Table of Contents:

• Taxonomy Information
• Lifecycle Information
• Genome Information
• Biosafety Information
• Culturing Information
• Epidemiology Information
• Diagnostic Tests Information
• Infected Hosts Information
• Phinet: Pathogen-Host Interaction Network
• Lab Animal Pathobiology & Management
• References
• Data Provenance and Curators

1. Species:
   1. Francisella tularensis (Website 9):
      1. GenBank Taxonomy No.: 263
      2. Description: Francisella tularensis is a small, aerobic, pleomorphic, gram-negative, intracellular and extracellular coccobacillus. It is the causative agent of the disease tularemia(Parola and Raoult, 2001).
      3. Variant(s):
         • Francisella tularensis biogroup tularensis. (Website 10):
           • Common Name: biovar type A.
           • GenBank Taxonomy No.: 119856
           • Parents: Francisella tularensis
           • Description: Francisella tularensis biogroup tularensis (also known as nearctica, type A),(Website 10). is predominantly found in mammalian hosts and arthropod vectors of North America(Parola and Raoult, 2001). It is the most virulent of the F. tularensis subspecies and accounts for approximately 90% of tularemia cases in North America,(Choi, 2002). where rabbits (Sylvilagus) are important reservoirs(Parola and Raoult, 2001). The virulent Schu 4 strain of F. tularensis is type A(Dennis et al., 2001).
         • Francisella tularensis biogroup holarctica. (Website 11):
           • Common Name: biovar type B.
           • GenBank Taxonomy No.: 119857
           • Parents: Francisella tularensis
           • Description: Three biovars of F. tularensis biogroup holarctica have been suggested; biovar I (erythromycin sensitive), biovar II (erythromycin resistant), and biovar japonica(Ellis et al., 2002). Francisella tularensis biogroup holarctica (also known as palaearctica, type B) is more widely distributed in nature and is found in Europe, Asia, and to a minor extent in North America. This subspecies is linked to waterborne disease of rodents and hares, and it is considered to be less pathogenic for mammals than F. tularensis subsp. tularensis(de la Puente-Redondo et al., 2000). A live vaccine strain of F. tularensis (F. tularensis LVS) was derived from a virulent type B strain(Website 17). Vaccine strains 15 and 155 were transferred to the United States from Moscow in 1956. Cultures grown from reconstituted ampules showed that both strain 15 and strain 155 segregated into two colony types, designated blue colony variant or grey colony variant depending on their appearance when viewed microscopically under oblique light. The blue colony variant was shown to be more virulent and immunogenic in small animals than the grey colony variant. Mice immunized with the blue colony variant were protected when challenged with the fully virulent Schu 4 strain. Lyophilized preparations of the blue colony variant were prepared and a live vaccine strain (LVS) was derived after five passages through mice(Ellis et al., 2002).
         • Francisella tularensis holarctica japonica :
           • Parents: Francisella tularensis biogroup holarctica.
           • Description: Francisella tularensis biogroup palaearctica japonica belongs to F. tularensis biogroup holarctica (palaearctica) and is found primarily in Japan(Choi, 2002).
         • Francisella tularensis biogroup mediaasiatica. (Website 12):
           • GenBank Taxonomy No.: 135248
           • Parents: Francisella tularensis
           • Description: Francisella tularensis subsp. mediaasiatica has been found only in central Asia in a part of the former Soviet Union(de la Puente-Redondo et al., 2000).
         • Francisella tularensis biogroup novicida. (Website 13):
           • GenBank Taxonomy No.: 264
           • Parents: Francisella tularensis
           • Description: F. tularensis biogroup novicida was isolated from a Utah water sample in 1950(Farlow et al., 2001). There are only a few known isolates of this biogroup(Johansson et al., 2001). and it is of low virulence(Parola and Raoult, 2001).

1. Francisella tularensis Information
   1. Stage Information:
      1. Vegetative cell:
         • Size: Francisella tularensis is 0.2-0.5 x 0.7-1.0 microns.
         • Shape: Francisella tularensis is a pleomorphic coccobacilli.
         • Picture(s):
           • Gram Stain Smears of Bacillus anthracis, Yersinia pestis, and Francisella tularensis (Dennis et al., 2001)
             
             
             
             Description: Gram Stain Smears of the Agents of Anthrax (Bacillus anthracis), Plague (Yersinia pestis), and Tularemia (Francisella tularensis), Demonstrating Comparative Morphology, Size, and Staining Characteristics. A, B. anthracis is a large (0.5-1.2 x 2.5-10.0 micrometer), chain-forming, gram-positive rod that sporulates under certain conditions (Gram stain of organism from culture; original magnification x250); B, Y. pestis is a gram-negative, plump, nonspore-forming, bipolar-staining bacillus that is approximately 0.5-0.8 x 1-3 micrometer (Gram stain of smear from infected tissue; original magnification x250); C, F. tularensis is a small (0.2 x 0.2-0.7 micrometer), pleomorphic, poorly staining, gram-negative coccobacillus (Gram stain of organism from culture; original magnification x500) (inset, direct immunofluorescence of smear of F. tularensis; original magnification x400. Sources: A and B, Sherif Zaki, Centers for Disease Control and Prevention; C, Armed Forces Institute of Pathology. Used with permission(Dennis et al., 2001).

1. Genome of Francisella tularensis
   1. Description: The genome of the Schu 4 strain of Francisella tularensis (a virulent type A strain) is being sequenced through a project funded by the United States Army Medical Research and Material Command, UK Ministry of Defence, Swedish Ministry of Defence, and the US Defence Advanced Research Projects Agency. Information regarding that project can be found in Website 16(Website 16). Preliminary results from this project suggest a total genome size of less than 2 Mbp, making this one of the smaller bacterial genomes(Ellis et al., 2002, Prior et al., 2001). The genome of F. tularensis LVS (a type B strain) is being sequenced through the Biology and Biotechnology Research Program at Lawrence Livermore National Laboratory(Website 17). Information regarding that project can be found in Website 17.
2. Genome of Francisella tularensis biogroup novicida.
   1. Plasmid pFNL10(Website 15)
      1. GenBank Accession Number: AF121418
      2. Size: 3990 bp(Pomerantsev et al., 2001, Website 15).
      3. Gene Count: Plasmid pFNL10 has 6 ORFs(Pomerantsev et al., 2001).
      4. Description: Plasmid pFNL10 is found in Francisella tularensis biogroup novicida. F. tularensis biogroup novicida is the only member of the genus that carries a native plasmid(Pomerantsev et al., 2001).

