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In the province of Voyvodina 18 cases of post-vaccinal encephalitis have been recorded, three of which were fatal.The estimated morbidity rate was 0.6 per 10(5) after revaccination, and 3.9 per 10(5) after primary vaccination. The virological studies described, as well as other findings referred to in this report, are consistent with the possibility of an autoimmune aetiology of the post-vaccinal encephalitis cases observed.
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While post-vaccinal encephalitis in children is unfortunately well known, its occurrence in adults is rather exceptional. The calendar of a poly vaccination situated so close to each other, most probably account for such an evolution. The case reported concerns a man of 27 years who presented 10 days after a polyvaccination (7 vaccines in 2 months) altered consciousness, epileptic fits, right hemiplegia, vegetative dysfunctions and meningeal status. Evolutionary clinical course led to death in 21 days. Neuropathological findings showed lymphocytic infiltrates in the cortex and basal ganglia, congestive aspect with petechial areas in the white matter and inflammatory meningeal infiltrates. All viral investigations both in the blood, brain and cerebrospinal fluid remained negative. Post-vaccinal encephalitis is reviewed. Vaccination cannot be condemned, but in case of polyvaccination lapse of time in between vaccines should be longer so as to prevent such exceptional evolution and fatal course.
Revaccination between 2 and 5 years after the last vaccination induced higher complement-fixation titres than revaccination 7-63 years after the last vaccination. The highest CF titres were reached during the 3rd to the 5th week after vaccination.Fifty-two serum samples, taken 137 or more days after a successful vaccination, all showed CF titres lower than 1/2.In a group of successfully vaccinated persons with no post-vaccinal complications, 65 out of 66 had a successful ;take' after one or two subsequent vaccinations.Sera of persons receiving primary vaccination showed significantly lower CF titres than sera of revaccinated persons. Cases of post-vaccinal encephalitis showed greater antibody response than uncomplicated successfully vaccinated cases in both the primary vaccination and revaccination groups. The antibody response in revaccinated persons with post-vaccinal encephalitis was greater than that in the group of successfully revaccinated cases without encephalitis.A group of 26 naturally hyporeactive persons completely failed to ;take' even after vaccination repeated between 3 and 10 times (average 5 times per person). The frequency of seropositives in this group, and the height of their CF titres, were significantly lower than in the group of successfully vaccinated persons. These findings support the view that untreated persons who repeatedly fail to ;take' with the vaccine must not be considered immune.In vaccinated persons treated with immunoglobulin (with or without simultaneous treatment with Marboran) antibody production was apparently diminished. Treatment of patients with Marboran significantly lowers the capacity of the vaccine to ;take'.
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Using decision analysis, we estimated the benefits, risks and costs of routine childhood immunization against pertussis. Without an immunization program, we predict that there would be a 71-fold increase in cases and an almost fourfold increase in deaths (2.0 to 7.6) per cohort of one million children. With a vaccination program, we predict 0.1 case of encephalitis associated with pertussis and five cases of post-vaccination encephalitis; without a program, there would be only 2.3 cases of encephalitis associated with pertussis. Community vaccination would reduce by 61 per cent the costs related to pertussis. Our analysis supports continuation of vaccination in routine childhood immunization programs, but suggests the need for more reliable data on complications from the vaccine, further study of the epidemiology of pertussis and development of a less toxic vaccine.
In experiments on rabbits it was found that although administration of inactivated smallpox vaccine did not induce a demonstrable antibody response in the serum it enhanced the immune response to subsequent inoculation with live vaccine. The dose of inactivated vaccine corresponded to 8 x 10(7) PFU before inactivation (by (60)Co gamma-radiation); the dose of live vaccine was 1.2 x 10(5) PFU. When the interval between the two inoculations was 7-days, virus-neutralizing antibody appeared after 5 days and reached levels 2-4 times those obtained with live vaccine alone. With longer intervals (up to 60 days) the enhancement of the immune response was even greater. It seems likely that use of the two-step method may reduce the incidence of post-vaccination encephalitis and clinical studies to determine the optimum conditions for safety and efficacy are at present being undertaken.
Experiments were conducted on guinea pigs sensitized with the AK C-vaccine components. In intracardiac injection with smallpox vaccine there was shown a possibility of development of marked hemodynamic disturbances, of the inflammatory-dystrophic processes of irreversibel character, with a subsequent neuronophagia and demyelinization. Injection of smallpox vaccine into the circulation of intact guinea pigs was accompanied by development in the nervous system of insignificant circulatory disturbances and of the inflammatory dystrophic phenomena of reversible character. A method of immunofluorescence was used and the antigen of the vaccine virus was revealed in the neurons of the brain and the spinal cord of the sensitized and intact animals. Marked hemodynamic and insignificant inflammatory-dystrophic processes were revealed in the nervous system of a child which died of the post-vaccinal encephalitis; an antigen of the smallpox virus was found by the immunofluorescent method in the nerve cells and the vessels in various portions of the nervous system.
