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Tularemia in a kidney transplant recipient: an unsuspected case and literature review.

Tularemia is a zoonotic infection that has rarely been reported in transplant recipients. The authors present a case of unsuspected tularemia in a kidney transplant patient that was diagnosed by isolation of Francisella tularensis in the blood. The patient was treated successfully with antibiotics. During diagnostic workup, a laboratory technician was exposed to tularemia by inhalation of the culture plate and received postexposure prophylaxis. This report emphasizes the importance of exposure history in the investigation of fever in an immunocompromised host and the special precautions needed when a virulent infectious organism is suspected.

Aged↗

Ciprofloxacin for treatment of tularemia in children.

BACKGROUND: Children with tularemia are, irrespective of severity of disease, usually subjected to parenteral treatment with aminoglycosides. Based on available susceptibility testing, quinolones might be effective oral alternatives of parenteral therapy. These drugs cause arthropathy in immature animals, but this risk is currently regarded to be low in humans. PATIENTS AND METHODS: In 12 patients (median age, 4 years; range, 1 to 10) with ulceroglandular tularemia, a 10- to 14-day course of oral ciprofloxacin, 15 to 20 mg/kg daily in 2 divided doses, was prescribed. Microbiologic investigations included identification of the infectious agent by PCR and culture of wound specimens, as well as determination of antibiotic susceptibility of isolates of Francisella tularensis. RESULTS: Defervescence occurred within 4 days of institution of oral ciprofloxacin in all patients. After a median period of 4.5 days (range, 2 to 24), the patients were capable of outdoor activities. In 2 cases, treatment was withdrawn after 3 and 7 days because of rash. In both cases a second episode of fever occurred. All children recovered without complications. In 7 cases F. tularensis was successfully cultured from ulcer specimens and tested for susceptibility to ciprofloxacin. MIC values for all isolates were 0.03 mg/l. CONCLUSION: In our sample of 12 patients ciprofloxacin was satisfactory for outpatient treatment of tularemia in children.

Administration, Oral↗

Sequential metabolic alterations in the myocardium during influenza and tularemia in mice.

Mice with generalized influenza or tularemia of similar lethality were studied in an effort to compare biochemical responses of the myocardium during infections of viral and bacterial etiology. A progressive loss of body weight characterized the course of both infections. Accompanying this, the myocardial content of protein and the activities of lactate dehydrogenase, citrate synthase, and cytochrome c oxidase all decreased. However, myocardial protein degradation appeared earlier and was more pronounced in influenza, and the protein changes were accompanied by a rapid decline of myocardial RNA. Activation of acid hydrolases, such as cathepsin D and beta-glucuronidase, occurred in tularemia but not in influenza, whereas leakage of beta-glucuronidase into the plasma occurred in both infections. Conversely, there was a considerably greater activation of myocardial catalase in influenza. These findings suggested that different control mechanisms or metabolic pathways were operative in the degradation of myocardial constituents in influenza as compared with tularemia. The absence of histological signs of myocarditis in either infection appeared to exclude any direct local effects of an inflammatory process on myocardial cells. Since the infections were of comparable lethality (based upon the inoculated dose of organisms), the observed differences in pattern and extent of metabolic responses of the myocardium to these infections may be attributed to different pathophysiological mechanisms evoked by the different microorganisms.

Animals↗

Pathogenesis of tularemia in monkeys aerogenically exposed to Francisella tularensis 425.

The pathogenesis of tularemia was studied in groups of rhesus monkeys (Macaca mulatta) that inhaled graded 10-fold doses ranging from 10 through 10(6) organisms of Francisella tularensis 425, a strain highly virulent for the white mouse but of reduced virulence for the domestic rabbit. Mean incubation periods ranged from 3 to 6 days followed by acute illness lasting 5 to 11 days with subsequent recovery of most animals. The higher inhaled doses resulted in shorter incubation periods, longer and more severe acute illnesses, and 18% mortality at the highest dose. Strain 425 multiplied in the lungs, disseminated to the regional lymph nodes, and became systemic. Maximal bacterial populations in tissues were reached by the 7th day after exposure of the animals regardless of the number of organisms inhaled. F. tularensis was no longer recoverable from any of six tissues examined 2 months after exposure. The most significant tissue changes occurred in the lungs; these consisted of foci of liquefaction necrosis, lobular consolidation, and pleural effusion and adhesions. The data indicate that the inhaled dose of strain 425 determined the maximal growth of the organism in the lungs which in turn influenced the severity of the usually self-limiting pneumonia and systemic infection. Although the monkey is less resistant to tularemia than is man, this laboratory animal when infected with F. tularensis 425 provides a useful model for the self-limiting type of human pulmonary tularemia usually observed in Europe and Asia but to a lesser extent in North America.

