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:


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.


Interferon gamma

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

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
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


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
          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


copyright 1999