[Comparative efficacy of homologous and heterologous biologicals against diphtheria].

AIM: Comparative assessment of efficacy of homologous and heterologous diphtheria antitoxins on the example of diphtheria intoxication. MATERIALS AND METHODS: Homologous hyperimmune sera were obtained through immunization of rabbits and guinea-pigs with diphtheria toxoid according to schedule. Immune rabbit sera contained 70 - 100 IU/mL of antitoxin antibodies and guinea-pig sera contained 60 - 80 IU/mL. Equine diphtheria antitoxin was used as a heterologous one. Measurement of antitoxin level using experimental animals is based on quantitative assessment of ability of studied sera to neutralize specific dermonecrotic effect of diphtheria toxin. RESULTS: Concentration of antitoxin in blood of different groups of guinea-pigs immunized 2 days earlier with either heterologous equine antitoxin or homologous antitoxin was 0.06 - 0.125. IU/mL. Animals from both groups were completely protected after administration of 5.64 LD50 of toxin. Alongside with it, 50 - 75% of animals which received homologous antitoxin were protected from higher doses of toxin, whereas all animals which received heterologous antitoxin died after administration of higher doses. After administration of identical doses of homologous antitoxin to rabbits its maximal concentration was observed on the next day, was stable up to 5 - 7 days after injection, decreased two-fold to 12th day and did not change further to 15 - 16 days after injection with subsequent another two-fold decrease to 30th day (then was stable for another 5 - 10 days). CONCLUSION: Administration of homologous antitoxin compared to heterologous analogue allows to prolong time of circulation of specific antitoxic antibodies in 3 - 4 times.

[Specific immunity in patients with diphtheria].

AIM: To study features of specific immunity in patients with diphtheria using data from clinic as well as from animal experiments. MATERIALS AND METHODS: Serum samples of 80 patients hospitalized to Infectious Diseases Clinical Hospital No. 2 in Moscow and treated with anti-diphtheria serum (manufactured by "Immunogen" Concern, Stavropol) were studied. Localized diphtheria of the oropharynx was diagnosed in 29 patients, diffused diphtheria--in 8, subtoxic--in 3, grade 1 toxic--in 19, grade 2 toxic--in 12, grade 3 toxic--in 9. Experimental part of the study was performed on outbred rabbits weighted 3-3.5 kg. Level of antitoxin in serum was measured in reaction of passive hemagglutination using commercial antigenic erythrocyte diagnostic kit (manufactured by Mechnikov Research Institute of Vaccines and Sera, Moscow). RESULTS: Intermittent administration of toxin to control rabbits which lack background immunity did not lead to changes in their immune status and after administration of anti-diphtheria antitoxin kinetics of its level in serum was analogous to that observed after administration of antitoxin to intact animals. Highest level of antitoxin (1.0-2.0 IU/ml) was observed 1-3 days after its administration, and to day 13-15 antitoxin was not detected in serum samples. Diphtheria antitoxin in concentration from 0.03 to 40.0 IU/ml was detected in serum samples in 59 of 80 (74%) studied patients. Only in 21 patients (26%) the antitoxin was not detected. CONCLUSION: Presence of antitoxin in serum argue for active immune response to infection and activation of immune memory mechansisms, which allow to predict less severe course of the disease. Absence of antitoxin in serum of patient admitted to hospital points that infectious process is developing on the background of no immunity that predicts the probable development of severe diphtheria.

[Assessment of different regimens of diphtheria serotherapy].

AIM: Efficacy of different treatment regimens with equine diphtheria antitoxin (EDA) was assessed on clinical samples as well as in experiments on animals. MATERIALS AND METHODS: Protective properties and serum concentration kinetics of heterologous antibodies was studied on 12 rabbits and 51 guinea pigs after intramuscular injection of different doses of EDA, in serum samples from 26 patients, which received one intramuscular injection of EDA in various doses as well as in serum samples from 10 patients with diphtheria of different severity, which were treated with EDA in total course dose 100,000-1,500,000 IU. Antitoxin concentration in serum sample was measured with passive hemagglutination assay as well as Jensen toxin neutralization test on rabbits. RESULTS: Experiments on laboratory animals received EDA in dose 150 IU/kg showed high protective effect. For example, rabbits with antitoxin level 1.0-1.25 IU/ ml in serum 24 hours after injection of EDA were 50-250 times resistant to dermonecrotic effect of diphtheria toxin compared with rabbits not received EDA. Guinea pig with antitoxin level 0.5-2.0 IU/ ml in serum 2-48 hours after injection of EDA in dose 150 IU/kg were all protected against 35-50 LD50 of diphtheria toxin. After termination of EDA injection there was sharp decrease of antitoxin level and it was not detected in serum 7 days after. Increase of antitoxin level in serum of animals was not adequate to quantity of injected EDA. Study of serum samples from 26 patients received one intramuscular injection of different doses of EDA showed that doses of antitoxin from 20,000 to 30,000 IU resulted in its presence in serum in concentration 0.5-3.0 IU/ml whereas injection of 50,000 IU or 70,000-100,000 IU resulted in serum concentrations 1.25-10.0 IU/ ml and 2.5-20.0 IU/ml respectively. CONCLUSION: Relatively low doses of EDA provided relatively high level of protection against diphtheria toxin that should be taken into account during treatment of diphtheria patients.

[The local manifestations of diphtheria]. / Mestnye proiavleniia difterii.

The development of diphtheria is characterized by a pronounced local process, but the description of local changes in the disease are based only on postmortem findings. 67 patients with different forms of diphtheria were examined. In 11 cases of descending croup bronchoscopic examination was carried out. As revealed in this study, at the primary stage of the disease films cover the whole of the air duct system, and the process is identical to that on tonsils. In the course of convalescence and under the action of specific antiserum films on the tonsils, the soft palate and the vocal cords disappeared, and films in the larynx, the trachea and bronchi could be easily separated from the mucous membrane, but always with the formation of erosions and even perforations in it. The character of the process was indicative of the absence of any specific action of diphtheria toxin on the mucous membrane at the site of the inoculation of the infective agent. No correlation between the severity of the course of diphtheria, the degree of edema and the frequency of the development of complications was noted.