1. Biosafety information for Francisella tularensis
   1. Level: Biosafety level 2 practices and containment should be used for routine diagnostic activities with clinical materials. Biosafety level 3 practices, containment, and facilities should be used for all manipulations of cultures and for experimental studies involving infectious materials with a potential for aerosol and droplet production (centrifuging, grinding, vigorous shaking, growing cultures in volume, and animal studies)(Dennis et al., 2001).
   2. Precautions: Laboratory coat, impervious gloves, and gown (with tight wrists and a tie in the back) should be worn when working with Francisella tularensis. Face masks should be worn when working with infectious material in biosafety cabinet. Bodies of patients who die of tularemia should be handled using standard precautions. Autopsy procedures likely to cause aerosols, such as bone sawing, should be avoided. Clothing or linens contaminated with body fluids of patients infected with F. tularensis should be disinfected per standard precaution protocols such as steam sterilization. Persons handling animals, especially rabbits, should wear impervious gloves. F. tularensis is susceptible to 1% sodium hypochlorite (10% bleach) and standard levels of chlorine in municipal water sources should be protective(Dennis et al., 2001, Website 4).
   3. Disposal: Decontamination before disposal, incineration of animal carcasses, steam sterilization of other laboratory waste(Website 4).

1. Cysteine heart agar with sheep blood :
   1. Description: Growth on plates. For culturing on plates of Francisella tularensis, use established inoculation and plating procedures. For tissues, use established laboratory procedure to inoculate media (grind or use a sterile wood stick). Tape plates shut in 2 places to prevent inadvertent opening (alternatives to taping are also acceptable) (Website 1). F. tularensis can be grown from such things as pharyngeal washings, sputum specimens, blood, and fasting gastric aspirates(Dennis et al., 2001). Although growth may be visible as early as 24-48 hours after inoculation, growth may be delayed and cultures should be held for at least 10 days before discarding. Under ideal conditions, bacterial colonies on cysteine-enriched agar are typically 1 mm in diameter after 24-48 hours of incubation, white to gray to bluish-gray, opaque, flat with an entire edge, smooth, and may have a shiny surface. By 96 hours, the colonies are typically 3-5 mm in diameter. On cysteine heart agar, F. tularensis colonies are characteristically opalescent and do not discolor the medium(Dennis et al., 2001). Figure 4 of Dennis et al. (2001), shows F. tularensis colonies with characteristic opalescence on cysteine heart agar with sheep blood (cultured at 37 degrees celcius for 72 hours)(Dennis et al., 2001). Figure A2A, (Website 1), shows F. tularensis Schu 4 strain growing on 6% sheep blood agar at 72 hours. Figure A2b, (Website 1), shows F. tularensis Schu 4 strain on chocolate agar after 72 hours(Website 1).
   2. Medium: F. tularensis grows best in cysteine-enriched broth and thioglycollate broth. It grows best on cysteine heart blood agar, sheep blood agar, and on cysteine-supplemented agar such as buffered charcoal-yeast agar, Thayer-Martin agar, and chocolate agar. Selective agar may be useful when culturing materials from nonsterile sites, such as sputum(Dennis et al., 2001, Website 1).
   3. Optimal Temperature: 35-37 degrees celsius(Dennis et al., 2001, Website 1).
   4. Picture(s):
      • Francisella tularensis Growth at 72 Hours After Inoculation (Dennis et al., 2001)
        
        
        
        Description: These Francisella tularensis colonies show characteristic opalescence on cysteine heart agar with sheep blood (cultured at 37 degrees celsius for 72 hours). Source: Centers for Disease Control and Prevention. Used with permission(Dennis et al., 2001).
2. Axenic culture in TSB-C :
   1. Description: Anthony et al., showed that Francisella tularensis grew in a cell-free medium of tryptic soy broth supplemented with 0.1% cysteine(Anthony et al., 1991). However, growth is slow and requires a large inoculum to obtain visible growth within 24 hours(Ellis et al., 2002).
   2. Medium: Francisella tularensis can be cultured in tryptic soy broth supplemented with 0.1% cysteine (TSB-C)(Anthony et al., 1991).
3. Axenic culture in Mueller-Hinton Broth :
   1. Description: Francisella tularensis can be grown axenically in modified Mueller-Hinton broth(Fortier et al., 1995). The addition of 0.025% ferric pyrophosphate appeared to enhance growth in this medium(Ellis et al., 2002).
   2. Medium: Francisella tularensis can be grown in modified Mueller-Hinton broth(Fortier et al., 1995).
4. Axenic culture in thioglycollate broth :
   1. Description: Francisella tularensis can be grown axenically in thioglycollate broth. In static thioglycollate broth, growth is first seen as a dense band near the top which diffuses throughout as growth progresses(Ellis et al., 2002).
   2. Medium: Thioglycollate broth(Ellis et al., 2002).
5. Intracellular growth on murine macrophages :
   1. Description: Murine macrophages support exponential intracellular growth of Francisella tularensis LVS where it remains in a vacuolar compartment throughout its growth cycle(Fortier et al., 1995). Macrophages (from a peritoneal cell preparation) are adjusted to 1 million cells per ml and incubated as cell pellets in polypropylene tubes in 5% CO2 at 37 degrees celsius before exposure to the bacteria. The macrophages are subsequently exposed to F. tularensis LVS at a multiplicity of infection of 1 for 2 hours at 37 degrees celsius in 5% CO2 in a humid environment(Fortier et al., 1995).
   2. Medium: Murine macrophages and associated F. tularensis bacteria were grown in Dulbecco Modified Eagle Medium (DMEM) with 10% heat-inactivated fetal bovine serum(Fortier et al., 1995).
   3. Optimal Temperature: 37 degrees celsius(Fortier et al., 1995).
   4. Optimal Humidity: Humid environment(Fortier et al., 1995).
   5. Doubling Time: 4 to 6 hours(Fortier et al., 1995).

