[REVIEW OF EPIDEMIOLOGIC SITUATION ON HEMORRHAGIC FEVER WITH RENAL SYNDROME (HERS) IN RUSSIAN FEDERATION IN 1990 - 2015].

AIM: Analyze HFRS morbidity in Russian Federation during the last 25 years (1990 - 2015). MATERIALS AND METHODS: Official statistics of Federal Service for Surveillance on Consumers' Rights Protection and Human Weillbeing (CPS), including Federal Centre of Hygiene and Epidemiology, were used for the analysis, as well as materials from regional departments of CPS and centers of hygiene and epidemiology. Epidemiologic analysis was the main method. Statistical treatment of the results obtained was carried out using gener- ally accepted methods of variation statistics with elements of system analysis. Results; For the studied period (1990 - 2015) 194 116 cases of HFRS were registered. Morbidity was registered in 8 federal districts of the Russian Federation in 58 subjects. The most intense epidemiologic situation was noted in Privolzhsky Federal District, that accounted for 86.4% of total HFRS morbidity during the -studied period. Analysis of morbidity was carried out in every federal district, most epidemically unfavorable territories are shown. CONCLUSION: The data presented on HFRS morbidity reflect -unfavorable situation for this disease in Russian Federation. Measures to prevent the emergence of diseases to reduce the general level of morbidity in Russian Federation are presented.

Dermatonecrotic lesions in rabbits caused by neuraminidase.

In an attempt to study the role of neuraminidase in cholera vibrio pathogenesis, the dermatonecrotic effect of a purified neuraminidase preparation was studied in rabbits. The experiments demonstrated that dermatonecrotic lesions resulted from intracutaneous injection of a purified neuraminidase preparation (0.5 specific human dose or 1 NU) as well as significant doses of cholera toxoid containing the enzyme (4,12,18 specific human doses).

[The effect of the characteristics of the interaction of their determinant of virulence with the metabolic and specific mechanisms of immunity on the persistence of infectious causative agents]. / Vliianie na persistentsiiu vozbuditelei infektsii osobennostei vzaimodeistviia ikh determinant virulentnosti s metabolicheskimi i spetsificheskimi mekhanizmami immuniteta.

The persistence of the causative agents of infections depends on the effectiveness of the function of their virulence determinants ensuring their nutrition in the host body and resistance to its nonspecific and specific mechanisms of protection. The presence of antigens, effective mechanisms of antigenic reconstruction and, probably, the optimum ratio of strong and weak antigens in pathogenic microorganisms facilitates their persistence in the body of an immune host.

[The antimicrobial action of the xanthine oxidase-xanthine system on the causative agent of cholera]. / Antimikrobnoe deistvie sistemy ksantinoksidaza--ksantin na vozbuditel' kholery.

As revealed in experiments on V. cholerae, the enzymatic link xanthine oxidase-xanthine produces a vibriostatic effect at the concentration of xanthine oxidase equal to 0.0125 g/l and a vibriocidal effect at the concentration of xanthine oxidase equal to 0.025 g/l in a medium with pH 7.5-7.6. In the presence of protein the antivibrionic activity of the xanthine oxidase link is decreased. The introduction of bivalent iron into the enzymatic link xanthine oxidase-xanthine enhances its vibriocidal action on V. cholerae.

[The effect of immune antibodies and the xanthine oxidase-xanthine enzymatic link on Vibrio cholerae]. / Vliianie immunnykh antitel i fermentnogo zvena ksantinoksidazy--ksantin na Vibrio cholerae.

As revealed in experiments on V. cholerae, highly diluted cholera antiserum enhanced the inhibitory action of the enzymatic link xanthine oxidase-xanthine-Fe2+ on the multiplication of V. cholerae, while low dilutions of the antiserum weakened this action. Normal rabbit serum produced no such effect. The antivibrionic effectiveness of the immune molecular cycle, viz. antiserum--the xanthine oxidase enzymatic link, was found to depend also on the concentration of xanthine. Immune antibodies to cholera antigens activated the bacteriostatic action of the enzymatic link at the concentration of xanthine oxidase equal to 0.0125 g/l and its bactericidal action at the concentration of xanthine oxidase equal to 0.025 g/l. In this article the values of the specificity indices of immune interaction and immunological effectiveness, characterizing the effectiveness of immune molecular cycles (antibodies--the xanthine oxidase enzymatic link), are presented.

[Distribution of lymphocytes according to the cell cycle phases in T, B, D and O populations in human blood and the immune system organs of animals vaccinated against cholera]. / Raspredelenie limfotsitov po fazam kletochnogo tsikla v populiatsiiakh T, B, D, O v krovi liudei i organakh immunoi sistemy zhivotnykh, vaktsinirovannykh protiv kholery.

The work presents the results of the study (carried out by the method of continuous flow cytofluorometry) of changes in the distribution of lymphocytes and their populations (obtained by means of distributing cell electrophoresis) according to the phases of the cell cycle (G0 + G1; S; G2 + M) in the blood and spleen of guinea pigs, as well as in the blood of humans, before and after immunization with cholera vaccine. The results of the determination of DNA-synthesizing lymphocytes in the blood of immunized humans and animals have been shown to serve as an objective characteristic for the complex evaluation of the biological activity of cholera vaccines.

[Interserovar antitoxic immunity to Vibrio cholerae toxins]. / Mezhserovarnyi antitoksicheskii immunitet k toksinam kholernykh vibrionov.

