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PubMedDate not supplied

Case report. Tularemia in Ohio: report of two cases and clinical review.

Although unusual, human tularemia continues to be reported from areas of the United States which are not heavily endemic for the disease. Two patients with ulceroglandular tularemia diagnosed in Ohio are described. The causative microorganism, Francisella tularensis, is a small, pleomorphic gram negative coccobacillus which requires special microbiological media for laboratory isolation. In nature, the organism is usually transmitted to man by the handling of infected animal tissues and body fluids or by an arthropod vector. There are several clinical forms of tularemia of which the ulceroglandular type is most common. Laboratory diagnosis is usually made by demonstrating a four-fold increase in the serologic agglutinating antibody titer to Francisella tularensis. Streptomycin is the drug of choice in the treatment of tularemia.

Adult↗
PubMed1990

Tularemia in children caused by Francisella tularensis biovar palaearctica.

Existing data on tularemia infections in children caused by the biovar Francisella tularensis palaearctica (type B) are limited. The case histories of all patients younger than the age of 16 years in northern Finland who had tularemia, based on the antibody response, during the years 1967 to 1986 are reviewed. A total of 67 children, 28 girls and 39 boys, were identified as having had tularemia. The occurrence of the disease varied greatly among years. Most of the cases occurred in July, August and September. The epidemiology differed significantly from that reported for F. tularensis biovar tularensis (type A). This is most probably attributable to the different vector, which was the mosquito in our series, but the tick in areas where type A is common. There were also clear differences in the clinical picture. The ulceroglandular clinical type was the most common. The clinical symptoms and signs were usually quite benign, but the symptoms lasted for a median duration of 26 days. The patients were treated with different antibiotics and there were no differences in the outcome related to the treatment given. Prospective comparative investigations of antibiotic therapy given for tularemia are needed. It is also important to try to identify which strain is causing the disease in each case.

Adolescent↗
PubMed2002

Tularemia of the middle ear.

We report the case of a 10-year-old boy with prolonged fever who was found to have tularemia of the middle ear. Otolaryngologic cases including oropharyngeal and glandular or ulceroglandular forms of the head and neck region are estimated to account for 12% of all tularemia cases, but to date we have not seen a report of tularemia in the middle ear. The possibility of tularemia may not occur to a physician because of the wide variation of clinical manifestations.

Anti-Bacterial Agents↗
PubMedDate not supplied

The development of tools for diagnosis of tularemia and typing of Francisella tularensis.

Rapid development of molecular techniques for the diagnosis of infections and typing of microbes has been seen during the last 10 years. The present review exemplifies this development by presenting the work of the authors and others regarding techniques for the diagnosis of tularemia and typing of Francisella tularensis. The lack of rapid and safe methods for the laboratory diagnosis of tularemia was the rationale behind the development of methods for the direct detection of F. tularensis in clinical specimens. Today, detection by polymerase chain reaction has become an important adjunct to clinical decisions for the early diagnosis of tularemia. The elucidation of the epidemiology and epizootology of the disease has been hampered by the lack of suitable methods. During recent years several DNA-based methods that allow rapid identification of the four F. tularensis subspecies, including differentiation of strains of the two clinically important subspecies, the highly virulent type A strains and less virulent type B strains, have been developed. Since F. tularensis strains of any origin exhibit highly conserved genomic sequences, the availability of extensive genome sequence data was a prerequisite for the development of a typing system that allows discrimination of individual isolates. The most discriminatory method is based on multiple-locus variable-number tandem repeat analysis (MLVA) and uses highly variable parts of the F. tularensis genome. The method will be an important tool in future studies of the molecular epidemiology of tularemia.

Bacterial Typing Techniques↗
PubMed1984

Modifying effects of exercise on clinical course and biochemical response of the myocardium in influenza and tularemia in mice.

For a study of the interactions of strenuous physical exercise (daily swimming to exhaustion) and a viral as compared with a bacterial infection with regard to the clinical course and the biochemical response of the myocardium, influenza and tularemia of similar lethality were used in mice. In both infections, expected infection-induced catabolic alterations in the ventricular myocardium were evident 2 days before median lethality was achieved, with a more pronounced wasting in influenza than in tularemia. Exercise before inoculation (preconditioning) was beneficial in that the catabolic effects of both infections were limited and lethality in influenza was reduced. Thus, the myocardial protein-degrading effect of influenza did not occur with preconditioning, and oxidative tissue enzyme activities decreased less. In tularemia, cytochrome c oxidase activity was fully preserved with preconditioning, and activation of catalase was less pronounced. Exercise during ongoing infection counteracted the infection-induced decrease in the activities of glycolytic and oxidative enzymes in tularemia, but lethality and bacterial counts in the spleen were uninfluenced. Conversely, exhaustive exercise in influenza increased lethality and had no significant effect on cardiac enzymes. These exercise models caused no major alterations in activation of lysosomal enzymes (beta-glucuronidase and cathepsin D).

