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PubMed1991

In vitro susceptibility of Francisella tularensis to fluoroquinolones and treatment of tularemia with norfloxacin and ciprofloxacin.

The in vitro susceptibility of ten strains of Francisella tularensis to four fluoroquinolones (ciprofloxacin, norfloxacin, ofloxacin and pefloxacin) was investigated by determining the MBCs of these quinolones. The results were as follows (mean +/- SE): ciprofloxacin 0.13 +/- 0.03 mg/l, norfloxacin 0.24 +/- 0.07 mg/l, ofloxacin 2.16 +/- 0.78 mg/l and pefloxacin 0.51 +/- 0.50 mg/l. These concentrations can be achieved in clinical practice. In addition, four tularemia patients were treated with an oral regimen of 750 mg ciprofloxacin b.i.d. and one patient with norfloxacin 400 mg b.i.d. The fever experienced by these volunteers vanished within a couple of days and they were able to resume normal work one week after receiving the antibiotics without any relapses later. These in vitro and in vivo results show that orally administered fluoroquinolones are promising antimicrobial agents for the treatment of human tularemia.

Anti-Infective Agents↗
PubMed2003

Tularemia presenting as tonsillopharyngitis and cervical lymphadenitis: a case report and review of the literature.

In this report, we describe a 57-year-old woman with oropharyngeal tularemia who presented with tonsillopharyngitis and cervical lymphadenitis. Clinical and radiological manifestations and histopathological characteristics of this disease are discussed with a review of the world literature. The oropharyngeal form of tularemia should be considered in the differential diagnosis of cases involving tonsillopharyngitis and cervical lymphadenitis, particularly in those not responding to penicillin treatment.

Diagnosis, Differential↗
PubMed2005

Tularemia vaccine: past, present and future.

Francisella tularensis is a Gram negative intracellular pathogen that causes the highly debilitating or fatal disease tularemia. F. tularensis can infect a wide range of animals and can be transmitted to humans in a variety of ways, the most common being by the bite of an infected insect or arthropod vector. The attenuated F. tularensis live vaccine strain (LVS) has been used previously under investigational new drug status to vaccinate at-risk individuals. However the history of the strain and lack of knowledge regarding the basis of attenuation has so far prevented its licensing. Therefore the focus of current research is on producing a new vaccine against tularemia that would be suitable for licensing.

Animals↗
PubMed2005

[Tularemia. The disease and its epidemiology in France].

OBJECTIVE: This study had for aim to determine whether the epidemiologic features of animal and human tularemia observed in France could explain its re-emergence since 1993. MATERIALS AND METHODS: A retrospective study was made of outbreaks in animals and human cases and contamination. RESULTS: Twenty to sixty animal outbreaks were recorded every year but the number of cases was under-estimated. This indicates an increase in animal cases. Human cases or contaminations were associated with areas where animal cases had been recorded, except for a few cases more difficult to explain. Several factors are implicated: the disease is not known, except by hunters. Tularemia is more often described in hares but the disease may be present in other species. The disease and its forms should be documented for clinicians and biologists for an adequate clinical and bacteriological diagnosis. COMMENTS: Several factors in the epidemiology of the animal diseases have changed since 1993. It is necessary to be increasingly vigilant, for animal cases and human contamination. It is necessary to strengthen medical and veterinary supervision especially since Francisella tularensis may be used for bioterrorism.

Animals↗
PubMed2004

Did an epidemic of tularemia in Ancient Egypt affect the course of world history?

