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[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.

Adolescent↗

Tularemia: a 30-year experience with 88 cases.

Drawing upon our experience with 88 cases and a survey of the English literature, we reviewed the clinical, pathophysiological, and epidemiological aspects of tularemia. Tularemia can be thought of as two syndromes--ulceroglandular and typhoidal. This dichotomy simplifies earlier nomenclature and emphasizes the obscure typhoidal presentation. Clinical manifestations suggest that the two syndromes reflect differences in host response. In ulceroglandular tularemia the pathogen appears to be well contained by a vigorous inflammatory reaction. Pneumonia is less common and the patient's prognosis is good. In typhoidal disease there are few localizing signs; pneumonia is more common; and the mortality without therapy is much higher, suggesting that the host response is somehow deficient. Francisella tularensis is an extremely virulent pathogen capable of initiating infection with as few as 10 organisms inoculated subcutaneously. During an incubation period of 3 to 6 days the host responds first with polymorphonuclear leukocytes and then macrophages. Granulocytes are unable to kill the pathogen without opsonizing antibody leaving cellular immunity to play the major role in host defense. One to 2 weeks after infection, a vigorous T-lymphocyte response can be detected in vitro with lymphocyte blast transformation assays and in vivo with an intradermal skin test, which, unfortunately, is not commercially available. Humoral immunity, often used as a diagnostic modality, appears 2 to 3 weeks into the illness. Cellular immunity is long-lasting, accounting for the common reoccurrence of localized disease upon repeated exposures to the pathogen. There are no symptoms that distinguish the ulceroglandular from the typhoidal syndrome. A pulse-temperature dissociation is seen in less than half of the patients. The location of ulcers and enlarged lymph nodes give a clue to the likely vector since lesions located on the upper extremities are more commonly associated with mammalian, and those of the head and neck and lower extremities with arthropod, vectors. Pharyngitis, pericarditis, and pneumonia can complicate both syndromes, although the latter is much more common in typhoidal disease. Hepatitis, usually of a mild degree, is common and occasionally erythema nodosum is seen. No specific laboratory tests characterize tularemia, and cultures of the pathogen are often difficult to obtain because of the special growth requirements of Francisella tularesis and the inability of many clinical laboratories to handle the dangerous pathogen.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

Tularemia and rhabdomyolysis.

Rhabdomyolysis as a complication of tularemia occurred in four patients in Tennessee over a four-year period. All patients were severely ill and had renal failure. Tularemia was not suspected initially in any of these patients. One patient died of complications of rhabdomyolysis. At autopsy, multiple abscesses were present within skeletal muscle, suggesting that rhabdomyolysis resulted from direct muscle involvement with Francisella tularensis. Tularemia should be considered in the differential diagnosis of patients with an acute febrile illness and rhabdomyolysis. Conversely, in patients with acute tularemia, the possibility of rhabdomyolysis should be entertained early, especially in those with evidence of myoglobinuria and/or impaired renal function.

Adult↗

[Results of the study of bird droppings collected in the Lithuanian SSR for the purpose of searching out tularemia epizootics].

There are practically no records of cases of tularemia among humans in the Lithuanian SSR. Nevertheless, the mass sero-allergic survey of the population for tularemia, carried out 10-12 years ago, showed that 2.3% of the adult population in the Republic had had contacts with the causative agent of this infection. The work was aimed at the determination of the present activity of the foci of tularemia. During 6 years in 22 rural districts 2582 samples of avian excrements, containing bones and wool of small animals, were collected and studied by means of the antibody neutralization test (ANT). In 132 (5.1 +/- 0.4%) excrement samples collected on the territory of 12 districts Francisella tularensis antigen was detected. The average ANT titer was 45.2, the maximum titer (10 excrement samples) reached 1: 160. The study revealed the existence of the natural foci of tularemia in Lithuania at present, but their activity proved to be low. The most unfavorable situation was found to exist in western districts of the Republic.

Animals↗

Tularemia: review of eight cases of tick-borne infection and the epidemiology of the disease in Georgia.