1. Outbreak Locations:
   1. Tularemia is not a disease which is notifiable to the World Health Organization, and the worldwide incidence is not known(Ellis et al., 2002). It is primarily a disease of the northern hemisphere and is most common between 30 degrees and 71 degrees north latitude. Tularemia has been remarkably absent from the United Kingdom, Africa, South America, and Australia(Cross et al., 2000). F. tularensis is found throughout much of North America and Eurasia. In the United States, it has been found in every state excluding Hawaii, with most cases occurring in south-central and western states. In Eurasia, the greatest numbers are reported from northern and central Europe, especially Scandinavian countries and those of the former Soviet Union. F. tularensis is found mostly in rural areas, although urban and suburban exposures occasionally do occur(Dennis et al., 2001).
2. Transmission Information:
   1. From: Invertebrates, Wild vertebrates, Domestic mammals , To: Homo sapiens
      Mechanism: Humans become infected with Francisella tularensis through inoculation of the skin, conjunctival sac or oropharyngeal mucosa with blood or tissue while handling infected animals, or through contact with fluids from infected flies, ticks or other animals(Dennis et al., 2001, Website 4). Although the organism is reported to penetrate intact skin, most investigators believe that penetration occurs through sites of inapparent skin disruption(Cross et al., 2000). The bite of vectors including ticks, deerfly, mosquito, gnats, and bedbugs can also transmit the bacterium to humans(Dennis et al., 2001, Website 4, Choi, 2002). It is rarely spread through bites from animals(Website 4). Transmission from human to human has not been documented(Dennis et al., 2001, Website 4, Choi, 2002, Cross et al., 2000).
   2. From: Food , To: Homo sapiens
      Mechanism: Ingestion of food and drinking water contaminated with Francisella tularensis can be infective for humans(Dennis et al., 2001, Website 4, Choi, 2002).
   3. From: Water , To: Homo sapiens
      Mechanism: Ingestion of food and drinking water contaminated with Francisella tularensis can be infective for humans(Dennis et al., 2001, Website 4, Choi, 2002).
   4. From: Air , To: Homo sapiens
      Mechanism: Humans can become infected with Francisella tularensis by inhaling contaminated aerosols(Dennis et al., 2001, Website 4, Choi, 2002).
3. Environmental Reservoir:
   1. Mud-Infected_Animal_Carcass-Meat-Straw-Water:
      1. Description: Francisella tularensis can survive in: 7 degrees celsius mud for 14 weeks;(Website 4, Feldman, 2003). infected animal carcasses and organs for up to 133 days; non-frozen rabbit meat for 31 days; rabbit meat stored at -15 degrees celsius for at least 3 years; straw for 192 days; water for up to 90 days(Website 4).
   2. Wild vertebrates:
      1. Description: Rabbits, hares, and rodents (including water rats, squirrels, mice, and voles) are considered the be the most important reservoirs for Francisella tularensis(Dennis et al., 2001, Website 3, Parola and Raoult, 2001). Birds may also be infected(Website 4). These animals acquire infection through bites by ticks, flies, and mosquitoes, and by contact with contaminated environments(Dennis et al., 2001).
   3. Domestic mammals:
      1. Description: Domestic mammals including sheep, dogs, and cats can be infected with Francisella tularensis(Website 2, Feldman, 2003).
   4. Invertebrates:
      1. Description: Invertebrates such as ticks are common vectors of Francisella tularensis. In the United States, the important tick vectors are: Amblyoma americanum - the Lone Star tick, Dermacentor andersoni - the wood tick, and Dermacentor variabilis - the dog tick. Other vectors include deerflies, horseflies, and mosquitoes(Website 4, Feldman, 2003, Choi, 2002). Generally, biting flies are the most common vectors in Utah, Nevada, and California, while ticks are the most important vectors east of the Rocky Mountains(Ellis et al., 2002). In central Europe, the ticks Dermacentor reticulatus and Ixodes ricinus are important vectors. In the former Soviet Union, the bacterium is transmitted by both mosquitoes (Aedes, Culex, and Anopheles species) and Ixodes species of tick(Ellis et al., 2002).
   5. Air:
      1. Description: Contaminated aerosols are a source of human infection with Francisella tularensis(Dennis et al., 2001, Choi, 2002).
   6. Food:
      1. Description: Contaminated food (including fresh and frozen rabbit meat) is a source of Francisella tularensis infection(Website 4).
   7. Water:
      1. Description: Contaminated water is a source of Francisella tularensis infection(Choi, 2002). It is postulated that F. tularensis may survive in water in association with amebae(Berdal et al., 1996, Berdal et al., 2000).
   8. Soil:
      1. Description: Francisella tularensis can contaminate soil and vegetation(Dennis et al., 2001).
   9. Vegetation:
      1. Description: Francisella tularensis can contaminate soil and vegetation(Dennis et al., 2001).
4. Intentional Releases:
   1. Intentional Release Information:
      1. Description: Francisella tularensis has long been considered a potential biological weapon. It was one of a number of agents studied at Japanese germ warfare research units operating in Manchuria between 1932 and 1945; it was also examined for military purposes in the West. A former Soviet Union biological weapons scientist, Ken Alibek, has suggested that tularemia outbreaks affecting tens of thousands of Soviet and German soldiers on the eastern European front during World War II may have been the result of intentional use. Following the war, there were continuing military studies of tularemia. In the 1950s and 1960s, the US military developed weapons that would disseminate F. tularensis aerosols; concurrently, it conducted research to better understand the pathophysiology of tularemia and to develop vaccines and antibiotic prophylaxis and treatment regimens. In some studies, volunteers were infected with F. tularensis by direct aerosol delivery systems and by exposures in an aerosol chamber. A live attenuated vaccine was developed that partially protected against respiratory and subcutaneous challenges with the virulent Schu 4 strain of F. tularensis, and various regimens of streptomycin, tetracyclines, and chloramphenicol were found to be effective in prophylaxis and treatment. By the late 1960s, F. tularensis was one of several biological weapons stockpiled by the US military. According to Alibek, a large parallel effort by the Soviet Union continued into the early 1990s and resulted in weapons production of F. tularensis strains engineered to be resistant to antibiotics and vaccines(Dennis et al., 2001). In 1969, a World Health Organization expert committee estimated that an aerosol dispersal of 50 kg of virulent F. tularensis over a metropolitan area with 5 million inhabitants would result in 250,000 incapacitating casualties, including 19,000 deaths. Illness would be expected to persist for several weeks and disease relapses to occur during the ensuing weeks or months. It was assumed that vaccinated individuals would be only partially protected against an aerosol exposure. Referring to this model, the Centers for Disease Control and Prevention (CDC) recently examined the expected economic impact of bioterrorist attacks and estimated the total base costs to society of an F. tularensis aerosol attack to be $5.4 billion for every 100,000 persons exposed(Dennis et al., 2001).
      2. Emergency Contact: After seeking prompt medical attention, local and state health departments should be immediately notified if exposure to Francisella tularensis is suspected. If criminal activity is suspected, these agencies will notify the CDC and the FBI(Website 3).
      3. Delivery Mechanism: In biological warfare it is anticipated that the bacteria would be delivered as a cloud to the target population, making entry through the airways into the lungs the most common route, although ingestion and entry through skin wounds is also possible(Website 7).
      4. Containment: Disinfection of contaminated articles may be accomplished using a 0.05% hypochlorite solution(Website 7).