The dynamics of the spreading, and the identity of a virulent epidemic, similar to bubonic plague or typhus, which hit Ancient Egypt in the middle of the Bronze Age, are hereby presented. Documented in medical papyri as well as archaeological findings, and re-echoed in biblical texts, a plague entered Egypt's main harbor, Avaris, around 1715 BC. As a result, the country was severely weakened at a time when it was already facing serious sociopolitical issues: crumbling central government, immigration, foreign influence, and the rise in power of the army and of warlords. The Hebrews, one of the ethnic groups within the Avaris area, appeared immune amidst the devastation of the plague. This immunity was key to identify the etiological agent of the epidemic: Francisella tularensis, the Gram-negative bacterium passed by ticks, and that causes tularemia. The disease manifests itself as either an ulceroglandular or a typhoid syndrome, accounting for its similarity with bubonic plague and typhus. Cellular immunity provides the main defense against F. tularensis, and is achieved through continuous contact with avirulent strains of the bacterium. Urban dwellers of Avaris, who had a limited contact to animals, would have been defenseless against the virulent strains, unlike the Hebrews, who lived off sheep and other animals. Attempting to consolidate Egypt's central government in the aftermath of the tularemia epidemic, led among others to the internment of the Hebrews in labor camps. The repressive measures against the Hebrews left traces in the subsequent archaeological layer (stratum F) at Avaris. As a corollary, the enslavement would set the stage for the exodus of the Hebrew community from Egypt at a later time.

Communicable Diseases↗
PubMed2002

Tularemia and Q fever.

The zoonotic infections caused by Francisella tularensis and Coxiella burnetii, tularemia and Q fever, respectively, are two less commonly encountered clinical illnesses that are becoming increasingly recognized as epidemiologically important human diseases. The prevalence of tularemia and Q fever can be positively impacted by increased awareness of the clinical entities that arise from infection by these arthropod-borne organisms. Improved recognition of these clinical syndromes will lead to greater diagnostic accuracy in recognizing these diseases in patients. Ultimately, more stringent measures to prevent infection may be required, through raising public awareness, since current therapeutic regimens for these two diseases are limited, and knowledge of the pathogenesis of these two organisms are still in developing stages.

Coxiella burnetii↗
PubMed1998

Tularemia in a common marmoset (Callithrix jacchus) diagnosed by 16S rRNA sequencing.

We report a case of tularemia in a common marmoset (Callithrix jacchus) diagnosed by determination of the isolate's 16S ribosomal RNA (rRNA) gene sequence. Pathological examination of the animal revealed a multifocal acute necrotizing hepatitis, interstitial nephritis, splenitis, and lymphangitis of the mandibular, retropharyngeal, and cervical and mesenteric lymph nodes. Moreover, multiple foci of acute necrosis were found in the epithelium of the jejunum and the interstitium of the lung. Bacteriological investigations revealed a septicemia. The isolated infectious agent was uncommon, not routinely diagnosed in our laboratory and therefore difficult to identify by conventional tools in a reasonable time and effort. thus, we decided to perform a genetic analysis based on the 16S rRNA gene sequence. Thereby, an infection with Francisella tularensis, the causative agent of tularemia, was unambiguously diagnosed. This shows the great advantage 16S rRNA gene sequencing has as a general identification approach for unusual or rare isolates.

Animals↗
PubMed2004

Pulmonary manifestations of other agents: brucella, Q fever, tularemia and smallpox.

Brucella, Q fever, tularemia, and smallpox are all rare infections in the United States but are potential agents of biologic terrorism. The pulmonary manifestations of these infections range from uncommon (brucella and smallpox) to expected (Q fever and tularemia). and all have clinical and radiologic presentations that can be confused with other, more endemic,diseases. Once the release of these agents has been determined, the diagnosis of presenting patients will be straightforward. The onus is on the clinician,however, to be able to recognize the first few, unexpected cases, because early identification will be paramount in helping curb the effect of the outbreak.

Bioterrorism↗
PubMed2005

A novel screening ELISA and a confirmatory Western blot useful for diagnosis and epidemiological studies of tularemia.

