DPT adverse reaction citations
Citations  DPT vaccines

SeeGeier, MR and Geier, DA  

Key realities about autism, vaccines, vaccine-injury compensation, Thimerosal, and autism-related research----Gary S. Goldman, Ph.D & P.G. King PhD

[1998] Thomas Vogt, Michael Landthaler and Wilhelm Stolz. Generalized eczema in an 18-month-old boy due to phenoxyethanol in DPT vaccine

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In one study, serious reactions to the DPT vaccine (including grand mal epilepsy and encephalopathy) were shown to be as high as 1 in 600. In another study, approximately one out of every 200 children who received the full DPT series suffered severe reactions.  Immunization: Survey of Recent Research, (United States Department of Health and Human Services, April 1983), p. 76.

A study revealed that 1 in 175 children who completed the full DPT suffered severe reactions ("Nature and Rates of Adverse Reactions  Associated with DPT and DT Immunizations in Infants and Children" [Paediatrics, Nov. 1981, Vol.68, No.5]) and a Dr.'s report for attorneys which found that 1 in 300 DPT immunizations resulted in seizures (The Fresno Bee, Community Relations, DPT Report, Dec 5, 1984).

Autism: A Unique Type of Mercury Poisoning By Sallie Bernard, Albert Enayati, B.S., Ch.E., M.S.M.E., Teresa Binstock, Heidi Roger, Lyn Redwood, R.N., M.S.N., C.R.N.P., Woody McGinnis, M.D.

"Acute Autoimmune Hemolytic Anemia Following DTP Vaccination: Report of a Fatal Case and Review of the Literature"

Amsel SG, et al.   Myocarditis after triple immunisation. Arch Dis Child. 1986 Apr;61(4):403-5. PMID: 3486636; UI: 86214173.        

Baraff LJ, et al.      DTP vaccine reactions: effect of prior reactions on rate of subsequent reactions. Dev Biol Stand. 1985;61:423-8. PMID: 3879687; UI: 86221308.    

These data strongly support the presumption that children who have had previous reactions following DTP immunization are more likely to have similar reactions upon subsequent immunization.

Baraff LJ et al (1988). 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.

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...

Neustaedter comment: Evaluation of these children by an independent pediatric neurologist…revealed significant language & learning difficulties. These included…ADD, motor abnormalities, borderline or low IQ, and mental retardation…drastically different than the government sponsored findings…."Only 4 of the 13 tested were unequivocally normal."

Baraff LJ, et al (1983) Possible temporal association between diphtheria-tetanus toxoid-pertussis vaccination and sudden infant death syndrome. Pediatr Infect Dis. 1983 Jan-Feb;2(1):7-11. PMID: 6835859; UI: 83169234.

Because diphtheria and tetanus toxoids pertussis (DTP) vaccine is routinely given during the period of highest incidence of sudden infant death syndrome (SIDS), this study was undertaken to determine if there is a temporal association between DTP immunization and SIDS. Parents of 145 SIDS victims who died in Los Angeles County between January 1, 1979, and August 23, 1980, were contacted and interviewed regarding their child's recent immunization history. Fifty-three had received a DTP immunization. Of these 53, 27 had received a DTP immunization within 28 days of death. Six SIDS deaths occurred within 24 hours and 17 occurred within 1 week of DTP immunization. These SIDS deaths were significantly more than expected were there no association between DTP immunization and SIDS. An additional 46 infants had a physician/clinic visit without DTP immunization prior to death. Forty of these infants died within 28 days of this visit, seven on the third day and 22 within the first week following the visit. These deaths were also significantly more than expected. These data suggest a temporal association between DTP immunization, physician visits without DTP immunization and SIDS. PMID: 6835859, UI: 83169234

Bernier RH, et al (1982). Diphtheria-tetanus toxoids-pertussis vaccination and sudden infant deaths in Tennessee. J Pediatr. 1982 Sep;101(3):419-21. No abstract available. PMID: 7108666; UI: 82268390.

Braun MM, et al (1998). Report of a US public health service workshop on hypotonic-hyporesponsive episode (HHE) after pertussis immunization. Pediatrics. 1998 Nov;102(5):E52. PMID: 9794982; UI: 99017237.

Basa, SN, "Paralytic Poliomyelitis Following Inoculation With Combined DTP Prophylactic. A review of Sixteen cases with Special Reference to Immunization Schedules in Infancy", J Indian Med Assoc, Feb 1, 1973, 60:97-99.

Briukhanova LK, et al (1979). [Lyell's syndrome following vaccination with diphtheria-pertussis-tetanus vaccine in a 9-month-old child]. Pediatriia. 1979 Feb;(2):60-1. Russian. No abstract available. PMID: 450585; UI: 79200814.

Berg, J M, "Neurological Complications of Pertussis Immunization," Brit Med Jour, July 5,1958; p 24.

Cupic V,et al, "[Role of DTP vaccine in the convulsive syndromes in children]," Lijec Vjesn 1978 Jun; 100 (6):345-348. [Article in Serbo-Croatian (Roman)]

Cherry JD, et al.    Recurrent seizures after diphtheria, tetanus, and pertussis immunization. Cause and effect v temporal association. Am J Dis Child. 1984 Oct;138(10):904-7. No abstract available.PMID: 6332526; UI: 84304044.

