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BACKGROUND: In the summer of 2000, an outbreak of primary pneumonic tularemia occurred on Martha's Vineyard, Massachusetts. The only previously reported outbreak of pneumonic tularemia in the United States also occurred on the island in 1978. METHODS: We conducted a case-control study of adults with pneumonic tularemia and investigated the environment to identify risk factors for primary pneumonic tularemia. Patients with confirmed cases were residents of or visitors to Martha's Vineyard who had symptoms suggestive of primary pneumonic tularemia, were ill between May 15 and October 31, 2000, and had a positive laboratory test for tularemia. Controls were adults who had spent at least 15 days on Martha's Vineyard between May 15 and September 28, 2000. RESULTS: We identified 15 patients with tularemia; 11 of these cases were primary pneumonic tularemia. Francisella tularensis type A was isolated from blood and lung tissue of the one man who died. Patients were more likely than controls to have used a lawn mower or brush cutter in the two weeks before the illness or before an interview, for controls (odds ratio, 9.2; 95 percent confidence interval, 1.6 to 68.0) and during the summer (odds ratio, undefined; 95 percent confidence interval, 1.8 to infinity). Lawn mowing and brush cutting remained significant risk factors after adjustment for other potentially confounding variables. Only one patient reported being exposed to a rabbit while cutting brush. Of 40 trapped animals, 1 striped skunk (Mephitis mephitis) and 1 Norway rat (Rattus norvegicus) were seropositive for antibodies against F. tularensis. CONCLUSIONS: Study of this outbreak of primary pneumonic tularemia implicates lawn mowing and brush cutting as risk factors for this infection.
Sixteen cases of tularemia transmitted by arthropods are used to characterize arthropod-borne tularemia in Japan. Arthropod-borne tularemia accounted for 1.2% of a total of 1,374 cases of tularemia observed between 1924 and 1996. The number of cases reported in Japan was low when compared with the number of cases reported in the United States. Arthropod-borne tularemia, however, is increasing and has reached 10.1% incidences during the last 16 yr. No arthropod-borne cases were reported prior to 1951. The occurrence of tularemia infection caused by contact with diseased hares was diphasic with the higher peak occurring during the winter, whereas the occurrence of arthropod-borne tularemia was common from spring to autumn. Among the 16 cases that we studied, 5 were initiated by tick-bites, 5 by the crushing of ticks found on domestic dogs, and 1 by an unidentified insect. In the remaining 5 cases, the vectors were not identified although arthropod bites were confirmed. These arthropod-borne cases were observed exclusively in the northeastern area of Honshu, the main island of Japan, and the age of patients ranged from 23 to 74 yr. The arthropod vectors associated with tularemia and factors influencing incidence of arthropod-borne tularemia in Japan are discussed.
Histopathology of tularemia, caused by type-B strain, tuberculosis, and sarcoidosis were compared in lymph node biopsy specimens from ten patients with tularemia, 26 with tuberculosis, and 14 with sarcoidosis. In very early tularemia there were only reactive changes without necrosis. Abscess necrosis with or without epithelioid cell reaction was observed during the second week and caseous necrosis during the fourth week. Argyrophil fibers were absent from necrotic lesions in tularemia, but, often, also in tuberculosis. In most cases of tularemia and in half the cases of tuberculosis, the inflammatory process extended beyond the capsule of the lymph node. In some cases, tularemia could not be histologically differentiated from tuberculosis, but tularemia was always differentiated from sarcoidosis. Our series of lymph node tularemia seems to represent a milder disease than those cases published earlier. Tularemia should be considered in the differential diagnosis with tuberculosis, toxoplasmosis, and cat-scratch disease.