Aerosols↗

Competitive enzyme immunoassay for antibodies to a 43,000-molecular-weight Francisella tularensis outer membrane protein for the diagnosis of tularemia.

Antibodies against a 43,000-molecular-weight Francisella tularensis outer membrane (OM) protein (43K protein) were measured in paired serum specimens from 23 patients with tularemia and matched against antibodies in sera from 25 patients with nontularemic infectious diseases and from 25 blood donors. Antibodies were measured by a competition enzyme-linked immunosorbent assay which tested the ability of human serum to compete with rabbit anti-43K protein antibodies for its binding to the F. tularensis OM coat. The sera from nontularemic patients and from blood donors, in dilutions of 1:16 and 1:64, respectively, showed no or very low levels of antibodies. All of the tularemia patients showed positive tests with the first, the second, or both of the serum specimens examined. For instance, with serum diluted 1:64, each of the serum specimens showed a sensitivity of 95.7% and a specificity of 96%. When used for antibody competition in Western blotting (immunoblotting), the rabbit anti-43K selectivity blocked the binding of human serum antibodies to the 43,000-molecular-weight protein. This protein was immunoaccessible in Formalin-killed F. tularensis. These data indicate an important role of the 43,000-molecular-weight OM protein in the immunobiology of tularemia and emphasize its potential usefulness as an antigen in serodiagnostic tests.

Antibodies, Bacterial↗

Immunohistochemical demonstration of Francisella tularensis in lesions of cats with tularemia.

An immunohistochemical test was developed and validated for detection of Francisella tularensis antigen in tissues of cats with fatal tularemia. Ten cases of naturally occurring tularemia in cats were positive both by isolation of F. tularensis and immunohistochemical identification of F. tularensis antigen. Nine additional cases with lesions typical of tularemia were positive for F. tularensis antigen, although bacterial cultures were not performed. Immunohistochemical identification of F. tularensis in formalin-fixed tissue is valuable for establishing a rapid etiologic diagnosis under circumstances where fresh tissues may not be available for isolation and identification of the organism.

Animals↗

Head and neck manifestations of tularemia.

Tularemia is a relatively uncommon infectious cause of cervical lymphadenopathy. The records were studied of 81 patients hospitalized in western Arkansas with the diagnosis of tularemia over the period of 1970 to 1980. Fourteen cases (17%) had symptoms or findings referable to the head and neck at some time during the disease. Delay in treatment was prolonged in some cases by failure to consider tularemia as a possible diagnosis. The pertinent epidemiology, pathogenesis, clinical manifestations and treatment are briefly reviewed.

Adult↗

Radiographic spectrum of pleuropulmonary tularemia.

Pleuropulmonary disease was seen in 50 of 62 patients (81%) with proven tularemia. Radiographic findings included patchy subsegmental air space opacities (74%), hilar lymphadenopathy (32%), and pleural effusion (30%). Less common manifestations were air space opacification of an entire lobe or segment, cavitation, oval opacities, pericardial effusion, linear opacities and septal lines, apical and miliary disease resembling tuberculosis, a mediastinal mass, empyema with bronchopleural fistula, and residual cystic changes, calcification, and fibrosis. Pleuropulmonary tularemia may be easily misdiagnosed as other infectious diseases, neoplastic diseases, and occasionally cardiac or other pericardial disease. It should be considered whenever patients from endemic areas present a perplexing radiographic and clinical picture. Such patients should have the benefit of a serologic examination for tularemia, since this disease may be effectively controlled with appropriate antibiotics.

Adolescent↗

Tularemia.

Tularemia is a rare but potentially fatal disease that develops in numerous wild and domestic animals, including lagomorphs, rodents, cats, and humans. The disease occurs throughout much of the United States and should be considered in the differential diagnosis of acute febrile illness, particularly when risk factors such as contact with wild mammals or tick exposure are present. Veterinarians may be at increased risk of acquiring tularemia from contact with infected animals, but standard precautions should greatly reduce this risk. Outbreaks of tularemia warrant investigation, especially given the possibility of the use of F tularensis as an agent of bioterrorism.

Animals↗

Tularemia as a cause of fever in a squirrel monkey.

