Research document and recommendation for Dan Burton,
Representative from Indiana,
House Government Reform Committee,
regarding: Vaccines: finding a balance...
MECHANISMS OF VACCINATION SEQUELAE a sampling from scientific literature
August 3, 1999
final by Teresa Binstock Researcher in Developmental and Behavioral Neuroanatomy email: email@example.com
This letter does not recommend that all vaccinations be discontinued; instead, this document offers a sampling of scientific evidence delineating mechanisms by which vaccination-induced neuropathy and vaccination-induced intestinal problems occur in some individuals, including children plunged into the autism-spectrum soon after a vaccination. For reasons set forth hereinbelow, my conclusion is as follows:
In light of a growing body of scientific information, vaccination- exemption criteria ought be expanded, especially in regard to infants, toddlers, and women of childbearing age.
Despite using restrictive criteria, many studies have documented a relationship between vaccinations and adverse neurologic sequelae (eg, 1-8). Some of these studies focused upon febrile seizures during short time periods after various vaccinations. More recent studies have documented brain regions that are affected by febrile seizures (9-11); and these brain regions correspond to brain regions implicated in autism-spectrum disorders (eg, 12). In the very least, these two research domains offer a mechanism whereby some children's deterioration into the autism-spectrum may have occurred.
When a child is vaccinated, a complex physiological process is initiated. For instance, a 1997 article documented that in human infants, a primary effect of the MMR vaccination is a prolonged pulse of endogenously created interferon gamma (13). This finding, in conjunction with other studies about interferon gamma, supports the anecdotal documentation by numerous parents of children whose gastrointestinal and/or neurologic function deteriorated subsequent to a vaccination. One of interferon gamma's most important effects is that of increasing permeability of tissues that normally have highly restricted permeability. Two such tissues are the intestinal tract and the blood-brain barrier. Interferon gamma is now realized to increase permeability in both of these tissues (eg, 14- 17); and the increased permeability can have pathological significance. Intestinal permeability increased by interferon gamma can lead to increased translocation of pathogens (eg, 18); and increased permeability of the blood- brain barrier is associated with a variety of pathologic states, ranging from CNS-infiltration of peripheral pathogens, to CNS-entry of activated B-cells and T-cells of the human immune system (19-24).
Measles virus and measles vaccination impair immunity
For nearly two decades, Diane E. Griffin and colleagues at Johns Hopkins have been documenting the mechanisms by which measles and measles vaccinations impair immunity, thereby increasing risk of reactivation of current infections and increasing the likelihood that a newly acquired infection will be more serious (25-29). By subjecting an an infant to an MMR around the time of his or her 1st birthday, a physician not only causes the pre-toddler to have impaired immunity for several weeks or months thereafter, but this impairment in immunity occurs during what for some children is an extended period of normally occurring "transient hypogammaglobulinemia of infancy", ie, a time between (a) the decline of maternal antibodies in the infant's blood, and (b) the gradual strengthening of the infant's own immune defenses (eg, 30-32). In other words, a naturally occurring period of increased susceptibility to infection in some pre-toddlers is the very time at which the MMR and its immune-impairment are mandated. To administer the MMR during a time of naturally lower immunity (in some children) means that those children would be at increased risk of having an increased pathogen load in peripheral tissues as the MMR-induced pulse of interferon gamma increased permeability in the intestinal and blood-brain barriers. Cytomegalovirus (CMV) provides an example, because infants can be congenitally or neonatally infected but remain asymptomatic even though the CMV remains within the child (33). For some such children, a vaccination that impairs immunity would be permissive for increased viral replication. Furthermore, that same vaccination (eg, the MMR), via its pulse of endogenous interferon gamma, would increase blood-brain barrier and gastrointestinal permeability concurrently with increased viral replication occurring in the presence of vaccination-impaired immunity.