The immunochemical affinity of V. cholerae enterotoxins, serovars Inaba and Ogawa, has been shown in animal experiments on cross antitoxic immunity in the small intestine, the passive hemagglutination test and the toxin neutralization test. However, antitoxic interaction with both enterotoxins is characteristic only for antibodies to V. cholerae of serovar Inaba, while in animals immune to Ogawa toxin the choleragenic effect of enterotoxins produced by V. cholerae of both serovars in retained. The possible mechanisms of one-sided cross interserovar antitoxic immunity in cholera are discussed.

[Correlation of the antibody concentrations in the cells, subcellular structures and blood serum of rabbits immunized with cholera vaccine]. / O sootnoshenii kontsentratsii antitel v kletkakh, subkletochnykh strukturakh i syvorotke krovi krolikov, immunizirovannykh kholernoi vaktsinoi

Experiments were conducted on animals. Following immunization with cholera vaccine there were revealed vibriocidal antibodies, sometimes -- agglutinating, but no vibriolysins in the cells of the mucosal epithelium of the small intestine, of the liver, the spleen and in the fractions obtained from the cells with the aid of differential centrifugation. This corresponds to the high titre of vibriocidal antibodies in the serum and a relatively low titre of the other types of antibodies. In parenteral immunization with various doses of cholera vaccine the concentration of vibriocidal antibodies reached 10(1)-10(7) per 1 mg of protein, which was millions of times less than in the blood serum.

[The bacteriophage lysis-susceptibility properties of Vibrio cholerae strains isolated in separate regions of Dagestan in 1994]. / Fagolizabel'nye svoistva shtammov Vibrio cholerae, vydelennykh v otdel'nykh raionakh Dagestana v 1994 g.

The study of the properties of V. cholerae strains isolated in June-September 1994 in the Daghestan revealed that they belonged, according to their specific properties, to typical representatives of V. eltor, serovar Ogawa, but a great part of them (67.2%) was not lysed by diagnostic cholera bacteriophages. Experiments with different batches of diagnostic cholera bacteriophages showed the necessity of their further improvement.

[The epidemiology of cholera in Derbent District. The characteristics of the epidemic process]. / Epidemiologiia kholery v Derbentskom raione. Kharakteristika épidemicheskogo protsessa.

Cases of cholera in the Derbent District of the Daghestan took predominantly mild and moderate clinical forms. The ratio of patients to Vibrio carriers was 1:1.25. The etiological agent of the epidemic was V. eltor, serovar Ogawa. Cholera patients were of greater epidemiological importance as the sources of infection in comparison with Vibrio carriers. Carrier state after convalescence was observed in 1.1% of cases. The population was infected with cholera, as a rule, through everyday contacts and in more rare cases by the water route. The highest rate of contamination with V. cholerae was registered in the age group of 0-2 years.

[The epidemiology of cholera in Derbent District, Dagestan. The routes of the importation and spread of cholera]. / Epidemiologiia kholery v Derbentskom raione Dagestana. Puti zanosa i rasprostraneniia kholery.

The epidemic of cholera in the Derbent District of the Daghestan was imported into the region. 172 cholera patients and 204 Vibrio carriers were registered in 23 settlements of the region during the period of June 26 to October 12, 1994. The wide spread of this infection was facilitated by high migration activity of the population and the belated introduction of measures for limiting migration. The most severe outbreaks of cholera were observed in Derbent and in the villages of Mamedkala and Morskoe.

[The use of a new strain of Vibrio cholerae O139 as a producer of an enteric chemical vaccine]. / Ispol'zovanie novogo shtamma Vibrio cholerae O139 v kachestve produtsenta énteral'noi khimicheskoi vaktsiny.

Conditions for the submerged cultivation of a strain of V. cholerae O139, were worked out. These conditions ensured a high yield of biomass, soluble O-antigen and exoenzymes (proteinase, phospholipase A) into the culture medium, which exceeded their production by strains of serovar O1, respectively, 2, 3, 4 and 8 times. The preparation, isolated from the culture fluid and lyophilized, contained up to 50% of O-antigen and exoenzymes. In experiments on white mice the preparation exhibited low toxicity (LD50 was equal, on the average, to 1.2 mg) and immunogenicity (ED50 was equal to 3-5 micrograms) with respect to V. cholerae O139, which corresponded to the protective potency of commercial vaccine against V. cholerae O1 infection.

Antivibrionic activity of some glycolytic cycle enzymes of animal cells.

The antivibrionic activity of crystalline preparations of five enzymes of the glycolytic cycle of animals cells was investigated. Phosphorylase "a" (0.5 mg/ml), aldolase (15 mg/ml) and pyruvate kinase (0.1 mg/ml) were found to inhibit the proliferation of Vibrio cholerae cells; phosphoglucomutase and glyceraldehyde-3-phosphate dehydrogenase at a concentration of 0.25 mg/ml were found to be vibriocidal. A mixture of these enzymes containing 0.062 mg/ml of phosphorylase "a" and 0.125 mg/ml of each phosphoglucomutase, aldolase, glyceraldehyde-3-phosphate dehydrogenase and pyruvate kinase showed vibriocidal activity.

Lipid peroxidation during experimental cholera intoxication.

Cholera intoxication in albino mice was induced by intraperitoneal injection of endotoxin in doses of LD(16), LD(25), and LD(50) and combination of endo- and enterotoxin in doses equivalent to LD(25). Dose-dependent activation of superoxide dismutase, phasic changes in the contents of MDA and conjugated trienes and dienes, and modulatory influence of enterotoxin on catalase activity in the blood were observed during intoxication.