In the literature there are no data on the possibility of obtaining in experiment non-fatal tularemia infection (persistence) in rodents highly sensitive to it (Group I) when using highly virulent strains circulating in nature for infection by natural routes. Our detailed experiments on 1483 adult voles Microtus rossiaemeridionalis Ogn. (syn. M. subarvalis Meyer et al.) of laboratory origin using virulent strains of Francisella tularensis holarctica Ols. et Meshch. and natural alimentary infection by feeding on bodies of died animals or forced dosed administration of a mixture of dead and living bacteria to the voles through the oesophagus demonstrated the possibility of the animals to survive tularemia with subsequent long-term chronic carrier state of the infectious agent. They also confirmed the ability of voles to eat readily cadavers of their kin (cannibalism, necrophagia). Experiments with the fully virulent strain 503 and feeding on cadavers were carried out on 439 voles. 203 animals died from acute tularemia, 43 from side effects and 193 survived. Two of the latter (0.5%) exhibited chronic bacterial carrier state, and agglutinins to tularemia microbe (1:320) were found in their blood. From 309 voles subjected to dosed feeding, 153 died from acute tularemia, 27 from side effects and 129 survived. Two of them were bacterial carriers and 6 (1.9%) showed agglutinins (1:160-1:1280). In experiments with strain 165, spontaneously less virulent for guinea pigs, 433 voles were fed on cadavers. 170 of them died from acute tularemia, 53 from side effects, and 210 animals survived. Among the latter, 14 animals (3.2%) were found immune to 100 LD50 of the highly virulent strain 1298. In dosed feeding of 302 voles with the strain 165, 90 animals died from acute tularemia, 59 from side effects, and 153 survived, including 63 animals (20.7%) immune to 100 LD50. The surviving immune voles exhibited seroconversion and long-term persistence of the infectious agent in the internal organs (up to day 257-313--period of observation), accompanied bacteriuria in some cases. Histological examination of the kidney revealed, for the first time, important pathological changes of glomerulonephritis type with elements of pyelonephritis. Protracted stay of the agent in the organism of the vole does not affect its virulence. Persistence of tularemia agent in the organism of voles highly sensitive to tularemia in alimentary administration to them of living and dead bacteria is achieved as a result of anticipatory development of immunological reactions in response to a massive dose of killed antigen, against the background of which the accumulation of simultaneously administered
The behavior of leukocytes, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) in tularemia caused by Type B of Francisella tularensis was analyzed in different clinical forms and severities of disease in 101 adult tularemia patients. The mean leukocyte count was 8.3 X 10(9)/l and the leukocyte differential count was also usually normal. The behavior of leukocytes was similar in different clinical forms and severities of tularemia. The changes in differential counts were milder than reported earlier. Both CRP and ESR were higher in severe than in milder forms of tularemia (p less than 0.05 and p less than 0.01, respectively), and CRP was higher in pulmonary than in ulceroglandular tularemia during the second week (p less than 0.05). There were high individual CRP concentrations of up to 225 mg/l in acute tularemia but there were also low CRP values (10-40 mg/l). Thus the behavior of CRP in tularemia resembled that seen in tuberculosis, and CRP did not always allow differentiation of tularemia from viral diseases.
Tularemia pneumonia may complicate the various clinical presentations of tularemia, or present as an uncommon zoonosis. Approximately 200 cases of tularemia are reported in the United States per year, and 10% to 20% present with pneumonia either as a primary event or as a complication of ulceroglandular or typhoidal tularemia. Tularemia pneumonia also occurs with the other tularemic forms, glandular, oculoglandular, and oropharyngeal tularemia as a result of secondary bacteremic spread to the lungs. Pneumonia usually occurs within 2 days to months after infection. The mortality rate of primary tularemic pneumonia and pneumonia complicating typhoidal tularemia is high. The clinical and roentgenographic presentations of tularemia pneumonia are highly variable and is one of the zoonotic atypical pneumonias. Tularemic pneumonia may mimic fungal and bacterial pneumonias, tuberculosis, or malignancy. The diagnosis of tularemic pneumonia should be considered in any patient presenting with an atypical pneumonia with the finding of an ulcer and/or lymphadenopathy and a history of outdoor activity. Serum agglutination tests and ELISA are the basis of serological diagnosis. Francisella tularensis can be cultured from the sputum, skin ulcer, pleural fluid, and the lymph nodes, but cultures should not be obtained because of the danger to laboratory personnel. The drug preferred for treatment of tularemic pneumonia is streptomycin for 1 to 2 weeks.
