[Various mechanisms of formation of chronic tularemia in highly-sensitive animal species (Microtus rossiae-meridionalis)]. / K voprosu o nekotorykh mekhanizmakh formirovaniia khronicheskoi tuiaremii u vysokochuvstvitel'nykh vidov zhivotnykh (vostochnoevropeiskaya polevka).

Experiments on voles belonging to the tularemia-sensitive species Microtus rossiae-Meridionalis, infected with Francisella tularensis highly virulent strain 503, have been carried out with the aim of studying the pathogenesis of chronic tularemia. The experiments have been made with the use of live and killed microbial cells. The significance of the multiple oral administration of killed bacteria to voles for the development of the atypical form of infection has been shown. The possibility of the early (on day 2) formation of antibodies in the blood of some of the animals has been established. Repeated feeding has been found to lead to almost 100% seroconversion in the animals. This fact can be attributed to the rapid spread of the antigen (1-5 hours) in the organs of individual animals. Besides, the causative agent is present in large amounts in lymphoid formations of the intestinal tract and in the lumen of the intestine, which creates conditions for the early contact of the massive dose of the antigen with immunocompetent cells and for the rapid development of systemic and local immune response. Morphological study indicates the presence of the rapid (24 hours) proliferative reaction of the cells making up the lymphoid apparatus of the intestine, their plasmocytic and macrophagal transformation. Thus, after the infection of voles with a mixture of live and killed bacteria the development of the early phases of the infectious process occurs simultaneously with the systemic and local transformation of the macroorganism, which contributes to the benevolent course of the infectious process in some of the animals.

[Detection of tularemia pathogens in patients with the use of an immunofluorescence reaction]. / Obnaruzhenie vozbuditelia tuliaremii u bol'nykh s pomoshch'iu reaktsii immunofliuorestsentsii.

For the first time three cases of the detection of Francisella tularensis, made by means of the direct immunofluorescence test in the fluid obtained from punctured buboes or in purulent matter taken from patients with the ulcerous bubonic form of tularemia, are presented. The simplicity of the test and its capacity of yielding rapid results make it possible to recommend this test, together with other diagnostic methods, for the clinical diagnosis of tularemia.

[Possible atypical course of tularemia (persistence) in the common vole Microtus arvalis Pall]. / O vozmozhnosti atipichnogo techeniia tuliaremii (persistentsii) u obykhnovennoi polevki Microtus arvalis Pall.

The possibility of the atypical course of tularemia with the prolonged persistence of Francisella tularensis in common voles (M. arvalis), the twin species of East European voles (M. rossiaemeridionalis), was studied. Experiments were made on 33 animals grown in the laboratory. F. tularensis strain 165 was used. The animals were infected by feeding them according to the previously developed scheme. 7 out of 33 voles showed the atypical course of tularemia: in 3 voles the disease took a prolonged course with bacteriuria and death on days 25-34; 3 other voles with bacteriuria registered before days 33, 66 and 172 (the term of observation) survived. The surviving animals were killed on day 183, and the presence of bacteria in their organs and seroconversion were established. One vole excreted no bacteria with urine and had no bacteria in its organs (the animal was examined on day 156), but in its blood specific antibodies were detected. To determine bacteriuria, the immunofluorescence test was used together with biological assays. Thus, M. arvalis, like M. rossiaemeridionalis studied earlier, can harbor F. tularensis at the period between epizootics. When voles of the former species penetrate stacks of straw and hayricks, conditions appear for the transfer of the infection to the latter species, M. rossiaemeridionalis. Therefore, in the foci of the meadow-field type each of these two species of voles may be not only of epizootic, but also of epidemic importance.

Persistence of Francisella tularensis McCoy et Chapin tularemia agent in the organism of highly sensitive rodents after oral infection.

