Mechanism of the changes in the animal reactivity to tularemia in mixed infection]

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.     

Comparative study of the effectiveness of amikacin and streptomycin in experimental tularemia

In vitro study on antibacterial activity of amikacin in comparison to that of streptomycin revealed a high sensitivity of tularemia microbes of three geographical races to it. Amikacin showed a high therapeutic activity in treatment of albino mice infected with tularemia. The prospects of amikacin use in prophylaxis and treatment of tularemia are defined by its antibiotic activity against streptomycin-resistant forms of the tularemia causative agent.     

Specific effect of attenuated strain of Francisella tularensis on the development of radiation induced lesions in experimental animals and effictiveness of antibacterial therapy for lesions induced by radiation combined with virulemt strain of the bacteria

For study of the effects of whole-body gamma-radiation (1 and 4 Gy) on the response of the body to administration of vaccines and virulent strains of tularemia 206 outbred white mice were used. The results of the study shown that the administration of attenuated bacterial cells in 5 days after exposure to radiation (1 and 4 Gy) caused more severe post-radiation effects and the increase in the number of died animals. The severity of the disease was less if mice were vaccinated in 26 days after irradiation (4 Gy). The treatment of tularemia in irradiated mice twith Riphampicin (daily peroral administration, 5 mg/mouse, duration of treatment--7 days) administered in 4 hours after infection was effective and caused high survival of affected mice. The results show effectiveness of the riphampicin treatment of tularemia in the animals exposed to sublethal dose of radiation.     

An experimental study of mixed tularemia and Omsk hemorrhagic fever infection in muskrats]

Musk-rats were infected simultaneously and at three-day interval with tularemia and Omsk hemorrhagic fever (OHF); the course of this mixed infection under the mentioned conditions were studied. Virological, microbiological and morphological data indicated that infection of musk-rats with OHF and tularemia caused development of mixed infection in them. A more severe course of mixed infection was associated with enhanced vascular affections caused by the action of the OHF virus. An inhibition of tularemia caused by the OHF development was noted in the course of mixed infection.     

Survival of <Emphasis Type="Italic">Francisella tularensis</Emphasis> Type A in brackish-water

Martha’s Vineyard (MV), Massachusetts has been the location of two outbreaks of pneumonic tularemia; landscaping activities have been associated with risk, suggesting environmental inhalation exposure. We determined whether salinity or other components of brackish-water present in a location with endemic tularemia may prolong survival of F. tularensis. In addition, we demonstrate for the first time that F. tularensis Type A appears similar to Type B with respect to environmental stability. The results of this study suggest an explanation for why MV is the site of pneumonic tularemia transmission as opposed to sites in the southcentral USA, where tularemia is more commonly reported: Bacteria may be more prone to surviving in salt-influenced soil or moisture in the island setting.     

Role of gamasids in the epizootiology of tularemia]

10 strains of Francisella tularensis were isolated from 4 species of gamasid mites, Laelaps muris, L. multispinosus, Hyperlaelaps amphibius and Haemolaelaps glasgowi, in natural nidi of tularemia in the Tumen district. Under experimental conditions L. muris is often infected with tularemia agent on sick animals but preserves it at an indoor temperature not more than a week and does not transmit it transovarially. Haemogamasus ambulans preserve the agent within the same period. L. muris and Hirstionyssus isabellinus do not transmit the tularemia agent to healthy animals through a bite.     

Rise in the epizootic activity of a natural focus of steppe-type tularemia in Stavropol Territory and its epidemic consequences

One of recurrent autumn and winter rises in the epizootic activity of the steppe-type focus of tularemia in the Stavropol Territory is described. During the tularemia epizooty of 1981-1982 the population of common voles (Microtus arvalis) was very numerous, while the population of house mice (Mus musculus) was comparatively scarce. Francisella tularensis strains were isolated from different species of rodents (Microtus arvalis, Mus musculus, Apodemus sylvanicus, Rattus norvegicus, Lepus, etc.), from fleas and ticks, as well as from environmental objects (well-water, hay). 38 cases of the disease among nonvaccinated persons, mainly in rural areas, were registered. Anginous-bubonic tularemia was the dominant form of the disease. A complex of measures aimed at the detection of tularemia and its liquidation among the population was carried out.     

