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A boy with a persistent febrile illness accompanied by exudative pharyngitis found to be due to tularemia is described. The role of tularemia as a cause of exudative pharyngitis is discussed.
Aptamers are powerful candidates for molecular detection of targets due to their unique recognition properties. These affinity probes can be used to recognize and bind to their targets in the various types of assays that are currently used to detect and capture molecules of interest. They are short single-stranded (ss) oligonucleotides composed of DNA or RNA sequences that are selected in vitro based on their affinity and specificity for the target. Using combinatorial oligonucleotide libraries, we have selected ssDNA aptamers that bind to Francisella tularensis subspecies (subsp) japonica bacterial antigen. F. tularensis is an intracellular, nonmotile, nonsporulating, Gram-negative bacterial pathogen that causes tularemia in man and animals. Just as antibodies have been used to detect specific targets in varying formats, it is possible that nucleic acid-binding species or aptamers could be used to specifically detect biomolecules. Aptamers offer advantages over antibody-based affinity molecules in production, regeneration and stability due to their unique chemical properties. We have successfully isolated a set of 25 unique DNA sequences that specifically bind to F. tularensis subspecies japonica. When tested in a sandwich Aptamer-Linked Immobilized Sorbent Assay (ALISA) and dot blot analysis, the aptamer cocktail exhibited specificity in its ability to bind only to tularemia bacterial antigen from subspecies japonica, holarctica (also known as palaearctica) and tularensis but not to Bartonella henselae. Moreover, there is no binding observed either to pure chicken albumin or chicken lysozyme. Thus, it appears that this novel antitularemia aptamer cocktail may find application as a detection reagent for a potential biological warfare agent like F. tularensis.
The paper presents the results of a long-term comparative study of the infection of Ixodes tick imagoes with the pathogen of tularemia by using the biological assay and antibody neutralization test. The infection rates determined by both methods were found to be identical or close. If there was a difference in the rates in some years, it was not statistically significant. A statistically significant difference could not be found in the infection rates for ticks and in the dependence on their species composition though the level of infection in representatives of one species greatly differed from that in others. The serological study of Ixodes tick imagoes, aimed at determining their infection with a tularemia pathogen, yielded the results which are comparable with those of the biological assay and may be used in epizootological studies without using the biological test or by significantly limiting its use.
In experiments on guinea pigs immunized with Francisella tularensis 15, or live tularemia vaccine (LTV), the level of heterologous protective effect to dangerous infectious diseases caused by Yersinia pestis, Burkholderia pseudomallei, B. mallei, Mycobacterium tuberculosis was studied. The study revealed that during the first 4 weeks after the subcutaneous immunization with LTV the level of resistance of the immunized animals to heterologous infective agent reliably increased as indicated by the survival rate of the animals, as well as by the survival time of those killed by infection, in comparison with the controls. Later (on day 150 after immunization) differences in death rate between the groups perceptibly decreased. Nevertheless, the 1 1/2-fold increase of the survival time of the challenged immunized animals in comparison with the controls proved the possibility of using immunization with LTV for the urgent prophylaxis and treatment not only of tularemia, but also of plague, glanders, melioidosis and tuberculosis.
The effect of the combined use of doxycycline and glucosaminylmuramyl dipeptide (GMDP) on the primary immune response to antigens of tularemia vaccine was studied on CBA male mice with the use of the multifactorial design of experiment. Antibodies to the blood serum of the immunized animals were determined by the passive hemagglutination test with the use of the tularemia antigen diagnosticum. The delayed type hypersensitivity was estimated by changes in the weight of the extremities of the experimental and control animals treated with the antigen and saline solution, respectively. The multifactorial experiments provided precise quantitative characteristics of the optimal dose-time schedule for the combined use of GMDP and doxycycline.
Guinea pigs immunized with live tularemia vaccine have been found to possess pronounced resistance to Venezuelan equine encephalomyelitis virus infection. Antiviral resistance induced by the vaccine has been found to persist for 1 month. One of the possible mechanisms, though not the only one, of this resistance is the stimulation of macrophages by tularemia vaccine, which results in the enhancement of their resistance to the cytotoxic action of the virus.
Erythrocytes treated with polysaccharide from Past. tularensis are specifically agglutinated by the sera of persons recovered from tularemia or vaccinated against it, and by the sera of animals immunized with living cultures. The serum hemagglutination titer is correlated with the amount of antibody as measured by the quantitative precipitin method with polysaccharide, but not with the bacterial agglutination titer. The meaning of the results is discussed.
A case of oropharyngeal tularemia mimicking a peritonsillar abscess is presented. This diagnosis should be entertained in patients who are seen initially with ulcerative-exudative pharyngitis with or without tonsillitis and whose routine cultures are negative and/or are unresponsive to penicillin. Institution of appropriate therapy depends largely on the clinical diagnosis because cultures on ordinary media are routinely negative, and it takes several days for antibody titers to reach diagnostic significance.
In June 1978, three cases of tularemia pneumonia occurred in persons residing in the Washington, DC, area. The patients, all men, became ill three to four days after a brief session training their hunting dogs in an undeveloped wooded area adjacent to a housing complex. One of the dogs, which later died, had captured a wild rabbit during the training session. All three men had handled the rabbit while familiarizing their dogs with the rabbit's scent. The men had no other common exposure that was a likely source of infection.
