Aspects of pertussis, pertussis vaccination and adverse events associated with aluminum adsorbed vaccines
Sammanfattning: The thesis originates in a clinical study of one of the new acellular pertussis vaccines performed in Göteborg in the 1990s. The monocomponent vaccine, pertussis toxoid adsorbed to aluminium hydroxide, had previously been shown to have an efficacy of 71%. The first aim of the study was to see if the vaccine could induce herd immunity, with protection also of unvaccinated individuals, by mass vaccination of infants and children. A second aim was to study epdemiologic, clinical and immunologic characteristics of parapertussis, a disease related to pertussis. Further aims were to descibe the incidence, clinical picture and prognosis of two rare vaccine-related side effects, persistent pruritic nodules and delayed hypersensitivity to aluminium, in participants in the vaccine trials and in recipients of other aluminium adsorbed diphtheria-tetanus-pertussis vaccines. METHODS. All children in the Göteborg area born during the 1990s were offered three doses of pertussis vaccine. The incidence of pertussis was followed by the number of positive pertussis cultures and hospitalisations due to pertussis before and during the mass vaccination. Parapertussis cases were identified in a previous vaccine efficacy trial and in clinical routine. Children with persistent itching nodules were found through passive reporting and active search for cases. Aluminium allergy was tested with an epicutaneous test. Symptoms were evaluated by examination of afflicted children, yearly structured questionnaires and/or telephone interviews. RESULTS More than 60,000 children were vaccinated with the pertussis vaccine. Numbers of positive cultures decreased drastically during the mass vaccination, both in vaccinated children and in unvaccinated infants and individuals ≥15 years. - 81 patients with parapertussis were identified. The duration of their disease was shorter and their symptoms milder than seen in patients with pertussis. Antibody levels against FHA and pertactin were similar after both diseases while pertussis toxin antibodies only increased in pertussis patients. - Persistent itching nodules at the injection site were found in 645 children (almost 1 % of all vaccinees). The itching was often severe and long lasting (about 4 years) in children followed until recovery. Contact allergy to aluminium was demonstrated in 352 of 455 children tested (77 %) with pruritic nodules and in 17 of 211 (8 %) of asymptomatic siblings, who had received the same vaccine. - 19 cases of itching nodules in recipients of currently used aluminium adsorbed vaccines were described. 15 were tested for aluminium allergy, all with positive results. CONCLUSIONS A monocomponent pertussis toxoid vaccine induced a high degree of herd immunity against pertussis with indirect protection of unvaccinated individuals. Parapertussis is an uncommon disease causing similar, but usually milder, symptoms as pertussis. Antibodies against FHA and pertactin, but not pertussis toxin, were induced. Aluminium adsorbed vaccines from three different producers can cause long-lasting, intensely itching nodules and hypersensitivity to aluminium.
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