CASE DESCRIPTION: A 3-year-old female squirrel monkey (Saimiri sciureus sciureus) was examined because of sudden onset of lethargy and fever. CLINICAL FINDINGS: On initial examination, the monkey was weak and febrile and had petechiae on both thoracic limbs. Following collection, blood samples were slow to clot. During the next week, the monkey developed anemia and thrombocytopenia; Francisella tularensis was isolated from blood samples. TREATMENT AND OUTCOME: Treatment with gentamicin resulted in the monkey's gradual return to health, but inguinal lymphadenopathy developed after drug administration was discontinued. Francisella tularensis was isolated from a fine-needle aspirate of an enlarged lymph node. Treatment with streptomycin resulted in resolution of infection. By use of biochemical and molecular tests, the microbial isolate was characterized as F tularensis subsp holarctica. Results of a microagglutination assay confirmed that the monkey had developed serum antibodies against F tularensis. CLINICAL RELEVANCE: With timely diagnosis, treatment of tularemia in the squirrel monkey was successful. Francisella tularensis is the cause of a highly infectious zoonotic disease, and infection with this microorganism is enzootic in wildlife throughout the Northern Hemisphere. Tularemia should be considered in the differential diagnosis of febrile disease in animals of any species. Even limited or indirect exposure of humans or other animals to outdoor environments in which reservoir hosts and arthropod vectors are present can lead to transmission of F tularensis. Francisella tularensis is a class A agent of bioterrorism, and all cases of tularemia (regardless of species) should be reported to public health officials.

Animals↗

Missed sentinel case of naturally occurring pneumonic tularemia outbreak: lessons for detection of bioterrorism.

BACKGROUND: Family physicians are likely to care for patients that have been exposed to diseases associated with bioterrorism. Persons with seemingly nondescript initial disease symptoms could be harbingers of a larger outbreak, whether naturally occurring or purposefully created. METHODS: We report a missed sentinel case of pneumonic tularemia associated with a naturally occurring outbreak. The patient's initial clinical symptoms and signs were nondescript, and the diagnosis was recognized by subsequent blood tests. The medical literature was searched using the key words "tularemia," "bioterrorism," "index of suspicion," and "sentinel case." RESULTS AND CONCLUSIONS: Being alert to possible unexpected causes of a pneumonic summer illness in a patient with associated weight loss might have led to an earlier diagnosis of this sentinel case tularemia and its association with the subsequent outbreak. Individual patients are likely to visit a physician's office after a purposeful bioterrorism event. Greater efforts must be made to increase awareness in all primary care physicians who might see patients exposed to a bioterrorism illness.

Bioterrorism↗

Endemic tularemia, Sweden, 2003.

Tularemia cases have been reported in Sweden since 1931, but no cyclical patterns can be identified. In 2003, the largest outbreak of tularemia since 1967 occurred, involving 698 cases. Increased reports were received from tularemia-nonendemic areas. Causal factors for an outbreak year and associated geographic distribution are not yet understood.

Adolescent↗

Epidemiologic and molecular analysis of human tularemia, United States, 1964-2004.

Tularemia in the United States is caused by 2 subspecies of Francisella tularensis, subspecies tularensis (type A) and subspecies holarctica (type B). We compared clinical and demographic features of human tularemia cases from 1964 to 2004 from 39 states in which an isolate was recovered and subtyped. Our data indicate that type A and type B infections differ with respect to affected populations, anatomic site of isolation, and geographic distribution. Molecular subtyping with pulsed-field gel electrophoresis further defined 2 subpopulations of type A (type A-east and type A-west) that differ with respect to geographic distribution, disease outcome, and transmission. Our data suggest that type A-west infections are less severe than either type B or type A-east infections. Through a combined epidemiologic and molecular approach to human cases of tularemia, we provide new insights into the disease for future investigation.

Adult↗

[Role of gamasids in the epizootiology of tularemia].

10 strains of Francisella tularensis were isolated from 4 species of gamasid mites, Laelaps muris, L. multispinosus, Hyperlaelaps amphibius and Haemolaelaps glasgowi, in natural nidi of tularemia in the Tumen district. Under experimental conditions L. muris is often infected with tularemia agent on sick animals but preserves it at an indoor temperature not more than a week and does not transmit it transovarially. Haemogamasus ambulans preserve the agent within the same period. L. muris and Hirstionyssus isabellinus do not transmit the tularemia agent to healthy animals through a bite.