A novel enzyme-linked immunosorbent assay (ELISA) and a confirmatory Western blot (WB) to detect human antibodies against Francisella tularensis were evaluated. The ELISA was based on partially purified lipopolysaccharide (LPS), the WB on whole antigen of F. tularensis. Positive WB showed a typical LPS ladder. Sensitivity and specificity of the ELISA, as assessed in 104 positive sera and 1149 'normal' sera from healthy young adults, were 99.0% and 97.1% respectively. Sensitivity of the WB was close to 100%, whereas specificity was 99.6%. Antibodies against the LPS of F. tularensis were detected in four of the 'normal' sera in both ELISA and WB. The assays were further evaluated using sera of individuals from Norway, Sweden and Kosovo suspected to be infected in tularemia outbreaks. Results revealed that the combination of ELISA and WB is suitable for laboratory confirmation of tularemia as well as for large-scale epidemiological studies.

Antibodies, Bacterial↗
PubMed1999

Tularemia--an unusual cause of a solitary pulmonary nodule in the post-transplant setting.

We report a case of tularemia presenting as a solitary pulmonary nodule following syngeneic PBSC transplant. Seven months after undergoing a syngeneic PBSC transplant for AML, our patient presented with fever without localizing signs. Chest X-ray revealed a solitary pulmonary nodule. Culture of a CT guided needle aspiration revealed Francisella tularensis. The patient was successfully treated with ciprofloxacin. His fever resolved and clearance of the nodule was documented on a CT scan 2 months after diagnosis and initiation of treatment. To our knowledge, this is the only reported case of tularemia occurring in the post-transplant setting. The possible relationship between transplant-induced immune dysfunction and the occurrence of this rare infection is discussed.

Anti-Infective Agents↗
PubMed2001

Tularemia epidemic in northwestern Spain: clinical description and therapeutic response.

This study describes the clinical characteristics of tularemia in Spain's first epidemic outbreak and the therapeutic response and compares the efficacy of 3 antibiotics (streptomycin, ciprofloxacin, and doxycycline). For 142 cases of tularemia, the therapeutic failure rate was 22.5%; ciprofloxacin was the antibiotic with the lowest percentage of therapeutic failures and with the fewest side effects.

Adolescent↗
PubMed2006

Live vaccine strain Francisella tularensis is detectable at the inoculation site but not in blood after vaccination against tularemia.

INTRODUCTION: Live vaccine strain (LVS) Francisella tularensis is a live, attenuated investigational tularemia vaccine that has been used by the US Army for decades to protect laboratory workers. Postvaccination bacterial kinetic characteristics of LVS at the inoculation site and in the blood are unknown and, therefore, were assessed in a prospective study. LVS vaccination of laboratory workers provided the opportunity to compare culture with polymerase chain reaction (PCR) for the detection of F. tularensis in human clinical samples. METHODS: Blood and skin swab samples were prospectively collected from volunteers who received the LVS tularemia vaccine at baseline (negative controls) and at 5 specified time points (days 1, 2, 7 or 8, 14 or 15, and 35 after vaccination). Bacterial culture and PCR of whole blood samples (17 volunteers) and inoculation site swabs (41 volunteers) were performed. RESULTS: The culture and PCR results of all blood samples were negative. Results of real-time PCR from the inoculation site samples were positive for 41 (100%) of 41 volunteers on day 1, for 40 (97.6%) of 41 volunteers on day 2, for 24 (58.5%) of 41 on day 7 or 8, for 6 (16.7%) of 36 on day 14 or 15, and for 0 (0%) of 9 on day 35. Positive results of bacterial cultures of the inoculation site samples occurred significantly less frequently, compared with PCR testing, with 4 (9.8%) of 41 volunteers having positive results on day 1 (P<.001) and 4 (9.8%) of 41 on day 2 (P<.001); all results from subsequent days were negative. CONCLUSIONS: F. tularensis LVS genomic DNA was detected in the majority of samples from the inoculation site up to 1 week after LVS vaccination, with real-time PCR being more sensitive than culture. Our data suggest that bacteremia does not occur after LVS vaccination in normal, healthy human volunteers.

Adult↗
PubMed1993

Tularemia: treatment failures with outpatient use of ceftriaxone.