In the period 1960 to 1979, 177 cases of tularemia occurred in residents of Georgia. A tick bite was the implicated source of exposure in eight cases (4.5%), whereas 91 cases (51.4%) were associated with direct contact with infected rabbits. In Georgia and other southeastern states, the epidemiology of human tularemia infection primarily involves rabbits. However, a diagnosis of tularemia should still be considered in this region in a febrile patient with or without a primary lesion or reported exposure to rabbits. A history of having been bitten by a tick may be the major clue in determining the diagnosis. A primary ulcerative lesion on the legs or in concealed body areas such as the axillary or intergluteal regions, is commonly the presenting sign in the patient with tick-borne tularemia.

Adolescent↗

[Effectiveness of the tularemia-antibody erythrocyte diagnostic agent for the detection of specific antigen and antibodies to it].

The authors demonstrated the efficacy of utilization of tularemia antibody erythrocytic diagnostic agent. Data are presented indicating a strict specificity and a high sensitivity of this diagnostic agent for detection of the Vi-antigen both in the tularemia microbe cultures and in the suspensions of the organs of rodents which perished of tularemia, irrespective of the state of cadaver. There was revealed relationship between the sensitivity of the diagnostic agent and the virulence of the tularemia microbe cultures. A possibility of using the diagnostic agent in the antigen neutralization test for detection of specific antibodies in the sera of patients, who sustained the disease, and of the vaccinated humans and animals was revealed.

Animals↗

LIVE TULAREMIA VACCINE I. : Host-Parasite Relationship in Monkeys Vaccinated Intracutaneously or Aerogenically.

Eigelsbach, H. T. (Fort Detrick, Frederick, Md.), J. J. Tulis, M. H. McGavran and J. D. White. Live tularemia vaccine. I. Host-parasite relationship in monkeys vaccinated intracutaneously or aerogenically. J. Bacteriol. 84:1020-1027. 1962.-Bacteriological, histological, immunohistochemical, and serological studies were made on monkeys administered live tularemia vaccine strain LVS by either of two routes. Comparative data are presented on nonvaccinated monkeys exposed via the respiratory route to a highly virulent strain of Pasteurella tularensis. Tissue changes resulting from either aerogenic or intracutaneous vaccination were mild, and consisted primarily of the proliferation of histiocytes without the formation of granulomas. The vaccine strain was isolated from the site of vaccination of animals inoculated dermally, from the lungs of animals vaccinated aerogenically, and from the regional lymph nodes, liver, and spleen of both groups; it was not isolated from the blood or bone marrow. Proliferation of the vaccine strain at the site of dermal inoculation and in the lungs of animals exposed aerogenically was observed within 24 hr; in both groups, the maximal viable population was reached within 3 days and maintained through the 10th day. A reduction in the number of viable vaccine organisms had begun by the 14th day; isolations were obtained only from the regional lymph nodes on the 28th day, and the vaccine strain was not isolated from any of the tissues cultured on the 90th day. Because the monkey is less resistant to tularemia than is man, the benign response of this animal to live tularemia vaccine indicates that the vaccine might also be safe for man when administered by either the dermal or respiratory route.

Journal Article↗

Tularemia as a biological weapon: medical and public health management.

OBJECTIVE: The Working Group on Civilian Biodefense has developed consensus-based recommendations for measures to be taken by medical and public health professionals if tularemia is used as a biological weapon against a civilian population. PARTICIPANTS: The working group included 25 representatives from academic medical centers, civilian and military governmental agencies, and other public health and emergency management institutions and agencies. EVIDENCE: MEDLINE databases were searched from January 1966 to October 2000, using the Medical Subject Headings Francisella tularensis, Pasteurella tularensis, biological weapon, biological terrorism, bioterrorism, biological warfare, and biowarfare. Review of these references led to identification of relevant materials published prior to 1966. In addition, participants identified other references and sources. CONSENSUS PROCESS: Three formal drafts of the statement that synthesized information obtained in the formal evidence-gathering process were reviewed by members of the working group. Consensus was achieved on the final draft. CONCLUSIONS: A weapon using airborne tularemia would likely result 3 to 5 days later in an outbreak of acute, undifferentiated febrile illness with incipient pneumonia, pleuritis, and hilar lymphadenopathy. Specific epidemiological, clinical, and microbiological findings should lead to early suspicion of intentional tularemia in an alert health system; laboratory confirmation of agent could be delayed. Without treatment, the clinical course could progress to respiratory failure, shock, and death. Prompt treatment with streptomycin, gentamicin, doxycycline, or ciprofloxacin is recommended. Prophylactic use of doxycycline or ciprofloxacin may be useful in the early postexposure period.