1. Organism Detection Test:
   1. Gram stain (Website 1):
      1. Time to Perform: 2-to-7-days
      2. Description: Gram staining of Francisella tularensis organisms reveals the presence of tiny (0.2-0.5 microns X 0.7-1.0. microns) pleomorphic, poorly staining, mainly single cell, Gram-negative coccobacilli. The Gram stain interpretation may be difficult because the cells are minute and faintly staining(Website 1).
   2. Growth on chocolate agar (Ellis et al., 2002):
      1. Time to Perform: 2-to-7-days
      2. Description: The Centers for Disease Control and Prevention guidelines recommend the use of cysteine heart agar supplemented with 9% heated sheep red blood cells (CHAB) if growth on general microbiological agars indicates the presence of Francisella tularensis(Ellis et al., 2002). A heavy inoculum will yield visible growth in 18 hours, but the appearance of individual colonies may require 2 to 4 days of incubation. F. tularensis grows slowly at 37 degrees celsius and poorly at 28 degrees celsius, and this can be exploited to distinguish F. tularensis from Yersinia pestis, Francisella philomiragia, and F. tularensis biogroup (subspecies) novicida, all of which grow well at 28 degrees celsius(Ellis et al., 2002). On CHAB, F. tularensis colonies are 2 to 4 mm in size, greenish-white, round, smooth, and slightly mucoid. On media containing whole blood there is usually a small zone of alpha-hemolysis surrounding the colonies(Ellis et al., 2002).
2. Immunoassay Test:
   1. cELISA - capture enzyme-linked immunosorbent assay (Grunow et al., 2000):
      1. Time to Perform: 1-hour-to-1-day
      2. Description: A capture enzyme-linked immunosorbent assay (cELISA) using two monoclonal antibodies (Ft-11 and Ft-27) that are specific for lipopolysaccharide (LPS) of Francisella tularensis subspecies holarctica and Francisella tularensis subspecies tularensis was reported in 2000. The cELISA showed no cross-reactivity with Francisella tularensis subspecies novicida, Francisella philomiragia, Brucella spp., Yersinia spp., Escherichia coli, and Burkholderia spp(Grunow et al., 2000). An important step in the test was the extraction of LPS from the bacteria. The extraction resulted in a 10-fold increase in sensitivity, inactivation of infectious bacteria in subsequent steps, and the lysis of eukaryotic cells (which released intracellular bacteria). The detection limit of the cELISA using LPS-extracted samples was 10 e3 bacteria / milliliter in phosphate buffered saline and 10 e4 bacteria / milliliter in human serum. The assay was also reported to have a similar level of sensitivity in spiked human urine, sputum, and stool(Grunow et al., 2000).
   2. Enzyme-linked immunosorbent assay (Website 5, Ellis et al., 2002, Syrjala et al., 1986, Website 19):
      1. Time to Perform: 1-hour-to-1-day
      2. Description: Because of the difficulty and danger of culturing Francisella tularensis, most cases of tularemia are currently diagnosed using the clinical presentation and / or serological evidence(Ellis et al., 2002). A measurable antibody response to Francisella tularensis usually occurs in 50-70% of cases about 2 weeks after the onset of disease(Website 5, Ellis et al., 2002). Titers reach a maximum in 4-8 weeks(Website 5). Enzyme-linked immunosorbent assay (ELISA) has been used for detection of serum antibodies by using a sonicate of the LVS strain and F. tularensis nonviable cells in phenolized saline are available commercially from BD (Becton, Dickinson, and Company; Franklin Lakes, New Jersey)(Website 19). The ELISA detected either IgM, IgA, or IgG in the sera of patients during the second week of tularemia. The antibodies generally persisted and were detectable by ELISA at high titer for six months(Syrjala et al., 1986).
   3. Immunochromatographic Assay (Dipstick) (Grunow et al., 2000):
      1. Time to Perform: minutes-to-1-hour
      2. Description: An immunochromatographic assay using an affinity purified polyclonal antibody and a monoclonal antibody to lipopolysaccharide (LPS) of Francisella tularensis live vaccine strain (LVS, biogroup holarctica) was reported in 2000. The test could detect 10 e6 and 10 e6-e7 bacteria / milliliter of phosphate buffered saline (PBS) or human serum, respectively. The detection limit was increased ten-fold to 10 e5 bacteria / milliliter of PBS and 10 e5-e6 bacteria / milliter of human serum if an LPS extraction method of sample preparation was used. This makes the immunochromatographic test approximately 100 times less sensitive than the capture ELISA that employs monoclonal antibodies Ft-11 and Ft-27. The test was completed in approximately 15 minutes after extraction of LPS, with high bacterial loads showing a positive signal in less than 1 minute. The authors suggest that this assay is a fast and simple method for field diagnosis of tularemia, but the diagnosis should be confirmed by more sensitive techniques such as capture ELISA or PCR(Grunow et al., 2000).
   4. Agglutination (Ellis et al., 2002):
      1. Time to Perform: minutes-to-1-hour
      2. Description: Because of the difficulty and danger of culturing Francisella tularensis, most cases of tularemia are currently diagnosed using the clinical presentation and / or serological evidence(Ellis et al., 2002). A measurable antibody response to Francisella tularensis usually occurs in 50-70% of cases about 2 weeks after the onset of disease(Website 5, Ellis et al., 2002). Titers reach a maximum in 4-8 weeks(Website 5). Agglutination is an accepted method for detection of serum antibodies. F. tularensis nonviable cells in phenolized saline are available commercially from BD (Becton, Dickinson, and Company; Franklin Lakes, New Jersey)(Website 19). A fourfold increase in titer during illness or a single titer of 1:160 or greater is considered diagnostic for infection(Ellis et al., 2002).
3. Nucleic Acid Detection Test:
   1. Species, subspecies, strain identification (de la Puente-Redondo et al., 2000, Johansson et al., 2001, Farlow et al., 2001, Ellis et al., 2002, Forsman et al., 1994, Johansson et al., 2000b):
      1. Description: Various methods based on nucleotide sequence have been employed to identify Francisella species, subspecies, and strains. Species identification: Primer pairs based on 16S rRNA gene sequences were used to differentiate Francisella tularensis from the closely related Francisella philomiragia(Forsman et al., 1994). (studies show a sequence similarity of at least 98% between the two species(de la Puente-Redondo et al., 2000). Subspecies identification: Repetitive extragenic palindromic element PCR (REP-PCR), enterobacterial repetitive intergenic consensus sequence PCR (ERIC-PCR, and random amplified polymorphic DNA (RAPD) analyses were all used successfully for subspecies determination of Francisella tularensis(de la Puente-Redondo et al., 2000). Also, a specific PCR has been developed which produces amplicons of different lengths (target unknown), has been used in combination with the 17 kDa lipoprotein PCR to distinguish F. tularensis subspecies holarctica (biovar type B, less pathogenic) from strains of other F. tularensis subspecies(Ellis et al., 2002, Johansson et al., 2000b). Strain identification: Suitable methods for strain determination of Francisella tularensis were designed based on the presence of tandem repeat sequences. Two articles in the same issue of the Journal of Clinical Microbiology describe the use of either "multilocus variable-number tandem repeat analysis" (MLVA),(Farlow et al., 2001). or "short-sequence tandem repeat" (SSTR) analysis(Johansson et al., 2001).