Cherry, J.D (1988)., Brunell, P.A., Golden, G.S., Karzon, D.T., (1988), Report of the task force on pertussis and pertussis immunization, Pediatrics 81:6 Part 11 (June 1988) Supplement pp 936-984.

Excerpt: The rate of severe reactions does not differ significantly between the acellular and whole-cell vaccines when used at 24 months of age. The decrease in severe reactions is slight, if any. The category "sudden death" is also instructive in that the entity disappeared following both whole-cell and acellular vaccines when immunisation was delayed until a child was 24 months of age. It is clear that delaying the initial vaccination until a child is 24 months, regardless of the type of vaccine, reduces most of the temporally associated severe adverse events.

Extract: For more than 25 years, it has been known that pertussis vaccine is a reliable adjuvant for the production of experimental allergic encephalitis.   This experimental allergic encephalomyelitis is mediated by sensitized lymphocytes rather than serum antibody mechanisms. Pertussis vaccine has also been used as an adjuvant in the following experimental autoimmune diseases: thyroiditis, myocarditis, glomerulonephritis, uveoretinitis, and hemolytic anemia.  Except for the adjuvant effect upon antibody responses to specific vaccines, there is no evidence that any of the experimental adjuvant activities of pertussis vaccine, and specifically LPF, occur in vaccinated children.

Jacobson V et al (1988). 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.

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)...

Ciofi degli Atti ML, et al.    Severe adverse events in the Italian and Stockholm I pertussis vaccine clinical trials. Dev Biol Stand. 1997;89:77-81. PMID: 9272334; UI: 97418329.

Cody CL, et al (1981). Nature and rates of adverse reactions associated with DTP and DT immunizations in infants and children. Pediatrics. 1981 Nov;68(5):650-60. PMID: 7031583; UI: 82081582.
In 784 DT and 15,752 DTP immunizations given to children 0 to 6 years of age who were prospectively studied for reactions occurring within 48 hours following immunization, minor reactions were significantly more frequent following DTP vaccine. The ratio of reaction rates associated with DTP and DT immunizations (DTP/DT) for selected local and systemic reactions was as follows: local redness, 37.4%/7.6%; local swelling, 40.7%/7.6%; pain, 50.9%/9.9%; fever, 31.5%/14.9%; drowsiness, 31.5%/14.9%; fretfulness, 53.4%/22.6%; vomiting, 6.2%/2.6%; anorexia, 20.9%/7.0% and persistent crying, 3.1%/0.7%. Following DTP immunization nine children developed convulsions and nine developed hypotonic hyporesponsive episodes. No sequelae were detected following these reactions. Publication Types: Clinical trial PMID: 7031583, UI: 82081582

Cavanagh, NPC (1981); Brett, EM; Marshall, WC; Wilson, J; The Possible Adjuvant Role of Bordetella Pertussis and Pertussis Vaccine in Causing Severe Encephalopathic Illness: a Presentation of Three Case Histories; Neuropediatrics 12: 374-381 (1981)

The clinical and some laboratory details of three children who had severe neurological sequelae after either infection with Bordetella pertussis or immunisation with diphtheria, tetanus and pertussis vaccine and oral polio vaccine are reported. Each of these patients had had a recent or concurrent viral illness. The severity of their encephalopathic illness may have been due to an adjuvant role of B. pertussis or a component of the vaccines they received.

Cavanagh, NPC (1981); Brett, EM; Marshall, WC; Wilson, J; The Possible Adjuvant Role of Bordetella Pertussis and Pertussis Vaccine in Causing Severe Encephalopathic Illness: a Presentation of Three Case Histories; Neuropediatrics 12: 374-381 (1981)
The clinical and some laboratory details of three children who had severe neurological sequelae after either infection with Bordetella pertussis or immunisation with diphtheria, tetanus and pertussis vaccine and oral polio vaccine are reported. Each of these patients had had a recent or concurrent viral illness. The severity of their encephalopathic illness may have been due to an adjuvant role of B. pertussis or a component of the vaccines they received.

Blumberg DA, et al.    Severe reactions associated with diphtheria-tetanus-pertussis vaccine: detailed study of children with seizures, hypotonic-hyporesponsive episodes, high fevers, and persistent crying. Pediatrics. 1993 Jun;91(6):1158-65. PMID: 8502521; UI: 93275702.  

Cherry JD et al (1993). 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.

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.

Ditchburn, Robert K(1979); Whooping Cough after stopping pertussis immunisation; British Medical Journal; 1979, 1, 1601-1603; 16, June 1979;

Summary and Conclusions: An epidemic of whooping cough occurred in a rural practice in Shetland, containing 144 children under 16. Before July 1974, all children were immunised against pertussis, but after that date immunisation was stopped. Of the 134 children studied, 93 had been immunised. Sixty five of the children developed whooping cough. The incidence of infections was similar in those who had and had not been immunised. The incidence was also similar in those born before and after July 1974. There was not evidence to support the routine use of pertussis immunisation in rural Shetland.