In the literature there are no data on the possibility of obtaining in experiment non-fatal tularemia infection (persistence) in rodents highly sensitive to it (Group I) when using highly virulent strains circulating in nature for infection by natural routes. Our detailed experiments on 1483 adult voles Microtus rossiaemeridionalis Ogn. (syn. M. subarvalis Meyer et al.) of laboratory origin using virulent strains of Francisella tularensis holarctica Ols. et Meshch. and natural alimentary infection by feeding on bodies of died animals or forced dosed administration of a mixture of dead and living bacteria to the voles through the oesophagus demonstrated the possibility of the animals to survive tularemia with subsequent long-term chronic carrier state of the infectious agent. They also confirmed the ability of voles to eat readily cadavers of their kin (cannibalism, necrophagia). Experiments with the fully virulent strain 503 and feeding on cadavers were carried out on 439 voles. 203 animals died from acute tularemia, 43 from side effects and 193 survived. Two of the latter (0.5%) exhibited chronic bacterial carrier state, and agglutinins to tularemia microbe (1:320) were found in their blood. From 309 voles subjected to dosed feeding, 153 died from acute tularemia, 27 from side effects and 129 survived. Two of them were bacterial carriers and 6 (1.9%) showed agglutinins (1:160-1:1280). In experiments with strain 165, spontaneously less virulent for guinea pigs, 433 voles were fed on cadavers. 170 of them died from acute tularemia, 53 from side effects, and 210 animals survived. Among the latter, 14 animals (3.2%) were found immune to 100 LD50 of the highly virulent strain 1298. In dosed feeding of 302 voles with the strain 165, 90 animals died from acute tularemia, 59 from side effects, and 153 survived, including 63 animals (20.7%) immune to 100 LD50. The surviving immune voles exhibited seroconversion and long-term persistence of the infectious agent in the internal organs (up to day 257-313--period of observation), accompanied bacteriuria in some cases. Histological examination of the kidney revealed, for the first time, important pathological changes of glomerulonephritis type with elements of pyelonephritis. Protracted stay of the agent in the organism of the vole does not affect its virulence. Persistence of tularemia agent in the organism of voles highly sensitive to tularemia in alimentary administration to them of living and dead bacteria is achieved as a result of anticipatory development of immunological reactions in response to a massive dose of killed antigen, against the background of which the accumulation of simultaneously administered

[Mechanism of the changes in the animal reactivity to tularemia in mixed infection]. / O mekhanizme izmeneniia reaktivnosti zhivotnykh k tuliaremii pri smeshannoi infektsii.

Experiments were conducted on albino rats infected with listeria or salmonelloses, and then with tularemia; differences were revealed in the duration of manifestation of nonspecific resistance associated with peculiarities of pathogenesis and immunogenesis of the background infections. One of the significant factors causing an increase of albino rats resistance to tularemia in mixed infection was activation of the immunomorphological reaction promoting accelerated development of specific immunity reactions to this infection.

[Detection of the causative agent of tularemia in the organs of animals in the early stages of development of the infection]. / Obnaruzhenie vozbuditelia tuliaremii v organakh zhivotnykh na rannikh étapakh razvitiia infektsii

A study was made of a possibility of detection of the causative agent of tularemia in the organism of albino mice at early stages of development of the infection after subcutaneous infection with 1, 10 and 100 microbial cells of strains No. 503/834 (Holarctic race) and Schu (nearctic race). The following examinations were made: cultivation on nutrient media, immunofluorescent study, the antibody neutralization test and the passive hemagglutination test with erythrocytic diagnostic agents. The microbe could be regularly revealed three days after the infection. Detection of the causative agent was possible in individual cases at the earlier dates by seeding and by the fluorescent antibody method. Although by cultivation it is possible to reveal individual microbes, but the growth appears on the 3rd--5th day and later. The most rapid response (1.5--2 hours) results (on the presence of the microbe) can be obtained with the aid of the fluorescent antibody method. Application of the mentioned tests with the erythrocytic diagnostic agents permits to obtain data not only on the presence of the causative agent, but also on its quantity of the causative agent in the organism of the infected animal. The mentioned methods provide the most complete characteristics of the dynamics of the accumulation of the microbe in the animal organism.

[Use of the immunofluorescence method to detect the causative agent of tularemia in developing chick embryos]. / Primenenie immunofliuorestsentnogo metoda s tsel'iu obnaruzheniia vozbuditelia tuliaremii v razvivaiushchikhsia kurinykh émbrionakh

There was shown a possibility of using the immunofluorescent method for detection of the causative agent of tularemia in the developing chick embryos, infected with the virulent strains 503 (holoarctic race) and Schu (nonarctic race). The greatest accumulation of bacteria was revealed in the yolk sacs, and the least--in the chorionallantoic fliud; the greatest accumulation of bacteria was observed on the 3rd--4th days after the infection. In infection with various doses of the causative agent--from 1 milliard to 1 microbial cell-positive results were noted in 92.3% of cases (according to the data of fluorescent microscopy) and in 77.3% of cases (according to the data of light microscopy), this pointing to a greater sensitivity of the method of fluorescent in comparison with the light microscopy. Immunofluorescent method can be recommended for detection of the causative agent of tularemia in the yolk sacs of chick embryos.