There has been an epidemic of inflammatory diseases that has paralleled the epidemic on iatrogenic immune stimulation with vaccines.

Extensive evidence links vaccine-induced immune overload with the epidemic of type 1 diabetes.

More recent data indicates that obesity, type 2 diabetes and other components of metabolic syndrome are highly associated with immunization and may be manifestations of the negative feedback loop of the immune system reacting to the immune overload.

The epidemic of diabetes/pre-diabetes appears to be accelerating at a time when the prevalence of obesity has stabilized, indicating that the negative feedback system of the immune system has been overwhelmed.

The theory of vaccine induced immune overload can explain the key observations that have confounded many competing hypotheses.

The current paper reviews the evidence that vaccine-induced immune overload explains the disconnect between the increase in pre-diabetes and nonalcoholic fatty liver at a time when the obesity epidemic is waning in children.

Introduction

Twenty years ago it was predicted that a massive increase in immunization would result in a massive increase in people with chronic immune related diseases like type 1 diabetes, autoimmune diseases, and asthma [1].

A massive increase in immunization has occurred. In the United States for example since just 1999 children are scheduled to routinely receive over 80 additional vaccines over their childhood as explained below. The increase in immunization has been followed by a huge increase in inflammation associated disorders.

Diseases like autism, type 1 diabetes, asthma, food allergies, many autoimmune diseases, obesity, type 2 diabetes, NASH and metabolic syndrome have increased many-fold in children. The rate of change of several closely followed diseases appear to be accelerating while others have decelerated. This paper describes how the theory of vaccine-induced immune overload can explain many observations about the changes in the epidemics.

Many hypotheses have been proposed to find alternate explanations for these epidemics, such as the hygiene hypothesis for autoimmune diseases and poor diet or decreased exercise for the obesity epidemic.

These hypotheses don't readily explain the recent changes in the rates of these diseases.

For example, the prevalence of obesity in US children has stabilized while junk food and leisure activities persists, and the epidemics of autoimmune diseases continue to rise at a time where hygiene does not seem to increase.

Recently publications have provided evidence that vaccines are responsible for the epidemics of both autoimmune diseases such as type 1 diabetes as well as the epidemic of type 2 diabetes, obesity and metabolic syndrome [2]. One major problem with vaccines is the concept of one size fits all.

Package inserts of almost all vaccines recommend a dose based on age. In order for a vaccine to be a commercial success it is expected to induce a protective immune response in well over 90% of children. In order for this to happen a dose, based on age, must stimulate a protective immune response in those with the weakest immune system.

In the process of doing this, the other 90% or more of children have their immune system overstimulated. The process of over-stimulating the immune system time and time again increases the risk of inflammatory diseases like autoimmune diseases, and allergies which cause even more inflammation.

The clinical manifestation of disease depends on one's physiologic response to inflammation as has previously been reviewed[3]. Inflammation causes the release of cytokines which can trigger autoimmune diseases but also stimulate cortisol production, the major negative feedback loop of the immune system.

According to the theory, inflammation-induced cortisol production varies based on race [3] which can be explained by the presence of genes that alter cortisol production. Individuals who produce a lot of cortisol in response to inflammation have a tendency to develop a Cushingoid like response that includes obesity, type 2 diabetes/insulin resistance, hypertension, and dyslipidemia which is called metabolic syndrome.

Evidence that vaccines cause type 1 diabetes has been well-established. Data from a large prospective clinical trial of the Haemophilus vaccine [4] as well as epidemiology data [5] support vaccines as a major causative agent for type 1 diabetes. The data from the clinical trial validates an animal toxicity model [4]. The findings were verified by others [6].

Discontinuation of vaccines has been repeatedly shown to be followed by declines in the rates of type 1diabetes [5,7]. Evidence that vaccines cause type 2 diabetes, obesity and metabolic syndrome has been reviewed recently [2]. Evidence includes the observation that the discontinuation of school age BCG vaccination in Japan was followed by a decrease in type 2 diabetes in children in Japan [8].

Since 1999 the routine pediatric immunization schedule [9,10] increased by 80 vaccines. This number is derived by the fact that multivalent vaccines contain specific vaccines to each separate strain.

The following vaccines have been added: pneumococcus (13 valent), meningococcus (4 valent), human papilloma virus (4 valent), hepatitis A (1 valent), rotavirus (4 additional valent), influenza (3 valent per year x 18 years=54).

<<snip>>

Parallel Epidemics of Autoimmune/Inflammatory Diseases

The theory of vaccine-induced immune overload explains the parallel epidemics of multiple different autoimmune diseases. It is a known fact that the pathophysiology is shared in many autoimmune and inflammatory diseases.