Ehrengut W, "Bias in evaluating CNS complications following pertussis immunization." Acta Paediatr Jpn, 1991 Aug; 33(4):421-427

Ehrengut W at Institute of Vaccinology and Virology, Hamburg, Germany states, "Bias in the evaluation of CNS complications following pertussis immunization are the following: 1) Notifications of post-immunization adverse events, 2) Publications by vaccine producers on the frequency of adverse reactions, 3) Comparison of permanent brain damage after DPT and DT immunization, 4) Pro-immunization, 5) Immunization associated viral encephalitis, 6) Accuracy of statistics, 7) Personal. A review of these points indicates an underestimation of CNS complications after pertussis immunization."

Farooqi IS, et al. Early childhood infection and atopic disorder. Thorax. 1998 Nov;53(11):927-32. PMID: 10193389; UI: 99209469.Griffin MR, et al, "Risk of seizures after measles- mumps-rubella immunization," Pediatrics 1991 Nov;88 (5):881-885.

Greco D, et al, "Case-control study on encephalopathy associated with diphtheria-tetanus immunization in Campania, Italy," Bull World Health Organ 1985;63 (5):919-925.

Geraghty KC.DTP immunization and SIDS.J Pediatr. 1984 Jul;105(1):169-71. No abstract available.PMID: 6610735 [PubMed - indexed for MEDLINE]

Gross TP, et al.    Bulging fontanelle after immunization with diphtheria-tetanus-pertussis vaccine and diphtheria-tetanus vaccine. J Pediatr. 1989 Mar;114(3):423-5. No abstract available.PMID: 2921685; UI: 89157244.   

Griffin MR et al (1990). 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.

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...

Hurwitz EL, Morgenstern H. Effects of diphteria-tetanus-pertussis or tetanus vaccination on allergies and allergy-related respiratory symptoms among children and adolescents in the United States. J Manipulative Physiol Ther 2000;23: 1-10.
A new study in the Journal of Manipulative and Physiological Therapeutics1 supports the findings of three previous studies that children who receive diphteria-tetanus-pertussis (DTP) or tetanus vaccines are more likely to have a "history of asthma" or other "allergy-related respiratory symptoms." The study reviewed data from the Third National Health and Nutrition Examination Survey, which was conducted by the National Center for Health Statistics from 1988 to 1994. The survey data included interviews (by proxy with parents) of 13,944 infants, children and adolescents (2 months through 16 years old). http://www.chiroweb.com/archives/18/07/05.html

Haneberg B, et al (1978). Acute hemolytic anemia related to diphtheria-pertussis-tetanus vaccination. Acta Paediatr Scand. 1978 May;67(3):345-50. PMID: 654911; UI: 78183820.

Three infants developed severe hemolytic anemia following the second or third diphtheria-pertussistetanus vaccination. Direct antiglobulin tests were positive, and the infant most severely affected also had reduced serum complement levels, indicating an immunological mechanism for the hemolysis. The presence of IgM on the erythrocytes from 2 of the infants could be demonstrated by antiglobulin tests or immunization experiments. Heat eluates of the erythrocytes from one of the infants contained antibodies to tetanus and diphtheria toxoids, as well as to Bordetella pertussis, suggesting that these antibodies were antigenically bound to the erythrocytes. Virus antibodies or isoagglutinins, present in the serum, were not found in the eluate. No antibodies against the vaccine components could be demonstrated in eluates of erythrocytes from control subjects. In vivo experiments showed that tetanus and diphtheria toxoids were easily bound to human erythrocytes. This finding could help explain the pathogenesis of the autohemolysis. PMID: 654911, UI: 78183820

 Hannik, C.A 9 (1978) and Cohen, H. Changes in plasma insulin concentration and temperature of infants after pertussis vaccination, Third International Symposium on Pertussis, 1978, 297.

Abstract: Infants injected with DTP-Polio vaccine with a pertussis component of 16 International Opacity Units per dose showed slight but significant elevation in concentration of plasma insulin and temperature. These two phenomena are not interrelated. It is suggested that infants who show serious reactions following pertussis vaccination suffer from a failure to maintain glucose homeostasis.

Hewlett (1983), EL; Roberts, CO; Wolff, J; Manclark, CR; Biphasic Effect of Pertussis Vaccine on Serum Insulin in Mice; Infection and Immunity; July 1983; p 137-144

Abstract: Administration of pertussis vaccine, consisting of whole-killed Bordetella pertussis organisms, causes hyperinsulinemia and enhanced secretion of insulin in response to a variety of secretagogues in rats and mice. In examining the time course and properties of this phenomenon, we discovered two distinct and separate effects of the bacteria on glucose and insulin levels in mice. First, a heat-stable (80C for 30 min) component causes a brief hyperinsulinemia which is measurable by 1 h. maximal at 8 h. and ends in less than 48 h. This effect appears to be due to B. pertussis endotoxin and is associated with a transient, mild hypoglycemia. Second, there is a heat-labile component of the B. pertussis organism which induces a sustained (>14 days), dose-dependent hyperinsulinemia which reaches a maximum at 5 to 7 days and has no associated hypoglycemia. The two effects are further distinguishable in the early, endotoxin-induced hyperinsulinemia exhibits the normal suppressibility by exogenous epinephrine, whereas epinephrine markedly enhances the hyperinsulinemia occurring at 7 days. These two effects of B. pertussis appear to me mediated by different mechanisms and may be important in the well-recognised reactogenicity of pertussis vaccine in humans.

