SEARCH · Search PubMed
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
A seriously ill patient with circulatory collapse, fever, acute renal failure, and progressive respiratory failure had dramatic improvement after treatment with imipenem/cilastatin sodium. During the treatment period, a diagnosis of tularemia was established serologically. This case suggests the efficacy of imipenem/cilastatin in the treatment of tularemia.
Brucellosis and tularemia are classical zoonotic diseases transmitted from an animal reservoir to humans. Both, wildlife and domestic animals, contribute to the spreading of these zoonoses. The surveillance of the animal health status is strictly regulated for domestic animals, whereas systematic disease monitoring in wildlife does not exist. The aim of the present study was to provide data on the prevalence of anti-Brucella, anti-Francisella and anti-Yersinia antibodies in wild boars from North-Eastern Germany to assess public health risks. A total of 763 sera of wild boars from Mecklenburg-Western Pomerania hunted in 1995/1996 were tested using a commercially available Brucella suis ELISA, an in-house lipopolysaccharide (LPS)-based Francisella ELISA, and commercially available Western blot kits for the detection of anti-Francisella and anti-Yersinia antibodies. The Yersinia enterocolitica O:9 LPS is able to induce serological cross-reactions indistinguishable from brucellosis due to a similar immunodominant epitope in the Brucella O-polysaccharide. The Yersinia Western blot assay was, therefore, based on five recombinant Yersinia outer proteins which have been proved to be specific for the serodiagnosis of yersiniosis. Anti-Brucella, anti-Francisella and anti-Yersinia antibodies were detected in 22.0%, 3.1%, and 62.6% of the wild boars, respectively. The high seroprevalence of tularemia and brucellosis in wild boars indicates that natural foci of these zoonoses are present in wildlife in Germany. However, the impact of transmission of zoonotic pathogens from wildlife to livestock is unknown. Only careful and systematic monitoring will help to prevent the (re)emergence of these zoonotic diseases in domestic animals and consequently human infection.
A total of 1372 cases of tularemia observed in Japan since 1924 were analysed. More than 90% of the cases were reported in the north-eastern part of the main island of Japan. After World War II, more than 40 cases were reported yearly for 20 years. Since 1966, however, there have been less than 10 cases per year. Ninety-three % of the cases were caused by contact with infected wild rabbits. The pattern of monthly distribution showed a peak in December and also a lower peak in May. The number of patients older than 40 years of age and the proportion of cases in females have gradually increased. In the earlier survey periods almost 70% of the cases were engaged in agriculture but at present this rate is less than 50%. The changes in the occurrence of tularemia in Japan is thought to be related to the change of life style caused by the rapid growth of the Japanese economy after World War II.
Approximately 8 years after treatment for tularemia, 14 of 22 (63.6%) individuals tested still had a positive microagglutination test for Francisella tularensis antibodies. An enzyme-linked immunosorbent assay for anti-F. tularensis outer membrane antibodies was positive for 55% (immunoglobulin A [IgA]), 95% (IgG), and 27% (IgM) of the late-phase sera, but with antibody levels significantly reduced from those in the acute-phase sera. IgG and IgA antibody levels in the late-phase sera showed significant correlation with levels in the acute-phase sera. The IgG/IgM ratio calculation discriminated between acute-phase and persistent antibodies for most sera, but Western blot (immunoblot) patterns did not. Immunoblotting indicated that the F. tularensis lipopolysaccharide is a major target for antibodies in both groups of sera. Our results substantiate the need for caution in the interpretation of positive serological test results for tularemia, which could result from disease occurring years earlier.
The serodiagnostic efficiencies of five different approaches to detecting antibodies (immunoglobulins G, A, and M) developed in clinically proven infections with Francisella tularensis have been assessed. Fifty serum samples from patients suffering from tularemia during an outbreak in Sweden were compared with samples from 50 healthy blood donors (controls) by using an enzyme-linked immunosorbent assay (ELISA), microagglutination (MA), Western blotting (WB), an indirect immunofluorescence assay (IIFA), and flow cytometry (FC). ELISA, WB, and FC were based on the use of preparations of lipopolysaccharides (LPS) of the live vaccine strain of Francisella tularensis subsp. holarctica (ATCC 29684) as a capture antigen. Whole methanol-fixed bacteria were used for IIFA and MA. Optimized protocols yielded a diagnostic sensitivity and specificity of 100% for WB, MA, and FC, 98% for ELISA, and 93% for IIFA. A total of 6,632 serum samples from individuals between the ages of 18 and 79 years, representatively recruited from all regions of Germany, were screened to estimate and confirm the positive predictive value (PVpos) of the ELISA. Serum samples from 15 (0.226%) individuals tested positive for F. tularensis-specific antibodies by ELISA and confirmatory WB. The resulting prevalence-dependent PVpos of 10.2% and specificity of 98.1% were consistent with our findings for tularemia patients and controls. We conclude that the combined usage of a screening ELISA and a confirmatory WB based on LPS as a common antigen, as well as the MA, is a suitable serodiagnostic tool, while the quality of the IIFA is hampered by subjective variations of the results. FC is a promising new approach that might be improved further in terms of multiplex analyses or high-throughput applications.