Tularemia, an infection caused by the coccobacillus Francisella tularensis, can be a difficult disease process to diagnose and treat. The difficulty in treating this disease is related to the pathophysiology of the infection and the toxicity of the antimicrobial agents presently recommended for treatment. Recent in vitro data have suggested that antimicrobial drugs other than standard agents (streptomycin, gentamicin, chloramphenicol, or tetracycline) may be effective. We present eight cases of documented failure of outpatient use of ceftriaxone in the treatment of tularemia. Our data suggest that while ceftriaxone may have excellent MICs in vitro, these MICs do not necessarily correlate with successful in vivo outcomes.

Adolescent↗
PubMed1994

Streptomycin and alternative agents for the treatment of tularemia: review of the literature.

Because of the recent lack of availability of streptomycin--currently considered the drug of choice for the treatment of tularemia--we reviewed the literature on alternative drugs that have been used for this purpose. In addition, we reviewed data on the in vitro susceptibility of Francisella tularensis to a wide variety of agents. The rate of cure for streptomycin was 97%, with no relapses. For gentamicin and tetracycline, respectively, the rates of cure were 86% and 88%, the rates of relapse were 6% and 12%, and the rates of failure were 8% and 0. The duration of therapy with gentamicin and a delay in its initiation may have affected outcome in severe cases. For chloramphenicol and tobramycin, cure rates were 77% and 50%, respectively; relapse rates were 21% and 0; and failure rates were 2% and 33%, respectively. Treatment with imipenem/cilastatin was successful in one case, and that with ciprofloxacin or norfloxacin was successful in six cases; in contrast, therapy with ceftriaxone was ineffective in eight cases. On the basis of this review, we conclude that gentamicin is an acceptable alternative to streptomycin for the treatment of tularemia.

Francisella tularensis↗
PubMed1995

Relapse of tularemia after aminoglycoside therapy: case report and discussion of therapeutic options.

We describe a patient with ulceroglandular tularemia who initially responded to therapy with gentamicin but then clinically relapsed. Ciprofloxacin was subsequently given for 28 days, and the patient was clinically cured. Aminoglycosides have been considered the drugs of choice in the treatment of tularemia; however, potential alternative treatments do exist. We review the English-language literature on this topic.

Adult↗
PubMed1983

Clinically mild tularemia associated with tick-borne Francisella tularensis.

Between May 9 and July 3, 1979, 12 cases of glandular or ulceroglandular tularemia occurred in residents of the Crow Indian Reservation in southcentral Montana; only 13 cases had been reported from this geographic area in the preceding 25 years. The illness was mild, characterized by fever and cervical or occipital adenopathy. Systemic symptoms were self-limited although residual lymphadenopathy was common. Francisella tularensis was isolated from ticks (Dermacentor variabilis), the suspected vector. The strains of F tularensis did not ferment glycerol and thus were identified as type B rather than the more virulent type A. None of 83 adults hospitalized in an urban area 50 miles from the reservation had agglutination titers of antibody to F tularensis of greater than or equal to 1:40 compared with eight of 77 patients at the reservation hospital (P less than 0.01). Mild tularemia in reservation residents may have gone unrecognized; similar illness due to type B F tularensis may occur elsewhere.

Adult↗
PubMed1991

Epidemiologic characteristics of human tularemia in the southwest-central states, 1981-1987.

From 1981 through 1987, a total of 1,041 cases of tularemia in humans were reported in Arkansas, Kansas, Louisiana, Missouri, Oklahoma, and Texas; this represents 60% of the cases reported in the United States during this same time period. The state of Arkansas reported the highest total (420 cases). Annual incidence rates per one million population ranged from 36.3 in Arkansas to less than 5.0 in Kansas, Louisiana, and Texas. Epidemiologic data were available for 1,026 cases. The majority of cases were white (88%) and male (75%). May, June, and July were the months of onset of symptoms for 52% of the cases. For the cases with known exposure history, 63% reported an attached tick and 23% had exposure to rabbits. Other animals associated with human infection were squirrels, cats, and raccoons. The case-fatality ratio was 2%. Public health efforts to prevent human tularemia cases in the six southwest-central states should focus on reducing exposure to ticks.

Adolescent↗