Animals↗
PubMed1972

Infection-immunity in tularemia: specificity of cellular immunity.

The relationship between hypersensitivity and cellular resistance to infection with facultative intracellular parasites was studied in mice by using infection-immunity in tularemia as a model system. Delayed hypersensitivity to antigenic fractions of Francisella tularensis was first detected 6 to 7 days after immunization with viable F. tularensis vaccine, at which time immunity against challenge infection developed. Both immunity and delayed-type sensitivity reached maximal levels by 9 to 10 days. Immediate hypersensitivity occurred after immunization with both viable and nonviable tularemia vaccines but could not be correlated with resistance since nonviable antigens were not protective. Attempts to relate resistance to F. tularensis with nonspecific immunity factors were unsuccessful. Immunization of mice with BCG vaccine stimulated protection against infection with F. novicida and Salmonella typhimurium but provided no protection against infection with F. tularensis. Moreover, viable tularemia vaccine, while inducing marked protection against challenge with specific organisms, afforded no protection against infection with S. typhimurium or S. enteritidis. It is concluded that cellular immunity in tularemia involves an immunologically specific component.

Animals↗
PubMed2000

Comparative analysis of PCR versus culture for diagnosis of ulceroglandular tularemia.

PCR and culture were comparatively evaluated for their abilities to demonstrate Francisella tularensis in wound specimens from tularemia patients during an outbreak in Sweden in 1998. For transport of the specimens used for PCR, a buffer solution containing a nuclease inhibitor was used, and for transport of the specimens used for culture, a commercial transport system was selected after experimental comparison of various systems. Of 40 patients with culture- and/or serology-verified ulceroglandular tularemia, PCR detected F. tularensis DNA in 30 (75%) patients, whereas culture detected bacterial growth in 25 (62%) patients. Compared to data from a previous study, the present inclusion of a nuclease inhibitor in the transport medium did not improve the sensitivity of the PCR, whereas the sensitivity of the culture procedure was significantly increased by selection of the system used for transport. Among eight patients with clinically suspected tularemia but with negative serology and culture, specimens from four patients showed detectable DNA. In three of these patients the diagnosis was verified by the demonstration of an F. tularensis-specific T-cell response in vitro. In conclusion, PCR was more sensitive than culture for demonstration of F. tularensis in wound specimens. Besides, we showed that tularemia may proceed without development of serum antibodies, and in these patients, PCR may be of special importance for verification of the diagnosis.

Adult↗
PubMed1969

The role of endotoxin during typhoid fever and tularemia in man. IV. The integrity of the endotoxin tolerance mechanisms during infection.

Volunteers infected with Salmonella typhosa develop a remarkable hyperreactivity to the pyrogenic and subjective toxic activities of homologous (S. typhos) and heterologous (Pseudomonas) endotoxins. The present studies quantitate this augmented reactivity and demonstrate by three differing approaches that significant tolerance to these endotoxins can be readily induced within the framework of the hyperreactive state. Thus, (a) tolerance induced before illness by repeated daily intravenous injections of the endotoxins remained demonstrable during overt illness, (b) daily intravenous injections of the endotoxins begun during overt illness evoked progressively increasing tolerance, and (c) continuous intravenous infusions of S. typhosa endotoxin during illness rapidly induced a pyrogenic refractory state. Despite unequivocal activation of the endotoxin tolerance mechanisms by any of the above methods, the febrile and toxic course of typhoid fever proceeded unabated. Similarly, in other volunteers with Pasteurella tularensis infection, continuous intravenous infusions of S. typhosa endotoxin evoked initial hyperreactive febrile and subjective toxic responses followed by rapid appearance of a pyrogenic refractory state without modification of the underlying clinical illness. These observations suggest that circulating endotoxin plays no major role in pathogenesis of the sustained fever and toxemia during typhoid fever and tularemia in man. The mechanisms responsible for the systemic hyperreactivity to endotoxin during typhoid fever and tularemia were further investigated. Low grade endotoxemia, nonspecific effects of tissue injury, impaired ability of the reticuloendothelial system to clear circulating endotoxin, and production of cytophilic antibodies capable of sensitizing leukocytes to endotoxin did not appear responsible. Inflammatory reactions to intradermal S. typhosa endotoxin increased significantly during typhoid fever. However, since no such dermal hyperreactivity developed to Pseudomonas endotoxin during typhoid fever nor to S. typhosa endotoxin during tularemia, the systemic hyperreactivity to bacterial endotoxins during typhoid fever and tularemia could not presently be ascribed to enhanced levels of acquired hypersensitivity.