Iwasa, S (1985), Ishida, S; Akama, K; Swelling of the Brain in Mice Caused by Pertussis Vaccine – Its Quantitative Determination and the Responsible Factors in the Vaccine; Japanese Journal of Medicine; 38, 53-65, 1985
Summary: Intracerebral injection of vaccine into the mouse induced swelling of the brain. The swelling reached the maximum in the intensity by day 1 and persisted for several days. A method for quantitative determination of the brain-swelling activity of the vaccine was developed. A positive regression coefficient was found only between the brain-swelling and the lymphocytosis-promoting activities. Such activity was no longer shown with the vaccine heat-treated for 30 min. at 80C, but it was restored upon addition of the lymphocytosis-promoting factor (LPF) that caused no brain swelling itself. The activity, therefore was ascribed to cooperation of LPF and a certain heat-stable component other than endotoxin contained by pertussis vaccine.

Illingsworth R.     Skin rashes after triple vaccine. Arch Dis Child. 1987 Sep;62(9):979. No abstract available.PMID: 3499867; UI: 88048489.  

Iwasa, S (1985), Ishida, S; Akama, K; Swelling of the Brain in Mice Caused by Pertussis Vaccine – Its Quantitative Determination and the Responsible Factors in the Vaccine; Japanese Journal of Medicine; 38, 53-65, 1985
Summary: Intracerebral injection of vaccine into the mouse induced swelling of the brain. The swelling reached the maximum in the intensity by day 1 and persisted for several days. A method for quantitative determination of the brain-swelling activity of the vaccine was developed. A positive regression coefficient was found only between the brain-swelling and the lymphocytosis-promoting activities. Such activity was no longer shown with the vaccine heat-treated for 30 min. at 80C, but it was restored upon addition of the lymphocytosis-promoting factor (LPF) that caused no brain swelling itself. The activity, therefore was ascribed to cooperation of LPF and a certain heat-stable component other than endotoxin contained by pertussis vaccine.

Jacob J, et al.   Increased intracranial pressure after diphtheria, tetanus, and pertussis immunization. Am J Dis Child. 1979 Feb;133(2):217-8. No abstract available.PMID: 420195; UI: 79121860.
Jaber L, et al.     Infectious episodes following diphtheria-pertussis-tetanus vaccination. A preliminary observation in infants. Clin Pediatr (Phila). 1988 Oct;27(10):491-4. PMID: 3262480; UI: 89003899.
Katafuchi Y, et al.   [Acute cerebellar ataxia and facial palsy after DPT immunization]. No To Hattatsu. 1989 Sep;21(5):465-9. Japanese. PMID: 2803799; UI: 90027813.

Kulenkampff, M (1974), Schwartzman, JS, Wilson, J; Neurological Complications of Pertussis Inoculation; Archives of Disease in Childhood; 1974, 49, 46

Abstract: Findings are presented in 36 children, seen in the past 11 years, who are believed to have suffered from neurological complications of pertussis inoculation (given as triple vaccine). The clustering of complications in the first 24 hours after inoculation suggests a causal rather than a coincidental relation. Possible contributory factors were present in one-third of patients studied and support the view that idiosyncratic features are present in the patients, not the vaccine. A prospective review is urged. It is recommended that pertussis vaccine should not be given to patients with a history of fits, or a family history of fits in first-degree relatives, or to those who have had a reaction to previous inoculations, those who have had recent intercurrent infection, or those with presumed neurological deficit.

Lenard HG, Fest U, Scholz W.  [Complications of pertussis immunization (author transl)] Monatsschr Kinderheilkd. 1977 Jun;125(6):660-7. German. PMID: 18670 [PubMed - indexed for MEDLINE]

16 cases of neurological disease and/or death shortly after pertussis immunization are reported. Eight patients had convulsions, six with ensuing permanent defects. Severe polymyositis was observed in one case. Five infants died 12 h to 4 days after vaccination: two after acute encephalopathy and three in the form of a sudden unexpected death (SID). In two fatal cases the morphological changes in the brain corresponded to those of pertussis encephalopathy: neuronal degeneration in various parts of the cortex, especially in the region of the ammons horn, and in the cerebellum. There were no signs of inflammation. Three cases underwent forensic autopsy and death was attributed to bronchopulmonary infection. Complete neuropathological work-up was only done in one case, in which the brain was normal. The critique of episodical reports and the demand for prospective studies is appreciated. Knowledge of all possible forms of complications, however, is indispensable for future investigations. Polymyositis and SID have so far not been listed as abnormal reactions to immunization. The majority of our cases became known accidentally from hospital sheets or from discussions with collegues. For a detection of all possible cases a greater awareness of doctors for the problem of pertussis immunization appears necessary. Only another 23 cases have been reported to the health authorities of the state of Lower Saxony during the last 6 to 7 years. Of those, nine were either harmless reactions or diseases probably unrelated to vaccination. Two were cases of SID, 12 and 72 h after vaccination. It is concluded that only a minor proportion of possible complications is presently reported to the health authorities.

