid paralysis (NPAFP). In 2011, there were an extra 47,500 new cases of NPAFP. Clinically indistinguishable from polio paralysis but twice as deadly, the incidence of NPAFP was directly proportional to doses of oral polio received. Though this data was collected within the polio surveillance system, it was not investigated. The principle of primum-non-nocere was violated. The authors suggest that the huge bill of US$ 8 billion spent on the programme, is a small sum to pay if the world learns to be wary of such vertical programmes in the future."

Polio eradication: a complex end game
BMJ 2012;344:e2398
"They also noted that while India was declared polio-free in 2011, at the same time there were 47500 cases of NPAFP (Non Polio Acute Flaccid Paralysis), which increased in direct proportion to the number of polio vaccine doses received. Independent studies showed that children identified with NPAFP “were at more than twice the risk of dying than those with wild polio infection.

"According to their report, nationally, the NPAFP rate is now twelve times higher than expected. In the states of Uttar Pradesh and Bihar – which have pulse polio vaccination every month – the NPAFP rate is 25 and 35 fold higher than the international norms (Ramesh Shankar, Mumbai 2012).

Ron Law (Assaulting alternative medicine: worthwhile or witch hunt? BMJ.com 10 March 2012) recently addressed the polio situation in India: eradication has been achieved by re-naming the disease. Poliomyelitis paralysis which occurs even after 30+ vaccination doses, is now called acute flaccid paralysis (AFP) or polio-like paralysis; hardly a great success of vaccination or comfort to the parents of the more than 60 000 affected children.

Earlier redefinition of poliomyelitis had been introduced in the US: a disease with residual paralysis which resolves within 60 days changed into a disease with residual paralysis which persists for more than 60 days. Cases of paralysis which resolve within 60 days (99% of cases) are diagnosed as viral or aseptic meningitis.

According to MMWR (1997; 32[29]: 384-385), there are 30 000 to 50 000 cases of viral/aseptic meningitis per year in the US. Considering that in the pre-vaccine era the vast majority (99%) of the reported cases were non-paralytic (corresponding to aseptic or viral meningitis), vaccination has actually increased the incidence of poliomyelitis. Before mass vaccination there were a few hundred or few thousand cases of polio in some outbreaks, while now it is up to 50 000 cases every year."

Dosing schedule of pneumococcal vaccine linked with increased risk of getting multiresistant strain
JAMA, 2010; (304)10:1099
"Infants who received heptavalent pneumococcal conjugate vaccination at 2, 4, and 11 months were more likely than unvaccinated controls to have nasopharyngeal (in the nasal passages and upper part of the throat behind the nose) acquisition of pneumococcal serotype 19A, a leading cause of respiratory pneumococcal disease, according to a new study."

Bordetella pertussis Strains with Increased Toxin Production Associated with Pertussis Resurgence
Emerging Infectious Diseases Volume 15, Number 8—August 2009
"We present evidence that in the Netherlands the dramatic increase in pertussis is temporally associated with the emergence of Bordetella pertussis strains carrying a novel allele for the pertussis toxin promoter, which confers increased pertussis toxin (Ptx) production. Epidemiologic data suggest that these strains are more virulent in humans. We discuss changes in the ecology of B. pertussis that may have driven this adaptation. Our results underline the importance of Ptx in transmission, suggest that vaccination may select for increased virulence, and indicate ways to control pertussis more effectively."

Vaccine-related mumps infections in Thailand and the identification of a novel mutation in the mumps fusion protein
Biologicals. 2013 Mar;41(2):84-7
"An outbreak of nine cases of mumps was reported from a total of 97 vaccinated nursing students at two medical colleges in Thailand in 2010, 16-26 days after administration of MMR vaccine containing the L-Zagreb mumps strain. Symptoms ranged in severity from fever and parotid swelling to orchitis. Clinical samples were obtained from seven patients and three were suitable for further study. Sequencing confirmed that the SH gene of the mumps virus in the unpassaged clinical specimens was identical to the L-Zagreb SH gene in the vaccine. Further analysis of the viral genome identified nucleotide position 5170 as a novel mutation which corresponds to an amino acid change in the fusion protein. This study provides another virologically confirmed example of mumps resulting from the L-Zagreb vaccine strain."