Adult↗
PubMed1996

Similar pleural fluid findings in pleuropulmonary tularemia and tuberculous pleurisy.

Biochemical and cellular characteristics of pleural fluid from two patients with pleuropulmonary tularemia and 39 patients with tuberculous pleurisy were compared. High pleural fluid concentrations of adenosine deaminase, lysozyme, and beta 2-microglobulin occurred in both diseases. As is the case with tuberculous pleural effusions, pleural fluid in tularemia showed an abundance of lymphocytes, predominantly CD4-positive T lymphocytes. The similar pleural fluid findings suggest analogous local pathogenetic mechanisms in tularemia and tuberculosis. In the diagnostic evaluation of a lymphocyte-rich exudative pleural effusion with a high adenosine deaminase concentration, a possible cause to consider is tularemia.

Aged↗
PubMed2002

The 2000 tularemia outbreak: a case-control study of risk factors in disease-endemic and emergent areas, Sweden.

A widespread outbreak of tularemia in Sweden in 2000 was investigated in a case-control study in which 270 reported cases of tularemia were compared with 438 controls. The outbreak affected parts of Sweden where tularemia had hitherto been rare, and these "emergent" areas were compared with the disease-endemic areas. Multivariate regression analysis showed mosquito bites to be the main risk factor, with an odds ratio (OR) of 8.8. Other risk factors were owning a cat (OR 2.5) and farm work (OR 3.2). Farming was a risk factor only in the disease-endemic area. Swollen lymph nodes and wound infections were more common in the emergent area, while pneumonia was more common in the disease-endemic area. Mosquito bites appear to be important in transmission of tularemia. The association between cat ownership and disease merits further investigation.

Agriculture↗
PubMed2004

An outbreak of tularemia in Western Black Sea region of Turkey.

The aim of this study was to investigate the source and the size of a tularemia outbreak in a village located in a non-endemic area. Five patients from the same village were admitted to hospital with the same complaints all within one week of September 2001. Tularemia was suspected and a diagnosis was made after physical and anamnesis examinations. The village was visited the same week that the patients were admitted to the hospital, in the January and April 2002. The villagers were examined and screened serologically by microagglutination method and the water sources were investigated bacteriologically. A total of 14 people were found to be infected from the outbreak and the oropharyngeal form was the only clinical presentation. Antibody titers ranged between 1 : 80 and 1 : 640. The patients responded well to the aminoglycoside plus tetracycline therapy. Examination of the pipewater and three springs revealed that all the water sources were contaminated by coliforms, however, Francisella tularensis could not be isolated in glucose-cystine medium. Antibody levels stayed stable or decreased seven months after. Tularemia had not been reported in this area before, so the first patients were misdiagnosed. In conclusion tularemia should be considered in differential diagnosis of patients with fever, sore throat and cervical lymphadenopaties.

Adolescent↗
PubMed1999

Tularemia: a case transmitted from a sheep.

Tularemia is an arthropod-borne infectious disease caused by Francisella tularensis, a gram-negative microorganism that normally resides in a wide range of wild and domestic animals. The disease is characterized by a sudden onset with high fever, headache, malaise, chills, myalgia, and arthralgia. A short time after exposure, an inflamed and ulcerated lesion rapidly appears at the site of entry. A regional lymphadenopathy follows the cutaneous presentation. Cultures from the lesions or blood generally give negative results. Histopathologic examination reveals either a nonspecific inflammatory infiltrate or an infectious granuloma. The most useful laboratory procedure in the diagnosis of tularemia is serologic tests. Streptomycin, gentamicin, and tetracycline are the drugs of choice in the treatment. Quinolones are also effective. Tularemia is fairly rare in Turkey. We present a typical case of ulceroglandular tularemia transmitted from a sheep to a young man.

Adult↗
PubMed2002

[Tularemia--history, epidemiology, clinical aspects, diagnosis and therapy].