The host response to experimental murine tularemia was examined in different inbred mouse strains. The kinetics of growth of Francisella tularensis live vaccine strain (LVS) in the livers and spleens of A and C57BL/6 mice were monitored, and it was observed that mice of the A strain were more susceptible to the proliferation of LVS than were C57BL/6 mice. The difference was most marked 5 days following infection, when the number of bacteria isolated from the spleens of A mice was found to exceed that of C57BL/6 mice by 100-fold. In addition, the C57BL/6 strain exhibited a more pronounced splenomegaly 8 days after infection than did the A strain. When the response of other inbred strains was evaluated by determining the splenic count of LVS on day 5 postinfection, several levels of antiularemic resistance were observed. Mice of the AKR, BALB/cBy, C57BL/10, and SJL strains were found to be most resistant, while SM mice were most susceptible to the proliferation of LVS. The DBA/2, CBA, 129, C3H/HeJ, and A strains expressed a resistance phenotype which was intermediate between the two extremes, with A and C3H/HeJ mice being somewhat more susceptible than DBA/2, CBA, or 129 mice. The trait of resistance or susceptibility was analyzed genetically in (C57BL/6 x A)F1 hybrid mice and in F2 generation and recombinant inbred (RI) mouse strains derived from C57BL/6 (resistant) and A (susceptible) strain progenitors. The F1 progeny exhibited a level of resistance to infection which was similar to that of the resistant parent. In both the F2 generation mice and the RI strains, a continuous spectrum of resistance levels was observed. The results of these experiments indicate that the genetic background of the host influences host resistance to experimental murine tularemia and that multiple genetic loci are involved in this response.
We describe a 58-year-old man with tularemia and expanding gamma delta T cells in his peripheral blood lymphocytes (PBL) (32.7% of total PBL). In the present work, we analyzed the T-cell receptor V gamma/V delta repertoire of these cells by making use of the polymerase chain reaction and flow cytometry and found that they were mostly CD4- CD8- CD3+ V gamma 9/V delta 2+. The sequence analysis of 16 cDNA clones encoding the V gamma 9-J region revealed that the V gamma 9-Jp combination was strikingly overrepresented but that the junctional (N) region was heterogeneous. This suggested that the gamma delta T cells in PBL from a patient with tularemia were polyclonally expanded.
Francisella tularensis LVS is an effective live vaccine strain used for cutaneous vaccination against tularemia in man. In mice, injection of LVS causes invasive disease and subsequent development of immunity that is characterized by effective control of otherwise lethal doses of the organism. In the present investigation, it is shown that LVS-immune mice controlled an intradermal infection much more effectively than did naive mice; bacterial counts in skin samples were 1.5 to 2.0 log10 lower 24 h after injection and 6 log10 lower 72 h after injection in immune mice. Moreover, in contrast to naive mice, no bacteria were demonstrated in samples from livers and spleens of immune mice. By immunohistochemistry, skin samples from immune mice showed an intense staining for interleukin-12 (IL-12) and a moderate staining for tumor necrosis factor alpha (TNF-alpha) at 24 h postinoculation, after which staining for both cytokines faded. In naive mice, the staining for IL-12 was weak at all time points and no staining for TNF-alpha was observed. No staining for gamma interferon (IFN-gamma) was observed in any group before 72 h. At that time point, skin samples from immune mice showed moderate staining and skin samples from naive mice showed weak staining. Reverse transcriptase PCR showed an induction of mRNA of the three cytokines in the skin within the first day after injection. A quantitative analysis demonstrated higher IFN-gamma and TNF-alpha mRNA levels in immune mice at 24 h postinoculation. In conclusion, immunization with F. tularensis LVS conferred a capability to respond to cutaneous reinfection, with rapid local expression of IL-12, TNF-alpha, and IFN-gamma, and this expression was paralleled by containment and mitigation of the infection. The cytokine response may be part of a local barrier function of the skin, important to host protection against tularemia.