1. Human
   1. Taxonomy Information:
      1. Species:
         1. Homo sapiens (Website 14):
            • Common Name: Homo sapiens
            • GenBank Taxonomy No.: 9606
            • Description: Humans become infected with Francisella tularensis in various ways, including bites by infective arthropods, handling infectious animal tissues or fluids, direct contact with, or ingestion of, contaminated water, food, or soil, and inhalation of infective aerosols. Persons of all ages and both sexes appear to be equally susceptible to tularemia. Certain activities, such as hunting, trapping, butchering, and farming, are most likely to expose adult men. Laboratory workers are especially vulnerable to infection, either by accidentally inoculating themselves or by inhaling aerosolized organisms(Dennis et al., 2001).
   2. Infection Process:
      1. Infectious Dose: The infectious dose for humans, when Francisella tularensis is injected intradermally, is 10 to 50 organisms(Cross et al., 2000),
      2. Description: Francisella tularensis can infect humans through the skin, mucous membranes, gastrointestinal tract, and lungs. It is a facultative intracellular bacterium that multiplies within macrophages. The major target organs are the lymph nodes, lungs and pleura, spleen, liver, and kidney. Left untreated, bacilli inoculated into skin or mucous membranes multiply, spread to the regional lymph nodes and further multiply, and may then disseminate to organs throughout the body. Bacteremia may be common in the early phase of infection. F. tularensis enters and replicates in resident or inflammatory macrophages, thus escaping host defenses. Once inside, the organism inhibits phagolysosome fusion. Acidification of the phagosome is required for acquisition of iron and for growth of F. tularensis(Dennis et al., 2001),
      3. Picture(s):
         • Immunofluorescence of F. tularensis LVS-infected murine resident paritoneal cells (Fortier et al., 1995)
           
           
           
           Description: Immunofluorescent photographs of Francisella tularensis LVS-infected murine resident peritoneal cells (PC) using the F. tularensis-specific monoclonal antibody FRAN4, and stained at 24, 48, and 72 hours (B, C, D respectively) post-infection. All immunostaining was cell associated. The frequency of infected cells per culture and the intensity of immunofluorescence per infected cell each increased with time after infection. Used with permission(Fortier et al., 1995).
         • Electron-micrograph analysis of in vivo-infected peritoneal cells (Fortier et al., 1995)
           
           
           