Anti-Bacterial Agents↗

Clinical manifestations of tularemia in Japan--analysis of 1,355 cases observed between 1924 and 1987.

A total of 1,355 cases of tularemia observed between 1924 and 1987 in Japan were viewed on the basis of clinical manifestations and the results were compared with those in the United States. The incubation period varied from one day to over one month. In 75.5% of cases, the symptoms of illness appeared within seven days with the peak on the third day. A sudden onset of flu-like symptoms was generally observed, and 92% of cases was followed by regional lymph node swelling which mostly appeared in axillary and cubital regions. They were observed predominantly at the left rather than the right side. In contrast with the cases in the United States, the number of cases of ulceroglandular type in Japan was only one third of those of glandular type. None of the pleuropulmonary cases or fatal tularemia have been reported in Japan. The number of oropharyngeal cases has remarkably increased after World War II, and is still on the rise, presumably because of the change of dietary habits in Japan. All these characteristics of Japanese tularemia are assumed to be caused by low virulence of Japanese strains of Francisella tularensis.

Axilla↗

Prevalence of ticks infected with Francisella tularensis in natural foci of tularemia in western Slovakia.

The prevalence of ticks infected with F. tularensis was followed during a systematic surveillance in endemic area of tularemia in western Slovakia over the years 1984-93. Ticks were collected from vegetation in localities of Podunajské Biskupice, in the vicinity of the capital of Slovakia, Bratislava, near the river Danube. In total 6033 ticks, mostly adults of Dermacentor reticulatus and Ixodes ricinus (4994 and 1004, respectively) and 35 nymphs of Haemaphysalis concinna, were examined for the presence of F. tularensis. Out of 4542 starving ticks, 34 F. tularensis strains were isolated predominantly from D. reticulatus (30), and to a smaller extent also from I. ricinus (3) and H. concinna (1). Natural infection with F. tularensis was further proved from 1491 adults of D. reticulatus fed on laboratory animals, rabbits and white mice, together in 27 cases. From that, 21 times it was by positive isolation either from suspensions of partly or fully engorged ticks and their feaces, or from spleens of animals dead after the feeding of ticks. In addition, solely the development of antibodies against the agent was confirmed in 6 rabbit hosts. The presence of F. tularensis in all the above mentioned tick species and namely the relatively high and permanent infestation of D. reticulatus adults, ranging between 0.5-2% during the followed time period, demonstrated the maintenance of active natural focus of tularemia in the area under study. The present paper also emphasizes the epidemiologic consequence of various species of ticks in endemic foci of tularemia and the aspect of possible ways of transmission of the agent to humans.

Adult↗

Experimental murine tularemia caused by Francisella tularensis, live vaccine strain: a model of acquired cellular resistance.

We have established a model of experimentally-induced tularemia in mice, using the live vaccine strain of Francisella tularensis. A sublethal, intravenous inoculation of this organism caused in C57BL/6 strain mice an acute infection which lasted approximately 12 days. The clearance of Francisella from the bloodstream was shown to be complete by 5.5 hours postinfection. At this time, approximately twice as many bacteria were isolated from the spleen as from the liver. Mice which had recovered from a primary infection demonstrated a significant resistance to re-infection with autologous Francisella, a memory which persisted for at least 15 weeks. Resistance to experimental tularemia could be passively transferred from infected mice to naive mice by means of non-adherent spleen cells. Cells capable of adoptive transfer of resistance were present at a maximal concentration 7 days following infection, and persisted in significant numbers within the spleen cell population for at least 20 days after infection. Treatment of mice with serum from recovered animals caused a decrease in resistance when measured in the livers, and an increase in resistance when measured in the spleens. Suppression of T cell-mediated immunity during infection by treatment with cyclosporin A resulted in a dramatic increase in the tissue bacterial counts. Cyclosporin A-induced suppression of antitularemic resistance was first noted 2-3 days following infection and remained apparent for at least 8 days. The results of these experiments demonstrate that resistance to experimental murine tularemia is mediated predominantly by a cell-mediated mechanism. This mechanism involves T cells which become activated as early as 2-3 days following infection. Experimental, non-lethal infection with Francisella tularensis is thus an excellent model for investigating the mechanisms of acquired cellular immunity.

