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Query: UMLS:C0085584 (encephalopathy)
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The effect of Bordetella pertussis vaccine on the cerebral vascular permeability in the mouse was studied by a radio-isotope method (131I-labelled HSA). Intravenous injection of 4 x 1010 heat-killed pertussis organisms caused a measurable increase in permeability in normal mice. Cryoinjury to the cerebral hemispheres resulted in a striking increase in vascular permeability at 24 h. This declined within 48 h and stabilized at a level fractionally higher than normal at 7 days ("healed lesion"). When pertussis organisms were injected into mice bearing ("healed lesion"). When pertussis organisms were injected into mice bearing "healed lesions" the increase in permeability was similar in magnitude to that in uninjured brain. The effect was increased by a second administration of pertussis 24 h after the first. The action of pertussis on a newly inflicted cryoinjury was protective. It is suggested that permeability changes in the cerebral vessels may be involved in the evolution of the encephalopathy attributed to the use of Bordetella pertussis vaccine in man.
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PMID:The effects of Bordetella pertussis vaccine on cerebral vascular permeability. 1 80

During 1974, eight of 37 (22%) Bordetella organisms isolated from patients in Cincinnate were Bordetella parapertussis. This is in contrast to other experience in the United States where parapertussis has comprised less than5% of the Bordetella species isolated and suggest that B parapertussis infection may be more common in this country than generally recognized. The failure to appreciate the presence of this infection may result from the lack of cultures taken from children with mild disease and the failure todistinguish B parapertussis from B pertussis. Ccultures were obtained from family members of three of the children with B parapertussis, and B pertussis was isolated from members of two families, including the mother and sister of a child who died of pneumonia and encephalopathy. These cases suggest that patients with severe disease associated with B parapertussis should be carefully evaluated for the possibility of dual infection caused by b pertussis.
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PMID:Bordetella parapertussis. Recent experience and a review of the literature. 19 93

The specific local and humoral immunological situation of the child, by permitting or not (+/- specific IgA-S) the passage of the Bordetella toxins to the bloodstream and the formation or not (+/- specific circulating IgG) of Circulating Immune Complexes (CIC), brings back to Type III Immunoreactions the pathogenesis of the pertussis encephalopathy and the reactions provoked by intramuscular vaccine. Since the antihistaminics and antiserotoninics can prevent the CIC precipitation, the Author believes that this would imply the indication to the usage of antihistaminics or antiserotoninics to prevent bot the neurologic complications of the illness and the systemic reactions to the intramuscular vaccine.
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PMID:[Physiopathology of pertussis encephalopathy. Prophylaxis. Pathogenesis of the "reaction" against intramuscular pertussis vaccine. Vaccination with "shield"]. 168

A multidisciplinary workshop held from September 29 to October 1, 1989, at Airlie House, Warrenton, Virginia, considered the neurologic complications of whooping cough and pertussis vaccine. Pertussis mortality in the U.S. in 2-3/1000 cases. Seizures occur in 1.9% of cases, and encephalopathy in 0.3%. Reviewing all data, it appears likely that a combination of one or more bacterial toxins, asphyxia, CO2 retention and loss of cerebral vascular autoregulation is responsible for neurologic symptoms. The timing of the encephalopathy suggests that it results from increased lysis of bacteria, and release of endotoxin. The encephalopathy is not confined to the paroxysmal phase. In evaluating side-reactions to the vaccine, the following must be kept in mind: 1. Vaccines are not standardized between manufacturers. 2. For a given manufacturer, vaccines are not standard from one batch to the next. 3. 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.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Workshop on neurologic complications of pertussis and pertussis vaccination. 198 Dec 51