Susceptibility of the common hamster (Cricetus cricetus) to Francisella tularensis and its effect on the epizootiology of tularemia in an area where both are endemic

Francisella tularensis is a highly infectious zoonotic agent causing the disease tularemia. The common hamster (Cricetus cricetus) is considered a pest in eastern Europe, and believed to be a source of human tularemia infections. We examined the role of the common hamster in the natural cycle of tularemia using serologic methods on 900 hamsters and real-time polymerase chain reaction (PCR) on 100 hamsters in an endemic agricultural area. We collected 374 Ixodes acuminatus ticks from the hamsters and tested them by real-time PCR. All tests were negative. To examine clinical signs, pathology, and histopathology of acute tularemia infection similar to the natural infection, two hamsters were infected with a large dose of a wild strain of F. tularensis ssp. holarctica. After a short period of apathy, the animals died on the eighth and ninth days postinfection. The pathologic, histopathologic, and immunohistochemical examination contributed to the diagnosis of septicemia in both cases. Our results confirmed previous findings that common hamsters are highly sensitive to F. tularensis. We conclude that although septicemic hamsters may pose substantial risk to humans during tularemia outbreaks, hamsters in interepizootic periods do not act as a main reservoir of F. tularensis.     

Phase variations of Francisella tularensis lipopolysaccharide in human infection and immunization

The comparative study of the specificity of antibodies in human sera after tularemia infection and immunization with live tularemia infection was carried out with the use of passive hemagglutination and immunoblotting techniques. The sera of tularemia patients contained two different types of immunoglobulins: strictly specific to the antigenic epitopes of F. tularensis Iipopolysaccharide (LPS) and strictly specific to F. tularensis subsp. novicida LPS. Such phenomenon may be due to phase variations of the antigenic structure of F. tularensis LPS in the body of a slightly susceptible host. The immune sera of vaccinated were found to contain antibodies, strictly specific only to F. tularensis LPS. At the same time in one vaccinee by the presence of pronounced postvaccinal reactions was found sharply defined interaction between serum imunoglobulins and F. tularensis subsp. novicida LPS. As the result, the data on the possibility of the antigenic modification of F. tularensis in tularemia infection in humans were obtained. At the same time antigenic epitopes, characteristic of faintly pathogenic and closely related F. tularensis novicida LPS, appeared in the structure of F. tularensis LPS.     

Ixodid ticks of Pavlodar Province and their participation in the circulation of tularemia infection

Investigations carried out in Pavlodar Province have shown that 7 species of ixodid ticks, Ixodes crenulatus, I. lividus, I. persulcatus, I. laguri laguri, Dermacentor marginatus, D. reticulatus, Haemaphysalis concinna, and one brought species, Hyalomma asiaticum, parasitize domestic animals and wild mammals. Maximum activity of pasture ticks of the genus Dermacentor falls on the end of April--beginning of May, that of H. concinna on the beginning of June. The growth in the abundance of pasture ticks, recorded during the last years, is favoured by the increase in the cattle live stock, its seasonal movements and pasture area reduction. Natural nidi of tularemia become more active. Since 1977 221 cultures of tularemia agent have been isolatid from pasture ticks. H. concinna takes the most active part in the infection circulation.     

Occurrence of natural tularemia foci in Kamchatka

The focus of tularemia in the Ust-Kamchatsky region belongs probably to the flood-plain and swamp type with muskrats and tundra voles being the main carriers. In autumn 1980 for the first time three cultures were isolated in this region: 1 from a tundra vole and 2 from muskrats. The presence of antibodies to tularemia antigen in Norway rats was revealed in the passive hemagglutination test.     

Patterns in the change in the number of carriers and epizootic activity in a floodplain local natural focus of tularemia in Voronezh Province]

Prolonged study of the population of Arvicola terrestris L. in connection with tularemia epizootic among these animals showed this animal to serve as the principal carrier of tularemia infection in the Povorinsk natural focus. Epizootics proved to originate with a definite threshold count of Arvicola terrestris L.; this threshold constituted about 30% of the trapped animals. Dynamics of the epizootic activity was characterized by alterations of cycles of various duration, coursing by waves, with 2--3-year periods. Reduction of the epizootic intensity coursed during a decade in 2 waves with 3-year periods, and during a 7-year period--in one 3-year wave. During the epizootics with the character of a 2-year wave the population of the principal carrier diminished, and with a 3-year wave the count of Arvicola terrestris L. decreased during the first year, and began to increase during the second year, despite the persistence of the epizootic. Detection of regularities attending the changes in the population of the principal carrier of the infection and its connection with the epizootics permitted to make long-period prognoses of the epizootic activity and to plan antiepidemic measures in the focus.     

Seroprevalence study of Francisella tularensis among hunters in Germany

In 2005 and 2006, Francisella tularensis unexpectedly reemerged in western Germany, when several semi-free-living marmosets (Callithrix jacchus) in a research facility died from tularemia and a group of hare hunters became infected. It is believed that hunters may have an elevated risk to be exposed to zoonotic pathogens, including F. tularensis. A previous cross-sectional study of the German population (n=6883) revealed a prevalence of 0.2%. Here, we investigated 286 sera from individuals mainly hunting in districts with emerging tularemia cases (group 1) and 84 sera from a region currently not conspicuous for tularemia (group 2). Methods included standard enzyme-linked immunosorbent assay (ELISA), Western blot analysis and indirect immunofluorescence assay. We found five out of the 286 hunters (1.7%; 95% CI 0.6-4.0%) in group 1 positive with standard ELISA and Western blot, but none in the Berlin area (group 2; 95% CI 0-0.04%). Group 1 showed an elevated risk for hunters to be seropositive for F. tularensis compared with the cross-sectional study (OR=7.7; P<0.001). This indicates a higher prevalence for tularemia in hunters of a suspected endemic region of Germany.     