Leung A. Congenital heart disease and DPT vaccination.Can Med Assoc J. 1984 Sep 15;131(6):541. No abstract available.PMID: 6332664 [PubMed - indexed for MEDLINE]

Leung AK, et al (1987). Erythema multiforme following diphtheria-pertussis-tetanus vaccination. Kobe J Med Sci. 1987 Aug;33(4):121-4. No abstract available. PMID: 3501037; UI: 88092135.

Levine, S (1973); Sowinski, R; Hyperacute Allergic Encephalomyelitis: A localised form produced by passive transfer and pertussis vaccine; American Journal of Pathology; 73:247-260, 1973

Abstract: A hyperacute form of experimental allergic encephalomyelitis (EAE) has been produced previously by administering pertussis vaccine to rats actively immunised with neural antigen or given passive transfer of lymphoid cells from donors with EAE. Now, a localised form of hyperacute EAE has been produced within 1 day of passive transfer. The speed with which pertussis acts tends to exclude antibody production as the mechanism for conversion of EAE to the hyperacute form. With this rapid system, it has been found that pertussis, or its histamine-sensitising factor, inhibited the host mononuclear cell component of the pervascular lesions. When the immune injury was sufficiently severe (high doses of donor EAE cells), the decrease in the number of mononuclear cells was accompanied by an increase in the amount of fibrin and the number of neutrophils in the lesions. This inverse relationship may be explained by the loss of the protective effect of mononuclear cells on vessels, a concept for which there is increasing evidence.

Leung AK, "Anaphylaxis to DPT vaccine." J R Soc Med 1985 Feb; 78(2):175.

(1985) Recurrent Abscess Formation Following DTP Immunizations: Association with Hypersensitivity to Tetanus Toxoids; Pediatrics, 1985

Adverse local reactions to vaccines containing diphtheria and tetanus toxoids and pertussis antigen (DTP) are common but generally benign. Most often, these reactions are manifested by erythema, induration and tenderness occurring at the injection site 12 to 24 hours following immunization. Less frequently, abscess formation may complicate intramuscular injections and these may be staphylococcal, clostridial, or sterile in etiology. Tetanus toxoid has been associated with a reaction incidence of 3% to 13%, and adverse reactions appear to be related to the number of prior immunizations and the height of preexisting antibody responses. However, recurrent abscess formation associated with hypersensitivity to one or more of the components of the DTP vaccine has not been reported previously. The purpose of this paper is to describe a child with recurrent local abscess formation following DTP immunizations. Results of delayed-type hypersensitivity (DTH) skin tests suggested that hypersensitivity to tetanus toxoid was causally related to her adverse local reactions. A testing procedure is suggested for patients with recurrent, severe, or progressive local reactions to DTP immunizations.

Mazurin, A V, et al, "Severe Allergic Reaction with Hemorrhagic Syndrome Following the Administration of DPT Vaccine", Vop Okhr Materin Dets, Mar 1964, 9:87-89.

Menkes, J.H (1990). and Kinsbourne, M., Neuropediatrics 21 (1990) 171-176, Workshop on Neurologic Complications of Pertussis and Pertussis Vaccination,

In evaluating side-reactions to the vaccine, the following must be kept in mind: Vaccines are not standardized between manufacturers.

For a given manufacturer, vaccines are not standard from one batch to the next.

Unless the vaccine is properly prepared and refrigerated, its potency and reactivity varies with shelf life.

In fact, the whole question of vaccine detoxification has never been systematically investigated.

Listed in order of increasing severity, observed adverse reactions include irritability, persistent, unusually high-pitched crying, somnolence, seizures, a shock-like "hypotensive, hyporesponsive" state, and an encephalopathy. Since the neurologic picture is not specific for pertussis vaccination, its temporal relationship to the vaccination is the critical variable for determining causation.

Although the majority of seizures following pertussis vaccination are associated with fever, it was the consensus of the neurologists attending the workshop, that these do not represent febrile convulsions, but are non-benign convulsions.

The incidence of post-vaccine encephalopathy is difficult to ascertain. The most carefully conducted retrospective case-control study reported that the relative risk of a previously normal infant for the onset of an illness leading to encephalopathy with permanent subsequent disability was 4.2 time greater during the first 72 hours following DPT vaccination than in controls. From this study, the risk for permanent brain damage following DPT has been calculated as 1:310,000 doses. (my note – 1:310,000 doses translates to an actual risk of 1:62,000 – this figure is from the National Childhood Encephalopathy Study which excluded any child whose seizure lasted for less than 30 minutes and who was not hospitalised as a result of their seizure. )

It was the consensus of the workshop, and in particular of the participating neurologists, that although the vaccine may possibly accelerate neurologic signs or symptoms in some children, and a small proportion of apparent complications may be coincidental, there was no inherent difficulty in assigning cause and effect to the vaccine and subsequent permanent neurologic residua.