A large number of parents are convinced that their child's descent into the autism-spectrum began soon after a major vaccination such as the HepB, DPT, or MMR. Increasingly, medical literature is documenting the vaccination-related mechanisms by which immunity is impaired by vaccinations and by which neurologic and gastrointestinal sequelae may ensue. As examples, this document offers citations (a) about vaccination-induced interferon gamma and its effects upon permeability of intestinal tissue and of the blood-brain barrier, and (b) about how a measles vaccination induces prolonged impairment of immunity. In addition, other concerns regarding advense vaccinal events ought be addressed by the committee. Specifically, A. The post-vaccination time-periods studied for negative effects have been too brief, especially (i) since the mechanisms by which vaccination sequelae can occur are diverse and, (ii) since, given the epidemiology of childhood pathogens, when combined with effects induced by a vaccination-induced pulse of interferon gamma, there is likely to be much inter-individual variation in vaccination-induced pathology and related data. B. Febrile seizures and their sequelae are important, but they are not the only mechanism by which vaccination-induced neuropathy or gastroinestinal difficulty can occur. Interferon gamma's effects upon MHC-I and MHC-II presentation should also be considered in regard to not uncommon "asymptomatic" infections common in infants (33). C. Some individuals have impaired antibody responses to a vaccinal antigen (34). When a child or woman of childbearing age is found to have missing antibodies for a common vaccinal antigen, there are at least two possibilities to be considered: One, that the person's vaccinal immunity has subsided, or Two, that he or she has an immune weakness specific for that pathogen-specific antigen ought be watched more closely for vaccinational responses or infectious episodes that might have neurologic or other adverse effects (35-36). For a child or woman with seemingly low vaccinal antibodies, additional immune testing ought preceed hasty decisions to vaccinate, especially since at least some vaccines impair immunity, thereby creating the possibility of a woman of childbearing age acquiring an infection she might otherwise have successfully immunosuppressed. D. This document is but a preliminary sketch, the proverbial tip of a very large iceberg. In other words, solidly researched findings of the last ten years are revealing numerous mechanisms by which vaccination-induced pathologies can occur. Vaccination guidelines need revision.
Recommendations to the Committee
As a researcher who listens to parents of autism-spectrum children and who has perused medical literature regarding various mechanisms by which negative vaccination-induced sequelae can occur, my suggestions to the Committee are as follows:
1. In studying vaccination-induced pathologies, longer post-vaccination time periods and a variety of vaccination-pathology mechanisms ought be considered. 2. US infants and toddlers are receiving too many vaccinations too soon. 3. Sick kids or recently sick kids ought not be vaccinated. 4. The criteria for vaccination-exclusion and vaccination-delay ought be expanded significantly.
Sincerely and respectfully, Teresa Binstock Researcher in Developmental and Behavioral Neuroanatomy Denver
A series of autism-related webpagesContents email to: Teresa Binstock
1. Tonz O, Bajc S. [Convulsions after whooping-cough vaccination]. [Article in German] Schweiz Med Wochenschr 1980 Dec 20;110(51):1965-71. ab: Convulsions or status epilepticus in 11 infants after pertussis vaccination are reported. In 3 cases grand mal epilepsy persisted and 2 children developed infantile epileptic encephalopathy (Lennox syndrome). On the basis of our own experience, the incidence of seizures approximates 1:4800 infants vaccinated or 1:12 800 vaccinations. According to a recent prospective study from the USA, the incidence of seizures may be closer to 1:600 infants... 2. Hirtz DG et al. Seizures following childhood immunizations. J Pediatr 1983 Jan;102(1):14-8 1983. ab: In 1.4% of children who experienced a seizure during the first seven years of life, the seizure followed within two weeks of an immunization procedure. We report 40 postimmunization seizures in 39 children enrolled in the Collaborative Perinatal Project. Ten seizures followed diphtheria-pertussis-tetanus (DPT) immunization, and 10 followed measles immunization. All but one of the seizures were associated with fever, often high. Thirty-seven seizures lasted less than 30 minutes. More than half of the children had a personal or immediate-family history of febrile seizures. One of the children had a right focal seizure lasting six hours after DPT immunization and had a significant speech deficit on long-term follow-up... 3. Murphy JV et al. Recurrent seizures after diphtheria, tetanus, and pertussis vaccine immunization. Onset less than 24 hours after vaccination. Am J Dis Child 138(10):908-11 1984. ab: Twenty-two patients with recurrent seizures that started less than 24 hours after immunization with diphtheria, tetanus, and pertussis (DTP) vaccine were retrospectively studied. The initial seizure generally occurred after one of the first three DTP vaccine immunizations, and followed that immunization by less than 12 hours... 