Tularemia in inactive natural foci

The data on the epidemiological and epizootological manifestations of tularemia on the territory of the Ulyanovsk region are presented. The characteristics describing the process of the of Francisella tularensis circulation as well as the environmental objects, most important for the manifestations of tularemia infection, are given.     

Hepatic abscess complicating ulceroglandular tularemia.

In a patient with the clinical features of classic ulceroglandular tularemia a solitary hepatic abscess was found during an ultrasound examination. Hepatic tularemia has rarely been reported since the advent of specific therapy, which prevents the disease from reaching the disseminated state. This case, however, shows that the liver can be involved early in the course of tularemia. Increased serum levels of hepatic enzymes may be the only sign of such a complication.     

Comparative study of the basic immunological reactions for assessing tularemia immunity in inoculated persons or those who have had the disease

In the comparative study of immunological tests used for the determination of immunity to tularemia in vaccinees the greatest number of persons with the positive reaction was detected by means of the tularine skin test. Former tularemia patients retained allergic skin reaction to this test irrespective of the time of the disease.     

Tularemia in deer mice (peromyscus maniculatus) during a population irruption in Saskatchewan, Canada

Type B tularemia caused by Francisella tularensis subsp. holarctica was diagnosed in deer mice (Peromyscus maniculatus) found dead at four sites in west-central Saskatchewan during April and May 2005. The occurrence of tularemia coincided with a decline in the number of deer mice in part of a large area (>22000 km(2) ) in which deer mice had been extremely abundant during the autumn of 2004 and spring of 2005, and in which mice caused damage to crops in the autumn of 2004. This is apparently the first report of tularemia as a cause of death of wild deer mice. The bacterium isolated from deer mice was atypical in that cysteine was not required in the media used for isolation. Three isolates tested were genotypes not previously identified in Canada. There were no reports of human disease in the area.     

A rapid method of evaluation of the effectiveness of antibacterial drugs]

Efficacy of antibiotics in the treatment of experimental tularemia was studied comparatively on various biological models. It was shown that the antibiotics which proved active against the tularemia microbe in albino mice when studied by the rapid and routine methods were highly efficient in the treatment and prevention of experimental tularemia in rabbits and baboons (hamadryas). The experiments showed basic possibilities to perform rapid estimation (for at least 2 days) of drug efficacy in experimental glanders and melioidosis in golden hamsters. The rapid method developed by the authors was recommended for the use in primary estimation of the efficacy of new drugs in the treatment of tularemia, glanders and melioidosis.     

Infections with Francisella tularensis biovar palaearctica in hares (Lepus timidus, Lepus europaeus) from Sweden

The occurrence of tularemia was studied in 1,500 hares submitted to the National Veterinary Institute, Uppsala, Sweden for postmortem examination during 1973 through 1985. A total of 109 tularemia cases was recorded based on the fluorescent antibody (FA) test for Francisella tularensis and on the gross and microscopic pathology. Tularemia was diagnosed only in the varying hare (Lepus timidus) and not in the European brown hare (Lepus europaeus). The geographical distribution of the 109 cases indicates that tularemia has not spread in Sweden during the last 45 yr, with the exception of an endemic occurrence of the disease on the island of Stora Karls? in the Baltic sea. The disease was most frequent in the autumn and only a few cases were recorded during winter. Cases were not seen in the spring. The annual prevalence varied, with several cases in 1974 and 1981, but there were no cases in 1976 and 1980. The postmortem findings in hares dying of tularemia in the autumn were characterized by focal coagulative necrosis in liver, spleen and bone marrow, with high numbers of bacteria FA-positive for F. tularensis. In hares dying during winter months, the most characteristic findings were hemorrhagic enteritis and typhlitis, although necrotic lesions could occur in liver, spleen and bone marrow. Diseased hares on the island of Stora Karls? were demonstrated to be infected with ticks, while hares on the mainland of Sweden generally were fed upon by mosquitoes. Twenty-six of the 109 hares with tularemia were examined bacteriologically and F. tularensis biovar palaearctica was isolated from eight. The lung extract antibody test for F. tularensis was performed in 18 of the 109 hares. All were negative. In addition to the field study, an experimental study with F. tularensis biovar palaearctica was performed. Four varying hares and three European brown hares were inoculated. None of the hares died from tularemia, and generalized infection was not demonstrated.     

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