…In implicating pertussis vaccination in the evolution of subsequent neurologic residua, a careful consideration of the mechanism for vaccine-induced brain damage plays an important supporting role. Pertussis toxin has been shown to alter cellular signalling. It also affects the catecholaminergic and GABAergic systems in the brain. Although normally a protein the size of PT would not be able to cross the blood-brain barrier, factors known to disrupt the blood-brain barrier include brief hypertensive episodes such as might occur during a coughing paroxysm, hypoxia and prolonged seizures, whether or not they are accompanied by hypoxia. In addition, a direct endotoxin-mediated attack on the endothelial cells could create a local defect of the blood-brain barrier.

In summary, it was the consensus that there is sufficient experimental data to implicate both endotoxin and PT in adverse neurologic reactions to pertussis vaccine.

Murphy JV, et al.     Recurrent seizures after diphtheria, tetanus, and pertussis vaccine immunization. Onset less than 24 hours after vaccination. Am J Dis Child. 1984 Oct;138(10):908-11. PMID: 6206715; UI: 84304045.     

Miller D, et al(1985). Pertussis vaccine and whooping cough as risk factors in acute neurological illness and death in young children. Dev Biol Stand. 1985;61:389-94. PMID: 3879684; UI: 86221304.

The National Childhood Encephalopathy Study received reports on 1182 cases of serious acute neurological illnesses in children admitted to hospital in Britain. The frequency of risk factors in cases was compared with matched controls. A personal or family history of convulsions was found significantly more often in cases than in controls, but no such excess was found for a history of allergy. Case children were significantly more likely to have received diphtheria, tetanus and pertussis (DTP) vaccine within seven days before onset and to have a history of whooping cough during the month of onset. The risk of serious acute brain conditions after the disease was more than six times that of three doses of DTP. In addition, there is evidence that deaths attributed to whooping cough may seriously underestimate the number associated with pertussis infection. PMID: 3879684, UI: 86221304

Mathur R, et al. Bulging fontanel following triple vaccine. Indian Pediatr. 1981 Jun;18(6):417-8. No abstract available.PMID: 7287173; UI: 82029621.         

Miller DL, et al(1981). Pertussis immunisation and serious acute neurological illness in children. Br Med J (Clin Res Ed). 1981 May 16;282(6276):1595-9. PMID: 6786580; UI: 81209144.

The first 1000 cases notified to the National Childhood Encephalopathy Study were analysed. The diagnoses included encephalitis/encephalopathy, prolonged convulsions, infantile spasms, and Reye's syndrome. Eighty-eight of the children had had a recent infectious disease, including 19 with pertussis. Only 35 of the notified children (3.5%) had received pertussis antigen within seven days before becoming ill. Of 1955 control children matched for age, sex, and area of residence, 34 (1.7%) had been immunised with pertussis vaccine within the seven days before the date on which they became of the same age as the corresponding notified child. The relative risk of a notified child having had pertussis immunisation within that time interval was 2.4 (p less than 0.001). Of the 35 notified children, 32 had no previous neurological abnormality. A year later two had died, nine had developmental retardation, and 21 were normal. A significance association was shown between serious neurological illness and pertussis vaccine, though cases were few and most children recovered completely. PMID: 6786580, UI: 81209144

Miller D, et al (1993). Pertussis immunisation and serious acute neurological illnesses in children. BMJ. 1993 Nov 6;307(6913):1171-6. PMID: 7504540; UI: 94072962.
CONCLUSIONS--Diphtheria, tetanus, and pertussis vaccine may on rare occasions be associated with the development of severe acute neurological illnesses that can have serious sequelae. Some cases may occur by chance or have other causes. The role of pertussis vaccine as a prime or concomitant factor in the aetiology of these illnesses cannot be determined in any individual case. The balance of possible risk against known benefits from pertussis immunisation supports continued use of the vaccine.

Noble GR, et al (1987). Acellular and whole-cell pertussis vaccines in Japan. Report of a visit by US scientists. JAMA. 1987 Mar 13;257(10):1351-6. PMID: 3820444; UI: 87141495.

 
Nielsen AO, et al.    [Aluminum allergy caused by DTP vaccine]. Ugeskr Laeger. 1992 Jun 29;154(27):1900-1. Danish. PMID: 1509548; UI: 92376915.      

Osvath P, et al. (1979). IgE levels of infants with complications after pertussis vaccination. Allergol Immunopathol (Madr). 1979 Mar-Apr;7(2):111-4. PMID: 463714; UI: 79228768.