The author has processed data on early occurrence of tularemia in Southern Moravia collected from literature, materials of epidemical ward of the Regional Hygienic Station (RHS), Brno, and clinical documentation of patients treated for tularemia at the Clinic of infectious diseases, Brno. Tularemia has been appearing in Southern Moravia since autumn 1936. At that time, 290 people contracted the external (mainly ulceroglandular) form of this disease by handling tularemic hares. During the 60s, large severe epidemics of professionally-acquired pulmonary forms of tularemia, mainly in workers in 'cold divisions' of sugar factories, were occurring. The 25-year period of low occurrence of disease, which followed, was interrupted in 1978 with the curious epidemic of tularemia contracted through the alimentary tract in an old people's home. The transmission medium of the infectious agent was juice which had been made from fallen apples infected by little mouse rodents. In autumn 1994, the number of tularemia cases rose again and, during the season of 1998-1999, 115 cases of tularemia contracted mainly by handling tularemic hares were recorded. The author demonstrated the relationship among sources and modes of transmission of Francisella tularensis and clinical form of the disease using the group of patients treated at the Clinic of infectious diseases in Brno.
OBJECTIVE: We assessed the incidence, risk factors, and prognostic implications of tularemia pneumonia in Oklahoma from 1982 through 1987. DESIGN: We retrospectively reviewed all reported case-patients over the six-year period 1982-1987. SETTING: Department of Health in Oklahoma, where tularemia is known to be endemic. PATIENTS: Of 128 patients with tularemia who entered the study, 32 had pulmonary involvement. MAIN RESULTS: Compared to patients without pulmonary involvement, those with tularemia pneumonia were older (52 vs 32, p less than .0001), less likely to give a history of vector exposure (25% vs 7%, p less than .05), more likely to present with typhoidal illness (56% vs 15%, p less than .0001), hospitalized longer (11.6 vs 4.7 days, p less than .001), more likely to have a positive culture (9 vs 7, p less than .01), and more likely to die (4 vs 1, p less than .01). CONCLUSIONS: Patients with tularemia pneumonia often present without historical or physical examination findings that suggest the diagnosis; thus, tularemia pneumonia often cannot be distinguished from other cases of community-acquired pneumonia. Therefore, especially in areas where the disease is endemic, tularemia must be considered in patients with pneumonia.
Cases of tularemia were registered in the Crimea both before and after planned immunization. In 1981-1993 in 4.000 localities 35,100 mammals, 27,400 ectoparasites, 8,800 feces left by birds of prey and foxes and 900 environmental specimens were studied. 137 Francisella tularensis strains were isolated. Field mapping of the spread of F.tularensis and places of habitation of small mammals was carried out. The active polyhostal natural focus of tularemia was found to exist on the Kerch Peninsula, less affected by anthropogenic factors, where tularemia morbidity among humans, and tularemia epizootic coincided with the maximum rises in the number of myomorphs. The core of the focus constituted 2.4% of its area and were characterized by the stable complex of Ixodes ticks and the preservation of F. tularensis in the environment. In other regions of the flat part of the Crimea with considerable anthropogenic transformations of the landscape rises in tularemia epizootics and tularemia morbidity in humans were rare. In the mountainous part of the Crimea tularemia epizootics were registered only by the detection of specific antibodies and antigens.
Francisella tularensis is the etiological agent of tularemia, a serious and occasionally fatal disease of humans and animals. In humans, ulceroglandular tularemia is the most common form of the disease and is usually a consequence of a bite from an arthropod vector which has previously fed on an infected animal. The pneumonic form of the disease occurs rarely but is the likely form of the disease should this bacterium be used as a bioterrorism agent. The diagnosis of disease is not straightforward. F. tularensis is difficult to culture, and the handling of this bacterium poses a significant risk of infection to laboratory personnel. Enzyme-linked immunosorbent assay- and PCR-based methods have been used to detect bacteria in clinical samples, but these methods have not been adequately evaluated for the diagnosis of pneumonic tularemia. Little is known about the virulence mechanisms of F. tularensis, though there is a large body of evidence indicating that it is an intracellular pathogen, surviving mainly in macrophages. An unlicensed live attenuated vaccine is available, which does appear to offer protection against ulceroglandular and pneumonic tularemia. Although an improved vaccine against tularemia is highly desirable, attempts to devise such a vaccine have been limited by the inability to construct defined allelic replacement mutants and by the lack of information on the mechanisms of virulence of F. tularensis. In the absence of a licensed vaccine, aminoglycoside antibiotics play a key role in the prevention and treatment of tularemia.