The enzyme-linked immunosorbent assay (ELISA) was applied for immunological diagnosis of human tularemia, using lipopolysaccharide from Francisella tularensis as antigen. Sera collected from patients, healthy individuals, and vaccinated volunteers were investigated for antibodies against F. tularensis by ELISA and tube agglutination. In ELISA all sera were titrated with a polyspecific anti-immunoglobulin enzyme conjugate. A limited number of consecutive sera from individual patients were also investigated for immunoglobulin G (IgG) and IgM antibodies by means of immunoglobulin class-specific conjugates. On an average ELISA was more than 10-fold as sensitive as tube agglutination. Two weeks after onset of disease, sera from patients had significantly higher titers in ELISA than sera from healthy controls. High titers persisted after more than 2 years. Significant amounts of both IgG and IgM antibodies were present within 1 to 2 weeks after infection. The antibody activity increased during the first month, without any significant change of the relation between IgG and IgM titers. After 2.5 years the IgG/IgM titer ratio of sera from patients was significantly increased. Within 6 weeks after vaccination sera from about half of the vaccinees had significantly elevated titers in ELISA. Titers observed after vaccination were generally lower than those found after infection. An elevated ELISA titer can be of diagnostic importance by the end of the first week of illness. A significant increase of titer in consecutive serum samples indicates a diagnosis of tularemia. Determination of IgG and IgM antibodies may be of value in determing whether a positive titer of a single serum sample is of longstanding or recent origin.
A microagglutination test with safranin-stained Francisella tularensis antigen was compared with a conventional tube agglutination test for the serodiagnosis of tularemia. The microagglutination test was performed in round-bottom microtiter plates by using 0.025 ml of the antisera and of the antigen. The antibody titers obtained by using the microagglutination test were 8 to 64 times higher than those seen with the tube agglutination. By the microagglutination test, the serum agglutinins were detected 3 days earlier in rabbits and 9 days earlier in humans than by the tube agglutination test. The microagglutination test also detected residual circulating antibodies in humans more than 20 years after recovery from infection. These early agglutinins were shown to be in the immunoglobulin M class because of their sensitivities to 2-mercaptoethanol. No significant group agglutination reaction with Brucella abortus was observed. These observations indicate that the microagglutination test is a useful tool for the early and specific serodiagnosis of tularemia.
Cell-mediated immunity is essential for protection against the intracellular bacterium Francisella tularensis, which causes tularemia. Positive in vitro T-cell responses in the form of lymphocyte proliferation and lymphokine interleukin 2 (IL-2) and gamma interferon (IFN-gamma) secretion are found in memory immunity. Studies on the secretion of lymphokines with regard to the developing immunity to F. tularensis have not been published. Therefore, 14 subjects with no clinical history of tularemia were vaccinated with a live F. tularensis vaccine strain. The in vitro responses of five subjects (antigen-induced mononuclear cell and whole blood culture DNA synthesis and cytokine secretion) were measured twice a week throughout the period from 0 to 35 days after vaccination, and the peripheral blood lymphocyte subpopulations of nine subjects were determined between days 0 and 14. Positive reactions, i.e., responses exceeding those on day 0, were reached on day 10 with regard to the whole blood culture DNA synthesis response and IL-2 and IFN-gamma secretion and on day 14 with regard to the mononuclear cell DNA synthesis response and tumor necrosis factor alpha (TNF-alpha) secretion. No measurable IL-4 was found in either the immune or nonimmune supernatants. Since the secretion of TNF-alpha was related to immunization, this points to the specificity of the phenomenon, even though the type of secreting cell is not yet known. If it is shown later that specific T cells produce it, the TNF-alpha response and the negative IL-4 finding may speak for the importance of the Th1-like pattern in immunity to F. tularensis.