IgE levels of 31 infants who had severe complications after whooping cough vaccination, were determined by RIST. The patients had convulsions, encephalitis or anaphylactic shock symptoms. All but two had elevated IgE levels for their age. It is suggested that, in certain genetically predisposed human beings, pertussis antigen can also induce IgE synthesis, as has already been established in rodents. PMID: 463714, UI: 79228768

Omokoku B, Castells S. Post-DPT inoculation cervical lymphadenitis in children.N Y State J Med. 1981 Oct;81(11):1667-8. No abstract available.PMID: 6945501 [PubMed - indexed for MEDLINE]

Pokrovskaia NIa, "[Convulsive syndrome in DPT vaccination (a clinico-experimental study)]," Pediatriia 1983 May;(5):37-39. [Article in Russian]

Prensky AL, et al, "History of convulsions and use of pertussis vaccine," J Pediatr 1985 Aug; 107(2):244-255.

Pollock TM, et al (1983). Safety of pertussis vaccine. Lancet. 1983 Oct 1;2(8353):795-6. No abstract available. PMID: 6137630; UI: 84012855.
Reported 8children with anaphylaxis or collapse within 24 hours of DPT vaccination, for a rate of 6 cases per 100,000 children vaccinated

Poch GF, et al.    [Antidiphtheria vaccination as a factor precipitating multiple sclerosis]. Prensa Med Argent. 1966 Jul 29;53(30):1639-41. Spanish. No abstract available.PMID: 5989091; UI: 68120593.      

Robinson, DA (1983); Whopping cough vaccination: a review of the controversy since the 1981 DHSS report; Child Care Health Dev.; Sept-Oct 1983; 9 (5) 257-72

This article reviews the literature on the whooping cough controversy subsequent to the publication of the DHHS report in 1981. The report'’ reception is outlined and its influence on specific, topical issues such as contraindications, vaccine efficacy, and the calculation of ‘risk’ statistics is considered. The seriousness of the disease, the age of its victims and its treatment by antibiotics are also discussed with specific reference to recent epidemics. The implications of recent research findings for the continuation of the immunisation programme are presented. It is concluded the controversy continues.

Roberts SC.(1987). Vaccination and cot deaths in perspective. Arch Dis Child. 1987 Jul;62(7):754-9. PMID: 3498443; UI: 87325057.

In 1985 twin boys simultaneously succumbed to sudden unexpected deaths two to three hours after vaccination with diphtheria, tetanus, and pertussis vaccine (DTP). This occurrence again raises the question of whether an association of sudden infant death (SID) with vaccination is other than temporal. Taking the incidence of SID in conjunction with rates of infant vaccination in the United Kingdom, nine infants would be expected to die, each year by chance alone, suddenly within 24 hours of (and within each 24 hour period succeeding) vaccination with DTP. Twins are at a greater risk of SID than single born infants and occasionally are found dead together. A number of studies into DTP vaccination as a risk factor in SID have shown that SID is less common in vaccinated than in unvaccinated infants. PMID: 3498443, UI: 87325057

 
Schmitt-Grohe S, et al.  Minor adverse events in a comparative efficacy trial in Germany in infants receiving either the Lederle/Takeda acellular pertussis component DTP (DTaP) vaccine, the Lederle whole-cell component DTP (DTP) or DT vaccine. The Pertussis Vaccine Study Group. Dev Biol Stand. 1997;89:113-8. PMID: 9272341; UI: 97418336.
Scheifele DW, et al.   Role of whole-cell pertussis vaccine in severe local reactions to the preschool (fifth) dose of diphtheria-pertussis-tetanus vaccine. CMAJ. 1994 Jan 1;150(1):29-35. PMID: 8275406; UI: 94101519.

Skovrankova J, et al.   [Neurologic complications after vaccination against diphtheria, tetanus and whooping cough]. Cesk Pediatr. 1992 Feb;47(2):122-4. Czech. PMID: 1572012; UI: 92240734.     Stewart (1976), GT; Immunisation against whooping cough; British Medical Journal, 31 January 1976; letters:

Sir: In showing that 75% of infants below 3 months of age with whooping cough were admitted to hospital and that 42% of all hospital admissions of children notified as whooping cough were infants or 5 months or younger, Drs. Christina L. Miller and W.B, Fletcher (17 January, p 117) have indeed confirmed the widely-held belief that :in young infants whooping cough is still dangerous". They have not shown that "at all ages previous vaccination reduced the severity of the disease." What they have shown is that, among notified cases, a significantly higher proportion of the more severe cases and of those admitted to hospital were not immunised or were incompletely immunised. This does not mean that immunisation is necessarily protective. Of 8092 cases notified to them, 2940 (36%) were fully immunised while only 2424(30%) were definitely not immunised.

In the same issue (p128) Dr. ND Noah claims that "current vaccines provide young children with substantial protection against whooping cough". What he actually shows, in a single tabulation of notifications uncorrected for age, is that the incidence of whooping cough is lower in immunised than in non-immunised children. But the rate of notified infection was still relatively high (50 per 100,000) in 1974 in children fully immunised with the new vaccine. There is no evidence in either article that immunisation of older children protects younger ones.

Several questions arise:

What kind of immunisation is this for which success is being claimed? It is an immunisation which leaves those at highest risk (that is, below 6 months of age) unprotected and which, even when complete, is associated only with partial protection of those in the lowest risk groups.