           Description: Electron micrographs of peritoneal cells (PC) infected in vivo with Francisella tularensis LVS. (A) Macrophage infected with numverous LVS; (B) higher magnification of vacuole-contained LVS. F. tularensis replicated only within the macrophage subpopulation of PC. Used with permission(Fortier et al., 1995).
   3. Disease Information:
      1. Tularemia :
         1. Incubation: Generally, 3 to 5 days (range of less than 1-21 days) after cutaneous inoculation with Francisella tularensis, a papule appears. Ulceration of the papule occurs 2 to 4 days later(Cross et al., 2000),
         2. Prognosis:
            When treated, overall death rates from Francisella tularensis have been 4% or less, but were as high as 33% before the introduction of streptomycin(Cross et al., 2000),
         3. Symptom Information :
            • Syndrome -- Tularemia :
              • Description: Clinical manifestations of infection with Francisella tularensis can range from asymptomatic or inconsequential illness to acute sepsis and rapid death. Tularemia usually starts abruptly, with the onset of fever, chills, headache, malaise, anorexia, and fatigue. Other prominent symptoms may include cough, myalgias, chest discomfort, vomiting, sore throat, abdominal pain, and diarrhea. Fever (usually greater than 101 degrees fahrenheit) classically lasts for several days, remits for a short interval, and then recurs along with other symptoms. Without treatment the fever lasts an average of 32 days, while chronic debility, weight loss, and adenopathy may persist for many months longer(Cross et al., 2000). The clinical picture is usually dominated by one or more of the six forms of tularemia: ulceroglandular, glandular, oculoglandular, pharyngeal, typhoidal, and pneumonic. By the time medical help is sought, the systemic symptoms may abate, leading to confusion as to the correct diagnosis, particularly in the 25 to 50% of patients without an evident source of infection(Cross et al., 2000).
            • Syndrome -- Ulceroglandular tularemia :
              • Description: In ulceroglandular tularemia (the most quickly recognized form of tularemia), tick bites and animal contacts are the recalled exposure routes. The initial complaint is often of enlarged and tender localized lymphadenopathy. The site of inoculation may appear either before, simultaneously with, or from one to several days after the adenopathy. It starts as a red, painful papule in a region draining into the involved lymph nodes. The papule then undergoes necrosis, leaving a tender ulcer with a raised border. If untreated, the ulcer may take weeks to heal and leave a residual scar(Cross et al., 2000).
              • Observed:
                Ulceroglandular tularemia presents in 21 to 87% of tularemia cases(Cross et al., 2000),
            • Syndrome -- Glandular tularemia :
              • Description: Glandular tularemia occurs when there is regional lymphadenopathy, but no evident cutaneous lesion. Glandular tularemia represents the same process as ulceroglandular, except that the skin lesion either healed before disease presentation, was minimal, or overlooked(Cross et al., 2000).
              • Observed:
                Glandular tularemia accounts for 3 to 20% of cases in the United States and 62% of cases in Japan(Cross et al., 2000),
            • Syndrome -- Oculoglandular tularemia :
              • Description: Oculoglandular tularemia occurs when Francisella tularensis directly infects the conjunctiva of the eye by contact with contaminated fingers, liquids, or aerosols. Early complaints may include photophobia and excessive lacrimation. Examination may reveal eyelid edema, painful conjunctivitis, and chemosis. Some patients may exhibit small, yellowish conjunctival ulcers or papules. The eye symptoms are accompanied by regional lymphadenopathy. Visual loss is rare, but complications include corneal ulceration, dacrocystitis, and nodal suppuration(Cross et al., 2000).
              • Observed:
                Oculoglandular tularemia represents 0 to 5% of tularemia cases(Cross et al., 2000),
            • Syndrome -- Pharyngeal tularemia :
              • Description: Pharyngeal tularemia is the result of invasion of Francisella tularensis through the oropharynx following exposure to contaminated food, water, droplets, or aerosols(Dennis et al., 2001, Cross et al., 2000). In this form of tularemia, the patient primarily complains of severe sore throat pain. Exudative pharyngitis or tonsillitis is the rule, and one or more ulcers may be visible. Pronounced cervical or retropharyngeal lymphadenopathy may occur(Dennis et al., 2001). Tularemia should be suspected in an endemic area whenever a severe sore throat is unresponsive to penicillin therapy and routine diagnostics tests are inconclusive(Cross et al., 2000).
              • Observed:
                Pharyngeal tularemia represents 0 to 12% of cases and is being seen with increasing frequency in Japan(Cross et al., 2000),
            • Syndrome -- Typhoidal tularemia :
              • Description: Typhoidal tularemia manifests as a febrile illness caused by Francisella tularensis that is not associated with prominent lymphadenopathy and does not fit into any of the other major forms of tularemia. Typhoidal tularemia is the most difficult form to diagnose. Prominent symptoms include: fever with chills, headache, myalgia, sore throat, anorexia, nausea, vomiting, diarrhea, abdominal pain, and cough(Cross et al., 2000). Additionally, the patient may be delirious and develop shock(Ellis et al., 2002). Because the route of entry is usually not apparent, a history of outdoor activities with potential tick or animal exposure should be sought(Cross et al., 2000). Typhoidal tularemia has a mortality rate of 30 to 60%(Ellis et al., 2002).
              • Observed:
                Typhoidal tularemia occurs in 5 to 30% of tularemia cases(Cross et al., 2000),
            • Syndrome -- Pneumonic tularemia :
              • Description: Pneumonic tularemia refers to an illness whose initial presentation is dominated by pulmonary infection. It is the result of direct inhalation of Francisella tularensis or from secondary hematogenous spread to the lung. Primary pneumonic tularemia is a risk for certain occupations including sheep shearers, farmers, and laboratory workers(Cross et al., 2000). Aerosol release of F. tularensis would be expected to lead to signs of pneumonic tularemia, however, inhalational exposure commonly results in an initial picture of systemic illness without prominent signs of respiratory disease(Dennis et al., 2001). From 25 to 30% of patients have radiographic infiltrates without any clinical findings of pneumonia. Common symptoms include: fever, cough, no or minimal sputum production, substernal tightness, and pleuritic chest pain. Routine examination of sputum does not help to suggest the diagnosis. Infected pleural fluid is exudative, negative on Gram stain, and usually contains more than 1000 leukocytes / mm cubed; cells are predominantly lymphocytes, but neutrophilic effusions may occur. Acute radiographic changes may include subsegmental or lobar infiltrates, hilar adenopathy, pleural effusion, and apical or miliary infiltrates(Cross et al., 2000). These signs may be minimal or absent, and some patients will show only 1 or several small, discrete pulmonary infiltrates or scattered granulomatous lesions of lung parenchyma or pleura(Dennis et al., 2001).
              • Observed:
                As a primary infection, pneumonic tularemia is found in 7 to 20% of all tularemia cases. Secondary pneumonia may complicate any form of tularemia, however it is found in 83% of typhoidal tularemia and 31% of ulceroglandular tularemia(Cross et al., 2000),
         4. Treatment Information:
            • Streptomycin : ADULT DOSE: The minimum dosage of streptomycin that is effective for tularemia is 7.5 to 10 mg/kg intramuscularly every 12 hours for 7 to 14 days. An alternative regimen is 15 mg/kg intramuscularly every 12 hours for the first 3 days, followed by half of that dose to complete the treatment. In very sick patients, 15 mg/kg every 12 hours may be given throughout a 7 to 10 day course. Doses greater than 2 g/day do not increase efficacy,(Cross et al., 2000). and should not exceed this amount(Website 6). PEDIATRIC DOSE: The pediatric therapeutic regimen is similar to that of adults: 30 to 40 mg/kg/day, intramuscularly, divided in two doses for a total of 7 days. The alternative pediatric regimen is: 40 mg/kg/day, intramuscularly, divided in two doses for the first 3 days, followed by 20 mg/kg/day, intramuscularly, divided in two doses for the next 4 days(Cross et al., 2000). Dosing should not exceed 0.75-1.0 g/day in children(Website 6).