The landmark studies on tularemia by Dr Francis have been recognized by designating the causative organism Francisella tularensis rather than Bacterium tularense. A review of his original 1925 article clearly demonstrates the lasting value of critical clinical, epidemiologic, and laboratory studies. Except for expansion of knowledge concerning some aspects of the epidemiology and clinical spectrum and advances in treatment and prevention, the 1925 article is as contemporary as the current literature and textbooks.
A waterborne tularemia outbreak is described. Forty nine cases were identified in Sansepolcro, a small Medioeval town in the province of Arezzo, Tuscany, Italy. All cases had laterocervical or sub-mandibular adenitis, and occurred within a period of three weeks during March and April 1982. The study showed association between cases and the consumption of water from an unchlorinated water system. Francisella tularensis type 1 was isolated from wild hares captured in the area.
A 56-year-old man suffered from prolonged fever, sore throat and cough, followed by pleural effusion and reversible progressive ascending muscle weakness. The condition fulfilled the diagnostic criteria of Guillain-Barré syndrome. Tuberculosis was initially suspected because of lymphocyte predominance and high adenosine deaminase activity in the pleural fluid. Later, an agglutination titer of 10,240 to Francisella tularensis antigen was found and an infected hare exposure could be identified. Thus, the activity of adenosine deaminase may be high also in tularemia pleuritis.
Tularemia live vaccine (TLV), which is widely used in the CIS, did not increase the level of micronucleated polychromatic erythrocytes (MNPCEs) in mice up to 30 days after intradermal immunization. The clastogenic action of cyclophosphamide (CP) was decreased significantly from day 10 till day 20 after immunization. We have studied the duration of sleep induced by hexenalum in immunized mice, since it is known that rodent sleep induced by barbiturates depends on cytochrome P-450 activity. We have shown that between the level of MN PCEs induced by CP in immunized mice and the duration of hexenalum induced sleep in immunized mice, a high reverse correlation was observed (r = -0.97). We propose that the anticlastogenic effect observed in our experiment is due to a reduction in the cytochrome P-450 activity induced by TLV immunization. The present and previous results suggest that TLV may be a potent anticlastogenic factor for mice and rats with prolonged action.
Tularemia is an uncommon, highly communicable disease occurring with seasonal regularity in endemic parts of the United States. The varied signs and symptoms may confound the unwary physician. Two cases are reported illustrating the ulceroglandular and ingestion forms of the disease. Septic (typhoidal), oculoglandular, pleuropulmonary, glandular, and oropharyngeal forms also are described. Knowledge of the epidemiology and a high index of suspicion should lead the examining physician to ask revealing questions. The diagnosis is presumed upon clinical grounds and confirmed by serological testing. According to published reports delayed diagnosis can result in an overall mortality rate of 7% of cases; however, early diagnosis will lead to uncomplicated recovery in most cases.
T lymphocyte-mediated immunity is important for resistance to Francisella tularensis. To characterize the specificity of this immunity, we used membrane proteins and two lipopolysaccharide (LPS) preparations. Both membrane proteins were heat-modifiable, as indicated by their migration in sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE). One had an apparent molecular mass (Mm) of 120 kilodaltons (kDa) when solubilized in the SDS buffer at room temperature, but 17 kDa after heating. The respective values for the other protein were 35 kDa before and 40 kDa after heating. Both proteins were purified by a preparative SDS-PAGE. The LPS-containing preparations were isolated by aqueous phenol (WP) or PCP (phenol-chloroform-petroleum ether) extraction (LPS-R), and rendered protein-free by treatment with proteinase K. Lymphocytes from nine subjects immunized with a live tularemia vaccine from one to three years earlier responded specifically to both an F. tularensis whole cell antigen and the 17 kDa protein in the lymphocyte blast transformation test. By contrast, the 40 kDa protein and the two LPS preparations did not stimulate any detectable lymphocyte proliferation.
Anthrax, plague, Q fever, and tularemia are all potential inhalational bioterrorism agents. The pulmonary manifestations of these agents can be readily confused with each other as well as other more common diseases such as influenza and atypical pneumonia. This article reviews the threat potential, microbiology, pathogenesis, clinical features, diagnosis, and treatment of each of these agents and highlights the similarities and differences between their pulmonary presentations.
In order to begin understanding the immunological basis for immunity to tularemia, and to establish a baseline for judging the efficacy of potential novel vaccines, the present study examined the ability of the live vaccine strain of Francisella tularensis (F. tularensis) LVS, to elicit immunity in mice against subsequent systemic and aerosol challenge with highly virulent strains of the pathogen. The results show, that infection with LVS protects BALB/c mice against systemic challenge with virulent Types A and B F. tularensis. In contrast, C57BL/6 mice vaccinated with LVS were only rendered immune to systemic challenge with Type B F. tularensis. Neither mouse strain immunized with LVS was able to resist aerosol challenge with Type A F. tularensis, and only immunized BALB/c mice withstood exposure to aerosols of Type B F. tularensis.
Tularemia can present as an oto-rhino-laryngological disease. The clinical and radiological (CT) manifestations, diagnosis and treatment are discussed based on a case report where a patient with tonsillitis and enlarged cervical lymph nodes was admitted to the department of oto-rhino-laryngology of a hospital in Northern Norway. Francisella tularensis was isolated from the blood and there was a high titre of agglutinating serum antibodies to F. tularensis. The patient's contaminated drinking water well is the suspect source of infection.