[Clinical trials of the new skin test Diaskintest for the diagnosis of tuberculosis].

A new reagent for a skin test given the name Diaskintest has been designed for the screening diagnosis of tuberculosis and preclinical and clinical trials conducted. Preclinical trials were carried out on 315 laboratory animals (guinea-pigs, albino mice). The reagent Diaskintest was ascertained to be nontoxic, to have no sensitizing properties, to be safe and specific, and to induce no positive reactions in BCG-vaccinated animals and healthy guinea-pigs. Its specific activity was comparable with that of the national reference--purified tuberculin PPD-L-2. With progression of tuberculous lesions, the guinea-pigs showed higher responses to Diaskintest dilution and the BCG-vaccinated animals lacked responses to Diaskintest with increased delayed type hypersensitivity. The clinical trial was permitted by the Federal Service for Surveillance in Health Care and Social Development of the Russian Federation. Clinical trials were conducted in 150 persons. The safety, specificity, sensitivity of Diaskintest were first examined in the clinical studies and its action was compared with the results of tuberculin skin test (Mantoux test) with 2 TE of PPD L-2. Diaskintest was ascertained to be highly sensitive when given in a dose of 0.2 microg in 0.1 ml. In patients with active tuberculosis and new cases of Mycobacterium tuberculosis infection, the agent induced a positive skin reaction (a papule of more than 10 mm) in 98-100% of cases (p < 0.05). The agent caused no reaction associated with BCG vaccination. The specificity of the test was 93-100% with 95% significance. The rate of overexuberant reactions (vesicular necrotic changes, lymphangitis, and lymphadenitis) was 4-14% with 95% significance. Tuberculosis patients with significant immunopathological disorders might have no skin sensitivity to Diaskintest, as to PPD L-2 (a negative test). The findings substantiate the use of Diaskintest for mass epidemiological surveys for the differential diagnosis of tuberculosis and BCG vaccination-associated complications. The agent may be also used to evaluate the activity of the process in patients with tuberculosis and the efficiency of treatment in combination with other methods and to make a differential diagnosis of tuberculosis.

Presence of cytokines in biological preparations.

In vaccines produced in eukaryote cells as well as in commercial medical preparations of leukocyte interferon a number of cytokines such as IL-1beta, IL-6 and TNF-alpha have been detected. Among the vaccines examined in this study the highest level of IL-1beta was demonstrated in inactivated hepatitis A vaccine prepared in the green monkey kidney cell line 4647, that of IL-6 in inactivated rabies vaccine produced in Syrian hamster kidney (SHK) cell culture, and that of TNF-alpha in live poliomyelitis vaccine manufactured in VERO cells. A spontaneous and poliovirus-induced capacity of cell cultures to produce cytokines was detected. The level of cytokines produced depend on the kind of cell culture and the type of virus, a more pronounced effect being generated by types 1 and 2 poliovirus as compared with type 3. The presence of highly active cytokines in virus vaccines and interferon preparations points to the necessity of investigating the influence of the presence of cytokines on the biological activity of these preparations and to the advisability of standardizing and controlling the cytokine content.

The Origin of Adverse Reactions Induced by Vaccines.

The review deals with numerous etiologic factors that are responsible for the development of side-effects and complications after immunization. Different types of side-effects observed after administration of vaccines are classified as follows: pharmacological effects of vaccines; non-protective antibody formation; various forms of allergy; autoimmune reactions; immunomodulating and psychogenic effects of vaccines. Special attention is given to the characteristics of admixtures, which are contained in vaccines and may be a cause of adverse reactions, and to the immunologic safety of vaccines.