The lymphocyte immune reactivity of 12 tularemia patients to Francisella tularensis antigens prepared from the bacterial cell envelope was examined during a 14-week follow-up study. Lymphocyte blast transformation responses of peripheral blood mononuclear cells (PBMC) to different protein antigens appeared simultaneously 2 weeks after the first symptoms of tularemia, indicating that none of these antigens had any special role at the early phase of immunization. While the lymphocyte blast transformation responses of total lymphocytes to all bacterial antigens were negative in the week 1 samples, continuously growing F. tularensis-specific T-lymphocyte lines were obtained from PBMC at the same time, indicating that an immune response had already occurred. Later, the T-lymphocyte lines and lymphocyte blast transformation responses were similar. Lymphocyte activation among the PBMC was reflected in an increased number of HLA-DR antigen-expressing, CD4-positive T lymphocytes (CD4+ DR+). The mean secretion of soluble CD8 from F. tularemia antigen-stimulated PBMC increased 2 weeks after tularemia onset, but the mean number of CD8+ DR+ T lymphocytes did not vary during the study period and no correlation could be found between the soluble CD8 and number of CD8+ DR+ T lymphocytes. F. tularemia antigen-induced cytokine production was measured from the PBMC supernatants. High levels of tumor necrosis factor alpha were detected from the first week onwards. The highest levels of interleukin-2 and gamma interferon were recorded during the second and third weeks, respectively, after tularemia onset. Interleukin-4 could not be demonstrated in the lymphocyte supernatants.
INTRODUCTION AND PURPOSE: Marked activation of natural foci of tularemia in the known endemic area of Central Europe, comprising the borderland of Slovakia, Austria and the Czech Republic, led to an epidemic outbreak in western Slovakia and an increase in the number of human tularemia cases in the adjoining regions of northeastern Austria and southern Moravia from 1995 to 1997. The aim of this paper was to present the results of a longitudinal study on the prevalence of infection with Francisella tularensis in small mammals and ticks in six localities of western Slovakia and northeastern Austria from 1991 to 1997, and to draw attention to the importance of systematic surveillance of natural foci for epidemiologic prognoses and for taking preventive measures. METHODS: In Slovakia, three localities of the Záhorie lowland were monitored for 3 to 6 years (1991 to 1996) for the presence of F. tularensis in small terrestrial mammals. In Austria, small mammals and ticks from three localities were investigated for 1 to 3 years (1994 to 1997). Spleens of live-trapped animals (at 1- to 2-month intervals) and ticks collected by flagging (in 6- to 8-week intervals) were examined by inoculation of pools into white mice, or individually by cultivation. RESULTS: In four localities under investigation (three localities in western Slovakia and one in Austria), a nearly simultaneous flare-up of tularemia epizootics was recorded in the autumn of 1994. The highest mean prevalence of infection in small mammals was 3.9% in the last quarter of the year, which along with isolations of F. tularensis from Dermacentor reticulatus ticks collected from vegetation in the locality of Austria (1.3% positivity), indicated the high epizootic activity of foci. F. tularensis was isolated from five rodent species--Apodemus flavicollis, A. sylvaticus, Clethrionomys glareolus, Microtus arvalis and Sorex araneus. From 1995 to 1996, the persistent activity of the focus was repeatedly confirmed by isolations of F. tularensis from D. reticulatus ticks. In 1995 a natural focus of tularemia was detected in a further locality of Austria, where the agent was isolated from D. reticulatus. The increased epizootic activity of foci in the endemic region of Central Europe indicated a higher risk of acquiring tularemia for humans and was, in fact, followed by an epidemic outbreak in western Slovakia as well as by a large number of cases in Austria and the Czech Republic. CONCLUSION: Our findings clearly demonstrate that long-term surveillance of natural foci in endemic regions provides useful information on the activation of tularemia foci before the onset of epidemic outbreaks, thus permitting timely epidemiologic prognoses and the institution of preventive measures.
In June 2000, seven cases of tularemia were reported to the Oklahoma State Department of Health (OSDH) over an 18-day period. Enhanced tularemia surveillance by OSDH during July-September 2000 detected four additional cases. During 1995-1999, an average of six cases were reported each year. This report summarizes clinical and epidemiologic information from the investigation of the 11 cases, presents three case reports to illustrate different risk factors for tularemia, and underscores the danger of delayed diagnosis of tularemia and the risk for acquiring tularemia in laboratory settings. Physicians should consider tularemia in ill persons with fever who reside in or visit areas where the disease is endemic and who have been exposed to ticks or carcasses or tissue from rabbits or other animals.