Animals↗

The requirement for gamma interferon in resistance of mice to experimental tularemia.

The role of gamma interferon (IFN-gamma) in the host response to experimental tularemia was evaluated in a murine model. C57BL/6 strain mice were given a series of daily intravenous injections of 10(6) units (U) recombinant murine IFN-gamma prior to infection with Francisella tularensis LVS. Three days later, the number of bacteria in the tissues of IFN-gamma-treated mice was found to be less than that in control mice by a factor of 10-20. The effect of IFN-gamma on anti-tularemic resistance was dependent upon the administered dose, with as little as 10(4) U/mouse/day inducing a significant level of enhanced resistance. IFN-gamma was also effective in enhancing resistance to tularemia in the A/J mouse strain which, in comparison with the C57BL/6 strain, is more susceptible to infection. When C57BL/6 mice were treated with a monoclonal antibody directed against murine IFN-gamma, the number of Francisella recovered from their tissues 6 days following infection was increased by as much as 15 times, in comparison with control mice. The results of these experiments clearly indicate that the resolution of experimental murine tularemia is dependent, at least in part, on the participation of IFN-gamma.

Animals↗

Tularemia: the disease and the weapon.

Tularemia is a bacterial infection usually transmitted via arthropod vectors or direct contact with infected animals. Naturally occurring cases are relatively rare, and can result in six different clinical syndromes. Tularemia is also a potential agent of bioterrorism or biowarfare, and is categorized as a high-level threat. Effective antibiotic treatment is available, including potential use of oral antibiotics in a mass casualty situation. An awareness of potential clinical presentations of tularemia will facilitate timely intervention,appropriate diagnostic testing, and decreased morbidity in the event of a biologic attack with Francisella tularensis.

Animals↗

[Tularemia outbreak in the province of Cuenca associated with crab handling].

OBJECTIVE: To report the clinical and epidemiologic characteristics of 19 patients diagnosed of tularemia at our hospital following an epidemic outbreak occurred in our health area. METHODS: Retrospective analysis of clinical records of patients admitted to our hospital who were examined at the Infectious Diseases Clinic and had clinical findings and epidemiologic data consistent with tularemia during the period from June 1998 to March 1999. CASE DEFINITION: A patient was considered to fulfill the case definition when clinical symptoms, epidemiologic data and the following laboratory criteria were met: antibody titer to Francisella tularensis (tube agglutination test) > or = 1/128 in the convalescence serum specimen, seroconversion or recovery of the microorganism from biological material. RESULTS: Nineteen patients with a median age of 60 years. Males predominated (63.1% male patients); all of them had handled red crayfish from the same source (río Mayor). The incubation period ranged from 0 to 15 days (mean 4.88 days). All patients presented with the ulceroglandular form. Seventy-three percent of patients received doxycycline. Only one patient relapsed. Water samples from the reservoir of the depuration plant of the river were positive to F. tularensis by PCR. This same result was confirmed in stomach and hepatopancreas of crayfish fished in río Mayor in the second half of July. CONCLUSIONS: The most likely hypothesis of this outbreak was the contamination of the river water with animals dead from tularemia which, together with the characteristics of the transmission mechanism (wounds caused by crabs) had contributed to the acquisition of this disease in humans. Interestingly too, red crayfish as the source of infection.

Animals↗

Tularemia in Bursa, Turkey: 205 cases in ten years.