4. Jacobson V et al. Relationship of pertussis immunization to the onset of epilepsy, febrile convulsions and central nervous system infections: a retrospective epidemiologic study. Tokai J Exp Clin Med 13 Suppl:137-42 1988. Department of Neurology, UCLA School of Medicine. ab: A change in the pertussis immunization schedule in Denmark allowed a retrospective study examining the relationship of the time of onset of selected neurologic disorders with the time of pertussis immunization in two core cohorts of children. Records of 2,199 children with febrile seizures were reviewed and a significant association between first febrile seizures and the scheduled age of pertussis immunization was noted (p = 0.004)... 5. Baraff LJ et al. Infants and children with convulsions and hypotonic-hyporesponsive episodes following diphtheria-tetanus-pertussis immunization: follow-up evaluation. Pediatrics 81(6):789-94 1988. Department of Pediatrics, University of California, Los Angeles, School of Medicine. ab: In a prior prospective study, we evaluated the nature and rates of adverse reactions occurring within 48 hours following 15,752 diphtheria-tetanus-pertussis (DTP) immunizations. Nine children had convulsions, and nine had hypotonic-hyporesponsive episodes... No child had significant neurologic deficit, although four had minor neurologic abnormalities... 6. Griffin MR et al. Risk of seizures and encephalopathy after immunization with the diphtheria-tetanus-pertussis vaccine. JAMA 263(12):1641-5 1990. Department of Preventive Medicine, Vanderbilt University School of Medicine, Nashville, Tenn 37232-2637. ab: We evaluated the risks of seizures and other neurological events following diphtheria-tetanus-pertussis (DTP) immunization for 38,171 Tennessee Medicaid children who received 107,154 DTP immunizations in their first 3 years of life. There were 2 children with encephalitis; both had disease onset more than 2 weeks following DTP immunization. There were 277 children who had febrile seizures, 42 with afebrile seizures, and 37 with seizures associated with other acute neurological illness (acute symptomatic). The risk of febrile seizures in the 0 to 3 days following DTP immunization (n = 6) was 1.5 (95% confidence interval, 0.6 to 3.3) times that of the control period 30 or more days following DTP immunization... 7. Griffin MR et al. Risk of seizures after measles-mumps-rubella immunization. Pediatrics 1991 Nov;88(5):881-5 1991. ab: To evaluate the risks of seizures and other neurologic events following measles-mumps-rubella (MMR) or measles-rubella (MR) immunization, a retrospective cohort study was conducted among 18,364 Tennessee children enrolled in Medicaid who received MMR or MR immunizations in their first 3 years of life. One hundred children had seizures at some time between immunization and 36 months; there were no encephalopathies during this period. Four children had febrile seizures in the 7 through 14 days following MMR or MR immunization compared with 72 in the interval 30 or more days following MMR or MR immunization yielding a relative risk (95% confidence interval) of 2.1 (0.7 to 6.4). Although not statistically significant, this increase in febrile seizures in the 7- through 14-day interval following MMR immunization is coincident with the occurrence of fever following MMR immunization and is consistent with reports of other investigators. 8. Cherry JD et al. Pertussis immunization and characteristics related to first seizures in infants and children. J Pediatr 122(6):900-3 1993. Department of Pediatrics, University of California Los Angeles School of Medicine. ab: In a previous study in which we examined the relationship of pertussis immunization to the onset of neurologic disorders during 1967 and 1968 and during 1972 and 1973 in Denmark, there were 554 children with initial onset of epilepsy and 2158 children with first febrile convulsions... The cause of increased severity of febrile seizures apparently associated with pertussis immunization is unknown. 9. Tuunanen J et al. Decrease in somatostatin-immunoreactive neurons in the rat amygdaloid complex in a kindling model of temporal lobe epilepsy. Epilepsy Research. 26(2):315-327, 1997. 10. Tuunanen J et al. Status epilepticus causes selective regional damage and loss of gabaergic neurons in the rat amygdaloid complex. European Journal of Neuroscience. 8(12):2711-2725, 1996. 11. Chen K et al. Febrile seizures in the developing brain result in persistent modification of neuronal excitability in limbic circuits. Nat Med 1999 Aug;5(8):888-94. Department of Anatomy and Neurobiology, University of California, Irvine 92697-1280, USA. 12. Bachevalier J. Medial temporal lobe structures and autism: a review of clinical and experimental findings. Neuropsychologia. 32(6):627-48, 1994. 13. Pabst HF et al. Kinetics of immunologic responses after primary MMR vaccination. Vaccine. 15.1.10-4 1997. ab: To study the kinetics of humoral as well as cellular immunity to measles and to test for associated immunosuppression 124 12 month old children were studied twice, before routine MMR and either 14, 22, 30, or 38 days after vaccination... Interferon-gamma was the principal cytokine produced after primary measles immunization... 