The development and widespread uptake of a safe and efficacious aluminium adsorbed diphtheria-tetanus-pertussis vaccine (DTP) in the United States between 1933 and 1944 led to a gradual decline in whooping cough morbidity and instilled confidence in a vaccination programme which has been effectively maintained for over 40 years. T his contrasts with the turbulent history of pertussis vaccination in the United Kingdom where doubts as to the efficacy of available vaccines delayed their active national promotion until 1957, after which various reports resulted in further doubts over efficacy and safety. In 1974, the mass media became involved in the safety issue when the National Hospital for Sick Children case series of neurological events, which had occurred after DTP vaccination was made core material for a television documentary. The Department of Health and Social Security (DHSS) responded by establishing two retrospective studies of case records of post vaccination adverse events and two prospective studies. One of the latter, the National Childhood Encephalopathy Study (NCES) was regarded as the definitive case control study. A claim for damages, Loveday v Renton and The Wellcome Foundation, heard in the High Court of Justice in London, from early October 1987 until late February 1988 dealt with the general issue of whether, on the balance of probabilities, pertussis vaccine could cause permanent brain damage. The cornerstone of the claim that pertussis vaccine can cause permanent brain damage has always been the apparent clustering of onset of neurological disorders within the first 24-48 h after vaccination. One of the main finds of the NCES, however, which was not divulged in any published report but emerged in the course of the hearing, was that permanent brain damage did not occur within 48 h of DTP vaccination in any child in England, Scotland and Wales from mid-1976 to mid-1979 when 2 million doses of vaccine were used. The NCES, in this respect, completely undermined the evidence provided by various published case series. After a 61 day hearing, High Court judgment was given to the effect that the judge was not satisfied on balance of probability that pertussis vaccine can cause permanent brain damage in young children. Were it not for the fact that The Wellcome Foundation intervened in the action and obtained a court order giving access to the NCES cases records, some crucial information collected by the NCES might not have been brought to light.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Permanent brain damage and pertussis vaccination: is the end of the saga in sight? 257 Dec 13

A mouse model for encephalopathy induced by pertussis immunization has been described; it has features that closely resemble some of the severe reactions, including seizures and a shock-like state leading to death, occasionally seen after administration of Bordetella pertussis (whooping cough) vaccine. Susceptibility to encephalopathy maps to genes of the major histocompatibility complex and correlates as well with the genetic regulation of the level of antibody response to bovine serum albumin. In this study we have investigated which bacterial determinant is responsible for the encephalopathy. Two lines of evidence implicate pertussis toxin as the active bacterial component. Single-site mutants of B. pertussis with single affected virulence factors were tested. A mutant that produces a defective pertussis toxin had greatly diminished capacity to induce encephalopathy, whereas a hemolysin- and adenylate-cyclase-deficient avirulent mutant had the same activity in the mouse model as a virulent strain. Purified pertussis toxin plus bovine serum albumin was tested and found to induce the lethal encephalopathy, demonstrating that the toxin was the critical constituent of B. pertussis responsible for encephalopathy.
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PMID:Pertussis toxin is required for pertussis vaccine encephalopathy. 286 45

A mouse model for pertussis immunization encephalopathy has been described with features that closely resemble the severe adverse reactions occasionally seen after pertussis vaccine administration,m including seizures and a shock-like state leading to death. These reactions are produced with nearly one hundred percent efficiency provided that the mice immunized with Bordetella pertussis have 1) the appropriate major histocompatibility (H-2) genotype, 2) have been sensitized to bovine serum albumin (BSA), and 3) that the injected B. pertussis contained sufficient amounts of pertussis toxin. Antibody titres were measured in mice with haplotypes H-2d.s.k. that are highly susceptible to encephalopathy as well as in H-2b mice, that are totally resistant. Mice with H-2d.s.k. haplotypes were high responders to BSA, while H-2b (B10) mice were non-responders to BSA. Both H-2d and H-2b mice responded well to B. pertussis. Encephalopathy was induced in resistant H-2b mice with B. pertussis and passively administered anti-BSA antiserum, but not with B. pertussis and anti-(T,G)-A--L antibody. This indicated that B. pertussis and anti-BSA were absolutely required for development of encephalopathy. Encephalopathy could be induced in mice decomplemented with cobra venom factor and given BSA and B. pertussis. Several single-site mutants of B. pertussis affecting single virulence factors were induced with transposon Tn5. One of these mutants, BP357, deficient in pertussis toxin production, had a greatly reduced encephalopathic potential in the mouse model compared to the virulent strain BP 338, or to BP348, an adenylate cyclase and hemolysin double mutant, or to BP 349, a hemolysin mutant.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Murine model for pertussis vaccine encephalopathy: role of the major histocompatibility complex; antibody to albumin and to Bordetella pertussis and pertussis toxin. 287 26