Tularemia is a zoonotic disease caused by the coccobacillus F. tularensis. Small epidemics and sporadic cases were seen around Bursa since November 1988. In this study, a total of 205 cases of tularemia were observed. All the cases were diagnosed on clinical, bacteriological and serological grounds. The epidemics were thought to be waterborne. The majority of the patients were young and female. In most of the cases the disease presented itself in oropharyngeal form (83%). Analysing sera from the patients with microagglutination method demonstrated that titers were > or = 1:160 in approximately 85% of the cases, including the ones in subclinical form. Five of ten patients from who the bacteria was isolated were seronegative. Streptomycin was given to the most of the patients by combining with tetracycline, doxycycline or chloramphenicol. The early administration of these antibiotics (before the third week of disease) was found to be much more effective to resolve the infection. As a result, the main mode of transmission of F. tularensis is waterborne in our region. In our region, tularemia should be considered in differential diagnosis for the cases with fever, tonsillopharyngitis and cervical lymphadenopathy to make an early diagnosis and to design relevant treatment.

Adolescent↗

Histologic and molecular diagnosis of tularemia: a potential bioterrorism agent endemic to North America.

Francisella tularensis (FT), a zoonotic bacterium that causes tularemia, has received attention as a possible bioterrorism threat. We developed a PCR assay for use in fixed, processed tissues, which are safer to handle and allow archival testing. PCR analysis for a 211-bp fragment of the FT lipoprotein gene was performed on tissues from 16 cases of tularemia. In all, 14/15 cases with intact DNA (93%) were positive for FT by PCR. Frequent histologic findings in PCR-positive tissues included irregular microabscesses and granulomas in liver, spleen, kidney, and lymph nodes, and necrotizing pneumonia. Unusual cases featuring suppurative leptomeningitis and gastrointestinal ulcers were also seen. As this disease is endemic in North America, and has been identified as a potential bioterroristic threat, awareness of the clinicopathologic spectrum of disease and available detection methods is increasingly important. This PCR assay, the first designed for use in processed tissues, is an excellent method for diagnosis of tularemia.

Adolescent↗

A procedure for differentiating between the intentional release of biological warfare agents and natural outbreaks of disease: its use in analyzing the tularemia outbreak in Kosovo in 1999 and 2000.

The events of 11 September and the subsequent anthrax outbreaks in the USA have opened the world's eyes to the threat posed by terrorist groups, criminal organizations and lone operators who will stop at nothing to achieve their goals. The open or covert use of pathogens and toxins as biological warfare agents can no longer be ruled out. Against this background, the appearance of an unusual disease must be studied in order to clarify whether it is a natural or artificially caused occurrence. This issue was recently raised in discussions with local representatives and relief organizations during a tularemia epidemic in Kosovo from October 1999 to May 2000. This paper will present a procedure which attempts to use certain criteria to identify or rule out the use of biological warfare agents in the event of an unusual outbreak of disease. Data and findings gathered by routine epidemiologic and microbiological studies often provide only an indirect answer to this problem. For this reason, various criteria were formulated and points allocated to represent their importance, allowing us to deduce in a semiquantitative manner the degree of possibility of an artificial genesis of outbreaks. The significance and characterization of each criterion are discussed. An analysis of the tularemia epidemic in Kosovo based on the procedure described here indicates that a deliberate release of the causative agent of tularemia, Francisella tularensis, as a biological warfare agent is doubtful. In this paper, an approach is described to discriminate between the intentional use of biological warfare agents and natural outbreaks of infectious diseases. The developed model is flexible and considers the political, military and social analysis of the crisis-afflicted region, the specific features of the pathogen, and the epidemiologic and clinical characteristics of the epidemic.

Animals↗

Tularemia: emergence/re-emergence.

Francisella tularensis is a gram-negative coccobacillus and the etiologic agent of the zoonotic disease tularemia. First described in 1911 in Tulare County, California, it has since been reported throughout the Northern Hemisphere, with natural infections reported among an unusually wide range of vertebrates and invertebrates. In recent years, tularemia has emerged in new geographic locations, populations, and settings. This review will serve to highlight mechanisms contributing to the recent emergence of tularemia as well as a repertoire of diagnostic tools useful for detecting and diagnosing disease.

Animals↗