Patients with autoimmune disease often have more than one autoimmune disease or have a family history of multiple different autoimmune diseases.

It is thus not surprising that many inflammatory diseases are increasing along with type 1 diabetes, in fact it is expected. A wide variety of diseases have been reported to be increasing in children. There are insufficient data to know if the prevalence of the majority of inflammatory diseases is increasing.

However, given the number and variety diseases that are reported to be increasing in children it is likely many more are also increasing.

Epidemiology studies show a close linkage between type 1 diabetes and other autoimmune diseases. Type 1 diabetes is strongly linked with other autoimmune diseases in Type II polyglandular autoimmune syndrome [19]. In this syndrome 52% of patients have diabetes mellitus, 69% have autoimmune thyroid disease and 100%have Addison's disease.

Patients with type 1 diabetes and their close relatives are at increased risk for organ specific autoimmune diseases[20]. Some of the epidemiology data comes from studies of families where several members have autoimmune disease.

Family studies indicate type 1 diabetes is linked to the development of several different autoimmune diseases including organ specific autoimmune diseases and rheumatoid diseases. Close relatives of patients with type1 diabetes have an increased risk of a wide variety of different autoantibodies [21,22].

It has been found that depending on the family, type 1 diabetes is linked with either an increased risk of an organ specific autoimmune disease or a rheumatoid disease [23]. A large study of Mennonites showed a linkage between type 1 diabetes and other autoimmune diseases including organ specific and rheumatoid diseases [24].

Immune stimulation with alpha interferon increases the risk of type1 diabetes and a wide variety of other autoimmune diseases. People receive alpha interferon for the treatment of viral hepatitis and cancers. Alpha interferon has been repeatedly reported to cause type 1

diabetes in humans [25-28]. One of 40 patients receiving alpha interferon in a Japanese study developed anti-islet cell antibodies [28].

An Italian study found 14 of 11,241 patients receiving alpha interferon developed diabetes mellitus [29]. Alpha interferon also increases the risk of organ specific autoimmune diseases such as thyroiditis and autoimmune rheumatic diseases such as SLE, rheumatoid arthritis, psoriasis and sarcoid [30]. It has been reported that upon the administration of alpha interferon that the same patient developed both rheumatoid and organ specific autoimmune diseases [31,32].

It is well accepted that the diagnosis of autism is epidemic. Many cases of autism have a strong inflammatory component and the epidemic has already been linked to vaccine induced overload [33].

Autism epidemiological linked to diabetes and those with autism have a family history of increased risk for autoimmune diseases. Attention deficit syndrome is epidemic and epidemiologically linked to increased risk of immune disorders [34].

Many inflammatory mediated diseases other than diabetes are epidemic. The incidence of psoriasis has been reported to double in children [35]. Autoimmune anti-neutrophil cytoplasmic antibody vasculitis resulting in renal failure has also been increased [36].

Wegener's Granulomatosis has been reported to increase in children[37].

The incidence of inflammatory bowel disease is also increasing rapidly in children [38].

Data indicates vaccines can act to sensitize recipients to environmental antigens. The CDC [39] found several vaccines were associated with an increased risk of asthma including the Haemophilus influenzae type b, relative risk 1.18 (1.02 to 1.36) and

hepatitis B vaccine 1.20 (1.13 to 1.27).

It is not surprising then that there is a rise in food related allergens [40]. Peanut allergy has tripled in children since 1997 [41]. Immune mediated food related disease, celiac disease [42], has also increased substantially.

Conclusion

There has been an epidemic of inflammatory diseases that has paralleled the epidemic of iatrogenic immune stimulation with vaccines. The epidemic of diabetes/prediabetes appears to be accelerating at a time when the prevalence of obesity has stabilized, indicating that the negative feedback system of the immune system has been over-whelmed.

The theory of vaccine-induced immune overload explains the key observations that have confounded many competing hypotheses. Unfortunately, the prospective controlled trials of vaccines performed for licensure are either too small, too short in duration or inappropriately controlled (use other vaccines as controls) to appropriately study the relationship between vaccines and the epidemics. Furthermore, most epidemiological studies performed after-licensure of vaccines suffer from the same deficiencies.

The conclusions of this paper are based on data from a single clinical trial, animal toxicity studies, and epidemiological studies. While it would be ideal to have more clinical trial data, industry and government have been reluctant to provide such information.

However, conclusions regarding toxicity of many agents including cigarettes and asbestos were made without clinical trial data.

The author believes that the sum of the data described and reviewed in this paper supports a causal relationship.

References (673 words)

1. Classen JB (1998) Method and Composition for an Early Vaccine to Protect Against Both Common Infectious Diseases and Chronic Immune Mediated Disorders or Their Sequelae. USA Patent 5723283.