INTRODUCTION: Tularemia was an unknown zoonosis in our region until the first quarter of 1998. The outbreak that took place on those dates has made possible to study some scantly known characteristics of the disease, as are the determinants for the persistence of a high antibody titer. MATERIAL AND METHODS: Between March and May, 2001, a clinical-analytical control was carried out in 26 patients who showed tularemia in the first quarter of 1998. RESULTS: The clinical forms during the acute phase were: ulceroglandular (46.2% of patients), nodal (26.9%), typhoid (15.4%) and pharyngeal (11.5%). Antibiotics most prescribed were streptomycin and doxycycline. Nine patients showed sequelae three years later. The arithmetical mean of antibody titer declined from 1/1011 in 1998 to 1/187 in 2001. 76.92% of the patients maintained an antibody titer equal or higher than 1/160 three years after the acute phase. A significant relation between the initial antibody titer and the antibody titer registered in the late phase was observed. A relationship between final antibody titer and prescribed antibiotic, presence of sequelae, gender, or age was not demonstrated. CONCLUSIONS: The antibody titer in the presence of Francisella tularensis is high in an important percentage of the patients along years. We should reconsider the standard diagnostic criteria to our community, accepting as a certainty diagnosis exclusively the presence of a demonstrative culture or the existence of seroconversion.
A chronically draining subcutaneous mass was removed from the ventral cervical region of a 6-year-old spayed female Domestic Shorthair cat. The histopathologic diagnosis was severe locally extensive pyogranulomatous and necrotizing cellulitis. Bacterial culture yielded Francisella tularensis subsp. tularensis as the causative agent. Immunohistochemical evaluation of sections for F. tularensis was negative. One year later, the cat was euthanized because of progressive lethargy found to be due to hypertrophic cardiomyopathy with pulmonary thromboembolism. No evidence of cutaneous or systemic infection by F. tularensis was found at necropsy. This case appears to be a localized form of tularemia resembling the ulceroglandular form of tularemia in humans and suggests that bacterial culture may be more sensitive than immunohistochemistry in detecting organisms in cases of localized F. tularensis infection.
A wide range of microorganisms has been associated with cavitary pneumonia and pulmonary abscess. We present a case of serologically documented tularemia in an animal-hide handler who demonstrated multiple pulmonary infiltrates with cavitation. Inclusion of tularemia in the differential diagnosis of cavitary pneumonia in patients with exposure to animals is emphasized.
A 4-year-old spayed female Irish Setter was examined because of acute onset of lethargy, anorexia, and weakness. The dog had eaten an adult rabbit 36 hours earlier. Tularemia was suspected because of the rabbit exposure; however, other common diseases characterized by fever, malaise, and lymphadenopathy of acute onset were also considered (ie, ehrlichiosis and Rocky Mountain spotted fever). The dog was treated with doxycycline (5 mg/kg [2.3 mg/lb], PO, q 24 h) for 14 days as well as supportive treatment with a balanced electrolyte solution (lactated Ringer's solution [200 mL, SC]). The diagnosis was first established by results of bacteriologic cultures of fine-needle aspirates obtained from lymph nodes and confirmed by results of ELISA and a polymerase chain reaction assay Successful and timely antemortem diagnosis of tularemia in dogs can be accomplished through lymph node aspiration and bacteriologic culture.
Tularemia meningitis occurred in a previously healthy 64-year-old man from Northern Sweden. The patient was immunocompetent and recovered without sequelae. The bacterial isolate conformed by most criteria with the Euro-Asian biovar Francisella tularensis var. palaearctica. Tularemia meningitis may mimic meningitis caused by Mycobacterium tuberculosis.
In a tularemia epidemic during 1982 in northern Finland, 53 patients showed no peripheral portal of entry for infection or associated lymphadenopathy. Respiratory symptoms were observed in 72% of the patients. 26/38 cases had abnormal chest films. Hilar adenopathy was the most common finding (36%). Four patients did not receive antibiotics; 43 received tetracyclines, 5 streptomycin and 1 cefuroxime and amoxycillin. All patients recovered. 50 patients acquired the infection during common farming activities, such as making fresh hay with a hay-cutter, handling dry hay, threshing, etc. Thus, airborne transmission may be an important source of infection in normal farming activities in endemic areas of tularemia.
In 1997, an outbreak of human tularemia associated with hare-hunting in central Spain affected 585 patients. We describe the identification of Francisella tularensis biovar palaearctica in a second outbreak of ulceroglandular tularemia associated with crayfish (Procambarus clarkii) fishing in a contaminated freshwater stream distant from the hare-associated outbreak. The second outbreak occurred 1 year after the first.