              • Contraindicator: Streptomycin should not be used in patients with documented hypersensitivity, for long term therapy, or in patients suffering from non-dialysis-dependent renal failure. Streptomycin should be used with caution in patients with myasthenia gravis, hypocalcemia, and other conditions that depress neuromuscular transmission(Website 6).
              • Complication: Nephrotoxicity may be increased if streptomycin is coadministered with other aminoglycosides, cephalosporins, penicillins, amphotericin B, and loop diuretics. Aminoglycosides enhance neuromuscular blocking agents potentially causing respiratory depression(Website 6).
              • Success Rate: Antibiotic therapy of tularemia has been determined empirically; streptomycin treatment exhibits a 100% cure rate(Maurin et al., 2002).
            • Gentamicin : Gentamicin is an acceptable substitute to streptomycin(Website 6, Cross et al., 2000, Ellis et al., 2002). ADULT DOSE: 3 to 5 mg/kg/day, intravenously/intramuscularly, every 6-8 hours for 7 to 14 days(Website 6, Cross et al., 2000). The desired peak serum level is at least 5.0 micrograms/mL(Cross et al., 2000). PEDIATRIC DOSE: Less than 5 years: 2.5 mg/kg/dose, intravenously/intramuscularly, every 8 hours(Website 6). Greater than 5 years: 1.5 to 2.5 mg/kg/dose, intravenously/intramuscularly, every 8 hours OR 6 to 7.5 mg/kg/day, divided in 3 doses; not to exceed 300 mg/day(Website 6).
              • Contraindicator: Gentamicin should not be used for long term therapy, in patients suffering from non-dialysis-dependent renal failure, or in patients with myasthenia gravis, hypocalcemia, and other conditions that depress neuromuscular transmission(Website 6).
              • Complication: Coadministration of gentamicin with other aminoglycosides, cephalosporins, penicillin, and amphotericin B may increase nephrotoxicity; aminoglycosides enhance neuromuscular blocking agents potentially causing respiratory depression. Coadministration with loop diuretics may increase auditory toxicity of aminoglycosides with possible irreversible hearing loss of varying degrees(Website 6).
            • Ciprofloxacin : Ciprofloxacin has been found to be effective in treating tularemia in mice and in a recent outbreak in Spain, ciprofloxacin was the antibiotic with the lowest level of therapeutic failure and fewest side effects. Ciprofloxacin was also shown to be suitable for the treatment of tularemia in a case where relapse was evident after initial gentamicin therapy(Ellis et al., 2002).
              • Contraindicator: Fluoroquinolones (including ciprofloxacin) have been reported to cause cartilage damage in immature animals and are not approved for use in patients under 18 years old(Dennis et al., 2001).
            • Tetracycline : Tetracycline is bacteriostatic for Francisella tularensis so tetracycline should be given for at least 14 days to reduce the chance of relapse(Feldman, 2003, Cross et al., 2000). ADULT DOSE: 2 g/day in divided oral doses for at least 14 days(Cross et al., 2000). PEDIATRIC DOSE: 30 mg/kg/day (up to a maximum of 2 g/day) in divided oral doses for at least 14 days(Cross et al., 2000).
              • Contraindicator: Tetracycline is not recommended for children under the age of 8 years and is unsafe for use during pregnancy or lactation(Website 6, Cross et al., 2000). It should not be coadministered with antacids containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate; oral contraceptives; or anticoagulants(Website 6).
              • Complication: Photosensitivity may occur with prolonged exposure to sunlight or tanning equipment. Fanconi-like syndrome can occur with outdated tetracyclines. Tetracycline can decrease the effects of oral contraceptives, causing breakthrough bleeding and increased risk of pregnancy. It can also increase hypoprothrombinemic effects of anticoagulants(Website 6).
              • Success Rate: Because tetracycline is bacteriostatic for Francisella tularensis relapses can often develop after cessation of treatment(Feldman, 2003).
            • Chloramphenicol : In general, chloramphenicol should not be chosen to treat tularemia because of its potentially serious toxicity and the availability of more effective antibiotics(Cross et al., 2000).
   4. Prevention:
      1. Live attenuated vaccine derived from the avirulent live vaccine strain
         • Description: At present, a "live vaccine strain" (LVS) tularemia vaccine is under investigational new drug (IND) status in a protocol at the US Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Maryland, and is available only for at-risk US military personnel. It is administered by scarification (i.e., use of a bifurcated needle to produce multiple inoculations in the skin, similar to the vaccinia inoculation for smallpox). The availability of this vaccine in the United States for use beyond selected at-risk groups has been hampered by several obstacles. Data now required for licensure were not adequately documented during its development, prohibiting plans to license the current vaccine. Because the old method of growth using shaker culture does not meet current good manufacturing processes required for FDA licensure, the manufacturing processes and potency of the current LVS vaccine are being re-evaluated, and a new process using fermentation technology will be used(Website 18), The current LVS vaccine is based on research that goes back to the 1960s. It is a descendant of strain 15 developed by the former Soviet Union's Institute of Epidemiology and Microbiology, Gamalcia Institute, in Moscow, and was sold to the US military in 1956. In the early 1960s, USAMRIID isolated the LVS strain for preventive use in at-risk US military personnel(Website 18),
         • Efficacy:
           • Rate: Efficacy studies in civilian laboratory employees at Fort Detrick revealed that the vaccine was safe and significantly reduced the incidence of typhoidal tularemia from 5.70 to 0.27 cases per 1000 at-risk employee-years. Although the incidence of ulceroglandular tularemia was unchanged by the vaccines, the disease was found to be milder in the vaccine cohort. Worldwide, LVS has since been used as seed stock for tularemia vaccines(Website 18). In volunteer studies, the live attenuated vaccine did not protect all recipients against aerosol challenges with virulent Francisella tularensis(Dennis et al., 2001).
           • Duration:
         • Contraindicator: Vaccination is not recommended for post-exposure prophylaxis due to the short incubation of the disease(Dennis et al., 2001),
      1. Recommended preventative measures
         • Description: Avoiding exposure to the Francisella tularensis is the best mechanism for the prevention of tularemia. Wild animals should not be skinned or dressed using bare hands, or when the animal appears ill. Gloves, masks, and protective eye covers should be worn when performing such tasks and when disposing of dead animals brought home by household pets. Wild game should be cooked thoroughly before ingestion. Wells or other waters that are contaminated by dead animals should not be used. The most important measure to avoid tick bites in infested areas is wearing clothing that is tight at the wrists and ankles and that covers most of the body. Chemical tick repellants may also be of benefit. Frequent checks should be made for attached ticks so that they may be removed promptly; this must not be done with bare hands, and care should be taken not to crush the tick(Cross et al., 2000),
   5. Model System:
      1. Lab animals(Ellis et al., 2002)
         1. Model Host: .
            Mouse, guinea pig, rabbit, hamster, and cotton rat,
         2. Model Pathogens:
         3. Description: Most in vivo studies of F. tularensis involve the infection of inbred mice and this system is a model to study intracelluar pathogens. A 1946 study showed that Francisella tularensis strain Schu 4 was fully virulent in the mouse, guinea pig, rabbit, hamster, and cotton rat. Strains from all of the subspecies of F. tularensis are reported to be virulent in the murine and guinea pig models of disease, but only strains of F. tularensis subspecies tularensis are considered virulent in the rabbit model of disease. The virulence of the live vaccine strain (LVS) is dependent on the route of delivery to the animal; being fully virulent when delivered intraperitoneally and attenuated when delivered intradermally(Ellis et al., 2002),