Vaccine-derived poliomyelitis 12 years after infection in Minnesota
N Engl J Med. 2011 June 16;364(24):2316-23
This is the case of a 44 year old woman who had an immune deficiency and died from polio, which it is argued that she was carrying since her child was vaccinated.  "Type 2 vaccine-derived poliovirus was isolated from stool. The viral capsid protein VP1 region had diverged from the vaccine strain at 12.3% of nucleotide positions, and the two attenuating substitutions had reverted to the wild-type sequence. Infection probably occurred 11.9 years earlier (95% confidence interval [CI], 10.9 to 13.2), when her child received the oral poliovirus vaccine."

Live rubella virus vaccine long-term persistence as an antigenic trigger of cutaneous granulomas in patients with primary immunodeficiency
Clin Microbiol Infect. 2014 Jan 30
"Granulomas may develop as a response to a local antigenic trigger, leading to the activation of macrophages and T-lymphocytes. Primary immunodeficiency (PID) is associated with the development of extensive cutaneous granulomas, whose aetiology remains unknown. We performed high-throughput sequencing of the transcriptome of cutaneous granuloma lesions on two consecutive index cases, and RT-PCR in a third consecutive patient. The RA27/3 vaccine strain of rubella virus-the core component of a universally used paediatric vaccine-was present in the cutaneous granuloma of these three consecutive PID patients...  Persistence of the rubella vaccine virus was also demonstrated in granuloma lesions sampled 4-5 years earlier. The persistence of the rubella virus vaccine strain in all three consecutive cutaneous granuloma patients with PID strongly suggests a causal relationship between rubella virus and granuloma in this setting."

MMR varicella zoster virus vaccine
Reactions Weekly April 2014, Volume 1496, Issue 1, p 31
"A 12-year-old boy developed a skin rash following administration of MMR varicella zoster virus vaccine [route, dosage and outcome not stated].

The boy's medical history included DiGeorge syndrome and juvenile idiopathic arthritis, which was treated with etanercept. He inadvertently received the MMR varicella zoster virus vaccine during a well-child visit. Ten days later, he was hospitalised with a 2-day history of fever, conjunctivitis, rash and sore throat. His mother held further doses of etanercept. Upon admission, physical examination revealed a blanching morbilliform rash on his face, ears, neck, chest, back and limbs. He also had mild conjunctivitis, palatal petechiae with posterior pharyngeal erythema and mild post auricular cervical lymphadenopathy.

The boy began receiving aciclovir. Urine and skin samples were positive for measles virus, and were phylogenetically clustered as genotype A with Edmonston reference strain. He was diagnosed with vaccine-associated disease."

Yellow Fever Virus Vaccine–associated Deaths in Young Women
Emerg Infect Dis Oct 2011; 17(10):1891-1893
"Yellow fever virus (YFV) vaccine had been considered the safest of the live-virus vaccines. Rare neurologic adverse events, called yellow fever vaccine–associated neurotropic disease (YEL-AND), have long been recognized but are seldom fatal. However, in 2001, the vaccine was found to cause a serious, frequently fatal, multisystemic illness, called yellow fever vaccine–associated viscerotropic disease (YEL-AVD), which resembles the illness it was designed to prevent."

Neonatal vaccine-strain varicella-zoster virus infection 22 days after maternal postpartum vaccination
Pediatr Infect Dis J. 2012 Sep; 31(9):977-9
"A 25-day-old infant developed varicella 22 days after her mother received varicella vaccine postpartum. Infection with vaccine-strain varicella-zoster virus was confirmed by genetic analysis. The mother had no postvaccination rash nor did other contacts have rash or recent vaccination. The potential means of transmission to the infant are explored."

[Herpes zoster after varicella-zoster vaccination] 
Hautarzt. 2013 Feb;64(2):107-9
"A five-year-old girl, vaccinated against varicella-zoster virus (VZV) presented with clinical symptoms of herpes zoster in the 6th cervical dermatome. A VZV direct immune-fluorescence assay was negative three times but additional genotypical analysis showed a VZV strain genotype 2 (Oka vaccine strain). Therefore the diagnosis of a breakthrough varicella disease with the vaccine strain was established. An immunodeficiency was ruled out and the patient responded well to the initiated therapy. This case demonstrates that a negative VZV direct immunofluorescence assay does not exclude an infection with the vaccine strain."