Animals↗

[Laboratory diagnosis and serologic course in patients with tularemia].

BACKGROUND: Tularemia was practically unknown in Spain until the end of 1997, when an epidemic outbreak was declared. This paper presents the data on microbiological diagnosis of 55 patients who suffered from tularemia. PATIENTS AND METHODS: Thirty-two samples from 19 patients and 151 serum samples from 55 patients were obtained for culture. Serologic diagnosis was performed by tube sero-agglutination and microagglutination. Three types of tests were performed on all sera: Wright sero-agglutination (WSA), Coombs test against Brucella spp. and sero-agglutination against Yersinia enterocolitica O:3, Yersinia enterocolitica O:3, and Proteus OX 19. RESULTS: F. tularensis was found in two samples (6.25%) of the 32 received. Titers > or = 1/160 were obtained in 78.2% and 74.5% of the initial sera by tube sero-agglutination and microagglutination, respectively. Correlation between the two tests was 0.80 (p < 0.001). Prozone phenomenon was observed in 59.9% of the sera, while crossed reactivity to Brucella spp. and Proteus spp. was found in 9.3% and 22.8%, respectively. No crossed reactivity was observed with Yersinia spp. CONCLUSIONS: Culture of F. tularensis has low sensitivity. The correlation obtained between tube sero-agglutination and microagglutination is good. Both techniques are useful in routine diagnosis of tularemia, although microagglutination has some advantages over tube agglutination.

Adult↗

[Tularemia--an old and a new problem in the South Moravia Region].

BACKGROUND: The first epidemic of ulceroglandular forms of tularemia acquired in coincidence with the manipulation with tularaemic hares took place in 1936 in the surroundings of Breclav and Valtice. The largest epidemic took place in the 1960's when hundreds of agricultural workers in the initial phases of the production of sugar within sugar refineries were afflicted by pulmonary forms of this disease. In the subsequent period which was interrupted only by smaller local epidemics, the number of new cases were gradually decreasing to the minimum at the beginning of 1990's. However, since 1994, the number of cases has began to increase again, namely those afflicted by ulceroglandular and oroglandular forms. OBJECTIVES [corrected]: In consequence of the long absence of this disease in clinical practice, the diagnostic awareness has decreased, and therefore the author has decided to indicate and review the current basic data on epidemiology and clinical manifestations of tularaemia. GROUP OF PATIENTS AND METHODS: The author has analysed the documentation of 577 of adults afflicted by tularemia and medically treated at the clinic of the Faculty Hospital in Brno in the period form 1959 to 1999. The study reviews the onset of the disease and the pathway of transmission of infection and its clinical manifestation. MAIN RESULTS: Following the long-termed sporadic occurrence of tularaemia after major epidemics of pulmonary forms of this disease in 1960's, interrupted only by smaller local epidemics, the incidence has began to increase again in 1994. The number of pulmonary forms has decreased whereas the occurrence of ulcerulceroglandular and oroglandular forms has increased. Hares have become the source of infection again. CONCLUSIONS: The fact that tularemia has repeatedly become a threat in Southern Moravia should be taken into account in the assessment of diagnosis in cases with unclear lymphadenitis and febrile states which defy the penicillin treatment especially in winter. (Tab. 3, Fig. 3, Ref. 23.)

Czech Republic↗

[Long-term dynamics and prognosis for tularemia and pseudotuberculosis morbidity in the Iaroslavl region].

The trends and main factors influencing the fluctuations of the levels of tularemia and pseudotuberculosis morbidity in the Iaroslavl region were revealed by the methods of mathematical statistics (regress analysis, time-series analysis, etc.). Tularemia morbidity was 0.467 +/- 0.216 cases (1950-1997) and pseudotuberculosis morbidity was 0.979 +/- 0.297 cases (1979-1997) per 100,000 of the population. The multiple regression equations permitting the prognostication of tularemia and pseudotuberculosis morbidity in the Iaroslvl region were derived.

Humans↗

[Epizootic significance of white-toothed shrews in the natural focus of steppe type tularemia in the Stavropol' region].

The observations indicate that anthropogenic activities cause structural changes with time among tularemia pathogen carriers in the microfocus. The epizootic and epidemic values of animal species, such as dwarf hamsters and house mice, decrease while those of insect-eating animals, namely white-toothed shrews that refer to Group II increase, in terms of tularemia infection susceptibility. In white-toothed shrews, tularemia infection rates are 4-6-times greater than those in other small mammals that refer to Group I.

Animals↗