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A retrospective analysis was made of cases of laboratory-acquired infections with Francisella tularensis among civilian employees at Fort Detrick, Maryland. The incidence and clinical presentation of tularemia during the decade 1950-1959, when the phenol-killed Foshay vaccine was used routinely for immunization of employees, were compared with similar data from the first decade (1960-1969) after the live tularemia vaccine had come into use. The incidence of typhoidal tularemia fell (from 5.70 to 0.27 cases per 1,000 at-risk employee-years; P less than 0.001), whereas the incidence of ulceroglandular tularemia remained unchanged (from 0.76 to 0.54 cases per 1,000 at-risk employee-years). Ulceroglandular tularemia in employees immunized with live vaccine was characterized by clinical signs and symptoms that were milder than those in employees vaccinated with the Foshay vaccine.
An alternative to streptomycin for treatment of possible tularemia would be useful on occasions when a patient develops a perplexing pneumonia that does not respond to initial treatment. In geographic areas where tularemia is endemic, an antimicrobial drug that is bactericidal for Francisella tularensis and is also effective against a spectrum of common pulmonary pathogens, including the Enterobacteriaceae and most strains of Pseudomonas aeruginosa, would be desirable. The purposes of this report are (1) to describe observations regarding the in vitro susceptibility of Francisella tularensis to streptomycin, kanamycin, and gentamicin; (2) to describe in vivo efficacy of these drugs in mouse tularemia; (3) to describe the results in 10 patients with tularemia treated with gentamicin. Gentamicin was bactericidal for Francisella tularensis in vitro, was effective in mouse tularemia when given in large doses, and was effective in humans when given in the standard recommended dose.
We report the case of a 63-year-old man who developed ulceroglandular tularemia complicated by pneumonia following a cat bite. A review of the literature revealed 51 cases of cat-related tularemia reported since 1928. Details of 15 cases (including the present case) were available and analyzed. If, following feline contact, patients develop pneumonia or if patients with skin and soft-tissue infection fail to respond to therapy with penicillin, physicians should be alerted to the possibility of tularemia. A greater awareness of this complication following a cat bite or cat scratch is important for recognizing this uncommon infection.
Tularemia is a disease caused by the facultative intracellular bacterium Francisella tularensis. Here we demonstrate that during the first weeks of infection, a significant increase in levels of Vgamma9 Vdelta2 cells occurred in peripheral blood: in 13 patients analyzed 7 to 18 days after the onset of disease, these lymphocytes represented, on average, 30.5% of CD3+ cells and nearly 100% of gammadelta+ T cells. By contrast, after vaccination with the live vaccine strain (LVS) of F. tularensis, only a minor increase occurred. Eleven days after vaccination, gammadelta T cells represented an average of 6.7% and Vgamma9 Vdelta2 cells represented an average of 5.3% of T cells, as in control subjects. Since derivatives of nonpeptidic pyrophosphorylated molecules, referred to as phosphoantigens, are powerful stimuli for Vgamma9 Vdelta2 cells, this observation prompted an investigation of phosphoantigens in F. tularensis strains. The F. tularensis phosphoantigens triggered in vitro a proliferative response of human Vgamma9 Vdelta2 peripheral blood leukocytes as well as a cytotoxic response and tumor necrosis factor release from a Vgamma9 Vdelta2 T-cell clone. Quantitatively similar phosphoantigenic activity was detected in acellular extracts from two clinical isolates (FSC171 and Schu) and from LVS. Taken together, the chemical nature of the stimulus from the clinical isolates and the significant increase in levels of Vgamma9 Vdelta2 cells in peripheral blood of tularemia patients indicate that phosphoantigens produced by virulent strains of F. tularensis trigger in vivo expansion of gammadelta T cells in tularemia.
The relative role that humoral immunity plays in protection against infection with the intracellular bacterium, Francisella tularensis, remains controversial. Cellular immunity is thought to play the major and perhaps only role. The authors, in this article, investigate the immunologic and protective properties of immune serum collected from human recipients of the live tularemia vaccine (LVS). Sera of recipients of the vaccine demonstrated reactivity with the vaccine strain by enzyme-linked immunosorbent assay and Western blot analysis. This reactivity appeared to be directed primarily against the lipopolysaccharide of LVS and demonstrated complete cross-reactivity with fully virulent F. tularensis (Schu4). Pooled immune sera protected mice fully against a 10,000 LD50 challenge with the LVS strain relative to non-immune sera. The protection was abrogated by dilution or preadsorption with the LVS strain but not by preadsorption with Escherichia coli, which suggests specificity of protection. The authors conclude that antibodies to the LVS strain of F. tularensis are generated by live vaccination in humans and play a significant role in protection of mice against lethal challenge with the same organism. These antibodies crossreact completely with fully virulent F. tularensis, but whether they play a role in protection against fully virulent human tularemia strains requires further experimentation.
The presence of enlarged cervical lymph nodes is a diagnostic challenge in disease of the head and neck. Lymph node enlargement may be secondary to local or general infectious disease, to non-infectious systemic disease, or to lymphatic metastasis of tumoral processes. Among the many infectious processes that originate cervical lymph nodes is tularemia. This disease is uncommon in Spain, but was unusually frequent in Castilla-León in the last months of 1997, with 136 cases diagnosed in our hospital, 13 accompanied by lymph node enlargement of the head and neck. This article shows that tularemia should be considered in the differential diagnosis of cervical lymph node enlargement in our region.
Blood lymphocytes were prepared from 6 patients at various time intervals after the onset of tularemia and from 10 subjects after vaccination against this disease. Lymphocytes were also prepared from subjects who had been vaccinated 1 and 2 years previously. The lymphocytes were incubated in the presence of membranes of the vaccine strain. Lymphocytes obtained 2 weeks or later after onset of the disease responded to the membranes with increased deoxyribonucleic acid synthesis, whereas lymphocytes obtained earlier than 2 weeks after onset did not respond. Lymphocytes of the vaccinated subjects did not respond to the membranes of the vaccine strain before vaccination. Two to 4 weeks after vaccination lymphocytes from six of the vaccinees yielded a high response, and this response was consistently high for several months. Lymphocytes from four of the vaccinated individuals responded to a low extent only, and this was consistently low for several months. Lymphocytes from individuals vaccinated 1 year before testing responded to a similar extent to the membranes, as did lymphocytes from those who had been vaccinated 1 month previously. Lymphocytes from individuals vaccinated 2 years previously, however, showed a diminished response to the membranes. There was no correlation between titer of agglutinating antibodies and magnitude of lymphocyte reactivity.
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