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1. Lab Biosafety Containment:
   
2. Environmental Stability:
   
3. Methods of Enviromental Disinfection:
   
4. Use in Rodent Research:
   
5. Comparison between Human & Lab Animal:
   1. Infectious Dose:
      
   2. Excretion & Transmission:
      
6. Documented Human Laboratory Exposures:
   
7. Considerations with Animal Housing, Handling, and Disposals:
   1. Animal Housing and Handling
      
   2. Tissue and Carcass Disposal
      

Anthony et al., 1991: Anthony LSD, Burke RD, Nano FE. Growth of Francisella spp. in rodent macrophages. Infection and Immunity. 1991; 59(9); 3291-3296. [PubMed: 1879943].

Berdal et al., 1996: Berdal BP, Mehl R, Meidell NK, Lorentzen-Styr AM, Scheel O. Field investigations of tularemia in Norway. FEMS Immunology and Medical Microbiology. 1996; 13; 191-195. [PubMed: 8861027].

Berdal et al., 2000: Berdal BP, Mehl R, Haaheim H, Loksa M, Grunow R, Burans J, Morgan C, Meyer H. Field detection of Francisella tularensis. Scandanavian Journal of Infectious Diseases. 2000; 32; 287-291. [PubMed: 10879600].

Choi, 2002: Choi E. Tularemia and Q fever. Medical Clinics of North America. 2002; 86(2); 393-416. [PubMed: 11982309].

Cross et al., 2000: Cross JTJ, Penn RL. Francisella tularensis (Tularemia). 2393-2402. In: . Principles and Practice of Infectious Diseases, 5th edition. 2000. Churchill Livingstone, New York.

Dennis et al., 2001: Dennis DT, Inglesby T, Henderson DA, Bartlett JG, Ascher MS, Eitzen E, Fine AD, Friedlander AM, Hauer J, Layton M, Lillibridge SR, McDade JE, Osterholm MT, O'Toole T, Parker G, Perl TM, Russell PK, Tonat K. Tularemia as a biological weapon. JAMA. 2001; 285(21); 2763-2773. [PubMed: 11386933].

Ellis et al., 2002: Ellis J, Oyston PCF, Green M, Titball RW. Tularemia. Clinical Microbiology Reviews. 2002; 15(4); 631-646. [PubMed: 12364373].

Farlow et al., 2001: Farlow J, Smith KL, Wong J, Abrams M, Lytle M, Keim P. Francisella tularensis strain typing using multiple-locus, variable-number tandem repeat analysis. Journal of Clinical Microbiology. 2001; 39(9); 3186-3192. [PubMed: 11526148].

Feldman, 2003: Feldman KA. Tularemia. Journal of the American Veterinary Medical Association. 2003; 222(6); 725-730. [PubMed: 12675294].

Forsman et al., 1994: Forsman M, Sandstrom G, Sjostedt A. Analysis of 16S ribosomal DNA sequences of Francisella strains and utilization for determination of the phylogeny of the genus and for identification of strains by PCR. International Journal of Systematic Bacteriology. 1994; 44(1); 38-46. [PubMed: 8123561].

Fortier et al., 1995: Fortier AH, Leiby DA, Naraunan RB, Asafoadjei E, Crawford RM, Nancy CA, Meltzer MS. Growth of Francisella tularensis LVS in macrophages: the acidic intracellular compartment provides essential iron required for growth. Infection and Immunity. 1995; 63(4); 1478-1483. [PubMed: 7890413].

Grunow et al., 2000: Grunow R, Spettstoesser W, McDonald S, Otterbein C, O'Brien T, Morgan C, Aldrich J, Hofer E, Finke EJ, Meyer H. Detection of Francisella tularensis in biological specimens using a capture enzyme-linked immunosorbent assay, an immunochromatographic handheld assay, and a PCR. Clinical and Diagnostic Laboratory Immunology. 2000; 7(1); 86-90. [PubMed: 10618283].

Johansson et al., 2000b: Johansson A, Ibrahim A, Goransson I, Eriksson U, Gurycova D, Clarridge III J, Sjostedt A. Evaluation of PCR-based methods for discrimination of Francisella species and subspecies and development of a specific PCR that distinguishes the two major subspecies of Francisella tularensis. Journal of Clinical Microbiology. 2000; 38(11); 4180-4185. [PubMed: 11060087].

Johansson et al., 2001: Johansson A, Goransson I, Larsson P, Sjostedt A. Extensive allelic variation among Francisella tularensis strains in a short sequence tandem repeat region. Journal of Clinical Microbiology. 2001; 39(9); 3140-3146. [PubMed: 11526142].

Maurin et al., 2002: Maurin M, Mersail NF, Raoult D. Bactericidal activities of antibiotics against intracellular Francisella tularensis. Antimicrobial Agents and Chemotherapy. 2002; 44(12); 3428-3431. [PubMed: 11083651].

Parola and Raoult, 2001: Parola P, Raoult D. Ticks and tickborne bacterial disease in humans: an emerging infectious threat. Clinical Infectious Disease. 2001; 32; 897-928. [PubMed: 11247714].

Pomerantsev et al., 2001: Pomerantsev AP, Golovliov IR, Ohara Y, Mokrievich AN, Obuchi M, Norqvist A, Kuoppa K, Pavlov VM. Genetic organization of the Francisella plasmid pFNL10. Plasmid. 2001; 46; 210-222. [PubMed: 11735370].

Prior et al., 2001: Prior RG, Klasson L, Larsson P, Williams K, Lindler L, Sjostedt A, Svensson T, Tamas I, Wren BW, Oyston PCF, Andersson SGE, Titball RW. Preliminary analysis and annotation of the partial genome sequence of Francisella tularensis strain Schu 4. Journal of Applied Microbiology. 2001; 91; 614-620. [PubMed: 11576297].

Syrjala et al., 1986: Syrjala H, Koskela P, Ripatti T, Salminen A, Herva E. Agglutination and ELISA methods in the diagnosis of tularemia in different clinical forms and severities of the disease. The Journal of Infectious Diseases. 1986; 153(1); 142-145. [PubMed: 3941279].

Website 1: Laboratory Response Network: Level A procedures for identification of Francisella tularensis

Website 14: Homo sapiens: taxonomy browser

Website 15: Francisella tularensis var. novicida plasmid pFNL10, complete sequence

Website 16: Francisella tularensis, complete genome sequencing of the highly virulent Francisella tulerensis strain Schu 4

Website 17: Microbial genomics and applications

Website 18: Developing New Tularemia Vaccines

Website 19: Product Information for Francisella tularensis

Website 2: Disease fact sheet series: Tularemia (rabbit fever)

Website 3: Tularemia FAQ's

Website 4: Francisella tularensis: Material Safety Data Sheet

Website 5: Francisella tularensis as a Bioterrorist Agent

Website 6: Tick-borne diseases, Tularemia

Website 7: Tularemia. Biological Warfare Defense Information Sheet

de la Puente-Redondo et al., 2000: de la Puente-Redondo VA, Garcia del Blanco N, Guitierrez-Martin CB, Garcia-Pena FJ, Rodriguez Ferri EF. Comparison of different PCR approaches for typing of Francisella tularensis strains. Journal of Clinical Microbiology. 2000; 38(3); 1016-1022. [PubMed: 10698989].

 

PathInfo: Randy Vines, Krista Morris

HazARD: Rachel Liepman, Yongqun He (for the section of Lab Animal Pathobiology & Management)

PHIDIAS: Yongqun "Oliver" He

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