Clinical and immunological aspects of diphtheria and diphtheria vaccination / Bengt Björkholm.

Tese (doutor) - University of Göteborg, 1990

Diphtheria, which has for a long time been rare in Sweden, reappered in 1984. The aim of the present study was to analyse the diptheria outbreak 1984-86 in Göteborg and to study the immune status and vaccination response to diphtheria toxoid in volunteers and medical per-sonnel. During the Göteborg outbreak 13 clinical cases and 65 carriers of Corynebacterium diphtheriae were identified. Ten of the clinical cases and 49/65 healthy carriers were alcoholics. Three patients died and 6 developed neurologic complications. The patients with clinical symptoms and complications had low antitoxin levels (0.01 IU/ml), while 36/41 healthy carriers (88%) had antitexin titers ar or above this level at admission. Antitoxin levels following therapy with human immunoglobulin (10,000 - 20,000 IU) did not reach over 2 IU/ml. Forty percent of Swedish medical personnel (133/328) and 58% of blood donors (136/234) had antitoxin levels below 0.01 IU/ml, which is considered a protective level. The lowest antitoxin levels were found in age groups 30 years. Medical personnel with low prevaccination titers who were vaccinated with a low booster dose of diphtheria toxoid (2.5 Lf) failed to reach 0.1 IU/ml in 39% (28/72). It is suggested that such low doses are omitted. Two-hundred factory workers volunteered for a booster vaccination study with 3 and 7.5 Lf of diphtheria toxiod, respectively. Also 251 workers volunteered for a basic vaccination study with 7.5 and 15 Lf of diphtheria toxoid, respectively. The frequency of local reactions (5 cm) in the booster vaccination study and for the first two doses in the basic vaccination study ranged between 6 and 14%. Following the third dose in the basic vaccination study 35% of the vaccinees reported local reactions (5 cm) with the high dose (15 Lf) as compared to 11% in the 7.5 Lf dose group (p 0.001). In the booster vaccination study an antitoxin titer of at least 0.1 IU/ml was reached in 88% of the recipients of 3 Lf and in 94% of the recipients of 7.5 Lf of diphtheria toxoid. Diphtheria in these urban adult patients was not only associated with alcohol abuse but also with poor hygiene, low immunization levels and probably with introduction of a new strain from an exogenous reservoir. Diphtheria antitoxin levels were low in the population, especially in age groups 30 years. Low booster doses of diphtheria toxoid (52.5 Lf) did not give adequate immune responses in all vaccinees. A booster dose of 7.5 Lf gave a more adequate serological response and did not significantly increase the frequency of adverse reactions. For basic vaccination, a dose of 15 Lf gave a better serological response than 7.5 Lf still with only minor adverse reactions. However, at the third injection with this dose local adverse reactions increased significantly. For that reason 7.5 Lf of diphtheria toxoid ought to be an optimal dose for the third injection during basic immunization of adults.