What kind of epidemiology is this which advocates immunisation by excluding consideration of factors other than immunisation? It is admitted in both articles and is indeed obvious from the data that factors other than immunisation must influence susceptibility to whooping cough. If immunisation is to be tested for efficacy, the data must be standardised for domestic, demographic and social factors.

Whooping cough is much lower in incidence, hospital admissions are less frequent, and immunisation schedules are often better maintained in districts where socioeconomic conditions are favourable. Thereported association between protection and immunisation could be an expression of better social conditions and child care as much as of biological protection by pertussis vaccine.

What kind of editorial policy is this which publishes incomplete data and promotes far-reaching claims about the efficacy of immunisation but refuses to publish collateral data questioning this efficacy?

 

Paradoxically, the articles by Drs. Miller and Fletcher and Dr. Noah reinforce the suggestion made in my letter in your issue of 10 January (p 93) that evidence about the efficacy of pertussis vaccine is lacking. But the question remains.

Stetler, H.C. (1985), Orenstein, W.A., Bart, K.J., Brink, E.W., Brennan, JP, Hinman, A.R.; History of convulsions and use of pertussis vaccine; Journal of Pediatrics; 1985; 107:175-179

Abstract: Data on 2062 reports from the Monitoring System for Adverse Events Following Immunisation, Centres for Disease Control (CDC) were analysed to compare the risk of a personal or family history of convulsions in children who had a neurologic adverse event after receipt of diphtheria-tetanus-pertussis (DTP) vaccine with those who had a nonneurologic adverse event. Children with a neurologic event after DTP vaccine had a 7.2 times higher risk for personal history of convulsions (95% confidence limits 4.5 to 11.5) and a 4.5 times higher risk for family history of convulsions (95% confidence limits 3.1 to 6.7) than did children with an adverse event that did not affect the nervous system. Children with either a febrile or nonfebrile convulsion after receipt of DTP were significantly more likely to have a personal history of convulsions that children with a nonneurologic adverse event (P<0.001). Children with a febrile convulsion after receipt of DTP but not children with nonfebrile convulsions were significantly more likely to have a family history of convulsions than those with a nonneurologic adverse event. It is recommended that pertussis vaccination be deferred in children with a personal history of a convulsion until it can be determined that an evolving neurologic disorder is not present. If such disorders are found, these children should be given the combined paediatric diphtheria and tetanus toxoids (DT) vaccine to complete the series.

Tonz O (1980), Bajc S. [Convulsions after whooping-cough vaccination]. [Article in German] Schweiz Med Wochenschr 1980 Dec 20;110(51):1965-71.

Takuji Kumagai  Gelatin-containing diphtheria--tetanus--pertussis (DTP) vaccine causes sensitization to gelatin in the recipients http://www.elsevier.com:80/inca/publications/store/3/0/5/2/1/
Vaccine. Volume 18, Issue 15, 14-February-2000 pp. 1555-1561 Copyright (c) 2000 Elsevier Science Ltd All rights reserved.
Abstract Gelatin-specific T cell response was performed to determine whether a series of vaccinations with gelatin-containing DTP is a primary sensitization process in gelatin allergy. Thirty-seven recipients with gelatin-containing DTP who developed adverse reactions after vaccination and eight recipients of DTP without gelatin who also developed adverse reactions were studied. In addition, 10 subjects receiving gelatin-containing vaccine and 10 subjects inoculated with non-gelatin vaccine who did not show any adverse reactions were also investigated. All subjects inoculated with gelatin-containing DTP vaccine showed positive T cell responses against gelatin, however, occurrence of adverse reactions did not correlate with T cell responses. We conclude that DTP vaccine containing gelatin induces sensitization to gelatin in the recipients, but the mechanism of local reactions remains unknown.

Uberall MA, et al.   Severe adverse events in a comparative efficacy trial in Germany in infants receiving either the Lederle/Takeda acellular pertussis component DTP (DTaP) vaccine, the Lederle whole-cell component DTP (DTP) or DT vaccine. The Pertussis Vaccine Study Group. Dev Biol Stand. 1997;89:83-9. PMID: 9272335; UI: 97418330.

[1998] Thomas Vogt, Michael Landthaler and Wilhelm Stolz. Generalized eczema in an 18-month-old boy due to phenoxyethanol in DPT vaccine

Vesper J, et al.   [Problems of prevention, registration and evaluation of post-vaccination (DPT vaccine) neurogenic lesions in children from clinical and legal viewpoints. II. Problems in the evaluation of neurogenic post-vaccination lesions in childhood]. Psychiatr Neurol Med Psychol (Leipz). 1976 Mar;28(3):181-9. German. PMID: 9651; UI: 77013853.
Waight PA, et al.   Pyrexia after diphtheria/tetanus/pertussis and diphtheria/tetanus vaccines. Arch Dis Child. 1983 Nov;58(11):921-3. PMID: 6651330; UI: 84078600.

Walker AM, "Neurologic events following diphtheria- tetanus-pertussis immunization," Pediatrics 1988 Mar;81 (3):345-349.

Wilson J, "Proceedings: Neurological complications of DPT inoculation in infancy," Arch Dis Child 1973 Oct; 48 (10):829-830.

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