Pertussis vaccine was originally accused of provoking a short latency explosive encephalopathy with serious mental and physical consequences. Reports of recurrence of encephalopathy, worse after each dose, strengthened the notion of causality. Anecdotal associations can be no more than hypothesis-generating. With no distinctive clinical or pathological neurology, a major epidemiological study was necessary to answer the question "Does whooping cough vaccine cause brain damage in children"? The British national Childhood Encephalopathy Study (NCES) seemed to indicate that very rarely the answer was yes. Unfortunately the NCES confused disorders which might be notified as "encephalopathy" with actual brain damaging events, imaging a continuum of injury. Close scrutiny of the individual cases, as was possible during the recent test case in the High Court of London, shows that all the temporally associated cases with permanent sequelae had either viral encephalitis or Reye's syndrome. No cases were unexplained. There was an apparent excess of febrile convulsions in the first 24 hours, but all these children were normal at follow-up. The short latency explosive encephalopathy with adverse outcome predicted by the earlier case series did not occur. The NCES gives no support to the idea that pertussis vaccine damages children's brains. Contra-indications to DTP should be the same as to DT.
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PMID:A neurologist looks at neurological disease temporally related to DTP immunization. 307 4

Although the conventional Bordetella pertussis vaccine, which consists of killed whole organisms, has been shown to be effective in preventing disease, it has been associated with transient local and systemic reactions and may produce encephalopathy, though rarely. A new acellular pertussis vaccine containing partially purified protein antigens, filamentous hemagglutinin, and lymphocytosis-promoting factor hemagglutinin has been developed for use in Japan. We compared the immunogenicity and reactogenicity of conventional and acellular pertussis vaccine. Forty children aged 4 to 6 years and 40 children aged 18 to 24 months, all previously immunized at appropriate times with conventional diphtheria and tetanus toxoids and pertussis vaccine, were enrolled. We randomly assigned children to receive either conventional pertussis vaccine or acellular pertussis vaccine in a double-blind fashion. The diphtheria and tetanus components in both preparations were identical. Equivalent rises in pertussis agglutinin titers and antibodies to filamentous hemagglutinin and lymphocytosis-promoting factor hemagglutinin were measured in both vaccine groups at both ages that we studied. However, reaction rates to the two vaccines in both age groups were strikingly different. Acellular pertussis vaccine was significantly less reactogenic for fever, pain, fretfulness, abnormal gait, and local reactions at the vaccine administration site. If studies in progressively younger children confirm its reduced reactogenicity and equal immunogenicity, and if large-scale trials indicate its efficacy, the acellular pertussis vaccine may be a more appropriate candidate than the current vaccine.
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PMID:Diphtheria, tetanus, and pertussis vaccine. A comparison of the immune response and adverse reactions to conventional and acellular pertussis components. 352 66

Since 1975, acceptance of pertussis vaccine has fallen from over 70% to 50% or less in most parts of Britain. This permits evaluation of a continuing natural experiment in which the frequency and severity of whooping cough can be compared those of adverse events following injections of pertussis vaccine. National data show an increase in notifications of whooping cough in most parts of Britain since 1975. Hospital admissions show considerable variation between areas with relatively high rates in some areas of deprivation but very low rates in more affluent areas even where vaccine-acceptance is around 50%. Deaths of infants with whooping cough have decreased steadily since 1900, the rate since 1975 being the lowest ever. Active epidemiological surveillance in Glasgow, with a population of 216,000 children and 13,000 births annually, shows that outbreaks and severe cases requiring admission to hospital were concentrated consistently in a few areas of deprivation. There is a significant correlation between vaccine-acceptance and hospital admission by district of residence but analysis of variance shows this effect to be less than that of overcrowding in households and other deprivation variables. In each of three outbreaks studied prospectively (1974-5, 78-78 and 82) about 30% of cases occurred in children who had received three doses of pertussis vaccine. Such vaccination had a significant protective effect in children aged 1-4 years but not in older children. There was no evidence of a herd immunity sufficient to protect infants below age for vaccination. Admissions to hospital decreased during the period 1970-83. There were no deaths attributable to proven or suspected infections with Bordetella pertussis during the period 1972-1983. No cases of encephalopathy, permanent brain damage or lung damage were detected in a follow up of all cases notified, surveyed or admitted to hospital between 1975 and 1982. Collectively, these national and local data provided estimates of the frequency of infection, complications of infection, admission to hospital and death in children with whooping cough for comparison with local, national and published estimates of the frequency and severity of adverse reactions, encephalopathy, permanent brain damage and death after injections of pertussis vaccine. It is concluded that, in children living in non-deprived circumstances in Britain, the risk of pertussis vaccine during the period 1970-83 exceeded those of whooping cough. In some deprived sectors, the risks from whooping cough might have been marginally higher but there was no evidence that this was associated with any increase in deaths or permanent disabilities.
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PMID:Whooping cough and pertussis vaccine: a comparison of risks and benefits in Britain during the period 1968-83. 383 80


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