2. Classen JB (2012) Review of evidence that epidemics of type 1 diabetes and type 2 diabetes/metabolic syndrome are polar opposite responses to iatrogenic inflammation. Curr Diabetes Rev 8: 413-418.

3. Classen JB (2009) Evidence childhood epidemics of type 1 and type 2 diabetes are opposite extremes of an immune spectrum disorder induced by immune stimulants. Role of race and associated cortisol activity as a major determining factor of diabetes. Diabetes Metabol Syn Clin Res Rev 3: 67-69.

4. Classen JB, Classen DC (2002) 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 35: 247-253.

5. Classen JB (2008) Risk of vaccine induced diabetes in children with a family history of type 1 diabetes. Open Pediatr Med J 2: 7-10.

6. Wahlberg J, Fredriksson J, Vaarala O, Ludvigsson J; Abis Study Group (2003) Vaccinations may induce diabetes-related autoantibodies in one year-old children. Ann N Y Acad Sci 1005: 404-408.

7. Classen JB, Classen DC (2003) Clustering of cases of type 1 diabetes mellitus occurring 2-4 years after vaccination is consistent with clustering after infections and progression to type 1 diabetes mellitus in autoantibody positive individuals. J Pediatr Endocrinol Metab 16: 495-508.

8. Classen JB (2008) 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. Open Endocrinol J 2: 1-4. <<SNIP>>

11. May AL, Kuklina EV, Yoon PW (2012) Prevalence of cardiovascular disease risk factors among US adolescents, 1999-2008. Pediatrics 129: 1035-1041.

12. Classen JB (2011) Italian pediatric data support hypothesis that simultaneous epidemics of type 1 diabetes and type 2 diabetes/metabolic syndrome/obesity are polar opposite responses (i.e symptoms) to a primary inflammatory condition. JPEM 24: 455-456.

13. Classen JB (2008) Type 1 versus type 2 diabetes/metabolic syndrome, opposite extremes of an immune spectrum disorder induced by vaccines. Open Endocrinol J 2: 9-15. <<SNIP>>

19. Trence DL, Morley JE, Handwerger BS (1984) Polyglandular autoimmune syndromes. Am J Med 77: 107-116.

20. Batterle C, Zanette F, Pedini B, Presotto F, Rapp LB, et al. (1984) Clinical and subclinical organ specific autoimmune manifestations in type 1 (insulin dependent) diabetic patients and their first-degree relatives. Diabetologia 26: 431-436.

21. Hagglof B, Rabinovitch A, Mackay P, Huen A, Rubenstein AH, et al. (1986) Islet cell and other organ-specific autoantibodies in healthy firstdegree relatives to insulin-dependent. Acta Paediatr Scand 75: 611-618.

22. Lorini R, Larizza D, Livieri C, Cammareri V, Martini A, et al. (1986) Auto-immunity in children with diabetes mellitus and in their relatives. Eur J Pediatr 145: 182-184.

23. Torfs CP, King MC, Huey B, Malmgren J, Grumet FC (1986) Genetic interrelationship between insulin dependent diabetes mellitus, the autoimmune thyroid diseases, and rheumatoid arthritis. Am J Hum Genet 38: 170-187. <<SNIP>>

33. Classen JB (2013) Prevalence of Autism is Positively Associated with the Incidence of Type 1 Diabetes, but Negatively Associated with the Incidence of Type 2 Diabetes, Implication for the Etiology of the Autism Epidemic. Open Access Sci Rep 2: 1-3.

34. Chen MH, Su TP, Chen YS, Hsu JW, Huang KL, et al. (2013) Comorbidity of Allergic and Autoimmune Diseases Among Patients with ADHD: A Nationwide Population-Based Study. J Atten Disord. <<SNIP>>

37. Grisaru S, Yuen GW, Miettunen PM, Hamiwka LA (2010) Incidence of Wegener's granulomatosis in children. J Rheumatol 37: 440-442.

38. Lehtinen P, Ashorn M, Iltanen S, Jauhola R, Jauhonen P, et al. (2011) Incidence trends of pediatric inflammatory bowel disease in Finland, 1987-2003, a nationwide study. Inflamm Bowel Dis 17: 1778-1783.

39. DeStefano F, Gu D, Kramarz P, Truman BI, Iademarco MF, et al. (2002) Childhood vaccinations and risk of asthma. Pediatr Infect Dis J 21: 498-504.

40. Prescott S, Allen KJ (2011) Food allergy: riding the second wave of the allergy epidemic. Pediatr Allergy Immunol 22: 155-160.