In an attempt to establish the diagnoses of rabies post-vaccinal encephalitis (PVE) and early rabies encephalitis, paired serum and CSF levels of rabies neutralizing antibody (Rab) and rabies specific-IgM (RIgM) were compared in 12 PVE, 10 rabies and five control patients with similar presenting clinical features. Rapid methods of rabies antigen detection were evaluated in 17 patients. All 12 PVE patients had Rab in their serum and in eight it was also present in the CSF. These same eight had RIgM in the serum, and in seven also in the CSF. The CSF antibodies may have originated in the plasma since six patients had a high albumin quotient indicating leakage across the blood-brain barrier. Among the rabies patients, only the two vaccinated ones had serum Rab; this was also detected in the CSF of one and RIgM was in the CSF of the other. A raised IgG Index, indicating intrathecal synthesis of IgG was seen in five of 12 PVE patients. This did not correlate with the presence of CSF rabies antibody, suggesting production of antibody to other vaccine antigens of neural origin. The diagnosis of rabies encephalitis in life was made by antigen detection in a skin biopsy. No false positive results occurred and the method was as efficient as immunofluorescence of a post-mortem brain biopsy.
At the Swiss Serum and Vaccine Institute, Berne, a highly purified rabies vaccine presenting a high content of effective rabies virus glucoprotein antigen has been developed. The new vaccine is derived from embryonated duck eggs (PDEV). Immunizations performed according to the post-exposure schedule recommended for potent rabies vaccines by the WHO (6 injections on days 0, 3, 7, 14, 28 and 90) already induce protective antibody titers on day 14 (greater than 1 IU/ml). Use of the latest radioimmunological methods did not reveal the presence of myelin basic protein in the new rabies vaccine. Due to improvements of its preparation the rabies vaccine PDEV is an economical and highly efficient vaccine involving only a very remote risk of post-vaccinal encephalitis.
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Identification of the Negri bodies in the brain of an 8-year-old boy who died 8 days after a paralytic illness and 20 days after a dog bite, and who had received 9 injections of Semple's anti-rabies vaccine, provided evidence that he died of acute rabies encephalitis and not of post-vaccinal allergic encephalomyelitis. The Negri bodies in the human subject and those seen in the inoculated mouse differed in their morphological structure: the former consisted of a matrix of very fine granular material bearing larger granules or strands of higher electron-density resembling nucleic acids and representing products of host cell-virus interaction; and the latter showed better defined areas of granular matrix containing tubular, bullet-shaped and elongated forms of viral structures, and nucleocapsids or capsule-deficient cores, representing the virions, emerging from them. Fine structural examination of the patient's brain and of the inoculated mouse has provided evidence of the pleomorphism of the Negri bodies and the various stages of formation of viral material and virions in them, the animal alone showing the mature virions of rabies, and proving the infectivity of the Negri bodies of the human brain.
Various natural and synthetic interferon inducers stimulate postvaccination immunity to tick-borne encephalitis virus in mice. This capacity was found not only in macromolecular synthetic polyribonucleotides such as (poly I)-(poly C), (poly G)-(poly C), (poly A)-(poly U) and substances with much lower molecular weight such as copolymers of vinylpyrrolidone with maleic anhydride, crotonic acid or metacrylic acid but also in a low molecular interferon inducer tiloron. These and other interferon inducers examined (endotoxin S-typhi, statolon) exhibited no parallelism between the intensity of their stimulating effect of immunogenesis and levels of interferon production induced in mice and the associated resistance to tick-borne encephalitis. The results indicate a possibliity of using various interferon inducers for stimulation of post-vaccination immunity to tick-borne encephalitis.
Clinico-immunological studies on men were conducted using associated immunization by pair combinations of 8 commercial national vaccines (typhoid, plague, typhus, smallpox, tick-borne encephalitis, yellow-fever, cholera and sextaanatoxine). As for reactogenicity and immunological efficiency (serological studies), these pair associations can be subdivided into three main groups. The first group consists of pair combinations of vaccines that cannot exert any influence on immunogenicity of cause the development of frequent post-vaccination reaction or temporary disability (typhus, smallpox, tick-borne encephalitis, yellow-fever vaccines). These preparations are completely compatible in every combination. The second group includes plague and cholera vaccines that reduce its immunogenicity under the influence of more active antigens or increase its reactogenicity being associated with typhoid vaccine or sextaanatoxine. The third group is composed of typhoid vaccine and sextaanatoxine that have high reactogenicity and stable serological shifts. Associations of the first group are the most favourable for anti-epidemiological practice.