Tularemia was first described 90 years ago by McCoy as a disease of animals. At the beginning of twenties it was recognised by E. Francis as a disease transmittable from animals to man. Tularemia is caused by a gram-negative microbe Francisella tularensis. Epidemiological and clinical manifestations of the disease are highly diverse. The characteristic sign is the primary complex consisting from an initial ulceration and a regional lymphadenitis. In the Czech republic tularemia was first identified in 1936 in the south of Moravia and for the next years it occurred sporadically or in epidemic form also in the western Moravia, in north-west and east of Bohemia. It affected persons manipulating with the diseased animals, namely with hares, workers in animal farms and those working in cold sections of sugar mills. After a longer pause, during the last six years, the incidence of tularemia has increased again. That is why we decided to renew the understanding of the disease.

Animals↗
PubMedDate not supplied

[State of the natural foci of tularemia in the eastern part of the Northern Caucasian region].

The short characterization of the territory, known to contain the natural foci of tularemia, in the eastern part of the foothill area of the Caucasus is presented. The Caspian plain-foothill focus and the Terek-Kuma focus were shown to be the most dangerous among these foci. The severe outbreak of tularemia took place in the Terek-Kuma focus in 1999. Local epizootic could be stopped here only after the appearance of patients with clinical manifestations of tularemia. The epizootological survey of the territory for tularemia in 3 natural foci of Daghestan and in the natural focus of the Caucasian foothill area is carried out in an insufficient volume due to the complicated socio-political situation in the Chechen Republic and the insufficient financial support of the work on the study of the foci.

Animals↗
PubMed2003

Tularemia of the head and neck: a possible sign of bioterrorism.

Recent bioterror attacks and other world events have focused the medical community's attention on agents that might be used in biological warfare. One of these potential biological weapons is Francisella tularensis, a gramnegative coccobacillus that is one of the most infectious bacteria known. F tularensis can cause severe, even fatal, systemic tularemia. Under normal circumstances, F tularensis is transmitted by infected ticks, insects, and other animals. As a weapon of terrorism, the bacterium would likely be disseminated as an aerosol and contracted by inhalation. Because many cases of tularemia are characterized by head and neck symptoms, otolaryngologists should be familiar with the diagnosis and management of this disease. In this article, we describe a case of zoonotic tularemia that manifested as a neck mass, and we review the pathophysiology, diagnosis, and treatment of tularemia. We also summarize what is known about its potential as a biological weapon.

Adult↗
PubMed1991

A case of insect borne tularemia above the tree line.

A case of insect borne transmission of ulceroglandular tularemia in Canada above the tree line is presented. It seems likely from the available entomological data that a mosquito was the vector in this case. Mosquito vectors may be important in inducing the high seroprevalence of antibodies to F. tularensis above the treeline. This case is presented to make clinicians aware of the possibility of tularemia in cases of insect borne ulceroglandular disease in the arctic and, the necessity of measuring tularemia agglutinins in these patients. It should be noted that isolation of this organism poses a risk to laboratory personnel, and therefore should only be attempted in a reference laboratory. Therefore the diagnosis is based upon the finding, in the appropriate clinical context, of a four-fold rise in the tularemia agglutinins, or a single convalescent titre of 1:160 or greater.

Adolescent↗
PubMed2006

Tularemia re-emerging in European part of Turkey after 60 years.

The aim of this study was to investigate a tularemia outbreak in the Thrace region of Turkey. The outbreak occurred in Demirkoy village of Edirne, in 2005. Of 400 villagers, 266 were examined and their sera were taken. Throat swabs and lymph node aspirates were cultured. Specific antibodies in patients and domestic animals were screened by a microagglutination test. PCR assays and cultures of the samples of patients, animal tissues, and water sources were performed, along with active surveillance to identify risk factors. Seven out of 10 cases were diagnosed as oropharyngeal form; the remaining three patients were asymptomatic. The cultures for tularemia were negative; however, PCR assays were positive in one lymph node aspirate and in water from one spring. Some animals had the specific antibody at low levels. Increased rodent population in the vicinity, exposure to wild rabbits, and drinking from one of the springs were identified as risk factors with the risk ratios (and 95% confidence interval) of 10.5 (10.3-10.7), 6.5 (5.43-7.57), and 2.1 (1.1-2.5), respectively. Therapeutic and preventive measures were taken. When tularemia cases have been detected in a region even a few decades earlier, tularemia should be considered in the differential diagnosis of patients.

Animals↗
PubMed1990

[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.

Amikacin↗