14. Madara JL, Stafford J. Interferon-gamma directly affects barrier function of cultured intestinal epithelial monolayers. Journal of Clinical Investigation 83.2.724-7 1989. 15. Huynh HK, Dorovini-Zis K. Effects of interferon-gamma on primary cultures of human brain microvessel endothelial cells. American Journal of Pathology 142.4.1265-78 1993. "The results of these studies indicate that human brain microvessel endothelial cells respond to in vitro cytokine stimulation by undergoing profound morphological, functional, and permeability changes. We conclude that cerebral endothelium may play an important role in the initiation and regulation of lymphocyte traffic across the blood-brain barrier in inflammatory disorders of the human central nervous system." 16. Planchon SM et al. Regulation of intestinal epithelial barrier function by TGF-beta 1. Evidence for its role in abrogating the effect of a T cell cytokine. Journal of Immunology 153.12.5730-9 1994. "Maintenance of the integrity of the single-cell-thick intestinal epithelium as an in vivo barrier between environmental Ags and mucosal immunocytes is pivotal for health. The T cell cytokine IFN-gamma consistently disrupts this epithelial barrier in vitro..." 17. Adams RB et al. IFN-gamma modulation of epithelial barrier function. Time course, reversibility, and site of cytokine binding. Journal of Immunology 150.6.2356-63 1993. "...we suggest that IFN-gamma-induced changes in epithelial permeability may be a major cause of altered intestinal barrier function in vivo." 18. Berg RD. Bacterial translocation from the gastrointenstinal tract. Journal of Medicine 23.217-244 1992. 19. Banati RB, Graeber MB. Surveillance, intervention and cytotoxicity: Is there a protective role of microglia? Developmental Neuroscience 16.114-27 1994. 20. Benveniste EN. Inflammatory Cytokines within the central nervous system: sources, function, and mechanism of action. American Journal of Physiology 263.C1-C16 1992. 21. Hickey WF et al. T-lymphocyte entry into the central nervous system. Journal of Neuroscience Research 28.54-260 1991. 22. Cserr HF, Knopf PM. Cervical lymphatics, the blood-brain barrier and the immunoreactivity of the brain: a new view. Immunology Today 13.507-512 1992. 23. Stoll G, Jander S. The role of microglia and macrophages in the pathophysiology of the CNS. Prog Neurobiol 58.233 1999. 24. Matyszak MK. Inflammation in the CNS: balance between immunological privilege and immune responses. Prog Neurobiol 56.19-35 1998. 25. Karp CL et al. Mechanism of suppression of cell-mediated immunity by measles virus. Science 1996 Jul 12;273(5272):228-31. 26. Hussey GD et al. The effect of Edmonston-Zagreb and Schwarz measles vaccines on immune response in infants. J Infect Dis 1996 Jun;173(6):1320-6. "...measles immunization resulted in suppression of lymphoproliferation, which was most evident in infants with the highest antibody responses and most immune activation." 27. Auwaerter PG et al. Changes within T cell receptor V beta subsets in infants following measles vaccination. Clin Immunol Immunopathol 1996 May;79(2):163-70. "Measles produces immune suppression which contributes to an increased susceptibility to other infections. Recently, high titered measles vaccines have been linked to increased long-term mortality among some female recipients." 28. Ward BJ, Griffin DE. Changes in cytokine production after measles virus vaccination: predominant production of IL-4 suggests induction of a Th2 response. Clin Immunol Immunopathol 1993 May;67(2):171-7. Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205. 29. Wu VH et al. Measles virus-specific cellular immunity in patients with vaccine failure. J Clin Microbiol 1993 Jan;31(1):118-22. 30. Dressler F et al. Transient hypogammaglobulinemia of infancy. Acta Paediatrica Scandinavia 78.767-74 1989. 31. Cano F et al. Absent specific viral antibodies in patients with transient hypogammaglobulinemia of infancy. Journal of Allergy & Clinical Immunology 85.510-3 1990. 32. Glassman M et al. High incidence of hypogammaglobulinemia in infants with diarrhea. Journal of Pediatric Gastroenterology and Nutrition 2.465-71 1983. 33. Pass RF et al. Specific lymphocyte blastogenic responses in children with cytomegalovirus and herpes simplex virus infections acquired early in infancy. Infect Immun 34.1.166-70 1981. ab: Cell-mediated immune responses in 27 infants and children with cytomegalovirus (CMV) infection acquired between birth and 1 year of age were compared with responses in 13 children who had neonatal herpes simplex virus (HSV) infection. Infection was asymptomatic in 25 of 27 CMV-infected children... 34. Hayney MS et al. The influence of the HLA-DRB1*13 allele on measles vaccine response. J Investigative Medicine 44.261-3 1996. Mayo Clinic and Foundation, Rochester, MN. 35. McCusker C et al. Specific antibody responses to diptheria/tetanus revaccination in children evaluated for immunodeficiency. Ann Allergy Asthma Immunol 79.145-50 1997. 36. Epstein MM, Gruskay F. Selective deficiency in pneumococcal antibody response in children with recurrent infections. Ann Allergy Asthma Immunol 75.125-31 1995.
A series of autism-related webpagesContents email to: Teresa Binstock